Podcast appearances and mentions of shannon mckernin

An interview with Dr. Edouard Trabulsi from the Sidney Kimmel Medical College at Thomas Jefferson University on "Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline." This guideline outlines techniques available and provides recommendations on appropriate use of imaging for specified patient subgroups. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. My name is Shannon McKernin, and today I'm interviewing Dr. Ed Trabulsi from the Medical College at Thomas Jefferson University in Philadelphia, Pennsylvania, lead author on "Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline." Thank you for being here today, Dr. Trabulsi. Thanks, Shannon. Thanks for inviting me. So first, can you give us a general overview of what this guideline covers? Sure. So the purpose of this guideline, and it's fairly broad, is to try to come up with some recommendations and strategies for appropriate imaging for patients with advanced prostate cancer. Also, that includes patients that are newly diagnosed that are high or very high risk for having micrometastatic disease. Also, patients that have been treated and are suffering recurrence of disease as indicated by rising PSA. And then also, patients with metastatic disease, either on initial diagnosis, or on treatment and who are contemplating changing treatments. Also, it has a wide range of different patient populations that all fit in the category of advanced prostate cancer. And the idea is to try to figure out or make some recommendations on strategies for what imaging is appropriate for each of those groups of men. So what are the key recommendations for this guideline? Well, the big impetus for this guideline is the awareness of what we would consider next-generation imaging, meaning that there's a large group of new or novel imaging studies available and on the horizon. And we're trying to figure out the best way to fit them in in the context of traditional imaging in what we would call conventional imaging. So that would be-- conventional imaging would be imaging tests like CAT scan, radionuclide bone scan, prostate MRI, that sort of thing. Next-generation imaging would include some of the newer PET imaging scans, using different tracers and isotopes, and some of the new SPECT imaging scans, as well as full body MRI. And so how to interweave those different imaging tests is really what's proving to be not as straightforward as we'd like. And so we realized that we need to really approach this based on a clinical disease state model. So not just one monolithic category of advanced prostate cancer, but looking at specific scenarios. And we developed this guideline as a scenario-based algorithm. So the initial diagnosis of prostate cancer of men that are at high risk, what images we think about there; for men that have been treated and their PSA is rising, and so forth. And so we shouldn't jump to next-generation imaging across the board. We really should look very specifically at circumstances where these new, novel, and unfortunately, expensive imaging tests could have real clinical impact. So patients that are newly diagnosed that are high risk who have suspicious or equivocal conventional imaging, so they have a CAT scan or a bone scan or something that we're really not sure if something that we're seeing there might be an indication of disease, that's a good spot where next-generation imaging might be very helpful. For patients that have been treated and their PSA is rising, say, after surgery or, say, after radiation, and they get traditional, what we would call conventional imaging, and we don't see a source for the PSA, well, that is another scenario where a patient-- or a category where next-generation imaging should be considered. In that specific space, there actually are two PET imaging studies that have been approved by FDA in the US with C-11 choline, as well as the fluorine-18 fluciclovine scans. And then also overseas, or not yet approved in the US, there are other PET-based agents that are being used in that specific space. Another important aspect of this is that it should have real clinical impact. So if you have a man who unfortunately may be suffering, or evidence of recurrence of disease after surgery or radiation, but because of their comorbidities or age or patient preference, they're not necessarily going to be aggressive with additional therapy, then we probably don't need to chase some of these next-generation imaging studies in that man. In the confirmed metastatic patient population, that is a little more unclear in terms of what the benefit of next-generation imaging would be outside of the setting of a clinical trial. And in those patients, if it is thought that there would be a change in clinical treatment based on the results of the scan and of next-generation imaging, then that would be a scenario where those might be considered. But we wouldn't necessarily recommend them across the board. And so why is this guideline so important? And how will it change practice? Well, it's important and timely because of the tidal wave that we are expecting of novel, next-generation imaging that is going to become closer and closer to clinical practice. Patients are aware of these studies, and they're asking for them, even if they're not currently available or approved by an FDA or covered by a third-party insurance. There's been a plethora of research studies and new imaging tracers in Europe, Southeast Asia, and Australia. And so trying to get ahead of where they might fit in, and which patients might benefit now and in the future, was really one of the main drivers to come out with a strong position statement on the appropriate use of imaging. There's a lot of controversy about some of the implications of the next-generation imaging, such as the potential for false positives and the attendant prognostic tests, that that might trigger false negatives, and potentially offering clinicians or patients a more optimistic outlook than may be really present. And so figuring out specific scenarios and specific patient populations that would benefit from next-generation imaging is the real goal of this guideline. And so finally, how will these guideline recommendations affect patients? Well, the ultimate goal is to improve patient care and improve patient outcomes. And so by coming up with some reasonable templates and framework of where some of the next-generation imaging will fit in on a patient's disease spectrum and disease course will help them both to potentially indicate when treatment changes may be necessary, or to isolate areas of disease, and to importantly and accurately give their correct stage. And then that will translate, or we hope and expect, with more information and more accuracy in diagnosis, in better treatment plans and better patient outcomes. Great. Thank you for your work on this important guideline on Optimum Imaging Strategies for Advanced Prostate Cancer. And thank you so much for your time today, Dr. Trabulsi. Thank you so much. Thanks for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline and find additional resources, such as the guideline pocket card, go to www.asco.org/genitourinary-cancer-guidelines. And you can find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or the Google Play Store. And if you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

An interview with Dr. Scott Eggener of University of Chicago Medicine on "Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline." This guideline provides recommendations for available tissue-based prostate cancer biomarkers geared toward patient selection for active surveillance, identification of clinically significant disease, choice of postprostatectomy adjuvant versus salvage radiotherapy, and to address emerging questions such as the relative value of tissue biomarkers compared with MRI.  Read the full guideline at www.asco.org/genitourinary-cancer-guidelines  TRANSCRIPT If you like what you hear from the ASCO podcast, please let us know. Take our listener survey and help shape the future of the ASCO Podcast Network. Visit podcast.asco.org, and click on the survey link. Once again, that's podcast.asco.org. The survey will just take a few minutes to complete and will help us get to know you better. Thank you so much for listening. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at podcast.asco.org. My name is Shannon McKernin. And today I'm interviewing Dr. Scott Eggener from the University of Chicago Medicine, lead author on molecular biomarkers in localized prostate cancer ASCO Guideline. Thank you for being here today, Dr. Eggener. Thanks for having me, Shannon, and covering the guideline. So first, can you give us a general overview of what this guideline covers? Yeah, this guideline has been two years in the making and is an overview of the available molecular biomarkers to help clinicians and patients make smart decisions for men with localized prostate cancer. And that's in the newly diagnosed setting, as well as for certain patients that have undergone surgery and are considering adjuvant radiation therapy. And so what are the key recommendations for this guideline? So there was a lot of data that the team looked through with the help of the ASCO home office, and a Herculean amount of work went into it. There's a lot of commercially available tests out there. Most of them are quite expensive. And we are trying to make sense of the available literature and provide a guide to clinicians on what these tests are, which patients they might be relevant for, and how to interpret them. The key takeaways that the data that's been published for most of these biomarkers are purely prognostic. And there is good science and good data supporting them. But they have not been embedded in a rigorous fashion or within trials or validated to have the highest level of evidence. However, they can be used in certain situations to add additional info for the patient and clinician to try to make smart decisions based on prognostic information. Another key recommendation is that there are select patients that these can be helpful for. And we dive into a lot of the details on who these patients may be. Number one is a patient newly diagnosed with prostate cancer who is trying to determine whether to do treatment of the prostate cancer or embark on active surveillance. And some of those decisions are relatively easy and straightforward. But when the clinician and the patient are looking for all pieces of information to influence one way or the other, genomic or molecular biomarkers can be useful at that critical fork in the road. However, we made it very clear multiple times throughout the guideline that our group's recommendation is that the biomarkers should not be reflexively ordered for every individual newly diagnosed with prostate cancer. It seems wasteful and not an appropriate use of resources. The other situation clinically where these can be used are for men that have had previous surgery and are considering secondary radiation therapy, which can be given in an adjuvant or salvage manner. And there are some data suggesting that a specific test by Decipher, a genomic classifier, can be used to help inform whether adjuvant radiation would be appropriate or not. So that was a good overview. And this guideline also includes some special commentary sections with additional research questions that the expert panel wanted to address. So can you tell the listeners a little more about these important considerations? Yeah, it's critically important to know that these tests are not black and white. And they don't always clarify a data-based path forward. But we tried to emphasize in many different areas that integrating genomic or molecular information can be integrated into optimizing decisions. And the special commentary really dives into a lot of those details on working with the pathologists on selecting the appropriate biopsy sample to send to one of these laboratories. It gets into some of the specifics on interpreting the data, as well as the role of CLIA-approved labs and non-CLIA-approved labs for certain staining that's done internally within organizations or with biomarker panels. And so would you be able to expand a little more about which patients may benefit from having molecular biomarkers? Yeah, the sweet spot for some of these biomarkers include a couple different patient groups. The first one is what I alluded to earlier-- the man newly diagnosed with prostate cancer deciding whether to do active surveillance, which is a monitoring program, or to have treatment of the prostate typically by either surgery or radiation therapy. Again, worth emphasizing-- these tests are not appropriate for every newly diagnosed patient. And I would argue even for the man deciding between surveillance and treatment, there are specific men, perhaps those with higher volume low risk prostate cancer or lower volume favorable intermediate risk prostate cancer, that provides the ideal patient that may benefit from some of these tests. The second clinical scenario that was discussed amongst the group were patients where treatment intensification might be valuable. Again, these biomarkers are purely prognostic, and there's no high level evidence suggesting that treatment intensification leads to better outcomes. Although intuitively, the higher risk profile a patient has, either by clinical factors or biomarkers, there is a conceptual rationale that treatment intensification might prove beneficial. And the third category of patients that may benefit are those who have had prostatectomy where the pathology shows some adverse features, and there's a high likelihood of recurrence, and the clinician's decision is to guide the man on whether pure adjuvant radiation in the setting of an undetectable PSA or early salvage therapy at the time of biochemical recurrence would be more valuable. And there is one test that is commercially available that can help inform that decision. Great, so finally, what do you envision as the future of molecular biomarkers for localized disease? As we took an overview of the landscape in 2018 and 2019 of these molecular biomarkers, much of the group thought this was version 1.0 or 2.0 in this space. And it is our hope and likely scenario that not only will we have better data on some of the currently available biomarkers with higher levels of evidence from either correlative science from randomized trials or formally embedded into randomized trials, but also that there's a large amount of work being done to improve the quality of biomarkers and that, in the future, we'll see improvements on the currently available ones or newer biomarkers coming around that will be valuable for these men as they make decisions along their prostate cancer course. Great. Thank you for your work on this important guideline. And thank you for your time today, Dr. Eggener. Thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline and find additional resources such as the guideline's pocket card, go to www.asco.org/genitourinary-cancer-guidelines. And you can find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or in the Google Play Store. And if you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Shlomo Koyfman from the Cleveland Clinic, lead author on "Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Koyfman. It's a pleasure. So first, can you give us a general overview of what this guideline covers? Yeah, so this is an exciting guideline because it covers a topic that we don't usually think about in head and neck cancer in a formal way, and that is management of the neck in squamous cell cancer of the oral cavity and the oropharynx. So there's a lot of literature and guidelines out there on how to manage oropharynx cancer, which is becoming a more and more common cancer, especially in the HPV-positive era, less so on oral cavity. But a lot of times it's focused on people who don't get surgery, chemoradiation, or people who do get surgery and TORS, Transoral Robotic Surgery, and different approaches. But rarely do we have something focus on management of the neck per se, which is really, really important in these cancers and often overlooked in favor of the primary tumor itself. So these guidelines really take us through some salient questions in how to manage the neck in these two cancers. And what are the key recommendations of this guideline? The recommendations came off of six fundamental questions, three in oral cavity and three in oropharynx. There are some commonalities between the two and some differences. A lot of the fundamental questions revolve around surgical quality, and neck dissection is the standard surgical approach for management of the neck in these patients. And as we enter the quality era, how do we define benchmarks of surgical quality, which is one thing that it deals with. The other is when to do adjuvant therapy like adjuvant radiation or chemoradiation. We also deal with when to do surgery for the neck or to do nonoperative approaches like radiation or chemoradiation. And then lastly, how do you follow patients after you've treated them? So those are kind of the salient issues that we dealt with. And what we came out with was nothing earth shatteringly new, but I think the way it was organized and systematically put together, I think it's going to be really, really helpful for people. So some of the most important findings that this recommendation does, I think this is the first that incorporates surgical quality, as I mentioned before. So specifically neck dissection should have 18 or more nodes as multiple studies have shown that that's associated with better outcomes. And similarly we define for different diseases of oral cavity and oropharynx, and depending on what kind of tumor it is and where, what nodal levels should be dissected or treated, whether surgically or nonsurgically, and when to do just one side of the neck versus both sides of the neck. So I think there's a lot of good guidance there in terms of the surgical quality. From a standpoint of adjuvant therapy, we define pretty clearly indications for when after surgery for oral cavity cancer, for example, when radiation should be added and when chemoradiation should be added, and I think that's very helpful. And especially for the neck itself, there's been confusion about what happens if I have 30 nodes taken out and they're all negative but I have a big, large primary tumor. What do I do with the neck? Do I radiate it? Do I not radiate it at one side, both sides? And this guideline gives some pretty clear guidance in different scenarios about how to think about that, which is pretty novel and really important, I think. I get questions about this all the time. It comes up in tumor boards all the time, and it's pretty practical. And mostly what we say is if you have a primary tumor that's like a T3 or T4 oral cavity cancer or it approaches midline, either a contralateral neck dissection should be done or radiation should be done to the contralateral neck. And even if you have a lot of lymph nodes taken out and they're negative, if you have very high-risk primary tumor features like very large tumor or multifocal perineural invasion, those kinds of things, even with a negative neck dissection we still typically do treat the neck. So the next recommendation that's really helpful is who can be observed after surgery? And specifically low-volume N1 you can consider observing in oral cavity cancer, whereas N2 or N3 patients all need radiation or chemoradiation in the setting of extranodal extension and positive margins. We did come out pretty firmly advocating for bolus cisplatin 100 milligrams per meter squared every three weeks as recent studies suggest that weekly cisplatin or other regimens are not as effective, and we were pretty clear about that. We were pretty synchronized with recent ASCO-endorsed guidelines in oropharynx cancer that say similar things. In addition, one of the very important questions that comes up is a surgeon will say, well, I'm cutting out the neck tumor, and I know it comes to midline and he's got a bunch of nodes on the right side, but do I really need to do a left neck dissection? Aren't you going to radiate it anyway? And that comes up all the time. Is radiation adequate to manage a clinically negative neck in oral cavity cancer and oropharynx cancer? I think in oropharynx cancer everybody feels pretty comfortably yes. I think in oral cavity cancer it's been somewhat controversial. We favor neck dissections when possible, but if radiation is known to be happening, especially to an elective contralateral neck, that that is adequate therapy. However, we're pretty strong in the fact that neck dissections are the tried and true way to treat oral cavity cancer and that in a T2 or above tumor where a neck dissection is indicated, just resecting the primary and leaving the neck to elective radiation is not something that we thought there was enough evidence for to advocate, and we still advocate classic neck dissection first followed by adjuvant radiotherapy as indicated. One area of controversy that we did touch on is the issue of early stage tongue cancers and whether they need a neck dissection at all. And we came down pretty consistently with all of the co-authors on the guideline that we advocated for a neck dissection for all patients with oral cavity cancer unless it is a very small tumor that we define with very compliant patient who is amenable to very rigorous follow-up that has been done in Europe and in some other places with, specifically, people trained in careful neck ultrasound techniques. So all of those really help guide, both in early stage and more advanced stage, how to manage the neck and oral cavity cancer. And in oropharynx cancer, again, many of the same quality metrics apply. We have some guidance about when doing transoral robotic surgery how to reduce bleeding risk by ligating feeding blood vessels, which is an important addition. We also discuss the fact that, as opposed to lateralized oral cavity patients where a unilateral either neck dissection of radiation is often indicated, in oropharynx cancer the group felt very strongly that bilateral neck should be treated. And typically if tumors extend to midline or involve the posterior oropharyngeal wall, which has bilateral drainage, that either bilateral neck dissection should be performed in those cases or a unilateral neck dissection can be done as long as adjuvant radiation is planned to both necks. Finally, a couple of very important questions of who should not be treated surgically and who should be treated with a nonoperative chemoradiation based approach. In oral cavity cancer, as long as they were not metastatic, we felt people should be resected as long as they were surgically resectable and medically operable. In oropharynx cancer, however, anybody who had unequivocal extranodal extension of nodes into soft tissues or involvement to the carotid artery or extensive cranial-nerve involvement or skull-based involvement by extensive nodal disease are not good candidates for surgery and should be preferentially treated with chemoradiation. That was pretty strong. And finally, the other thing we gave clarity on is when we treat oropharynx cancer with chemoradiation, how do we follow them and when do we decide to do a neck dissection or not? And essentially we recommended a PET CT scan at 12 weeks. And as long as that was negative, a neck dissection should not be done. If you don't have a PET scan and you just have high quality CT or MRI but all of the neck disease has resolved, similarly there should be no neck dissection. And then most importantly, the situation we all face which is very complex is what happens when you have a PET CT done three to four months after treatment and you have small nodes that are still there? You have a little bit of uptake. The FDG avidity is much less than it was. There still is a lesion there, but it's much better and the patient is feeling well. And we felt pretty comfortable not doing a standard neck dissection on those patients but rather following them closely with a follow-up CT scan two to three months later and continual assessment and reserving surgery for obvious progressive disease. So why is this guideline so important, and how will it change practice? So this guideline is really important because head and neck cancer being not the most common cancer, and especially because head and neck cancer is not really one disease-- there's so many different diseases. Even oral cavity and oropharynx, there's quite a bit of variability in how we think about it. There's not a one size fits all recipe for how to manage people properly, and that leads to a lot of confusion and sometimes doubt as to what the best thing to do is in these patients. And that is a very common thing. So I think the most important reason why these guidelines are helpful is they're really clear. They give really clear guidelines of if you're going to do surgery, here's the expectations of what nodal levels to take out and how many nodes to take out. Here's when you should do adjuvant radiation. Here's when you should do adjuvant chemoradiation. Here's when you should treat one side of the neck. Here's when you should treat both sides of the neck. If you're not going to do surgery, here's when you do radiation. And for oropharynx cancer, here's when you can consider surgery. Here's where surgery is not the best idea. And when you treat them and if you do surgically, here's how you do it. If you do with radiation, here are the nodes that should be treated, the nodal levels. And finally, after you do that, how do you watch and act to make sure that people don't fail? So I feel like all of those things lend a lot of clarity to some complicated decision-making processes for these patients, and this really lends clarity to that, which should help kind of lend consistency of practice. That's really our goal. Our goal was there a lot of great docs taking care of these patients out there, but patients are treated in very different ways depending on who they're seeing and where you go. Our goal was to try to increase the consistency of how people are treated no matter where they are. And if practitioners, surgeons, radiation oncologists, medical oncologists see this guideline and kind of follow it and, of course, reach out with any questions at any time, then what we'll be able to do is kind of harmonize the way patients are treated in this country, which should help, I think, the quality of care. And finally, how will these guideline recommendations affect patients? They're going to affect patients because right now a lot of patients get great care, but there are some patients that are not getting ideal care either because maybe they're in parts of the country that don't have the same access to resources or they're in places where the volume of these kind of very complicated and yet not so common diseases aren't seen as high and there's confusion about how to manage them or what the quality metrics are. I think patients are going to be affected knowing, hey, if I'm going to have a neck dissection, here's what I should be asking to make sure my surgeon knows to do and does consistently to make sure it's of high quality. Here's where I think I should be treated with surgery, maybe I shouldn't be treated with surgery, and here's how to follow me. Because there is a lot of variability in how patients are treated, and sometimes there's too many surgeries being done, not enough surgeries being done. If they're being done, maybe they're not the best quality. Even if we don't treat with surgery and we do chemoradiation, we're watching them and we may not be following them as closely, and then people may be recurring and we're not picking it up closely enough. So I think it's going to harmonize, for patients, the way they're ultimately treated. If everybody in the country is treated relatively compatible with this guideline, I think the standard of care will go up across the board. Great. Thank you so much for your work on this important guideline, and thank you for your time today, Dr. Koyfman. Thank you so much. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Randy Taplitz from UC San Diego Health, lead author on Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. Thank you for being here, Dr. Taplitz. Thank you. So first, can you give us a general overview of what this guideline covers? Yes. I mean, I think we're all aware that infection in the setting of neutropenia associated with cancer chemotherapy is really a major cause of morbidity in these patients. And it's also important to be aware that prevention and appropriate management of febrile neutropenia and infection should thus be a critical focus in cancer care. So the focus of this particular guideline was to evaluate the risk and benefits of antimicrobial prophylaxis in these patients and really to determine evidence-based best practices for prevention of infection and how to go about doing that. So In this guideline, what we do is we identify the groups at risk for febrile neutropenia and really recommend settings for which prophylaxis with antibacterial, antifungal, antiviral medications are indicated. And then as well make recommendations for consideration of vaccination and other measures such as respiratory etiquette, and hand hygiene, and the like that will help reduce the risk of infection in these vulnerable patients. So since this is an update of a 2013 guideline, what are the major changes? And can you tell us a little bit about the research that informed this update? Yes. Really, when you update a guideline, one is informed by review of articles that encompass, in this setting, randomized clinical trials as well as meta analysis of interventions to prevent microbial infections in patients with neutropenia or other types of immunosuppression. And one example of this-- I think one of the better examples-- is we reviewed a large meta analysis of antibiotic prophylaxis in neutropenic patients after chemotherapy that showed that for fluoroquinolone prophylaxis resulted in really significant reductions in all cause mortality and febrile episodes, particularly in patients who were high risk, meaning the hematologic malignancy population and stem cell transplant population. And in that particular population, in fact, the number needed to treat to prevent one death was 29. So therefore, in that high risk population, really as with prior guidelines, the fluoroquinolone prophylaxis is recommended. However, we also reviewed other articles that include emerging data on some of the risks of fluoroquinolone prophylaxis. So for instance, the effect of fluoroquinolone on the intestinal microbiome and its association with selection of fluoroquinolone-resistant bacteria such as Gram-negative rods, as well as selection of organisms such as Clostridium difficile and enterococcus. And then we also reviewed fluoroquinolone toxicities. So what is added to this guideline are some qualifying statements alerting clinicians to really be aware for these concerns and to consider what the clinical spectrum of things like Clostridium difficile infection, et cetera, look like. In terms of antifungal prevention, including pneumocystis prevention, we really haven't made any major changes to this guideline with the exception that in this new guideline, the panel has also started looking at complications associated with immunotherapy and actually makes a suggestion that people consider pneumocystis prophylaxis in the setting of prolonged steroid use when it's used to treat immune-related adverse events that we've begun to see in increasing numbers associated with agents like checkpoint inhibitors and other immunotherapies. In terms of viral infections, the updated guidelines recommend risk assessment for hepatitis B reactivation and then treatment in accordance with other ASCO guidelines and yearly influenza vaccine, as well as really endorsing other vaccines as described in the Infectious Disease Society of America Guideline for Vaccination in Immunocompromised Hosts. So really, those are the main new events since 2013. And what are the key recommendations of this guideline? So the key recommendations-- the first thing is what we call a risk assessment. So after-- what one does is carefully assess, really, what the risk of febrile neutropenia is. And that includes assessment of patient, what the cancer is, and what the treatment-related factors are. And then after they're risk adjusted and risk assessed, then we take, in turn, different forms of prophylaxis that we consider. And so the first one that we always consider is antibiotic prophylaxis against bacterial infections. And the recommendation is still with the fluoroquinolone. And that's recommended for most patients who are at high risk for febrile neutropenia or profound, really prolonged neutropenia, such as those getting therapy for AML, or myelodysplastic syndrome, or stem cell transplant recipients, particularly with myeloablative regimens. In the lower risk groups, such as those with most solid tumors, fluoroquinolone prophylaxis is not recommend. In terms of antifungal prophylaxis, what is recommended is an oral triazole or Micafungin-- for patients, again, at risk for profound protracted neutropenia such as that AML, MDS, stem cell transplant group during that period of neutropenia. When the risk of invasive aspergillus is high, such as in patients with AML or MDS during the neutropenia period while getting chemotherapy, then the consideration of a mold-active triazole is recommended and in addition should be considered in the context of stem cell transplant recipients with graft versus host disease. In terms of PCP prophylaxis, PCP preventive therapies are recommended for those at high risk for PCP, which include those on greater than what we say 20 milligrams of prednisone equivalent a day for over a month, or based on purine analog use. Viral prophylaxis for HSV is recommended for seropositive patients undergoing allogeneic stem cell transplant or leukemia induction. And then as I mentioned before, patients at risk for hepatitis B reactivation are recommended treatment with a nucleoside reverse transcriptase inhibitor. And this is more carefully discussed in the ASCO Provisional Clinical Opinion on Hepatitis-B Virus Screening for Patients With Cancer Before Therapy. It's also recommended that a yearly flu vaccine is given to patients as well as given to family, household contacts, and health care workers. Other vaccination recommendations are as per the Infectious Disease Society of America Guidelines for Vaccination of Immunocompromised Hosts. And then the other things that are recommended are really review and repeat recommendation of adherence with hand hygiene, with respiratory etiquette, which is recommended and really required for all health care workers. And that out patients with neutropenia from cancer chemotherapy should avoid high risk activities, which include really contact with environments that have high concentration of fungal spores such as construction and demolition, high intensity gardening, et cetera. So those are really a summary of the key recommendations of this guideline. And finally, how will these guideline recommendations affect patients? I think it's important to remember that to ensure best practices on infection prevention, the literature needs to be reviewed frequently and guidelines need to be updated. I don't think that these current guidelines will dramatically change the preventive strategies that are used for patients, with the exception of perhaps a few extra vaccines-- some newer indications for pneumocystis prevention, hepatitis B reactivation prevention, those kinds of things. However, I think in reviewing the literature, it becomes clear what will we will need to be thinking about in the coming years, what we will need to be assessing. And a couple of those things are the dramatic increase in the use of immune-based therapies and how that will affect infection risk in patients with or without neutropenia. We need to be considering the effects of routine antibiotic prophylaxis on the microbiome and the risks that that might incur. And we need to really understand how new vaccines can be utilized. So yeah, I think these areas are really ripe for research and need to be followed closely to ensure optimization of these preventive strategies for our patients in the future. Thank you for your time today, Dr. Taplitz. You're quite welcome. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer this show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Manish Shah from New York Presbyterian Weill Cornell Medical Center, senior author on "Treatment of Patients with Early-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline." Thank you for being here today, Dr. Shah. Thank you, it's a pleasure and honor to be here. So first, can you give us a general overview of what this guideline covers? Yes, absolutely. So the "Treatment of Patients with Early-Stage Colorectal Cancer" is a resource-stratified guideline. And it focuses on the management of patients with early-stage colon cancer. It's different than the surveillance and screening guideline that was written simultaneously for ASCO as another resource-stratified guideline. We felt that this was a big enough topic that we should keep it separate. So it really talks about the management of pre-malignant lesions, as well as early-stage colon cancers, as well as rectal cancers. And the other aspect of this is that we really focused on how the guideline may apply in settings where there-- they don't have maximal resources, so basic or limited settings as well. So I would like to talk a little bit about how the guideline was created, because I think that's an important aspect. And it distinguishes it from typical other ASCO Guidelines. So the management of colon cancer or colorectal cancer, there's a lot of literature on this. And there are several guidelines that have been produced by colorectal cancer societies, or surgical societies, or from other countries like the EORTC, or Japan, or Korea, or even the UK. So in fact, there were, I think, 30 to 40 different guidelines that we reviewed. And we felt that, instead of doing a new literature search to kind of rehash much of the same information, we reviewed all the guidelines for certain quality measures to then select a handful of guidelines that we would use as the reference for each of our key questions or key points. And this was done in a formal process, the first by ASCO and Sarah, who was the ASCO staff who wrote the guideline, along with the members of the guideline panel. And in this process, I think that we have a pretty comprehensive guideline that covers the questions with the best evidence available. So what are the key recommendations of this guideline? Yeah, so we addressed some several questions with regard to key recommendations. The first question, for example, was, what's the optimal treatment for patients with colon cancer that would be clinical stage 1 through 3c? And we distinguish that from a non-obstructing cancer to obstructing cancers as well, because the management would be very different. And what we really sort of focused on is that these patients should have resection following oncologic principles. Then ideally, they should have an en bloc resection by a surgical oncologist to give the patients the best chance of care. But I think what's unique to resource-stratified guidelines, and what we have to do is sort of highlight the care that would be achieved in settings that have less resources. So a non-obstructing colon cancer in a basic setting should still have surgery and should still undergo an en bloc resection following standard oncologic principles. So that was, for example, one of the key points that was uniform across all the settings. Other things were how to manage [INAUDIBLE] colon cancer. So in more enhanced and maximal settings, sometimes there might be opportunity to place a colonic stent, for example, by either a colorectal surgeon or by someone who has specialized training in the placement of these stents. And that would be a preferred approach in both the enhanced and maximal guidelines, whereas in a more basic setting, the recommendation was to perform a resection and possibly, if required, if a resection was not possible, a diversion to overcome the obstruction in that localized setting. There were other recommendations that were also important. So for example, in early-stage rectal cancer, so clinical stage 1, T1 and 0 rectal cancer, in a maximal setting, these are sort of low-risk cancers without adverse features like high-grade or involvement of lymphovascular structures. The surgical oncologist and/or colorectal surgeon might consider a local excision such as the TEM procedure, which is a transendomucoscal resection. And in basic or limited settings, we would still recommend surgery in that setting following TME principles to achieve clear margins and a good surgical outcome, because we felt that, in basic-limited settings, the skill and the equipment necessary to do a local excision may not be available. Another recommendation that might highlight the differences between basic and limited settings versus a more maximal setting is the optimal strategy for post-treatment surveillance. So this is after resection of the stage 1 to 3 colorectal cancer. What would be the best way to monitor and surveil patients? And this is the recognition that the purpose of surveillance is to identify recurrence early at a time point where the patient may still be amenable to having local regional resection or resection of the metastatic lesion to change the outcome. So the current ASCO guidelines are to perform a medical history, and physical examination, and a CEA every six months for three to five years, have an abdominal and chest CT scan, in high-risk patients, every 6 to 12 months for three years, and a colonoscopy one year after the surgery, and then every five years or so after that, as indicated, up to age of 75. And that's what we recommended in the maximal and enhanced settings. But in a more basic setting, the recommendation was similarly medical history and physical exam every six months for three years, a CEA every six months for three years, a chest X-ray and abdominal ultrasound twice in the first three years, and a colonoscopy once i the first two years. And then if a colonoscopy is not available, we recommended a double-contrast barium enema or, for left-side tumors, a sigmoidoscopy to try to surveil the local regional extent of the the disease. So I think what we're trying to highlight is that we think that we can help patients for the management of localized early-stage colon cancer, both for treatment as well as for surveillance, and that these recommendations may vary a little bit in more limited settings, but with these recommendations, we can provide the best care for patients overall. And so why is this guideline so important? And how will it change practice? I think that the guideline is really important, because we recognize that we're practicing medicine in the United States, or in Europe, or wherever you practice, but the levels of resources that are available to us are not uniform. And so we really are getting to the aspect that cancer care is a global proposition. And ASCO should reflect that. And so the intention of these resource-stratified guidelines is to try to provide guidance into the best management for the indication across the spectrum of resources that are available. Interestingly, we've also heard from many people who practice in more resource-limited settings that they can use these guidelines to sort of advocate for their own area, to say that, based on our availability, we fit in a criteria that's basic or limited, but we really want to be an enhanced setting, and lobby their governments or their local officials to say, these are areas that we can improve on to take us to the next level, literally. And finally, how will these guideline recommendations affect patients? Yeah, at the end of the day, I think it's very important that we remind ourselves that we're doing this to improve patient care overall. I think, in maximal and enhanced settings, the guidelines kind of reiterate the best practices across [INAUDIBLE] of guidelines that were reviewed. So I think that's a very important thing. And they unify the treatment plan across different practices. But I think most importantly, in basic and limited settings, it provides a benchmark for what should be done. I think, for me, one key thing was that, even in basic and limited settings, we don't want to compromise oncology principles for a surgical resection. You know, it's not appropriate to just resect the tumor but leave some tumor behind to relieve an obstruction. We still need to manage that appropriately. And that is the expectation in a basic setting, for example. So I think that, overall, wherever you are, this guideline provides recommendations to help manage the patient across the resources that are available to you. I think that's very important, because we live in a heterogeneous environment where resources are not uniform across the world. Great, thank you for your discussion of this important guideline. And thank you for your time today, Dr. Shah. Oh, it's my pleasure. Thanks for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Lynn Henry from University of Utah Huntsman Cancer Institute on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." This guideline update includes data from the MINDACT and TAILORx trials to clarify the recommendations for patients with hormone receptor-positive, HER2 not overexpressed, axillary node-negative early breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines  TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin. And today, I'm interviewing Dr. Lynn Henry from the University of Utah Huntsman Cancer Institute, lead author on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you for being here today, Dr. Henry. Thank you very much for the invitation. So this guideline was updated to incorporate new data from the TAILORx and the MINDACT trials. So can you give us an overview of these trials and their results? Sure. So patients with hormone receptor-positive, HER2 negative breast cancer, are generally treated with anti-estrogen treatment and are sometimes also recommended to have chemotherapy. Since these tumors don't always respond well to chemotherapy, tests have been developed that provide more information about how much benefit, in terms of reduction of the likelihood of cancer coming back, an individual patient is likely to get from treatment with chemotherapy. It is important that the benefit of a treatment outweighs the risk of toxicity from the treatment. Two of those tests are called Oncotype DX and MammaPrint. And they have recently been tested in large clinical trials. So TAILORx is a large prospective trial that tested the Oncotype DX assay. In the Oncotype DX assay, a tumor is tested to get more information about how likely a cancer is to return and how much benefit the patient is likely to get from chemotherapy. Scores on this assay can range from 0 to 100. Previously, a study showed that patients whose tumors had scores of 10 or less, and who received five years of anti-estrogen treatment, were very unlikely to have their tumors return. So chemotherapy is not recommended for them. For patients with higher scores, above 30, we also already knew that chemotherapy is likely to decrease the chance of cancers in those patients, and, so, therefore, we generally recommend chemotherapy for women with higher scores. In the TAILORx trial, the recently reported trial, more than 6,700 women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer had their tumors tested and were found to have Oncotype DX recurrent scores between 11 and 25, which is in that intermediate range or at the higher end of the low range. Before this trial was conducted, many people with tumors like these, in the intermediate range, were treated with both chemotherapy and endocrine therapy because we weren't sure how much benefit they would obtain from chemotherapy, and we didn't want to leave out a potentially helpful treatment. In this trial, patients were randomized, or randomly assigned by a computer, to treatment with chemotherapy followed by endocrine therapy or to treatment with endocrine therapy alone. The trial was mainly looking at whether leaving out chemotherapy would increase the likelihood of invasive cancer returning. And, luckily, overall, the trial showed that the likelihood of cancer returning in those patients who got endocrine therapy alone, without chemotherapy, wasn't significantly different compared to those who were treated with chemotherapy followed by endocrine therapy. They also looked, specifically, at the group of women who were 50 years of age or younger. So mostly premenopausal women. Now, this was an exploratory question, meaning it provides information that may be correct, but it hasn't been as fully tested as the main question about what do we do for all women? In these younger women, there appeared to be some benefit from chemotherapy in those whose tumors had scores from 21 to 25, and, also possibly, in those whose tumors had scores from 16 to 20. Therefore, we still consider giving chemotherapy to younger women with Oncotype DX scores in the middle range, from 16 to 25, but not to women over age 50. So that was the TAILORx trial. The MINDACT trial was a bit different. It was testing the MammaPrint assay and the trial also included primarily women with hormone receptor-positive, HER2 negative breast cancer. But in this case, most women's sorry lymph nodes were negative, although a few women had up to three lymph nodes involved. In that trial, patient's risk of disease recurrence was assessed in two ways. First, it was assessed based on clinical factors. So the size of the tumor, how many lymph nodes were involved, and the estrogen receptor, progesterone receptor, and HER2 receptors. Second, it was assessed based on genomic factors-- that was using the MammaPrint test. So if patients were low for both clinical factors and genomic factors, they only were treated with anti-estrogen therapy. If they were high for both clinical factors and genomic factors, then they were treated with chemotherapy followed by anti-estrogen therapy. However, if they were high for one and low for the other, then they were randomized to either endocrine therapy alone or chemotherapy followed by endocrine therapy. So it was a little bit of a confusing trial. In the MINDACT trial, those patients who were thought to be high risk based on their clinical risk, so the size of the tumor, the number of lymph nodes, but then found to be low risk on the MammaPrint assay. They found that there was no benefit to treatment with chemotherapy in terms of how likely a woman was to develop distant metastatic disease. And if they were low risk, based on the clinical assessment, then there didn't appear to be a benefit of actually doing the test, the assay, because chemotherapy wouldn't be recommended for the patient, regardless of the results. So that was the MINDACT trial. So what are the new and updated recommendations for the guideline? Yes, so in this guideline, we, based on the TAILORx trial, we made new recommendations for use of the Oncotype DX results. All of these results apply to women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer. So for women older than age 50, if they have an Oncotype score of 25 or lower, then clinicians may offer endocrine therapy and no chemotherapy. However, for women age 50 or under, if they have an Oncotype score of 15 or lower, 15, then, clinicians may offer endocrine therapy and no chemotherapy. But if the score is 16 to 25, then chemotherapy can be considered in addition to endocrine therapy. So it made a difference in that gray area in the middle. For all women with score 26 to 30, chemotherapy may be considered. And for scores above 30, chemotherapy should definitely be considered. The data from the MammaPrint trial actually aren't that new. Results from that trial were originally published in 2016. However, that was after the original guideline was published, so we wanted to add these results to these updated guidelines for completeness. For a patient with hormone receptor-positive, HER2 negative, node-negative breast cancer, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then treatment with chemotherapy can be avoided. If a patient is thought to be at low clinical risk, the MammaPrint should not be used as chemotherapy can be avoided regardless. And for a patient with hormone receptor-positive, HER2 negative breast cancer, but who has one to three positive lymph nodes, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then it is possible that chemotherapy could be avoided, especially if only one lymph node is involved. So I think the bottom line for this part is that both of these tests-- there are now women who previously would have been recommended to have chemotherapy that maybe now we can avoid chemotherapy based on using these assays on their tumors. So why are these changes so important and how will they affect practice? Yes, that's a good question. Before the publication of the TAILORx trial, we had good information about how to treat patients who had either very low or very high Oncotype scores. But we really weren't sure how best to treat those patients who scores fell in the middle. Now, we have important information to guide decisions about chemotherapy for patients with intermediate scores. For many patients with scores in this range, these new results mean they will be able to avoid chemotherapy and just get endocrine therapy. While these results don't give us answers for every patient, they do provide more information that oncologists can use when having discussions with patients about the benefits and risks of chemotherapy. And what does this mean for patients with early-stage invasive breast cancer? And what should they talk to their doctors about? So as a result of both of these trials, we now have additional tools that can help oncologists provide more individualized treatment recommendations for patients and really assess whether or not chemotherapy, in addition to endocrine therapy, is likely to provide benefits. Knowing which patients' tumors will respond to chemotherapy can help some patients avoid unwanted side effects from a treatment that's not likely to actually give them much benefit. Now, these tests aren't appropriate for everyone and don't provide all the answers, but they are an important step in the right direction for providing more personalized treatment for women newly-diagnosed with certain types of breast cancer. Patients should talk with their doctors about whether these tests are right for them when they're making important decisions about whether or not they should receive treatment with chemotherapy. Great. Thank you, Dr. Henry, for this informative overview of the guideline. Keeping these clinical practice guidelines updated is really crucial and it takes a lot of careful thought to ensure these recommendations represent the evidence. So thank you for coming on the podcast to discuss the "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you very much for the opportunity to talk with you today. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Noam Yarom, Dr. Charles Shapiro, Dr. Deborah Saunders and Dr. Doug Peterson on "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." This guideline addresses the prevention and management of MRONJ in patients with cancer. This guideline is intended for oncologists and other physicians, dentists, dental specialists, oncology nurses, clinical researchers, oncology pharmacists, advanced practitioners, and patients with cancer. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of the ASCO podcasts at podcast.asco.org  TRANSCRIPT Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today, I'm interviewing a panel of authors from "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." So could I have you each introduce yourselves for the listeners today? Thank you, Shannon. I'm Dr. Deborah Saunders. I'm the president of the International Society of Oral Oncology and was the section head for the Systematic Review on "Medication-Related Osteonecrosis of the Jaw," with MASCC and ISOO. I was a proud part of the steering committee and one of the authors. Thank you, Debbie. My name is Dr. Douglas Peterson. I am professor of oral medicine in the School of Dental Medicine at the University of Connecticut Health Center in Farmington, Connecticut. I am also a faculty member in the Head and Neck Cancer Oral Oncology Program at the university's Neag Comprehensive Cancer Center. I'm a member of the steering committee for this clinical practice guideline and one of the co-authors as well. In addition, and as of June 2019, I have been serving as chair elect during this next year for ASCO's Clinical Practice Guidelines committee. Thank you, Doug. My name is Noam Yarom. I'm an all medicine specialist from the Sheba Medical Center in Tel Aviv University in Israel. I'm serving as a culture of this guideline, and it is a pleasure to be with you today. Thanks, Noam. I am Dr. Charles Shapiro, professor of medicine at the Mt. Sinai Hospital in New York. And I'm co-chair of the guideline "Medical-Related Osteonecrosis of the Jaw." And I'm happy to be here. Thank you all for being here today to discuss this guideline on the podcast. So first, can you give us a general overview of what this guideline covers. Sure. So you know, ASCO and MASCC, as well as ISOO decided that it would be great to provide a practical evidence-based approach in a multidisciplinary type setting to address this important topic that impacts all of our professions, that being medication-related osteonecrosis of the jaw. It's terminology and its definition and the path that's varied and even part of this publication identifies the need for us to move forward with a concise definition and similar terminology, that being medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw is defined as the presence of an exposed or bone that is probable by a probe in a patient that has a history or is undergoing present use of a bone-modifying agent. This being in the absence of any patients having received any radiation to the head and neck and the absence of metastatic lesions to the jaw. The importance of us identifying this definition and agreeing on the terminology allows us to move forward in future publication to better compare outcome and provide better prevention and treatment for our patients moving forward. And what are the key recommendations of this guideline? There are six clinical questions associated with this clinical practice guideline as well as a series of recommendations built within each of the clinical questions. Clinical question one is directed to the preferred terminology and definition for osteonecrosis of the jaw, both of the maxilla and the mandible, as associated with pharmacologic therapies in oncology patients. The panel recommends that the term medication-related osteonecrosis of the jaw, MROJ, be used when referring to bone necrosis associated with pharmacologic therapies. As Dr. Saunders has described, the definition contains three key elements-- current or previous treatment with a bone-modifying agent or angiogenic inhibitor, exposed bone, or bone that can be probed through an intra or extra-oral fistula in the maxillofacial region and that has persisted for longer than eight weeks. And third, no history of radiation therapy to the jaws and no history of metastatic disease to the jaws. Clinical question two is directed to specific steps that should be taken to reduce the risk of MRONJ. The recommendation begins with emphasizing the absolute importance of interprofessional communication of the oncology team with the dental team in advance of initiating the bone-modifying agent. For patients with cancer who are scheduled to receive a bone-modifying agent in a non-urgent setting, a comprehensive oral care assessment, including dental examination and periodontal examination and an oral radiographic exam when feasible to do so should be undertaken prior to initiating the BMA therapy. Once the dental care plan has been developed, it should be discussed with the dental team, the patient, and the rest of the oncology team and then implemented based on medically necessary dental procedures. These procedures should be performed prior to the initiation of the bone-modifying agent. Once the bone-modifying agent is implemented, there should be ongoing followup by the dentist on a routine schedule, for example, every six months following initiation of the BMA therapy. It's also important to realize that there are a series of modifiable risk factors which should be emphasized with the patient. For example, poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes mellitus, and tobacco use are all factors that have been associated with development of a MRONJ. All of these modifiable risk factors should be addressed, where appropriate, with the patient in advance of the bone-modifying agent. As far as elective dental alveolar surgery, these procedures, if they are not medically necessary, for example, extractions or alveoloplasties or implants, they should not be performed during active therapy with a bone-modifying agent being given at an oncologic dose. Now, exceptions to this may be considered when a dental specialist with expertise in prevention and treatment of MROJ has reviewed the benefits and risks of the proposed invasive procedures with the patient and the oncology team. In general, however, elective dental alveolar surgical procedures should be deferred while the patient is undergoing active therapy with a bone-modifying agent. If the dental alveolar surgery is performed, the patient should be evaluated by a dental specialist on a systematic and frequently scheduled basis, for example, every six to eight weeks until there is full mucosal coverage of the surgical site. And once again, communication between the dental team and the rest of the oncology team is absolutely paramount in assuring ongoing comprehensive care of the patient. Interestingly, there are still questions in the literature relative to whether or not there should be temporary discontinuation of bone-modifying agents prior to dental alveolar surgery. Unfortunately, there remains insufficient evidence to support or refute the need for discontinuation of the bone-modifying agent prior to dental alveolar surgery. And so the administration of the bone-modifying agent may be deferred at the discretion of the treating physician, in conjunction with discussion with the patient and the oral health provider. So it really becomes an individual judgment call by the treating physician relative to whether or not to temporarily discontinue the bone-modifying agent prior to dental alveolar surgery. Clinical question three involves the staging of MROJ. There are a number of well-established staging systems in the literature addressing severity and extent of MROJ. For example, the 2014 American Academy of Oral and Maxillofacial Surgeons Staging System is one example. Another example is the National Cancer Institute's Common Terminology Criteria For Adverse Events. And there is a 2017 International Task Force on O and J Staging System for MROJ that is available as well. So there are at least three well-established, widely utilized staging systems for MROJ. Having said this, it's important in the view of the panel that the same staging system should be used throughout an individual patient's MROJ course of care. And optimally, the staging should be performed by a clinician experienced with the management of MROJ. Clinical question four involves management of MROJ directly. Here, the recommendations talk in terms of initial treatment of MROJ, which is centered in conservative measures. Now, these conservative measures may include antimicrobial mouth rinses, antibiotics if clinically indicated, effective oral hygiene, and conservative surgical intervention such as a removal of a superficial bone spicule. In cases, however, of refractory MROJ, more advanced MROJ, aggressive surgical interventions, for example, mucosal flap elevations, bloc resections of necrotic bone may be used if MROJ is persisting and severely affects function despite conservative initial treatment. Clinical question five involves bone-modifying agents and whether they should be temporarily discontinued after a diagnosis of MROJ has been established. And once again, there is insufficient evidence to support or refute the discontinuation of the bone-modifying agents after a diagnosis of MROJ has been established. The bone-modifying agent may be deferred at the discretion of the treating physician, again in discussion with the patient and the oral health care provider. And finally, clinical question six involves what outcome measures that should be utilized in clinical practice to describe the response of MROJ lesion to treatment. During the course of MROJ treatment, the dentist, dental specialist, should communicate with a medical oncologist in an ongoing way, both the objective and subjective status of the lesion. The guideline presents a scale that can be utilized to describe the trajectory of the MROJ-- resolved, improving, stable, or progressive. The clinical course of MROJ may impact both local and systemic treatment decisions relative to the cessation or the recommencement of bone-modifying agents. So once again, it becomes very, very important that the ongoing interprofessional communication relative to the clinical course of MROJ-- resolved, improving, stable, or progressive-- be discussed with the oncology team. Great. Thank you, Dr. Peterson. So on that last note, how can oncologists, dental specialists, and dentists all work together to manage medication-related osteonecrosis of the jaw? Throughout these guidelines, we do emphasize the importance of collaboration among the cancer care team, dentist, and dental specialists in order to coordinate care and modify risk factors. It is very important that cancer care team and the dental care team speak the same language. Therefore, we spend time on clarifying the definitions, the diagnostic criteria, and staging of MROJ. As been said earlier, we have developed a new system to evaluate the response to treatment, which is based both on objective findings and symptoms. By using this scale, oncologists and dentists would be able to communicate more easily for the benefit of the patients. We emphasized the need for multidisciplinary discussion in a few critical points throughout the course of bone-modifying agent therapy. And it is most important in case of a planned oral surgery in a patient without MROJ or before aggressive surgical treatment of refractory MROJ. And how will these guideline recommendations affect patients, and what should they talk to their doctors about? There are a number of things that patients, providers, dental specialists, and medical oncologists can do to lessen the risk and prevent MROJ. Because the key to MROJ is prevention. Once MROJ is established, it's difficult to treat, impacting a patient's quality of life. So we want to prevent, reduce the risk of developing MROJ. Patients can do a number of things-- pursue good oral hygiene, stop smoking, or reduce smoking, and control their diabetes, for example. Those things lessen the risk of MROJ. Providers, dental providers, dental specialists, who are specialized in the area or providers, dentists otherwise in the community, when they encounter a patient that's contemplating bone-modifying agents, they can do what's called a complete dental screening exam, which involves a complete examination of the mouth, Panorex X-rays and X-rays as clinically indicated. We want to identify work in the mouth that needs to be repaired before initiating bone-modifying agents. That way, we don't have to deal with an emergent situation when it could be preventable prior to bone-modifying agents, because one of the single highest risk factors for MROJ is emergent dental work while you're on bisphosphonate or another anti-resorptive agent-- bone-modifying agents. So a dental screening exam is critical to prevent or reduce the risk of MROJ. And medical oncologists have a role too in communication with the dental specialists and really think hard about the indications for bone-modifying agents, whether it be for osteoporosis, whether it be for metastatic disease, and whether it be for anti-cancer effects. And finally, where can both patients and clinicians go to get more information on this topic or to find a dentist or a dental specialist? Now, as far as websites, ASCO, MASCC, and ISSO all have websites you can go to to find out more information about MROJ. Yeah, I think that's great advice. Our links for additional information are listed in the Clinical Practice Guideline as well. This is a really first step at a framework in trying to manage a side effect that affects our patients but is very multidisciplinary. And like Dr. Shapiro was saying, really the best way to prevent this is with proper communication between the dentist and the oncologist and making the patient aware of what is needed prior to commencement of these treatments. Well, it certainly sounds as though there are some important considerations for clinicians and patients. And I really hope that this guideline is widely read and makes a real impact on the management of osteonecrosis and the communication between oncologists, dental specialists, and dentists. So from me and all of our listeners, thank you all for coming on the podcast today to discuss "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline."   Thank you. Thank you for having us. Thank you very much for this opportunity to contribute to this important discussion. Thank you for allowing me to participate in this important podcast. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Charles Shapiro from Mount Sinai Hospital in New York and Dr. Joan Neuner from Medical College of Wisconsin, co-chairs of "Management of Osteoporosis in Survivors of Adult Cancers with Nonmetastatic Disease: ASCO Clinical Practice Guideline." This guideline includes recommendations on assessing risk factors and interventions, including pharmacologic and nonpharmacologic options. Read the full guideline at www.asco.org/survivorship-guidelines TRANSCRIPT Hi. My name is Clifford Hudis, and I am the CEO of the American Society of Clinical Oncology as well as the host of the ASCO in Action podcast. About twice a month, I interview thought leaders in healthcare care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues. You can find the ASCO in Action podcast on Apple podcasts or wherever you are listening to this show, and you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content, and offer enriching insight into the world of cancer care at podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. My name is Shannon McKernin and today on the ASCO Guidelines Podcast, I'm interviewing Dr. Charles Shapiro from Mount Sinai Hospital in New York, and Dr. Joan Neuner from the Medical College of Wisconsin, Milwaukee, co-chairs of management of osteoporosis in survivors of adult cancers with non-metastatic disease ASCO clinical practice guideline. Thank you for being here, Dr. Shapiro and Dr. Neuner. Thanks a lot. Pleasure to be here. So first, can you give us a general overview of what this guideline does cover? This guideline covers very important topics, that of osteoporosis and that of cancer survivorship. It's the coalescence of these two common problems that is the impetus for this guideline. It covers risk factors and what you can do as a cancer survivor to mitigate your risk. It covers screening and identification of the best test to use to measure your bone density, and it covers how to treat or pull the trigger for anti-osteoporosis drugs based on the guidelines that are contained within the document. And what are the key recommendations for this guideline? So we developed this guideline with three key guideline questions in mind. And they really required a fairly extensive search of the literature to address them. And we did that by looking to some of the literature outside of cancer in osteoporosis screening in other patients as well. So I'll sort of talk about it in terms of the three key questions. So the first question we had was, which patients with non-metastatic cancer are at increased risk for developing osteoporotic fractures? So that first question was, which patients are we really addressing in this guideline? And how do we assess whether they're at potentially increased risk? So in response to that, we strongly recommend that oncologists teaming with other physicians, including primary care doctors like myself, evaluate their patients to determine whether they're high risk. And so we provide a lot of details in an extensive document. But in our bottom line, we have a summary of the most common and the most severe risk factors. And those include things like advanced age, current smoking, excessive alcohol consumption, and a history of prior fractures, so already showing that they're at high risk for fractures. So we recommend you look to that list. And then add in your own clinical judgment, particularly about patients who have added risks from their cancer treatments. And so we do also talk about those patients. And in particular, we call out patients with specific anticancer therapies, for example, aromatase inhibitors given to breast cancer patients, antiandrogens or GnRH agonists given to breast cancer and prostate cancer patients and call out how they're at particular risk. And finally, in response to this question, we also recommend that you consider using a risk assessment tool. And here, I mention that we had to look to the non-cancer literature. So here, the WHO actually developed something called the Fracture Risk Assessment Tool, or FRAX. And we do recommend that you use this tool or something like it to help you to assess whether your patient is at high risk. And those are readily available on the web. Search FRAX-- F-R-A-X-- to use it. And, of course, we have links in the guideline. So that addresses the first question, which again was, which patients are at increased risk? And we have a list of risk factors that you should be considering and some references, particularly FRAX, to help you with thinking about those risk factors and how important any specific risk factor is. Our second question really dovetailed right on that. And that was, how should patients who are at increased risk, you've identified as part of that first question, to be at increased risk for osteoporotic fractures be screened? And here again, we look to the standard recommendations for patients who don't have cancer as well. And there are two ways that you could move towards, should you screen your patient or not? One could be your patient had one of those risk factors that we talked about and are listed in the document. The other is you use that FRAX tool and patients are more than average risk. And then we recommend patients be screened using one of the standard screening tools. The most common one, is called dual X-ray absorptiometry. And I want to specifically mention central dual X-ray absorptiometry, which means that the test is done on the hip and the lumbar spine. Those are readily available. All major medical centers have them, and many clinics have them as well. And so we do recommend that for screening. And then we offer some specifics about how frequently you might screen, because that's another question that often comes up. And so then our final question is once you determine that your patient is at high risk because their bone density test and/or their FRAX test shows that patients are at high risk, we do encourage talking to them about treatment options. And the first thing I want to say is essentially everyone that our guideline addresses, which is all patients who currently have or who are survivors of non-metastatic cancer, that they should consume a diet with adequate calcium and vitamin D. And so that's generally considered to be 1,000 to 1,200 milligrams of calcium and at least 800 to 1,000 IUs, international units, of vitamin D. We also strongly recommend exercises and call out some specifics. That you want to work on balance, flexibility, and resistance, if possible. And that you quit smoking and limit alcohol consumption. All very good things for the body generally, but also very good for the bones. Obviously, the meat of this guideline is also about pharmacologic intervention specifically. And since Dr. Shapiro treats so many patients with this, I'm going to ask him if he wants to comment further on specifics about pharmacologic treatments, when you think patients should get them. So thanks, Joan. So pharmacologic interventions include RANK ligand inhibitors, like Denosumab or IV or oral bisphosphonates. So clearly, if your patients are at risk, that means a hip fracture predicted at 3% or more or a non-hip vertebral fracture at 20% or more-- and you get these numbers from the FRAX calculator and other calculators in common usage-- then you pull the trigger and use one of these agents. Now we couldn't distinguish between the agents in terms of what's one was preferred. It depends on patient preference, comfort with the doctor in terms of how comfortable the doctor is using the agent, and other factors that go into the decision about which biphosphonate to use. Generally, the IV Zoledronic Acid and sub-cu Denosumab are used in the cancer populations. But oral biphosphonates can be used as well. And why is this guideline so important? And how will it change practice? Well, this guideline is so important because we know from survey studies that osteoporosis and preventing osteoporosis and treating osteoporosis in the cancer survivor population is underutilized. And this is an important point, because many people, especially with breast and prostate cancer and colorectal cancer and bone marrow transplants, will be long-term survivors. And we don't want to cure a patient just to have them fracture 10 or 20 years later. So that's the importance of the guideline. So it's the recognition that osteoporosis is treated the same, whether you're a cancer survivor or not. But the cancer treatments we use in routine practice can cause osteoporosis and bone loss. And that's the importance of this recommendation, as well as the particulars of who's at risk, the risk factors, screening, and pulling the trigger for treatment. So that's basically in a nutshell, why this guideline is so important and how it will change practice, because we hope that the guideline stimulates us, as health practitioners, to screen our patients for osteoporosis, recognize risk factors, and how to pull the trigger on treatment to prevent or treat osteoporosis in this population. It doesn't matter who follows patient, but the patient has to know who's going to follow the bone density and treatment for osteoporosis, whether it's comfort that an oncologist has with the whole process of screening and risk factors and pulling the trigger for bisphosphonates or Denosumab or endocrinologists, the rheumatologist, the primary care physician. The patient's got to know who's going to be responsible for what aspects of care, survivorship care. And this is a big part of survivorship care. So the treatment summary, which is a document that the patients get and is given to the primary care provider, should specify who will take responsibility for what aspects of survivorship care. And this is a big aspect of survivorship care, osteoporosis screening and treatment, if necessary. So it doesn't matter who does it, as long as it gets done. I would jumped in if I could, Charlie. Yes, so please jump in. So I guess the only other point that I wanted to make about how it might change practice is osteoporosis guidelines have been out since the late '90s, early 2000s. And so many patients probably have thought about osteoporosis and their risk in the past. But I did want to note that there have been a number of studies in the last five years showing that in primary care-- so family medicine and general internal medicine, like I practice-- that we're actually ordering fewer bone densities than we did in the past. And all the reasons for that aren't clear. Perhaps it's because of some concerns about the rare side effects of some of these medicines. Perhaps it's because the guidelines aren't clear because the data is not clear about how often we should test people who don't seem to be at high risk once they've had a first test. But nonetheless, there seems to already be some effects of this that the hip fractures, which had been decreasing are starting to look like they're rising again. So it really is important then if we're not going to screen very frequently everybody, that we are screening the people who really need it. And so then this guideline it calls that out that these are patients who because either their cancer treatment and the debilitating nature of that in some cases or the specific medications puts them at particular risk. Those are the ones that we can't omit this. Great. Finally, how will these guideline recommendations affect patients? You know, I think we're hoping that this will help in the care of cancer survivors and spark people to use things like survivorship care plans. Or if those don't work in your institution, other ways to make clear what the patients who are survivors are at risk for, both related to their cancer and outside their cancer, so that we can all work as teams of health care providers to make sure all of the things on those lists addressed. So we're hoping that with some very clear recommendations about how to address bone health that we can help those teams serve patients that they can. Obviously, it can also provide some really essential information for patients who are wondering what the things that need to be wondering about in this new phase of survivorship after cancer that they're dealing with. Dr. Shapiro, did you have anything to add to that question? Hopefully, we can prevent fractures in our cancer survivors by following these guidelines. It's really important that we prevent osteoporosis and hip fractures and vertebral fractures, because we don't want to cure the patient just that saddle them with osteoporosis and breaking a hip or breaking vertebral body 10 or 20 years down the line. So this will hopefully affect patients positively. And we intended the guideline to be for patients in terms of risk factors. And if you need a biphosphonate or anti-osteoporosis drug, then it's clear indications in the document who gets it and who doesn't. So I think that the effect we hope would be great on patients, that part of general health is osteoporosis screening. And just because you're a cancer patient doesn't absolve you from participating in all the health recommendations, including osteoporosis screening. As with all ASCO Survivorship Guidelines, we do hope that this one informs many conversations between patients, survivors, and providers. Thanks to your overview here today and your work on this guideline, more clinicians will be informed of the risk factors and possible interventions for osteoporosis and survivors of non-metastatic cancers. So I want to thank you both for coming on the podcast to discuss this guideline with me today. Thanks for having us. Yes, thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/survivorship-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe, so you never miss an episode.

An interview with Dr. Anna Falanga on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guideline Update." The guideline revises several previous recommendations. Most notably, direct oral anticoagulants (DOACs) have been added as options for VTE prophylaxis and treatment. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of ASCO's podcasts at podcast.asco.org  TRANSCRIPT Hi, my name is Clifford Hudis and I am the CEO of ASCO and the host of the ASCO in Action Podcast. About twice a month, I interview thought leaders in health care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues.   You can find the ASCO in Action Podcast on Apple Podcasts or wherever you are listening to this show, and you can find all 9 of ASCO’s podcasts which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Anna Falanga from the hospital Papa Giovanni XXIII in Bergamo, Italy. Senior author on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guidelines Update." Thank you for being here today, Dr. Falanga. Yes, thank you. I am very happy to talk on the update of the ASCO VTE guidelines. So this guideline was first published in 2007 with an update in 2013 and a reaffirmation in 2015. So what prompted this 2019 update? Thanks for this first question. I think that an update was urgently needed at this time. You know, before, the ASCO guidelines were published in 2007. And then an update was made in 2013, and the second one in 2015. But in 2015 was basically a confirmation of the previous 2013 update. Now the update was urgently needed, because in the very recent years there has been even more evidence of the relevance and impact of a venous thromboembolism in the cancer patients. But in addition, and very importantly, new data from prospective randomized clinical trials with the new drugs for the management of VT in the oncological patients have become available. In particular, as you know, low molecular weight heparins were largely used in the setting of the treatment and trauma prophylaxis in the cancer patients. And actually, the low molecular weight tapering have been the standard of treatment for many years. However, recently the results of prospective randomized clinical trials of direct oral anticoagulant, particularly, the anti-Xa inhibitors, Edoxaban and Rivaroxaban, for cancer associated with [INAUDIBLE] treatment support the role of this new oral agent in the VT management in this setting. And this is related to new politics in the VT management in these patients. So what are the key recommendations for this guideline update? The main changes to the previous recommendations are first that Rivaroxaban and Edoxiban, the two anti-Xa inhibitors oral anticoagulants have been added as an option for routine treatment in cancer patients in this update. Also, now we may offer thrombo prophylaxis with Apixaban, Rivaroxaban, or low molecular weight tapering to selected high-risk outpatients with cancer. And about other changes of these new guidelines compared to the last one include that patients with brain metastases have been addressed in the VT type treatment sections, whereas before, only patients with the primary tumors were mentioned in the previous edition. And finally, the recommendation regarding long-term postoperative thromboprophylaxis with low molecular weight heparin expanded to patients undergoing a major open or laparoscopic abdominal or pelvic surgery. These are the main changes that all I think are very, very important. Why is this guideline so important? And how does it affect practice? Well, I think that the question how these changes affect our practice is a very important question, because I believe that these guidelines reflect the new evidence that we have from the new data. And this data clearly expand our possibility to choose now between the different treatment options in the single patient in the cancer population. For instance, the new data show that treatment with [INAUDIBLE] anticoagulants compared to low molecular weight heparin lower the risk of a recurrent thrombosis. But in some instances there's a higher risk of bleeding, particularly in the gastrointestinal and urinary tract cancer patients. So therefore it is evident that the patient selection and the individualization of a therapy based on the patient characteristics and the type of cancer-- all these become very important. And we have the possibility now to choose between different treatments, or in the same patients we can change from one treatment to the other according to the face of the disease or complications if the patient is in a phase that is assuming chemotherapy with many side effects like nausea and vomiting. Of course, in these cases a parenteral injection is preferable for the management of a venous thromboembolism. Whereas in other instances, a long-term and oral intake is surely more convenient. So it depends also from the level of risk. But now for the six months treatment we can offer different choice of the oral treatment and also for high-risk patients the primary prophylaxis with Apixaban Rivaroxoaban, and a low molecular weight tapering can be chosen. And what should patients be aware of when it comes to VTE risks and treatments? I think that patients should be educated about the risk of a cancer associated with VTE. You know, there is that evidence that they are educated about it. And they know a lot better about neutropenia, and the fever associated with this the neutropenic condition and the other side effect. But they know very little about the possibility that they can experience venous thromboembolism.  So I think they should be taught on how to recognize the symptoms and alert their physician. You know, sometimes the symptoms are indistinguishable It can be just a little pain in the calf. And patients must know that these are to be considered important. They must alert their physician to undergo some test-- objective test-- to see if there is a real thrombosis in the leg or not. This is extremely important, because one important consequence of venous thromboembolism of the extremities is a pulmonary embolism that can be also fatal. So they must know about that. Also, I think they should know about the risk of bleeding associated with the anticoagulant treatment, and also that this risk of bleeding can be different in the different type of tumors. Finally, I think that also they must be told about the once they have, for instance, and episode of venous thromboembolism they have to receive a treatment for that, and these are usually six months to the minimum, and then we'll decide. So they must know what these are the efficacy and the safety profiles of the different drugs. They must know the differences in the route of administration and the other characteristics of the drug. So I think that their shared decision with the patients of the type of treatment must be an integral part of the decision making and is certainly desirable. Great. It sounds as though there's some important considerations for patients and important conversations which may be prompted by this guideline. So thank you for taking your time to discuss this with me today, Dr. Falanga. I thank you very much for this interview and talk that our colleagues and also the patients will be happy with these new guidelines of ASCO. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Subscribe through iTunes and Google Play. In this interview, ASCO President Dr. Howard A. “Skip” Burris discusses why he became an oncologist, the importance of mentors in his career, the most significant changes he’s witnessed in cancer care during the past three decades, and his vision for the coming year as he serves in this top volunteer position. Dr. Burris stresses that we can’t “divide and conquer, to conquer cancer,” a message underscored by his ASCO presidential theme, “Unite and Conquer: Accelerating Progress Together.” Find all of ASCO's podcasts at podcast.asco.org   Shannon McKernin: Hi. My name is Shannon McKernin, and I'm the host of the ASCO Guidelines Podcast series. When a new ASCO guideline publishes, we release a podcast episode featuring an interview with one or more expert panel members. Each episode highlights the key recommendations and the implications for patients and providers. You can find the ASCO Guidelines Podcast series on Apple Podcasts or wherever you're listening to this show, and you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Clifford Hudis: Welcome to this ASCO in Action podcast brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content offering enriching insights into the world of cancer care. You can find all of ASCO's podcasts including this one at podcast.asco.org. This ASCO in Action podcast is part of our series exploring policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals who care for people with cancer. My name is Clifford Hudis, and I am the CEO of ASCO as well as a host of the ASCO in Action podcast series. For today's podcast, I am delighted to be joined by Dr. Howard, or "Skip", Burris. He's ASCO's president for the 2020 term, and if we're lucky today, we'll find out why he's called Skip. In the meantime, Dr. Burris is joining me to share his vision for his presidential year. That is what he hopes to accomplish by this top ASCO volunteer leadership position is an opportunity to leave a lasting mark on our organization and indeed the larger oncology community. Skip, welcome and thank you for joining me today. Howard “Skip” Burris: Thank you for having me. Looking forward to the conversation. Clifford Hudis: So, Skip, every one of us comes to oncology for individual reasons and personal motivations, and I know that's true for you as well. So before we get into the details of your current role at ASCO, I think our listeners will be interested in learning why you became a medical oncologist when there are so many places to go in medicine, so many exciting specialties, what was it that drove you to choose taking care of patients with cancer for your career? Howard “Skip” Burris: Interesting question and story. I was driven to medicine really thinking that I wanted to do something that was meaningful, something that helped others. And I was influenced by actually a number of friends whose fathers were physicians when I was in high school. And as I initially went into the medical field, I thought surgery was so exciting, and I actually spent many of my electives doing surgical sub-specialties and in particular thoracic surgery. And it was an exciting time in the '80s with heart transplantation and bypass surgeries. And yet I also was dissatisfied with the fact that it seemed transactional. While important, and certainly lifesaving for those patients, these were surgeries and then, quote unquote, were done taking care of that patient. And then I had a seminal moment after rounds one day when we were in the intensive care unit. And I was talking to a patient, and the team moved on. And my attending yelled at me, “hey, Burris, what are you doing?” I looked at him and he said, “Come on. He's fixed. Let's go.” And I half smiled and I thought, well, this guy's got such an interesting story and he was terribly appreciative of the care he'd receive, but he looked at that attending as somebody had truly had saved his life. And so fast forward to fumbling through internship and trying to figure out really what type of specialty I might want to go into. And two groups of folks that I ran into contact with shaped my career. One were the oncology patients. Rounding on the oncology patients, doing that elective early in my internship, they were grateful. They were so appreciative. It was a great program in San Antonio. It was folks participating in clinical trials. And these were patients who not only wanted to help themselves but understood that what they were doing might help others. But really every person was so unique and had such a powerful story. And then secondly, the attendings that were taking care of those patients, the oncologists truly seemed to love what they were doing. And it was really those two groups, I thought these are the kind of patients I'd like to take care of, and these are the types of physicians that I'd like to practice with. And I began shifting as many rotations as I could as a resident into oncology, and I've enjoyed being an oncologist now for almost 30 years. Clifford Hudis: And so it was the patients, and it was the physicians really that in the end drove you into this specialty it sounds like, right? Howard “Skip” Burris: Yes. I had been taught early on, and I tell some of our younger folks today, working with people that you like and working with people that you respect is such an important part of the job. And then the service that you're providing knowing that folks are appreciative and there's a teamwork in that both the doctors and the patients in the field of oncology are so special. Clifford Hudis: So you just touched on a big part of what I think motivates or at least supports so many of our members throughout their careers and that is collaboration, working with others. And I can't help but imagine that your experience in terms of your education at West Point and your service with distinction in the Army has a relationship to that camaraderie, that connection, and that collaboration. How do you see that experience as preparing you for medicine, or maybe you think it didn't? Howard “Skip” Burris: Actually it did, and I appreciate the question, the opportunity to comment on that. Going to the US Military Academy, going to West Point for undergrad was a decision made because I wanted to go to a great school. It was a great scholarship package, the way they handled it. And I knew I'd get a great education and was attracted, one of these kids in high school who gravitated toward leadership positions, and going to an institution that would teach leadership was attractive. And then you realize as soon as you get to West Point, you're part of this big team. Everything you do during your years there is all about your group of individuals, your team, your squad, your company, surviving together, thriving together, and being successful. And, in fact, the motto that they teach is strength is one. And it was clear that you were at school with a talented group of folks who all wanted to be leaders, and everybody had to learn how to fit in, pick their place to lead, pick their place to be humble, pick their place to take charge. And those sorts of teachings and the mentors and the colonels and generals that were my teachers on that led the program, they were simple things but they were things that stuck with me forever, and I think they've served me well as a physician. One was around the simple concept of you know if no one's following, you might not actually be leading. And you got to stop and take a look behind you and see if while you're heading in whatever direction you might be going, if no one's following, you got to check yourself. I think a second thing that has stuck with me is better to be decisive than to be sure you're right. Very rarely are you sure you're right, and I think that teams even in medicine and maybe particularly in medicine really like a decisive leader. And I think that's something that is a great characteristic for physicians, gathering the appropriate data and making the decision and moving forward. But looking around and trying to emulate some of those folks who became leaders of the country was inspirational and then also gave you the opportunity to take away some of those teachings and try to embed them in terms how you carry yourself. One thing about the army it's very hierarchical, but the generals, you know, know that those privates are what's going to make them successful. So the chain of command and that respect for each other, respect for the position, and respect for their role on the team is very similar to the role of doctor to nurse to the support staff and the like. So it actually ended up being a great foundation for my career. Clifford Hudis: So it's interesting throughout medicine and especially in the last few decades, we have increased our emphasis on the role of mentoring. And I have I guess two questions which would be, one: how did you find mentors in your post military career given the strength of the leadership that you saw displayed there? And the other question is how did you translate that into your own service as a mentor? Howard “Skip” Burris: Yeah, so I think important-- I think picking the right mentor-- maybe picking the mentor where you resonate with that person and think that somebody who you'd like to model and picking that mentor who can teach you something and really has your best interests at heart I think are key. Picking the wrong mentor is something that could really set somebody off on the wrong track if they're not careful. I was very lucky. As I went into internship and residency, my chief of medicine was a fabulous mentor. He was one of those individuals who kept the patient first, was kind but firm, and just the thing I learned from him was what now we talked to as emotional intelligence, this fact that he was optimistic. He was very self-aware, and he was in control of his emotions. And no matter what we'd done or not done and however the result went, he was the steady hand, and I always looked up and thought, I want to be that person. I want to be the person who's calm in the storm, and I want to be the person that people look to and say he's not panicking, and he's got the situation where we're going to get through this together. So that was a great mentor in my chief of medicine. And then my other mentor during my oncology fellowship was a famous oncologist, still in the field today, in Arizona, Dr. Dan Von Hoff. I mentioned Dr. Von Hoff's name, he's been a Karnofsky Award lecturer. And Dr. Von Hoff was the one who got me interested in drug development and phase 1 clinical trials. And I would say that Dr. Von was a great mentor for a few specific reasons. One is he always pushed us in front of him. He didn't need to take the credit. He pushed us to be presenters, pushed us to be first authors, pushed us to be the person that was in front of the clinical trial. And that was something that really was important for somebody early in their career. And then secondly he really taught that perspective that it was a great responsibility both for the patient on the clinical trial and for overseeing that clinical trial and that while your title might be principal investigator, you might be the leader of the program that you really were beholden to those researchers that brought the drug forward and to those patients who were volunteering to participate in the study. And Dr. Von Hoff has always been a great person in that regard, and his Karnofsky Lecture was actually a highlight to and a tribute to all those patients who had participated in phase one trials through the years. So those were two mentors that really stood out and have impacted me throughout my career. Clifford Hudis: Do you see yourself I guess echoing those styles of mentorship or expanding on them? Do you see anything in your own role as a mentor that hearkens back to what you saw in West Point and in those mentors in medicine for you personally? Howard “Skip” Burris: I do think I've had embodied in me the patient centric, patient first approach. I am one of those physicians who has always wanted to get to know his patients, have always taken the social history as an important part. It's funny, a number of my longtime patients are comfortable calling me Skip on occasion. I actually know their stories and know who their family is, and I know what they're wanting to fight for in terms of grandchildren and trips and the like. So that I'd be really being grateful on having a relationship with the patient I think is something that has carried forward. I will say to my chief of medicine mentor I still aspire to that. I wish I was always as calm as he was. I wish I was always as optimistic as he was and had that sort of strength, but it is still something that's front of mind for me and something that I at least strive to be as much as I can. Clifford Hudis: So, reflecting on your career just for a little bit, I have a couple of questions. One is a general one and one more specific. But thinking generally first, you've been in medicine a long time. I guess you're around 30 years if I'm not mistaken. From your point of view, what do you see as the most significant change in the field that -- can be good or bad or whatever -- but that we have to think about and maybe help our trainees and younger members adapt to? Howard “Skip” Burris: Well, the flow of information, the speed at which we're making discoveries and just the educational challenges there are immense. And so, I think that is something where the speed of drug development and approvals just to throw one statistic out, eight new drugs approved in 1998, 48 new drugs are indications approved in 2018, so what a change over the past 20 years. I think the most significant change, though, is we knew early on in our careers-- you and I always knew that no two patients were alike. They might be in ERP or positive breast cancer that they really were not the same patient. They might be a adenocarcinoma, but they were really different. And now with the advances in pathology -- advances in molecular profiling, understanding biomarkers, we do know that no patients are alike. And we know that everybody has to be approached individually. The tendency has always been to want to lump patients into groups to make broad treatment recommendations. And that is part of the challenge with the education and information flowing forward. It is as simple as continuing to look at some of the prognostic indices that we have for some tumors, the next generation sequencing for others, whatever that test might be to really determine what's the best therapy for that patient. So those advances have really helped us in terms of looking at tumor biology and knowing whether we're thinking about an immunological approach to a patient or chemotherapy approach to a patient or whether it might be one of the new oral biologics. But that has been such a significant change. And only a few years ago, it seems like we were giving immunotherapy in the form of drugs like interleukin 2, and now we have these fabulous new checkpoint inhibitors that are in front of us. Thinking back to really something like tamoxifen being truly a targeted therapy now thinking about the dozens of drugs that are out there now that are targeting other biomarkers on patients. That really has been an amazing advance. Clifford Hudis: Well, I mean, I have to agree that this is certainly an exhilarating and challenging time in oncology, so maybe we can pivot to think about that and talk about your presidential year. What do you think are specifically the biggest challenges facing us? And let's call those challenges promising opportunities. Where do you think we have to focus right now? Howard “Skip” Burris: I think one very top of mind is the oncology workforce. Physicians, leveraging up the physicians, having enough nurses and enough nurses interested in oncology, attracting young physician talent into wanting to be an oncologist, and then the other ancillary health care providers, nurse practitioners and the like, we need a bigger and more robust workforce to take advantage of the opportunity given to us with the survivors. It's incredible when we think about the advances and the number of cancer survivors in this country, individuals either under treatment or surviving with the disease where we're talking in numbers approaching 20 million over the next two years so really very amazing in that regard. I think education, it is tough. We still have a lot of physicians particularly in the United States that are seeing multiple different tumor types during the day, and with the advances in information, it's just important that we as ASCO do our part in trying to educate and provide the information. And then with all these new advances, it becomes the challenge of clinical trial accrual. While many of these therapies have made important differences in patients' lives, we're still not curing enough patients. And so, there is room and certainly the need for better therapies. And so, in this busy workforce and in the challenges of having everyone aware of the opportunities, how do we improve clinical trial accrual? And then lastly, I'll just mention, of course, cost of care. That goes a little bit with patients living longer or taking therapy for a longer period of time sometimes in a chronic setting and then the cost of some of these new therapies. So those were certainly factors we're going to have to deal with. So, some big challenges for the field of oncology. Clifford Hudis: Well, hearing you run to that list-- workforce, research, cost, patients, and survivorship, all of that-- it sounds like it builds right up to your presidential theme of unite and conquer, celebrating progress together. That sounds like a lofty and aspirational statement, but I also see immediately connections back to again all those points you just made. Do I have that right? Can you unpack the meaning of that for us at least, as you see it? Howard “Skip” Burris: Yes, it's an interesting theme, unite and conquer, celebrating progress together. I specifically resonated with that. I have long taught my young attendings and my colleagues at Sarah Cannon that the challenge is too big and the needs too great for us to actually go with the divide and conquer mentality. We've actually got to be together as a team to get this accomplished and have the best care provided. So I have talked about uniting and conquering for many years here at Sarah Cannon, and I think it fits nicely when we think about the oncology workforce and the members of ASCO. And then accelerating progress together, there is a great need to step things up a bit. I think that can come in a few different fashions. I am excited about the emerging opportunities and real world evidence. I do think some of the clinical trials are getting smaller and more narrow to fit specific groups of patients. And then I think we're beginning to leverage up some of our physicians with technology, with advanced practice providers, nurse practitioners, physicians assistants, all those pieces coming together. And then I'll admit also having conquer in the phrase was important to me. The Conquer Cancer Foundation, ASCO's foundation, I think is so important. When you come back to some of these topics we just talked about, it's really one of our best ways to invest in and inspire young investigators. Some of the awards provided by Conquer Cancer and the mission it provides I think are really going to be key to ASCO's success. Clifford Hudis: I think that's a great vision, and it's certainly one that does resonate, not just with you but I think with many in the audience. You touched in that description on that diverse expertise that we all believe we need to make faster progress. And for me, of course, this reminds us of our upcoming meeting in Bangkok, which is looking at speakers from some of the unconventional fields. How do you see that diversity coming together to drive innovation in cancer research and care? Howard “Skip” Burris: It's an interesting opportunity for us, and I'll digress for a brief minute and then go to the Nashville Analogies. So, Sarah Cannon, based here in Nashville, and some of the things we've talked about really revolves around what it takes to put on a musical performance. So only one person might have the microphone at the time, but you've got the band and you've got the engineers and you've got the people that have setup the stage, sold the tickets. Every aspect of that's key to having that concert pulled off. And I think Breakthrough is a meeting and when you think about the oncology ecosystem not too different. We need and have invested in information technology. I mean some of those IT individuals are so key to doing a variety of things, getting data to us, sorting and analyzing data, we were seeing telemedicine coming at us, artificial intelligence and natural language processing, all those pieces, which then moves quickly into where the engineers or participating. Engineers and medicine, I think, are going to help make some of the greatest advances. I think certainly engineers in terms of how we're looking at robotics and surgery, how we're thinking about different techniques for radiation therapy, and even engineers getting involved in some of the drug discovery process. And then bioinformatics and we've talked about big data and the excitement behind that. I commented on real world evidence, but this whole idea of being able to have decision support through bioinformatics and the understanding that those experts bring to the table. Those are some of the things that'll be highlighted at the Breakthrough Meeting. I think those are individuals who are going to need to be core pieces to the cancer solution and to cancer centers. And it's just an exciting time, and I think this meeting will be a great place to highlight how those groups can come together and have a conversation. Clifford Hudis: So, we are now a few months into your presidency year. I have to ask: has there been anything that has surprised you about the experience, something that you did not expect as you entered into this leadership role? Howard “Skip” Burris: I think the one surprise is how many individuals want you to lend an ear with email and text, that's a little bit easier. But folks that want to stop and grab you and give you a suggestion. I say surprised by that because I think these members, our colleagues, folks that are participating in the oncology care field really have ideas, thoughts, and passions. The individuals that speak to me really want you to take their ideas seriously, think about it, and bring it forward. And I'm appreciative of that. I'm surprised that they wouldn't see me taking this role in this title as being an opportunity for them to have that conversation and want to push their idea of forward. But that's been both a surprise and yet a pleasant experience, and I've enjoyed the conversations. I will also comment and throw some kudos out. I knew the ASCO staff was smart. I knew the ASCO staff was very hard working. But as you become ASCO President and you're seeing and signing and reading and participating in their communications that they put out in a variety of fashions, just this sheer legislative communication they have back and forth with congressional staff and answering various health care initiatives. One, it's a high volume, two, ASCO's voice and input on this is really needed and appreciated and respected, and, three, we really have a very talented ASCO staff sitting with our organization, and I think that's something that it would be great for all 40-plus 1,000 of our members to really appreciate. Clifford Hudis: Well, you know I agree. Now I have to ask, in addition to your long history of volunteer leadership within ASCO and your current role, especially as president, you also have a busy day job. You're currently chief medical officer and president of clinical operations as well as executive director of drug development all at the Sarah Cannon Research Institute, which is a leading cancer center for clinical research in the country. You're also an associate of Tennessee oncology. Now I was once ASCO president myself, and I know how busy the role keeps you. How do you do it all, Skip? Howard “Skip” Burris: Well, you certainly did it, and I don't mind saying I looked at folks like yourself to understand how better manage my life. I do think I've become better at scheduling. Through the years, I've learned that if I don't schedule myself in, I don't schedule a family in, and schedule a little downtime, that can be hard. So, I have become more disciplined with that through the years. I think secondly, I've been blessed to have constant and consistent team. Same nurse practitioner for more than 15 years, same pharmacologist for more than 20 years, nurse, staff, et cetera, so that has helped and enabled me to delegate and empower them and others. And recruiting in great talent has been important. The work energizes me, and I have really enjoyed working with really smart people. And then lastly some credit to my wife, Karen. Surely after being elected president, Karen put me on a diet, and I think that's provided a little bit of extra energy for me as well. Clifford Hudis: And how's that working out? Howard “Skip” Burris: Yeah, it's going pretty well. She's been a great encourager for me, and we've been able to drop a few pounds. And we can button the jacket, and so that will help me out with the pictures and being onstage. Clifford Hudis: So that leads me to maybe a piece of low hanging fruit here, but at the end of this year when you look back on your year as ASCO president, what's the one thing you hope you've accomplished? And don't tell me it's dropping 20. Howard “Skip” Burris: No, I won't 'cause Karen would tell you dropping 30, but I'm open for dropping 20. I hope that when we look back on my presidential year that it will be seen as a year where we bridge some gaps and connected people to begin to have some conversations to really push some advances. I think this idea of connecting people and bridging the various stakeholders is important to me, that will come in a variety of ways. I think my educational chair Dr. Prowell, Tatiana, coming from the FDA and from Johns Hopkins and Dr. Melissa Johnson, the two of them bring a very unique perspective in. So how the committees are formed and who's engaged in planning the annual meetings and how we have various participants and speakers, I think we're hoping to engage more of the oncology workforce and care force in terms of participating in the meeting. I also hope that we'll begin to push this idea of why all should be a member of ASCO. I think there's nothing more important than being together as an association. There has been articles out of late touting why doctors should organize, so I'm also hoping during this year we see an increase in membership for years going forward. Maybe we can set some of that platform up. And then also really continue to energize and push the Conquer Cancer Foundation. I think it should be something that all of our members will be proud of to say that they've contributed to Conquer Cancer and that they'd invested in the future of oncology. So those are a few of the things I hope to get started. It's a fast year. I know it'll go by quickly, but I'm hoping some of those initiatives can get rolling and we can have that carry forward in years. And when we look back we'll think that I had a small part in getting some of those programs moving along. Clifford Hudis: Well, that's great. I want to thank you again, Skip, for joining me today. It's been a great conversation. I've appreciated especially hearing more about your vision and your hopes for the coming year as well as the impact you want to leave. I have to say at the opening I teased a little bit about how you came to be called skip, and you haven't shared that. So, this is your chance if you want to let the membership know why we call you Skip. That'd be great. Howard “Skip” Burris: Well thanks, Cliff. Howard A Burris, III and, of course, Howard, Sr lived down the street and Howard, Jr was in the same house with me. So, when I first came home from the hospital, my mom called me Skip. I have had that nickname since I was born. And I always talked about switching back to Howard when I went to college or after medical school or when I turned 40. And for whatever reason, personality, friends, I've always stayed a Skip. There is no middle name, Howard A Burris. A is just the initial. So, there's been no middle initial to fall back to. So, I think Skip's what it's going to be and that seems to be what's sticking with me through the years. So that's the story. Clifford Hudis: That's great. Well, I want to thank you again and want to remind our listeners until next time. We appreciate your taking the time to join us for this ASCO in Action podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple podcast or wherever you listen. And while you're there, be sure to subscribe so you never miss an episode. The ASCO in Action podcast, remember, is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org.

An interview with Dr. Kala Visvanathan from Sidney Kimmel Comprehensive Cancer Center, and Johns Hopkins Bloomberg School of Public Health on the guideline update. This update adds anastrozole to the options of pharmacologic interventions for breast cancer risk reduction based on recent practice changing data. Read the full guideline at www.asco.org/breast-cancer-guidelines.  TRANSCRIPT Hi. My name is Clifford Hudis, and I am the CEO of the American Society of Clinical Oncology as well as the host of the ASCO in Action podcast. About twice a month, I interview thought leaders in health care and experts in oncology. And we provide analysis and commentary on a wide range of cancer policy and practice issues. You can find the ASCO in Action podcast on Apple Podcasts or wherever you are listening to this show. And you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Kala Visvanathan from the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, and Johns Hopkins Bloomberg School of Public Health, co-first author on "Use of Endocrine Therapy For Breast Cancer Risk Reduction: ASCO Clinical Practice Guidelines Update." Thank you for being here, Dr. Visvanathan. Thank you as well for having me. So can you tell us about the phase III randomized trial, which provided the signal for this update? Yes. This was the IBIS-II trial that was reported out by Cuzick, et al in 2014. It was a double-blind, randomized placebo-controlled trial that assessed the safety and efficacy of Anastrozole, the aromatase inhibitor Anastrozole, at 1 milligram per day for five years. And the primary endpoint was the reduction of the incidence of breast cancer in postmenopausal women at increased risk of developing breast cancer. The trial itself was reported out with a median follow up of five years and the intention-to-treat analysis actually revealed that 85 women in the placebo group and 40 women in the Anastrozole group had developed both invasive and noninvasive breast cancer. What it showed was that there was a reduction in the incidence of breast cancer of 53% overall. It included both invasive and non-invasive breast cancer after a seven-year followup. And importantly, in subgroup analysis, similar to the other hormone endocrine therapy prevention trials, it also showed that the reduction in breast cancer risk among invasive cancers was limited to those individuals with ER-positive and PR-positive tumors. And the reduction in breast cancer incidence was among hormone-positive breast cancers. Another interesting point to mention here was that the five-year adherence was only slightly less in the Anastrozole arm compared to placebo. So it was well tolerated. And that was 68% in the Anastrozole group compared to 72% in the placebo group. And in all the subgroup analysis, there was no significant difference, except when they stratified by hormone replacement, women who had no prior hormone replacement, they saw a clear risk reduction. And this was not seen in women with prior hormone replacement therapy. And so what are the key recommendations for the update of this guideline? So based on these results, the update really adds Anastrozole as another option for endocrine prevention in women at increased risk. So specifically, we say that Anastrozole 1 milligram per day orally for five years should be discussed as an alternate to tamoxifen, raloxifene or exemestane in postmenopausal women for the reduction of breast cancer in women at increased risk. We also clarify further who are the women most likely to benefit from Anastrozole or the other endocrine prevention drugs. And these are women diagnosed with atypical hyperplasia, either ductal or lobular, or lobular carcinoma in situ or women with an estimated five-year risk of at least 3% based on the NCI Breast Cancer Risk Assessment tool or a 10-year risk of at least 5% based on the IBIS Tyrer-Cusick Risk Calculator. But we also give parameters for other risk models, and that is a relative risk of at least four times the population risk for women in the age group 40 to 45 and two times that of the population age group from 45 to 69. I think this is an important part of the recommendations, because up till now, the recommendations for women at increased risk have really followed the eligibility criteria for these trials, which were often a five-year risk, for example, of 1.7% in the NSABP trials. And here, we're trying to really highlight the importance of considering this women at higher risk where there is a clear benefit when you look at benefit-risk ratios. We also talk about the fact that Anastrozole should not be prescribed in women who are premenopausal and that it is really important that both patients and health care providers discuss the benefits and risks of Anastrozole along with the other risk-reduction agents when they are considering prescribing this. And then lastly, the importance of talking about specific adverse effects of Anastrozole, because here we're talking about a population of women at increased risk who are cancer free. And that includes baseline fracture risk, a measurement of bone mineral density as well as other adverse effects like joint stiffness, arthralgias, vasomotor symptoms, hypertension, dry eyes and vaginal dryness. So we think it's important that they have this discussion with women before the study. So what are some of the clinical considerations for the use of endocrine prevention pharmaceutical agents for breast cancer risk reduction? So in this guideline, we have introduced this section called Clinical Considerations to try to tackle some of the challenging questions that providers have when considering prescribing endocrine prevention. So I urge people to have a look at this section, because it's really a question-answer format. So one of the things we talk about first is what I just alluded to, how do you identify women at risk, where the benefit of endocrine prevention outweighs the risks? And we go through different risk calculations, and we give examples of clinical patients who fit into these risk categories. The second thing, which I think is an important thing, is we talk about a new study that came out while we were preparing this guideline update. And this was by De Censi, et al. And it's been published in the JCO on low-dose tamoxifen. This was a randomized trial in women with intra-epithelial neoplasia. So this includes women with atypical hyperplasia, lobular carcinoma, or ductal carcinoma in situ. So slightly different population. And the women were randomized to tamoxifen at 5 milligrams a day-- so this is 1/4 of the standard 20-milligram dose-- or placebo for three years. So remember-- or endocrine prevention trials were for five years. So this was a shorter duration. And then a median followup of five years, they reported out the results, and they saw half the number of neoplastic events, so DCIS or invasive cancer, compared to placebo. So the results were very comparable to the original NSABP-P1 trial and very promising. So the further I think, what has been a sometimes prevented uptake of these agents, has been the adverse effects of tamoxifen, for example, equal to uterine cancer. And in this study, they did not see an increase in the number of serious adverse effects, including deep venous thrombosis and endometrial cancer. They still saw an increase in hot flashes. So I think this is very promising data and could be an alternate option for some patients, where side effects are a problem or they're reticent to take prevention given the side effects. Another thing we tackle is the question of age when you start recommending hormone prevention. And here, this relates to we talk about at 70, not so much that you would stop it at 70, but at that age or 70 or above, you would actually make sure you're taking into consideration their life expectancy. So they should have a life expectancy of 10 years or greater. And you're also taking into consideration their breast cancer risk. So the question there was, is there an upper age limit for endocrine risk reduction therapy? And we think that, at least the panel thought that, in women 70 years of age or older, you should actually consider both the short-term risk. It should be at least in the range of 1% or more per year. So that would be women with atypical hyperplasia, a family history, or some with carcinoma in situ. We want to make sure they're active and that they have a life expectancy of 10 or more years. Another question we tackled here was, what is the duration of endocrine therapy in this setting for breast cancer risk reduction? And this comes in the context that now, in the treatment setting, a subset of women are given, for example, tamoxifen for more than five years. In terms of data, with the exception of raloxifene, where we do have longer-term data that is greater than five years, in women at increased risk of breast cancer from the osteoporosis prevention trial, where we see that even with women taking raloxifene for more than five years still have a benefit in terms of the breast cancer risk reduction. We don't really have data for any of the other agents in the preventive setting. So there is currently no data from randomized trials that any of these agents, except for raloxifene, should be given for longer than five years. And that is in the setting of women with osteoporosis. And then the last question that we tackle is to look at how you decide between taking an aromatase inhibitor endocrine prevention therapy or a SERM. And this is really only in postmenopausal women, because we still only have one option for premenopausal women, and that is tamoxifen. Here, we just go through step by step sort of the process of thinking about the side effects for each of these agents. And in the context of the woman who is considering endocrine therapy and tailoring it to their age, what symptoms they have, or other comorbidities. Finally, how will these guideline recommendations affect conversations between providers and women at increased risk for breast cancer? So I think, firstly, these guidelines, again, bring attention to breast cancer prevention and the need for us as a community, both providers and women, to move this field forward. And what do I mean by that is we need to be more systematic about identifying women who are truly at increased risk and then subsequently having these discussions with them about the options available. And so I think this guideline adds another agent to the list of agents we now have that can be used to reduce breast cancer risk or breast cancer incidence and also provide the opportunity to-- we look at this and think about how we might incorporate discussions on breast cancer risk reduction into clinical practice. We do also want to stress the importance of discussions on lifestyle factors or risk reduction in addition to these agents. So I think hopefully this guideline helps to, again, refocus attention on the issue and encourage both women to ask their providers about their breast cancer risk and then providers to re-look at this question about breast cancer prevention and how to identify those who are at risk and then discuss endocrine prevention in those at higher risk. I think this is particularly important as we think about our aging population and the increase we are expecting in breast cancer over the next 10 to 20 years. And then also, as we think about breast cancer is now the number-one cancer diagnosed, well, the prevention becomes even more important. Great. Thank you for your work on this guideline. It sounds like there may be many important conversations which happen between women and their providers based on the work and the research about breast cancer risk reduction. So thank you again for coming on the podcast to share with us today, Dr. Visvanathan. Thank you. I would like to thank ASCO for having these podcasts and also shining a light on breast cancer prevention and getting this information out to its listeners. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Subscribe through iTunes and Google Play. Dr. Melissa Dillmon, the Chair of ASCO's Government Relations Committee, joins ASCO CEO Clifford A. Hudis to discuss improving access to clinical trials for patients with Medicaid. Medicaid covers 20% of Americans, however unlike Medicare or private insurers, Medicaid is not federally required to cover the routine care costs associated with clinical trials.  Find all of ASCO's podcasts at podcast.asco.org Transcription Shannon McKernin: Hi. My name is Shannon McKernin, and I am the host of the ASCO Guidelines Podcast series. When a new ASCO guideline publishes, we release a podcast episode featuring an interview with one or more expert panel members. Each episode highlights the key recommendations and the implications for patients and providers. You can find the ASCO Guidelines Podcast series on Apple Podcasts or wherever you're listening to this show, and you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care, at podcast.asco.org. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Clifford Hudis: Welcome to this ASCO in Action podcast. This is ASCO's monthly podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and most importantly, the individuals who care for-- people with cancer. My name is Clifford Hudis, and I'm the CEO of ASCO, as well as the host of this ASCO in Action podcast series. For today's podcast, I am really delighted to be joined by Dr. Melissa Dillmon-- Missy-- the chair of ASCO's Government Relations Committee, and a longtime dedicated ASCO volunteer. Now, regular ASCO in Action podcast listeners may remember that just a few months ago, I spoke with one of our colleagues, Dr. Beverly Moy, the issue of financial barriers to clinical trial participation, and we focused on ASCO's work to address those barriers to try to make it easier for patients to enroll in clinical research studies. Today, we're going to follow up on that. Dr. Dillmon is going to join me as we drill down deeper into one of the barriers that we've touched on previously-- in this case, the lack of coverage of routine care costs that are associated with clinical trials, but very specifically, the challenges that are faced by patients who have Medicaid. Dr. Dillmon, welcome, and thank you for joining us today. Melissa Dillmon: Thank you, Cliff, for having me and discussing what I think is a very timely and important issue. Clifford Hudis: Since it's something I know you care deeply about, maybe you could start off at a high level and give us a little bit of background. What is it exactly that we're talking about here, when we talk about clinical research and coverage for patients with Medicaid? Melissa Dillmon: So Cliff, you know that in many cases, clinical trials provide the best or sometimes the only treatment option for our patients with cancer. And we live in a time when there is an incredibly rapid pace of development, with new investigational treatments that are dramatically altering the course of cancer for the better. Patients with Medicaid have a unique barrier to accessing clinical trials because Medicaid is the only payer that is not federally required to cover the routine cost of clinical trial participation. So Medicare and major commercial payers are required to have coverage for routine costs of clinical trial participation. Medicare provided this coverage beginning in the year 2000 after the Medicare National Coverage Determination Act protected their beneficiaries. The Affordable Care Act also requires insurers to cover routine patient care costs for trials participation. But Medicaid was not specifically called out or included in this requirement. So today, commercial payers and Medicare are paying for the routine cost of clinical trial participation, but Medicaid is not required in any of the states by the federal government to cover these costs. And we know that these patients have financial barriers to accessing basic medical care and preventative services anyway. So this lack of mandated coverage makes it even harder for some Medicaid patients to participate in potentially life-saving treatment trials. Clifford Hudis: I remember from, obviously in my days of doing clinical studies, there was often a lot of discussion about what was a routine cost of clinical care and what was a research cost. Can you expand a little bit on which parts of this are covered, or are they all covered, by these requirements? Melissa Dillmon: So routine care costs are the regular doctor's appointment or E&M charge, radiology exams, drugs to manage side effects, supportive care medications, laboratory tests. It is not the cost of the drug or anything specifically related to that, it's just the routine care costs that go along with cancer treatment care, whether that patient was on a trial or on a regular, on-label drug. Clifford Hudis: And in an ideal world, when this is working efficiently, this dovetails neatly with the fact that the non-routine care costs-- those things that are being required only because the participants involved in a very specific research study-- those costs are generally borne by a sponsor, right? Melissa Dillmon: Correct. So perhaps if there is a genomic sequencing that was required, or a special laboratory test to assess a response in a marker that was not a routine care cost, that's usually covered by the sponsor of the clinical trial. Clifford Hudis: And so just to make sure every listener is following, the irony here is without this requirement, in a sense, a person with good commercial insurance historically could find themselves not covered for the exact same costs that normally would have been covered solely because they're getting some treatment that is part of a clinical trial. And that seems like a perverse incentive in the wrong direction for all of us across all of society, right? Melissa Dillmon: Exactly, especially at a time when it's challenging to get enough people on clinical trial, and we're trying to get more people on clinical trials. We're trying to remove those barriers. Clifford Hudis: Right, and I would go even a step further and say it's a little bit of a paradox because it doesn't actually cost the insurer any more money for a person to be on a clinical trial and be covered for routine care. It's not as if they're getting an increased charge back because the patient's on a clinical trial. The research study is typically covering the non-standard research components of care anyway, right? Melissa Dillmon: Correct. And then oftentimes, if there's an investigational drug, they're taking the cost of the drug out of the picture. So in some ways, you're actually saving the insurer that money. Clifford Hudis: So it's funny, as well, a little paradox that Medicaid is the only major payer not federally required to cover their costs. Yet at the state level, I think-- and I just heard about another one today, I'll tell you-- some states have taken half steps or full steps to require Medicaid to cover the costs of clinical trial participation for patients, right? Melissa Dillmon: That's correct. About a dozen states have taken action, through written statutes, or regulations, or policies, to require their Medicaid plan to cover these costs. But that's only a dozen states. That leaves about 42 million Medicaid patients who do not have guaranteed ability to participate in clinical trials. Clifford Hudis: You know, I think some listeners may be surprised that you get that big number-- 42 million. And of course, that raises some basic questions about the reach, and scale, and extent of Medicaid. I think we should talk about that for a moment. So who has Medicaid as their primary insurance? That is, who is covered by Medicaid-- what kinds of patient populations and so forth? Melissa Dillmon: So Medicaid covers about 20% of Americans. Patients on Medicaid are often lower income. It's usually children, older adults, patients with disabilities, and some patients in rural areas are more likely to have Medicaid. So depending on where those dozen states are that have those statutes, those may be states that don't have as large rural populations or lower income patients. So racial and ethnic minorities are also overrepresented in Medicaid. For example, African-Americans represent about 12% to 13% of Americans, but 21% of patients receiving Medicaid are African-American. Hispanics represent 18% of the American census population, but 25% of patients on Medicaid are Hispanic. Clifford Hudis: So this is the same old issue, where certain racial features, as it were, are surrogates for lower socioeconomic status, and that's what you're describing, unfortunately. Right? Melissa Dillmon: Correct. Clifford Hudis: OK. And so we take this group of patients that are, in general, a little bit disadvantaged-- lower socioeconomic status as an average, perhaps more rural, which itself represents a barrier to care-- and then you add on the limitation in terms of clinical trial participation coverage. So how does this translate into an increased burden for this special population, as opposed to everybody else? Melissa Dillmon: Well, we already know that cost is a major barrier to participation in clinical trials. Patients who have larger income are more likely to participate in clinical trials, or be offered a clinical trial, or live in an area where there is a clinical trial available for them. Patients who have a lower income-- less than $20,000 per year-- have a much lower participation rate in clinical trials, and we are therefore missing a lot of patients who could be benefiting from those clinical trials and who could be contributing to the science. And these patients don't have the financial resources to pay for their routine cost of care. They cannot afford to pay the E&M visit, or for a chest x-ray, or a CAT scan on their own. So that would pose a huge barrier for them to even consider participating in a clinical trial. And one of the things that frequently is stated is, of course, this means that if you can't participate in a clinical trial, that they might be missing out on life-extending or life-saving therapy. And we have to admit that that, of course, is uncommon, but not impossible. But there are also more subtle ways that clinical trial participation can benefit the individual. Clifford Hudis: They may enjoy a higher quality of life with some experimental therapies sometimes. And the other thing, of course, is that we all, as a society, benefit it clinical research studies are concluded more quickly. We get an answer faster and we can move on to the next big thing or build upon what we've learned. So it isn't as if the cost of this is limited solely to people with Medicaid. It's something, I guess, we all pay, right? Melissa Dillmon: As a society, I think we suffer when patients are not able to participate in these studies.

An interview with Dr. Fabrice Andre from Institute Gustave Roussy, Paris Sud University, in Paris, France on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." This update provides updated recommendations on chemoendocrine therapy for patients who present with a hormone receptor positive, HER2 not overexpressed, axillary node negative early breast cancer. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Fabrice André from the Institute Gustave Roussy in Paris, France, lead author on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early Stage Invasive Breast Cancer. ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." Thank you for being here today, Dr. André. Thank you. So based on the title of this guideline, we know that this update was prompted by the results of the TAILORx trial. So can you tell us more about that trial and what its results were? Yes. So the TAILORx trial was a trial that randomized two treatment modalities, endocrine therapy versus chemotherapy endocrine therapy in patients who presented what we call an intermediate recurrence cohort. So before moving to the results, maybe we can discuss a little bit the background. What we knew from the past is the fact that patients who present a recurrence score below 11 should be treated with endocrine therapy alone, because they have the good outcomes. And patients who present recurrence score that is high, 31 but also can be more on 25, should receive chemotherapy. And we are talking about patients with hormone-receptor receptor positive, HER2-negative early breast cancer without lymph node involvement. And this is extremely important. So to summarize, it's a clinical trial that includes patients with hormone-receptor positive HER2-negative lymph node negative in early breast cancer, who present with recurrence score between 11 and 25. And the question is whether we can avoid adjuvant chemotherapy in these patients who present this intermediate score. So this is the general design and the question. In terms of research, what we have learned. We have learned that for patients above 50 years old, there is no difference between endocrine therapy and chemotherapy followed by endocrine therapy. So it means that this patient or these patients, we would consider endocrine therapy alone. Then, for patients below 50 years old, there was some difference. And I think we go further into the detail. There was some difference favoring the use of chemotherapy in the group of patients who presented with recurrence score from 16 to 25. And so what changes were made to the recommendations in this update of the guideline? So first, what were [INAUDIBLE] the previous guidelines. The previous guidelines were telling the clinician which genetic tests they could use in patients with hormone-receptor positive, HER2-negative early breast cancer. Now, the big change is that we are making guideline to explain how to use the test. And what is new is that we have made three important decisions. So first, for the patient is at the age above 50, now it is recommended clinician may recommend endocrine therapy alone for women older than 50 who present a recurrence score below 26. Before, the recommendation to use endocrine therapy alone was for patient's who present with low recurrence score. So it means now we have broadened-- we have increased the number of patients who could receive endocrine therapy alone and not receive chemotherapy. Then, for patients who present a recurrence score between 16 to 25 and who are below 50 years old, the clinician may offer chemotherapy followed by endocrine therapy, meaning that we are moving from [INAUDIBLE]. This intermediate score between 11 to 25 was what we call a [INAUDIBLE]. There was no recommendation on how to use the recurrence score. So right now, the update from the ASCO guideline is to provide recommendation on which treatment to administer in case a patient presents with intermediate recurrence score, and there are two different situations above 50 years old and below 50 years old. So why are these changes so important and how will they affect practice? So they will affect practice because for many reasons, I will say. In the US, they would affect practice because they increase the number of patients who will not receive adjuvant chemotherapy, because right now, we have an answer from randomized trial that we can avoid chemotherapy in women above 50 and from 11 to 25 recurrence score. So the impact in terms of public health would be that we could have a decrease in the use of chemotherapy or at least a better precision about who should receive adjuvant chemotherapy. Globally, this trial is going to provide an incentive and increase the level of evidence supporting the use of genetic tests. So it's important to remember that in a large number of countries, genetic tests are not reimbursed. But now, because lack of evidence, and here we have a randomized trial showing a level 1 evidence supporting the use of genetic tests. So we have two direct impacts of this trial. The first, inside US, where [INAUDIBLE] colleagues already use genetic tests, it provides better precision on who will receive adjuvant chemotherapy. And it's going to broaden the number of patients who will not receive. And globally, it's prospective randomized trial that we hope is going to incite payers to reimburse the genetic test in patients with early breast cancer. And so what does this all mean for patients with early stage invasive breast cancer? And what should they talk to their doctors about? So for patients with early breast cancer, so what are the messages for the patient? I think for the patient, the key message is that we are moving to precision medicine. We need a medicine that is extremely precise in terms of who should receive which treatments. And now, thanks to this trial, we are going to decrease the number of patients who receive chemotherapy, but also for the ones who will receive adjuvant chemotherapy, the value of the treatment, we need what the treatment provides to the patient is going to be very, very high. So what is important for patients is to understand that because of this trial, when we give them chemotherapy, we will know that the value of this treatment and the expected benefit is going to be higher than what we used to do in the past. So it's really fast forward and more precise medicine that consists in using molecular tests in order to provide or administer treatment with very high value. Great. Thank you Dr. André for your overview of this guideline update. This has been very informative. It's really good to hear that the expert panel has incorporated the latest research into the guideline and has carefully considered the implications for the patients. So thank you for coming on the podcast to discuss the "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx" Thank you. What people don't realize is we did hard work that ASCO doing with all these guidelines, and people are very committed, and they are [INAUDIBLE]. I mean, it's very reassuring for ASCO member to know that there are highly professional people who provide guidelines and it is also reassuring for the patients, for everyone. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

Subscribe through iTunes and Google Play. Lisa Lacasse, president of the American Cancer Society Cancer Advocacy Network, speaks passionately about the critical importance of advocacy and ACS CAN’s partnership with ASCO in reducing the cancer burden, in latest AiA podcast with host ASCO CEO Dr. Clifford Hudis. Find all of ASCO's podcasts at podcast.asco.org TRANSCRIPT Ad: Hi. My name is Shannon McKernin. And I am the host of the ASCO Guidelines Podcast Series. When a new ASCO guideline publishes, we release a podcast episode featuring an interview with one or more expert panel members. Each episode highlights the key recommendations and the implications for patients and providers. You can find the ASCO Guidelines Podcast Series on Apple Podcasts or wherever you're listening to this show. And you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content, and offer enriching insight into the world of cancer care at podcast.asco.org. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Clifford Hudis: Welcome to this ASCO in Action Podcast, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. This ASCO in Action Podcast is ASCO's podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Clifford Hudis. And I'm the CEO of ASCO, as well as the host of the ASCO in Action Podcast series. For today's podcast, I am really pleased to have Lisa Lacasse, president of the American Cancer Society Cancer Action Network, or ACS CAN, as my guest. Welcome, Lisa. Lisa Lacasse: Thanks so much, Cliff. It's really great to be with you today. I appreciate the invitation. CH: Well, I'm really delighted that you could join me today for this discussion. And I think there are probably hundreds of topics that you and I could discuss. But I want to start with the big picture first. The American Cancer Society, of course, is a very well-known, nationwide organization with a mission of saving lives and leading the fight for a world without cancer. Can you tell our guests about the American Cancer Society Cancer Action Network, ACS CAN? What's the relationship with ACS itself? And what exactly does ACS CAN do? LL: So thanks. That's a great question, Cliff. So many are very familiar with the American Cancer Society, which is a large, old organization that attacks cancer from every angle. The Society works to advance breakthroughs in research, treatment for patients, providing direction and information to help people manage their cancer care, and also mobilizes volunteers at the community level to really support patients in their fight against cancer. But we know that the fight to end cancer doesn't just happen in a doctor's office or a scientific lab. It really requires the government and all elected officials to join us to impact the disease. And so that effort to engage government requires advocacy. And that's where the American Cancer Society Cancer Action Network, ACS CAN, steps in. And we are the advocacy affiliate of the American Cancer Society. So ACS CAN simply urges lawmakers and rallies all of our community partners to lead in the fight against cancer. And together-- the American Cancer Society and the American Cancer Society Cancer Action Network-- although we're two independent organizations, we're working towards the same mission. However, ACS CAN uses different but complementary set of tools. So we obviously resemble ACS in a lot of important ways. We're both nonprofits. We are both absolutely, obviously evidence-based. And we're both supported by a vast army of volunteers. And we all focus on the ultimate goal of eliminating cancer as a major health problem. But ACS CAN advances this mission using tools that aren't fully available to ACS. One, an electoral program called Cancer Votes, which is really an effort to educate voters on important issues to cancer. And we also do a significant amount of lobbying. And that's not just in Washington DC, but in all 50 state capitals and many, many localities. And because of the breadth of that direct lobbying, that's often beyond what's allowable for a charity. So back in 2001, which is-- we're coming up on our 20th anniversary, which is very exciting-- the American Cancer Society Board really recognized that if we were going to achieve our goal to reduce the cancer mission, we had to do that by improving public policy. And so they decided to create ACS CAN. And my job as president is really to empower this huge network of grassroots advocates across the country. And with their staff partners-- we have about 200 people that work for ACS CAN-- every single day, they're imploring their elected officials, working with administrative officials to impact the cancer burden. CH: Well, I mean, that's a remarkable portfolio. And I would say, obviously that ACS CAN has been a key ally and a natural partner for us here at ASCO in our own mission to conquer cancer through research, education, and the promotion of the highest quality patient care. I know that ASCO shares many advocacy priorities with your organization, including our strong support for robust federal funding for cancer research, improving patient access to clinical trials, and addressing, among other things, the alarming rise in youth tobacco use-- something listeners will recall, we discussed in detail with Scott Gottlieb last year. So it's really a privilege to be able to talk to you about all of this. One of the efforts I think that many of our listeners would want to hear more about would be the Medicare Part D, six protected classes issue. I think earlier this year, ACS CAN mounted a very public outcry and a very visible advertising campaign against a proposal that would have potentially impeded or limited access to lifesaving drugs within the Medicare Part D program, specifically in the six protected classes. And we were proud to join your campaign. We at ASCO couldn't have been more pleased than we were with the impact. Can you explain why this effort was so necessary and talk to our listeners a little bit about how it turned out? LL: Absolutely. And I do want to say thank you to ASCO's partnership on this issue. It was really important. So this is a regulatory issue. As you mentioned, it's colloquially referenced as the "six protected classes." But that's policy that was established more than a decade ago to make sure that Medicare beneficiaries had access to innovative therapies. So really, the concept's fairly simple. If you're a health insurer and you provide a Medicare Part D plan to a Medicare beneficiary-- so you sell a Part D plan, which is a prescription drug plan-- you are, by definition, required to cover virtually all drug therapies that treat cancer, epilepsy, HIV/AIDS, mental illness, and organ transplant. And unfortunately, late last year, the Department of Health and Human Services proposed to alter that rule. And if the rule that they had put forth had been finalized, we believe it would have dramatically impacted access and affordability to critical medications for cancer patients who are part of the Medicare Part D program. So the proposal, although it was put forth as an effort to save Medicare money-- programmatically to save Medicare money-- we were really concerned that that approach would potentially have the exact opposite effect. We were worried that it would result in raising costs in other parts of the Medicare program and absolutely shifting costs to patients. So that certainly would have happened, because the proposed changes included, for example, excluding drugs from formularies or increasing the use of utilization management tools, such as step therapy. And we know that for a disease like cancer, specific drugs are very important for specific cancers. So if beneficiaries were unable to access their prescription drug that was most medically appropriate for them, they certainly would incur higher costs because it wouldn't be a covered medication. But we also were worried that they wouldn't get physician services, or they would need additional physician services because they weren't getting the right medication, and/or they would end up in the emergency room, which is all things that we know happen if you're not on the right drug regime for your cancer diagnosis. So had these proposed changes gone into effect, it really could have been devastating for cancer patients and survivors. And because of that, once we analyzed the proposed rule, we launched a multi-pronged campaign. It's one of the things that we take a lot of pride in, and we're able to address these issues in many different ways. But one of the most powerful is working in coalition. So ACS CAN and ASCO were joined by nearly 60 other patient and provider organizations. And we ran an advertising campaign-- a very visible advertising campaign. We did a Twitter Day of Action, where all of our volunteer advocates from all of our organizations directed their concern to HHS Secretary Alex Azar. We know that he heard from us. We got confirmation of that. And additionally, ACS CAN and ASCO were among more than 23 patient provider organizations actually went to the Hill for a day, did a lobby day on the hill-- again, making sure that our legislators, congressional members really understood the patient perspective of this proposed policy change. And then finally, ACS CAN did something that we actually don't do that often, which is we shot and ran some television spots. We really wanted to make sure that we were coming at this issue from many different directions because we felt it was so critical to our cancer patients and their need to have access to innovative drugs. So once we went through all of that, we were really proud and, more importantly, thrilled for our cancer patients. The final rule did not include all the proposed changes to the six protected classes that were put forth. These plans are not allowed to impose additional utilization management techniques such as prior authorization and step therapy if a cancer patient already has an established Medicaid regimen. And we really think-- we know, actually-- that HHS and the White House, hearing from doctors and patients and survivors in such an incredible coalition made the agency realize that this could be a very problematic rule. And so I want to, again, Cliff, say thank you to ASCO providing such a critical perspective from your physicians, your oncologists. They know firsthand what these barriers and delays can mean. And the partnership really, really worked. And we're proud of the outcome of that campaign. CH: Well, again, we want to applaud ACS CAN for your bold leadership on the issue and the wonderful success. It does show the tremendous impact that we can have with a unified, collective voice on behalf of people with cancer. So another issue that I guess, in a way, relates at least tangentially to this-- and I know is near and dear to your heart-- is federal funding, in this case for cancer research and for clinical trials. But before you started ACS CAN, which I think is more than a decade ago, as I understand correctly, you were the CFO of the NIH's Cancer Research Center. So how did that experience shape your understanding of the federal research infrastructure and the need for increased funding for cancer research at the federal level? LL: So it's a great question. And it is true. I was at NIH for nearly a decade, a decade ago. I have been at ACS CAN for just a little over 10 years now. And NIH is really a fascinating place to work. And I learned so much when I was on the NIH campus just up the road in Bethesda. And I would say most importantly and what has been most impactful is really through that time understanding that the pathways to discovery, particularly in cancer, are very long, and they're very complex, and they are extremely resource-intensive. And all parts of that journey-- every single step has to work well together from the very early scientific discoveries at the bench to ultimately bringing those discoveries to the bedside of patients. And the government has a critical role to play in that journey. Because a lot of that initial science, as you know, is risky, you really have to take a long view. And the very, very early clinical trials, which is what the clinical center focused on-- really phase 0 and phase 1, a few phase 2 trials, natural history trials-- those can only be done in certain types of facilities that have a lot of resources like the NIH Clinical Research Center. And then the other thing that I think about often as I'm doing my work is the many, many patients that I met while I was there at the Clinical Center. We had a 200-bed hospital, a huge outpatient center. And they really are the true heroes. I really think a lot about the many patients who knew that they were enrolling on trials that may or may not benefit them, but would potentially move us forward in the fight against cancer. And so I'm very passionate about the resources that are needed for NIH and NCI. And a lot of that is driven because of this, what I consider, a really transformative experience for me while I was at NIH. CH: Well, many listeners will remember that I occasionally talk about when I was president of ASCO back in 2013 and '14. And that was the end of an era-- about a decade-long era-- where we had flat funding in dollars. And that, of course, with inflation meant a relative loss of purchasing power and missed opportunities. And this really rallied our broad community. And this is a bit of a little detour, but one of the things that ultimately helped, I think, increase the enthusiasm of many of our members for political engagement and reduce some of our cynicism is that the last few years, we've seen, instead, a steady rise and consistent support for federal funding. And it's crossed party lines. It's clearly been bipartisan. I wonder-- I mean, we like to take some credit for it-- but, of course, I was one of thousands of people knocking on doors and one of many thousands of people repeating the message. But why do you think that we currently are enjoying a period of such steady and reliable bipartisan support? And as you answer that, I would ask you to think about the future. Do you think that support can continue? LL: Yeah. Look, I think it's a really important question. And I do think that one of the important things that we collectively lend to this discussion is a bipartisan lens. I mean, cancer does not discriminate. It is not political. We ran a big campaign, as you might remember, a few years ago that we dubbed the "One Degree Campaign," because if you are not your own cancer story, you are certainly not more than one degree away from a cancer story. I think there are a couple reasons why we've been able to rally support from a bipartisan standpoint. One is, I do think that people can clearly understand the important role government has in the fight against cancer. But also, just that our patients are very compelling storytellers. They are there, talking to their lawmakers on both sides of the aisle in Washington DC when they're in district about their experiences-- their own, personal experiences about their fight or their engagement with someone else in the fight against cancer, and how critically important federal investment is in what their experience has been. And I do think that when members hear those stories from people who've been directly impacted, or maybe they've experienced it themselves or seen it themselves, it's compelling. I think collectively, as a community, we're getting better at continuing to show the incredible impact that NIH has. And the statistics sort of bear this out, right. There has been incredible progress in diagnosing cancer, treating cancer, caring for people who have cancer. And in the last 50 years, every major medical breakthrough in cancer can be traced back to NIH and the NCI. So I think when we tell those stories, we remind so many people that people that they love are alive today because they have helped fuel that discovery. And they do that by appropriating money for NCI. And so to that end, we would like to call it an evergreen issue. Getting appropriations every year from Congress is something that we can never let up on. It is a sustained effort. And we must continue to really coordinate well among partners-- so between ACS CAN and ASCO and many, many of our cancer partners-- so that we're sure to be bringing a concerted, collective voice to this issue. And we certainly know, because we see it every day in our political lives, that Congress definitely has a habit of reacting to the latest crisis. And so we want to make sure that we don't want cancer to continue to be such a huge crisis. We want continued forward movement. And that's why it's so critical that we bring the patient voice to this issue. We are good partners, again, united with ASCO, ACS CAN, and others in One Voice Against Cancer, which we fondly call "OVAC," which is our coalition that continues to make the case on a regular basis to lawmakers and their staff. But I'm really seeing-- and, Cliff, I know you probably have through your career, as well-- but if we get the patient voice to an elected official, it's not hard for them to support our cause and to understand why these funds to NIH are so critically important to changing the face of this disease. CH: Well, one of the ways-- I mean, one of the most tangible, obvious ways that we do that and the patients see it, of course, is through clinical trials. Those advances you describe at the NIH have to lead to clinical trials before they can actually change a standard of care. And this is another policy area where we've been working together, in particular advocating for the passage of the Clinical Trial Act. This is legislation that would federally require Medicaid to cover those routine care costs that come with participating in clinical trials, which would bring Medicaid into line with every other major payer, including Medicare, for example. Can you talk a little bit about what impact this bill would have on patients with cancer? And I ask that, reminding everybody that we will shortly post another podcast where we discuss this in detail with Melissa Dillmon, who is the current chair of our Government Relations Committee and on the front lines. LL: And a shout-out to Dr. Dillmon, because she actually worked with us on a congressional briefing around the six protected classes. And she is a fabulous leader. So congratulations for getting her to work with you. Because her voice needs to be heard in these fights, as well. And I want to do a shout-out to ASCO for your leadership in this particular piece of legislation. So specifically with Medicaid-- I mean, Medicaid by definition obviously serves people facing financial challenges. So right now, it is, as you mentioned, the only major category of insurance where routine costs in cancer clinical trials aren't covered. And so just to be clear, there's the experimental part of a cancer trial, but there are also maybe just regular standard of care that a patient would be getting even if they weren't enrolled in the trial. And those are the costs that you're talking about in this piece of legislation, and that when we talk about the financial challenges of enrolling on a clinical trial, it's not the experimental part of the trial itself. It's really the care around that. So currently, only 12 states and the District of Columbia have state requirements that Medicaid cover these routine trial costs. So that means 38 other states, if a patient wants to enroll in a trial, they're responsible for 100% of that routine costs out of pocket, which we know very few Americans could afford, much less those on a limited incomes. So to us, we see this as essentially a ban on participation by Medicaid patients, which really doesn't make any sense since, by definition, those routine costs would certainly be covered if they were seeing a doctor just on a regular visit. And we also don't want to exclude this whole cohort of millions of patients that we want to have participate in these clinical trials, since that is a critical success factor, as you noted, getting discovery out there that can impact a cancer diagnosis. CH: Well, while we're on the topic of Medicaid-- and here we were focusing on coverage of its beneficiaries' participation in clinical research-- but can you talk a little bit about your Medicaid Covers Us campaign? How does that relate to this, if it does at all? Or what direction does that take us in? LL: So Medicaid Covers Us-- I really hope that people that are listening to the podcast can take a minute and go to our URL, which is medicaidcoversus.org. And this is a campaign that we launched last year. And although ACS CAN has a very long history of advocating for Medicaid, Medicaid is just an insurance coverage, right. It just happens to cover a lower level of income for patients. But really, the focus of that program is to improve access to screening, diagnosis, treatment, which happens if you have insurance coverage. So when the Affordable Care Act was passed, there was an opportunity to expand Medicaid, although it is optional for a state. ACS CAN has worked hard with many partners to actively advocate for expanding and really educating the public on how important Medicaid is in the insurance landscape. And so part of that-- what we realized is that we really wanted to make sure that people understood what Medicaid truly is. And one of the ways we are doing that is through this campaign. And this is a public education campaign that's really trying to create a dialogue for everyone who touches health care, which is really an entire community, to understand the importance. If you want to achieve a healthy community, healthy economy, health care is a really important part of that. And Medicaid plays an important role in health care. So we decided to pursue kind of this larger educational effort, and it's really been an exciting project. We have gotten a lot of opportunity to have many members of a community have this conversation. And we're excited about the role that we're able to play in continuing to make sure that people understand that quality cancer care needs access to insurance. And access to insurance for many, many people means access to Medicaid. CH: So really, in the last few moments we've talked about Medicaid from two perspectives. One is coverage for a substantial bloc of Americans at about 42 million, if memory serves me correctly. And the second is specific coverage of a vulnerable subset that is those beneficiaries who need access to clinical research for advanced cancer or cancer at all. Is that a fair summary of the two prongs of this effort? LL: 100%, 100%. And I think that we want comprehensive coverage. And Medicaid provides, again, a lifeline for so many patients. And we really want to work to address a couple of big challenges right now in Medicaid. One is that there still 15 states that have not fully expanded their Medicaid program. So that means that there are low-income parents, adults that are not able to access affordable health insurance. And we've seen through a significant amount of research that we've done on our end that there are a lot of cancer patients in the Medicaid program. So that program itself is very, very important to our mission. And then another issue that we're paying a lot of attention to and trying to make sure through ACS CAN that we're having influence on, our policy changes that are creating some barriers if you actually are in Medicaid-- things like what are known as 1115 waivers that are introducing things like work requirements, or maybe some other types of barriers like a lockout period that really create a significant barrier in a pathway for patients to make sure they continue to be able to seek care. So we want to make sure that for all Medicaid enrollees with serious conditions like cancer, that they're able, one, to continue to work-- if they are unable to work, though, that they don't lose their coverage. So we are continuing to work on many, many components of Medicaid, so both the public education and awareness, but also a lot of these very direct lobbying issues. CH: You know what's interesting, I was thinking as you described all that, the ability to understand the system and then help to constructively shape it is, in fact, the reason-- personally, I can tell you-- that I was so interested in making the career change to go from breast cancer doctor to ASCO CEO. You've been at ACS CAN in total, as we heard already, for just about a dozen years. But recently you stepped into the role of president for the organization. So thinking about all of this, I wonder, has your view of the organization and its role and potential changed over these years? And what are the things that you want to focus on, going forward with this tool that you now have at your disposal? LL: Yeah. So that's a great question. I'm almost at my six-month mark, so that's very exciting. And it's certainly interesting and always very, very different to work in an organization from a different vantage point. But as president, the first thing I'll say as I continue to be unbelievably impressed with our partnerships and our staff and our incredible volunteers nationwide and their ability to impact policy through very deliberate approaches that we have trained people on-- and when we're clear about the impact that we can have and we talk to our legislators about that impact, we've found a lot of champions. I continue to be very proud, but also convinced that the role of advocacy is critically important to the future of cancer and changing that future for more and more people to have more opportunities to successfully fight their diagnosis. And for organizational goals, I think we obviously want to continue to grow ACS CAN. The bigger our organization is, both from a network of volunteers to resources, the more influence I know that we can have. And then finally, a personal passion of mine is to make sure that our organization is relevant to the entire cancer ecosystem, but particularly everyone who is going to face a cancer burden. And we know that cancer burden is unequal in many, many segments of our population. So I feel a great responsibility and drive to work with my many colleagues, including you, Cliff, and ASCO, to do everything we can to very deliberately reduce the disparity of cancer. CH: Well, that's an inspiring way, I think, to wrap up this conversation. I can't thank you enough for joining me today for this ASCO in Action Podcast. ASCO and ACS CAN share so many common goals, as I'm sure everybody will hear through this conversation. And we are both dedicated to helping people whose lives have been affected by cancer. And when patients, survivors, families, cancer care providers work together the way we do, and so many others, it's clear that the results can be tremendous in terms of impact and change. So thanks again for leading this charge with us. LL: Well, Cliff, it really was my pleasure to do this today with you. And I look forward to many years of productive partnership between ASCO and ACS CAN. Thanks for having me today. CH: Sure. And for all of you listening, if you want to keep up with ASCO's advocacy efforts, I encourage you to visit our website. This is ascoaction, written as one word, .asco.org. And there's more information about ACS CAN and Medicaid Covers Us available at fightcancer-- that's written as one word-- .org. And, Lisa, I think you previously told us that there's a special website for Medicaid Covers Us. What's that URL again? LL: Medicaidcoversus.org. CH: I don't know how I forgot it. So until next time, thank you for listening to this ASCO in Action Podcast. If you enjoyed what you heard here today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. And while you're there, be sure to subscribe so you never miss an upcoming episode. The ASCO in Action Podcast is just one of ASCO's many podcasts. And you can find all of them at podcast.asco.org.

An interview with Dr. Anna Falanga on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guideline Update." The guideline revises several previous recommendations. Most notably, direct oral anticoagulants (DOACs) have been added as options for VTE prophylaxis and treatment. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of ASCO's podcasts at podcast.asco.org  TRANSCRIPT Hi, my name is Clifford Hudis and I am the CEO of ASCO and the host of the ASCO in Action Podcast. About twice a month, I interview thought leaders in health care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues.   You can find the ASCO in Action Podcast on Apple Podcasts or wherever you are listening to this show, and you can find all 9 of ASCO’s podcasts which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Anna Falanga from the hospital Papa Giovanni XXIII in Bergamo, Italy. Senior author on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guidelines Update." Thank you for being here today, Dr. Falanga. Yes, thank you. I am very happy to talk on the update of the ASCO VTE guidelines. So this guideline was first published in 2007 with an update in 2013 and a reaffirmation in 2015. So what prompted this 2019 update? Thanks for this first question. I think that an update was urgently needed at this time. You know, before, the ASCO guidelines were published in 2007. And then an update was made in 2013, and the second one in 2015. But in 2015 was basically a confirmation of the previous 2013 update. Now the update was urgently needed, because in the very recent years there has been even more evidence of the relevance and impact of a venous thromboembolism in the cancer patients. But in addition, and very importantly, new data from prospective randomized clinical trials with the new drugs for the management of VT in the oncological patients have become available. In particular, as you know, low molecular weight heparins were largely used in the setting of the treatment and trauma prophylaxis in the cancer patients. And actually, the low molecular weight tapering have been the standard of treatment for many years. However, recently the results of prospective randomized clinical trials of direct oral anticoagulant, particularly, the anti-Xa inhibitors, Edoxaban and Rivaroxaban, for cancer associated with [INAUDIBLE] treatment support the role of this new oral agent in the VT management in this setting. And this is related to new politics in the VT management in these patients. So what are the key recommendations for this guideline update? The main changes to the previous recommendations are first that Rivaroxaban and Edoxiban, the two anti-Xa inhibitors oral anticoagulants have been added as an option for routine treatment in cancer patients in this update. Also, now we may offer thrombo prophylaxis with Apixaban, Rivaroxaban, or low molecular weight tapering to selected high-risk outpatients with cancer. And about other changes of these new guidelines compared to the last one include that patients with brain metastases have been addressed in the VT type treatment sections, whereas before, only patients with the primary tumors were mentioned in the previous edition. And finally, the recommendation regarding long-term postoperative thromboprophylaxis with low molecular weight heparin expanded to patients undergoing a major open or laparoscopic abdominal or pelvic surgery. These are the main changes that all I think are very, very important. Why is this guideline so important? And how does it affect practice? Well, I think that the question how these changes affect our practice is a very important question, because I believe that these guidelines reflect the new evidence that we have from the new data. And this data clearly expand our possibility to choose now between the different treatment options in the single patient in the cancer population. For instance, the new data show that treatment with [INAUDIBLE] anticoagulants compared to low molecular weight heparin lower the risk of a recurrent thrombosis. But in some instances there's a higher risk of bleeding, particularly in the gastrointestinal and urinary tract cancer patients. So therefore it is evident that the patient selection and the individualization of a therapy based on the patient characteristics and the type of cancer-- all these become very important. And we have the possibility now to choose between different treatments, or in the same patients we can change from one treatment to the other according to the face of the disease or complications if the patient is in a phase that is assuming chemotherapy with many side effects like nausea and vomiting. Of course, in these cases a parenteral injection is preferable for the management of a venous thromboembolism. Whereas in other instances, a long-term and oral intake is surely more convenient. So it depends also from the level of risk. But now for the six months treatment we can offer different choice of the oral treatment and also for high-risk patients the primary prophylaxis with Apixaban Rivaroxoaban, and a low molecular weight tapering can be chosen. And what should patients be aware of when it comes to VTE risks and treatments? I think that patients should be educated about the risk of a cancer associated with VTE. You know, there is that evidence that they are educated about it. And they know a lot better about neutropenia, and the fever associated with this the neutropenic condition and the other side effect. But they know very little about the possibility that they can experience venous thromboembolism. s So I think they should be taught on how to recognize the symptoms and alert their physician. You know, sometimes the symptoms are indistinguishable It can be just a little pain in the calf. And patients must know that these are to be considered important. They must alert their physician to undergo some test-- objective test-- to see if there is a real thrombosis in the leg or not. This is extremely important, because one important consequence of venous thromboembolism of the extremities is a pulmonary embolism that can be also fatal. So they must know about that. Also, I think they should know about the risk of bleeding associated with the anticoagulant treatment, and also that this risk of bleeding can be different in the different type of tumors. Finally, I think that also they must be told about the once they have, for instance, and episode of venous thromboembolism they have to receive a treatment for that, and these are usually six months to the minimum, and then we'll decide. So they must know what these are the efficacy and the safety profiles of the different drugs. They must know the differences in the route of administration and the other characteristics of the drug. So I think that their shared decision with the patients of the type of treatment must be an integral part of the decision making and is certainly desirable. Great. It sounds as though there's some important considerations for patients and important conversations which may be prompted by this guideline. So thank you for taking your time to discuss this with me today, Dr. Falanga. I thank you very much for this interview and talk that our colleagues and also the patients will be happy with these new guidelines of ASCO. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TRANSCRIPT An interview with Dr. David Adelstein of the Cleveland Clinic on the ASCO PCO which provides statements on the role of treatment deintensification in the management of p16+ oropharyngeal cancer. Read the full PCO at www.asco.org/head-neck-cancer-guidelines The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. David Adelstein from the Cleveland Clinic Taussig Cancer Institute. Lead author on "Role of Treatment Deintensification in the Management of p16 Positive Oropharyngeal Cancer: ASCO Provisional Clinical Opinion."  Thank you for being here today, Dr. Adelstein. Thank you, Shannon. Before we get started, I'd like to first note the contributions of my panel co-chair, Drew Ridge, and those of all of the other panel members. And I'd like to extend a special thank you to ASCO for their support in allowing us to put this together and specifically Nofisat Ismaila who did a tremendous amount of work in allowing us to complete this provisional clinical opinion. First, can you give us an overview of the clinical issue for this PCO? Sure. So this really came out of the implications of human papillomavirus mediated oropharynx cancer. I think as most of the listeners know, over the last several decades we've recognized the fact that oropharynx cancer has a second ideology, that not all of it is caused by tobacco use, but that the human papillomavirus is now the major ideologic factor in North American and northern Europe. The importance of this is that the human papillomavirus-induced oropharynx cancer is a different disease. It has a number of different characteristics from the kinds of head and neck cancer we've seen in the past. It's a disease that tends to occur in younger patients, patients who are otherwise generally more healthy. It is unassociated with smoking, although it can occur in smokers. But it's much more frequent in nonsmokers. And I think most importantly, it's a disease that has a dramatically better prognosis than the tobacco related disease. Now over the last several decades, our ability to treat advanced head and neck cancer has improved significantly, because we've begun to incorporate non-operative treatments-- chemotherapy and radiation-- and have been more aggressive in our utilization of chemotherapy and radiation with significantly greater success than we had in the past. The problem with this kind of treatment is that it is quite rigorous. And there's a good deal of acute and, more importantly, late toxicity that patients experience from these kinds of approaches. Now as we became more familiar with the importance of HPV associated oropharynx cancer, we realized that there are subgroups of these patients who have cure rates that are in excess of 90%. And the question arose whether the kinds of rigorous chemotherapy and radiation therapy treatments that we were utilizing were really necessary. Was it necessary to cause this much acute and late toxicity in patients who in vast majority of cases were going to be cured of the disease. And it's important, because these are younger patients. And the late toxicities are going to have a major impact on their quality of life for a number of years. What came about was the notion of treatment deintensification, the idea that perhaps it would be possible to deintensify the kinds of treatments we were giving in select patients. It's a very compelling hypothesis for medical oncologists and radiation oncologists. But there are a number of problems as we try to test this hypothesis. The first problem is how do we identify the good risk patients? There are patients with HPV-positive disease who do not do so well-- the heavy smokers and patients with very advanced tumors. And we need to be careful if we're going to be talking about giving less treatment that we don't give less treatment to the patients who have a worse prognosis. We pick the best prognosis patients. There have been a number of what we call risk stratification schemes that have been developed looking at trying to identify the very good prognosis patients-- those patients who are HPV positive who don't smoke and who have relatively limited disease extent. There's not universal agreement on how best to define these patients. All we know is that they do exist, that you can look at patients with these characteristics and see very good outcomes. One of the issues that has come up is how do we utilize the American Joint Committee staging system-- AJCC the 8th edition. One of the things that AJCC 8 did which is new is that it defined a separate staging system for patients with HPV-positive oropharynx cancer, a system which is entirely different than the staging system that we've used for head and neck cancers for many years. This was based on the recognition that the prognosis of patients with HPV-positive disease is so good so that many patients who we would previously have considered to have stage 4 disease are now classified as having stage 1 tumors, because their prognosis is so good. And that can be confusing, because the typical thought process for an oncologist is that a patient with stage 1 disease should be treated with single modality therapy. The reason that the HPV-positive patients have such a good prognosis, however, is that many of them have been treated with combined modality therapies. And to make the assumption that because now they're classified as stage 1 is incorrect. It is they shouldn't be treated with less intensive treatments and can be confusing. AJCC 8th edition is a prognostic robust staging system, but it really doesn't help us in defining treatment. First problem is how best to define patients who are appropriate for deintensification. Second problem is, what do you do to deintensify? What constitutes meaningful deintensification? Well, over the last 10 or 20 years there have been some significant advances in our standard treatments for all head and neck cancers that weren't developed the idea of deintensification. We now have tremendous experience using transoral surgical techniques, which are generally minimally morbid, much less morbid than the former open techniques that previously were used, which allows consideration of surgery for many of these patients where we wouldn't have considered it before. Similarly, intensity modulated radiation therapy has been widely adopted, and d clearly an approach using radiation, which is far less difficult, far less toxic than the former 2D or 3D radiation planning techniques that used to be used. But if we talk about intensification, what kinds of things can we do to deintensify our treatments? Well, one thought is to reduce the radiation dose. Then the question is, how much reduction is reasonable? And how much reduction is going to actually impact on this toxicity? And are our toxicity measuring tools adequate to even detect the difference in reduction of a radiation dose? Many of our toxicity tools are very crude. Perhaps we should be using some of the patient-reported outcome quality of life instruments that are available. Other thoughts are, perhaps one can reduce the size of the radiation therapy field. Can we reduce the dose of the chemotherapy? Can we eliminate chemotherapy? Can we even use less intensive chemotherapy? Generally, the other treatments for this disease have employed high doses of cisplatin, which is a toxic agent. And then there the question has been asked as to whether we can reincorporate minimally morbid transoral surgical techniques in an effort to better pathologically stage patients and define more appropriate adjuvant treatment. Perhaps not all patients need adjuvant radiation or chemotherapy and radiation. All of these approaches are interesting. They're exciting. They're being tested. But all of the experiences is preliminary. And that really brings us to the third and the biggest problem in any deintensification approach. And that's the need to be certain that if we deintensify our therapy, we're not going to compromise outcomes. It would not be acceptable to give less treatment or less intensive treatment if our survival were compromised. And we have to be certain that we don't do this. So what has evolved over the past decade is a whole number of treatment approaches that have some very enthusiastic early results. But these are generally single arm phase 2 reports where there is no comparison to conventional treatment. And they become difficult to interpret, because the results in general are very good. I think what really raised a red flag for us and that really caused us to take notice was the results of the RTOG 1016 trial that we reported last year. And at the same time, the European de-escalate trial, both of which had a similar design. These were studies that were designed in an effort to see if treatment deintensification would be possible by randomly comparing the standard treatment radiation and cisplatin with what was felt to be a less intensive approach-- radiation and concurrent cetuximab. And cetuximab is an accepted agent in the United States for treating head and neck cancer. The assumption here is that the survival would be equivalent when these two arms were compared, but that the toxicity would be improved by giving the less intensive systemic agent-- the cetuximab. The surprise when the study was analyzed was that that assumption was incorrect, that the radiation and cetuximab arm-- the deintensified arm-- actually proved inferior in terms of survival. And this was in both trials-- both the RTOG trial and the trial from Europe. And that was a big note of caution, because it was somewhat unexpected. I think we learned from that kind of a study, from a good randomized-- a large randomized trial-- that even though the outcomes may appear to be good, we need to be very careful about deintensifying our treatment until we're sure that the survival is equivalent. So although it's tempting for the clinician to see these very exciting reports about administering less treatment with the idea of producing less toxicity, the guideline advisory committee for ASCO really thought it was important that we get the message out that this kind of approach is not a treatment standard. This remains an investigational approach, and that the treatment standards for this disease really haven't changed. So what are the provisional clinical opinions that were made by the expert panel? They made several statements. The first was to acknowledge that the idea of treatment deintensification is a very compelling hypothesis, and it does require careful and appropriate testing. The second was that even though we are now better at identifying good prognosis patients, and we've seen some very promising early results, and even though we're now reclassifying patients with previously advanced stage HPV-positive disease as stage 1 or stage 2 tumors, the treatment recommendations for this disease have not changed. And they're based on the results achieved using AJCC 6 and 7. Standard of non-operated management to patients who are eligible to receive cisplatin remains high concurrent radiation and high dose cisplatin given every three weeks. If patients undergoing a surgical resection, then adjuvant chemotherapy and radiation with radiation and high dose cisplatin every three weeks is recommended in those patients with high risk factors of positive surgical margins or external tumor extension. And most importantly, deintensification, though it's a compelling hypothesis, is something that should only be undertaken on a clinical trial. Why is this guidance so important? And how will it affect practice? Well, I think the important thing about this guideline is that it shouldn't affect practice. The practice shouldn't change. The standards of care are not altered. And that for the clinician, this remains something that is exciting, something that should encourage enrollment on a clinical trial, but that we haven't changed treatment standards. And finally, how will this guidance affect patients? So from a patient's point of view, I think there is continued reason for optimism. A patient with the diagnosis of an HPV-positive oropharynx cancer is a patient with a very good prognosis. Patients are increasingly sophisticated. They read about the potential for treatment deintensification, and recognize that this is not something which is an accepted standard. But it should encourage their participation in clinical trials if [INAUDIBLE] is offered. I think ultimately it's a remarkable thing when oncologists can consider the possibility of reducing treatment intensity because the treatment results have been so good. Great. Thank you for your overview of this PCO. And thank you for your time today, Dr. Adelstein. And thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full PCO, go to www.asco.org/head-neck-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Nancy Baxter from St. Michael's Hospital in Toronto, senior author on "Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Baxter. Thanks very much, Shannon, for speaking with me. I'm happy to share our work developing this guideline. So first, can you give us a general overview of what this guideline covers and the studies which provide the evidence? Absolutely. So use of adjuvant therapy for patients with stage III colon cancer is common, and it's effective. We know that these patients are at substantial risk of recurrence of their disease and that adjuvant therapy can reduce that risk. But we also know that comes with a cost. The most effective adjuvant therapy is FOLFOX or oxaliplatin-containing chemotherapy regimens. And we know that a really substantial number of people will end up with neurotoxicity, with peripheral sensory neurotoxicity, that can be long lasting and certainly affects their quality of life. So the whole question was whether the duration of oxaliplatin-containing chemotherapeutic regimens could be shortened when they're used for adjuvant therapy, so if we could give three months instead of six months. Because we know that if we give three months of therapy, the risk of neurotoxicity is much lower. So if we had the same effectiveness with the shorter duration, then we could spare patients the negative consequences of the agent given for a longer period of time. So in developing these guidelines, we looked at the results of international group of trials, the six trials from the IDEA collaboration. So these were six randomized trials in various jurisdictions that tried to look at this question, so three months of an oxaliplatin-based chemotherapeutic regimen for adjuvant therapy for stage III cancer versus six months duration of therapy. And so there was a planned analysis to bring all of these data together to develop the evidence base to make this recommendation. So our guideline and our systematic review basically identified this is the key piece of literature to base our recommendations and guidelines on. That's essentially the main study, so the meta-analysis of these six randomized controlled trials that formed the basis of the IDEA collaboration. So the IDEA collaboration studies-- there were six individual randomized trials that formed part of the IDEA collaboration. And they were conducted in Italy, Greece, Japan, North America, through CALGB/SWOG, the UK, Denmark, Spain, Australia, Sweden, and New Zealand, as well as France. So data came from, really, around the world. The median age of people in the studies was 64 years of age. And these people had a really good performance status, so almost all of these patients had an ECOG performance status of 0 or 1. So they were healthy patients that were in the study. And so some patients received CAPOX, and some received FOLFOX. That wasn't part of the randomization scheme. Other than the CALGB/SWOG study, this was up to the discretion of the investigator or patient. In the SWOG/CALGB study, only FOLFOX was given. And the authors planned a prespecified subgroup analysis to look at differences between CAPOX and FOLFOX. There was also a prespecified analysis to look at differences based on stage. What they found when they looked at the results was that, overall, the difference between groups in terms of the three months versus six months was that the hazard ratio between these two was 1.07, meaning a small difference between the groups in terms of recurrence or death between three months and six months overall. But because the prespecified confidence interval, noninferiority interval, for the difference in outcome was 1.12, the 95% confidence interval for the hazard ratio was above this. So it was 1.15, indicating that this prespecified noninferiority margin was exceeded. And so the study did not prove noninferiority of the three-month regimen. So we're left with an inconclusive result. So that's why our guidelines don't have a strong recommendation for the three months, because we can't rule out a small but potentially important difference between the two groups in terms of recurrence or death. Now, interestingly, when they looked at the prespecified subgroup analysis, which was looking at CAPOX versus FOLFOX, a difference was found. So they actually found that for FOLFOX chemotherapy, three months of therapy was inferior to six months of therapy, while for CAPOX, actually, three months and six months were the same. So it met the criteria of noninferiority. So these are kind of two different conclusions based on which type of chemotherapy was used. This was surprising to the investigators and was not expected. And certainly, it was not consistent with the randomized trials that we have comparing these regimens. So we therefore did not make any conclusions in our recommendations about CAPOX versus FOLFOX. But this is certainly something that requires further investigation in the future. In terms of stage, we did not find that there was an interaction between T stage or end stage when you looked at the differences between the three and the six month. And that was the prespecified analysis. But in non-prespecified analysis, which was the higher risk versus lower risk categories, you did find this difference where the patients with high-risk disease had inferior disease-free survival with three months versus six months of therapy, while those at low risk of disease, it seemed quite safe to give three months versus six months. So that's a long story. But essentially, because the high risk versus low risk analysis was not prespecified, there's a limitation to how strong our recommendations can be to have three months of therapy. However, given that the hazard ratio associated with three months versus six months of therapy for this lower risk group was only 1.01, indicating they were the same, and the risk of neuropathy was substantially higher with six months, this has led to us making recommendations that the three months of therapy is adequate for patients with low-risk disease after discussion with patients about the possible pros and cons. And what are the key recommendations of this guideline? Well, so the recommendations of this guideline do depend on the pathology, so how high risk the patient is. So based on the evidence from the IDEA collaboration, the researchers found that patients who had a high risk of recurrence-- so had T4 disease or heavily node-positive disease, N2 disease-- the six-month duration of therapy was better than the three-month duration of therapy. These studies and the meta-analysis were designed as noninferiority meta-analyses. But it was clear from the results that the three-month duration was inferior when compared to three months for these high-risk patients. So that seems clear, although we know that those patients will also be at more risk of neuropathy. And so that needs to be discussed with patients, as well. So for the second group, which are patients who are at lower risk of recurrence, what we found was there was less of a clear benefit of six months of therapy. The recommendation was that patients who are in this low-risk category-- so T1, T2, or T3 cancers that are N1, so not heavily node-positive-- clinicians can offer three months versus six months of therapy after having a discussion with their patients about the pros and cons of that. So the clinicians can go ahead and offer that to patients and still be within the common guidelines based on evidence for treatment of stage III colon cancer. So because there's some uncertainty after analysis of the IDEA collaboration, one of the really important recommendations that we make is about this shared decision-making approach. So the third recommendation that we make is that oncologists should discuss these factors with their patients who have stage III resected colon cancer and that the duration of therapy needs to take into account the tumor characteristics-- the surgical resection, the number of lymph nodes examined, the comorbidities, the patient functional status, all of these various things-- and there needs to be a discussion of the potential for benefit and the risk of harm based on the duration of therapy. And oncologists definitely discuss these things with their patients. And this just emphasizes how this is yet another component of the discussion that needs to be included, particularly when speaking with low-risk patients who are at substantial risk of harm from neuropathy and are unlikely to benefit greatly by extending chemotherapy to six months. So why is this guideline so important? And how will it change practice? Well, I think, until now, the standard recommendation has been six months of FOLFOX or six months of oxaliplatin-based chemotherapy. And again, there are many patients who have quality of life-affecting neuropathy because of this. So for a substantial proportion of patients who present to us with stage III cancer-- so those that are low risk-- I think this provides some options to them. So they can opt for a shorter duration of chemotherapy with a lower risk of toxicity. This saves time. This saves cost to the patient and to the system and potentially improves their quality of life without a great impact on outcome in terms of disease recurrence. So that's a substantial number, a substantial proportion of our patients, who can be treated in this way. So I think that this is a real benefit. Again, oncologists need to have a conversation with their patients about the pros and cons. But this is an option for their patients, whereas from an evidence-based perspective, it wasn't before the publication of the IDEA collaboration. Finally, how will these guideline recommendations affect patients? So for patients who have heavily node-positive disease-- so high-risk patients with T4 or N2 disease-- it's not going to affect care. So the expectation would be those patients would be treated with six months of therapy, similar to previous recommendations. So this will be for people who are at lower risk of disease recurrence, so patients with T1 to 3 tumors that are N1 positive, so not heavily node positive. So these patients will have the opportunity to opt for a shorter duration of therapy. So that's a major benefit to patients. Again, it's important that there's a discussion and that patients understand the pros and cons. But this is now an option for them, which is excellent. Thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Noam Yarom, Dr. Charles Shapiro, Dr. Deborah Saunders and Dr. Doug Peterson on "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." This guideline addresses the prevention and management of MRONJ in patients with cancer. This guideline is intended for oncologists and other physicians, dentists, dental specialists, oncology nurses, clinical researchers, oncology pharmacists, advanced practitioners, and patients with cancer. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of the ASCO podcasts at podcast.asco.org  TRANSCRIPT Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today, I'm interviewing a panel of authors from "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." So could I have you each introduce yourselves for the listeners today? Thank you, Shannon. I'm Dr. Deborah Saunders. I'm the president of the International Society of Oral Oncology and was the section head for the Systematic Review on "Medication-Related Osteonecrosis of the Jaw," with MASCC and ISOO. I was a proud part of the steering committee and one of the authors. Thank you, Debbie. My name is Dr. Douglas Peterson. I am professor of oral medicine in the School of Dental Medicine at the University of Connecticut Health Center in Farmington, Connecticut. I am also a faculty member in the Head and Neck Cancer Oral Oncology Program at the university's Neag Comprehensive Cancer Center. I'm a member of the steering committee for this clinical practice guideline and one of the co-authors as well. In addition, and as of June 2019, I have been serving as chair elect during this next year for ASCO's Clinical Practice Guidelines committee. Thank you, Doug. My name is Noam Yarom. I'm an all medicine specialist from the Sheba Medical Center in Tel Aviv University in Israel. I'm serving as a culture of this guideline, and it is a pleasure to be with you today. Thanks, Noam. I am Dr. Charles Shapiro, professor of medicine at the Mt. Sinai Hospital in New York. And I'm co-chair of the guideline "Medical-Related Osteonecrosis of the Jaw." And I'm happy to be here. Thank you all for being here today to discuss this guideline on the podcast. So first, can you give us a general overview of what this guideline covers. Sure. So you know, ASCO and MASCC, as well as ISOO decided that it would be great to provide a practical evidence-based approach in a multidisciplinary type setting to address this important topic that impacts all of our professions, that being medication-related osteonecrosis of the jaw. It's terminology and its definition and the path that's varied and even part of this publication identifies the need for us to move forward with a concise definition and similar terminology, that being medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw is defined as the presence of an exposed or bone that is probable by a probe in a patient that has a history or is undergoing present use of a bone-modifying agent. This being in the absence of any patients having received any radiation to the head and neck and the absence of metastatic lesions to the jaw. The importance of us identifying this definition and agreeing on the terminology allows us to move forward in future publication to better compare outcome and provide better prevention and treatment for our patients moving forward. And what are the key recommendations of this guideline? There are six clinical questions associated with this clinical practice guideline as well as a series of recommendations built within each of the clinical questions. Clinical question one is directed to the preferred terminology and definition for osteonecrosis of the jaw, both of the maxilla and the mandible, as associated with pharmacologic therapies in oncology patients. The panel recommends that the term medication-related osteonecrosis of the jaw, MROJ, be used when referring to bone necrosis associated with pharmacologic therapies. As Dr. Saunders has described, the definition contains three key elements-- current or previous treatment with a bone-modifying agent or angiogenic inhibitor, exposed bone, or bone that can be probed through an intra or extra-oral fistula in the maxillofacial region and that has persisted for longer than eight weeks. And third, no history of radiation therapy to the jaws and no history of metastatic disease to the jaws. Clinical question two is directed to specific steps that should be taken to reduce the risk of MRONJ. The recommendation begins with emphasizing the absolute importance of interprofessional communication of the oncology team with the dental team in advance of initiating the bone-modifying agent. For patients with cancer who are scheduled to receive a bone-modifying agent in a non-urgent setting, a comprehensive oral care assessment, including dental examination and periodontal examination and an oral radiographic exam when feasible to do so should be undertaken prior to initiating the BMA therapy. Once the dental care plan has been developed, it should be discussed with the dental team, the patient, and the rest of the oncology team and then implemented based on medically necessary dental procedures. These procedures should be performed prior to the initiation of the bone-modifying agent. Once the bone-modifying agent is implemented, there should be ongoing followup by the dentist on a routine schedule, for example, every six months following initiation of the BMA therapy. It's also important to realize that there are a series of modifiable risk factors which should be emphasized with the patient. For example, poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes mellitus, and tobacco use are all factors that have been associated with development of a MRONJ. All of these modifiable risk factors should be addressed, where appropriate, with the patient in advance of the bone-modifying agent. As far as elective dental alveolar surgery, these procedures, if they are not medically necessary, for example, extractions or alveoloplasties or implants, they should not be performed during active therapy with a bone-modifying agent being given at an oncologic dose. Now, exceptions to this may be considered when a dental specialist with expertise in prevention and treatment of MROJ has reviewed the benefits and risks of the proposed invasive procedures with the patient and the oncology team. In general, however, elective dental alveolar surgical procedures should be deferred while the patient is undergoing active therapy with a bone-modifying agent. If the dental alveolar surgery is performed, the patient should be evaluated by a dental specialist on a systematic and frequently scheduled basis, for example, every six to eight weeks until there is full mucosal coverage of the surgical site. And once again, communication between the dental team and the rest of the oncology team is absolutely paramount in assuring ongoing comprehensive care of the patient. Interestingly, there are still questions in the literature relative to whether or not there should be temporary discontinuation of bone-modifying agents prior to dental alveolar surgery. Unfortunately, there remains insufficient evidence to support or refute the need for discontinuation of the bone-modifying agent prior to dental alveolar surgery. And so the administration of the bone-modifying agent may be deferred at the discretion of the treating physician, in conjunction with discussion with the patient and the oral health provider. So it really becomes an individual judgment call by the treating physician relative to whether or not to temporarily discontinue the bone-modifying agent prior to dental alveolar surgery. Clinical question three involves the staging of MROJ. There are a number of well-established staging systems in the literature addressing severity and extent of MROJ. For example, the 2014 American Academy of Oral and Maxillofacial Surgeons Staging System is one example. Another example is the National Cancer Institute's Common Terminology Criteria For Adverse Events. And there is a 2017 International Task Force on O and J Staging System for MROJ that is available as well. So there are at least three well-established, widely utilized staging systems for MROJ. Having said this, it's important in the view of the panel that the same staging system should be used throughout an individual patient's MROJ course of care. And optimally, the staging should be performed by a clinician experienced with the management of MROJ. Clinical question four involves management of MROJ directly. Here, the recommendations talk in terms of initial treatment of MROJ, which is centered in conservative measures. Now, these conservative measures may include antimicrobial mouth rinses, antibiotics if clinically indicated, effective oral hygiene, and conservative surgical intervention such as a removal of a superficial bone spicule. In cases, however, of refractory MROJ, more advanced MROJ, aggressive surgical interventions, for example, mucosal flap elevations, bloc resections of necrotic bone may be used if MROJ is persisting and severely affects function despite conservative initial treatment. Clinical question five involves bone-modifying agents and whether they should be temporarily discontinued after a diagnosis of MROJ has been established. And once again, there is insufficient evidence to support or refute the discontinuation of the bone-modifying agents after a diagnosis of MROJ has been established. The bone-modifying agent may be deferred at the discretion of the treating physician, again in discussion with the patient and the oral health care provider. And finally, clinical question six involves what outcome measures that should be utilized in clinical practice to describe the response of MROJ lesion to treatment. During the course of MROJ treatment, the dentist, dental specialist, should communicate with a medical oncologist in an ongoing way, both the objective and subjective status of the lesion. The guideline presents a scale that can be utilized to describe the trajectory of the MROJ-- resolved, improving, stable, or progressive. The clinical course of MROJ may impact both local and systemic treatment decisions relative to the cessation or the recommencement of bone-modifying agents. So once again, it becomes very, very important that the ongoing interprofessional communication relative to the clinical course of MROJ-- resolved, improving, stable, or progressive-- be discussed with the oncology team. Great. Thank you, Dr. Peterson. So on that last note, how can oncologists, dental specialists, and dentists all work together to manage medication-related osteonecrosis of the jaw? Throughout these guidelines, we do emphasize the importance of collaboration among the cancer care team, dentist, and dental specialists in order to coordinate care and modify risk factors. It is very important that cancer care team and the dental care team speak the same language. Therefore, we spend time on clarifying the definitions, the diagnostic criteria, and staging of MROJ. As been said earlier, we have developed a new system to evaluate the response to treatment, which is based both on objective findings and symptoms. By using this scale, oncologists and dentists would be able to communicate more easily for the benefit of the patients. We emphasized the need for multidisciplinary discussion in a few critical points throughout the course of bone-modifying agent therapy. And it is most important in case of a planned oral surgery in a patient without MROJ or before aggressive surgical treatment of refractory MROJ. And how will these guideline recommendations affect patients, and what should they talk to their doctors about? There are a number of things that patients, providers, dental specialists, and medical oncologists can do to lessen the risk and prevent MROJ. Because the key to MROJ is prevention. Once MROJ is established, it's difficult to treat, impacting a patient's quality of life. So we want to prevent, reduce the risk of developing MROJ. Patients can do a number of things-- pursue good oral hygiene, stop smoking, or reduce smoking, and control their diabetes, for example. Those things lessen the risk of MROJ. Providers, dental providers, dental specialists, who are specialized in the area or providers, dentists otherwise in the community, when they encounter a patient that's contemplating bone-modifying agents, they can do what's called a complete dental screening exam, which involves a complete examination of the mouth, Panorex X-rays and X-rays as clinically indicated. We want to identify work in the mouth that needs to be repaired before initiating bone-modifying agents. That way, we don't have to deal with an emergent situation when it could be preventable prior to bone-modifying agents, because one of the single highest risk factors for MROJ is emergent dental work while you're on bisphosphonate or another anti-resorptive agent-- bone-modifying agents. So a dental screening exam is critical to prevent or reduce the risk of MROJ. And medical oncologists have a role too in communication with the dental specialists and really think hard about the indications for bone-modifying agents, whether it be for osteoporosis, whether it be for metastatic disease, and whether it be for anti-cancer effects. And finally, where can both patients and clinicians go to get more information on this topic or to find a dentist or a dental specialist? Now, as far as websites, ASCO, MASCC, and ISSO all have websites you can go to to find out more information about MROJ. Yeah, I think that's great advice. Our links for additional information are listed in the Clinical Practice Guideline as well. This is a really first step at a framework in trying to manage a side effect that affects our patients but is very multidisciplinary. And like Dr. Shapiro was saying, really the best way to prevent this is with proper communication between the dentist and the oncologist and making the patient aware of what is needed prior to commencement of these treatments. Well, it certainly sounds as though there are some important considerations for clinicians and patients. And I really hope that this guideline is widely read and makes a real impact on the management of osteonecrosis and the communication between oncologists, dental specialists, and dentists. So from me and all of our listeners, thank you all for coming on the podcast today to discuss "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline."   Thank you. Thank you for having us. Thank you very much for this opportunity to contribute to this important discussion. Thank you for allowing me to participate in this important podcast. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Alejandro Lazo-Langner from Western University in London, Ontario, senior author on Management of Cancer-Associated Anemia with Erythropoeiesis-stimulating Agents, ASCO/ASH Clinical Practice Guidelines Update. Thank you for being here today, Dr. Lazo-Langner. Thank you very much for the invitation to present the new guidelines. So this guideline has been updated now three times since its original publication in 2002. So how has this guideline changed over time? Since initial publication in 2002, this guideline has undergone a number of different changes. If you look at the initial series of recommendations in the 2002 guideline, it was really limited and it was fairly upfront recommending the use of erythropoiesis-stimulating agents in this setting. But during the last two updates in 2007 and 2010, that has changed significantly. And in the current guidelines, we have added some additional evidence that has been published in the last eight years. And now, in general, what we can tell is that the use of erythropoiesis-stimulating agents is now more restrictive than in the original guideline and is basically recommended for only one or two situations. There has been some other updates in the last iteration of the guideline that I can certainly discuss in more detail later. But basically, in general, the guideline has now, in the last iterations, restricted the recommendations that were much more general during the first edition of this guideline, almost all of them based on available and emerging evidence regarding the onset of their side effects with these medications. And can you give us a general overview of what this new guideline update covers, especially that new evidence that's emerged? Yeah. So the new guideline has changed a few items. And indeed, we-- the committee did a little bit of an overhaul in the recommendations that are not in the same order as they were in the previous editions. We can say that there is a couple of important updates. The first one would be addressing the use of biosimilars, which were not available in the previous guidelines. And we have addressed that in the current edition. The biosimilars have not been extensively studied in cancer, but they have. And so far, the committee considered that they were equivalent in terms of effectiveness and safety to the originator agents, both epoetin and erythropoietin. And the second most important update on the guideline is the recommendation of the concurrent use of iron supplementation in patients who are receiving erythropoietin-stimulating agents. The previous versions of the guideline just recommended the use of iron supplementation in patients with documented iron deficiency. However, in the last eight years, there's been a number of studies that have suggested that the concurrent use of iron supplementation, irrespective of the baseline iron status, does increase the efficacy of the agents. Third point is that, although this is not new, there's been more emerging evidence supporting the notion that all of the erythropoietin-stimluating agents increase the risk of thromboembolism. And this has been very consistent across all studies, and in particular derive from Julia Bohlius's systematic review and meta-analysis that was published a few years ago. And she's the lead author on these guidelines now. This has been confirmed, and I think that at this point this is probably the main limiting factor on the use of these medications. And the final minor update was that regarding the use of erythropoietin in patients with myelodysplastic syndrome. This guideline now suggests baseline serum erythropoietin level cut-off that might actually increase the chances of the erythropoietin-stimluating agents of being effective. This has been updated from the previous guidelines based on recent research. And what are the key takeaways of this guideline update? Well, the key takeaways is that if a clinician is deciding to use erythropoietin-stimluating agents, in agreement with the previous guidelines, the first thing that you have to consider is that you should not use these agents in patients that are receiving chemotherapy with a curative intent. And it should be reserved to patients in whom the chemotherapy is being given with a palliative intent. It should be only used to decrease the use of red blood cell transfusions. And if a clinician is to make a decision as to whether to use these agents or not, they should consider concurrent use of iron supplementation. But basically, the other consideration that needs to be made is that because of the confirmed increase in the risk of thromboembolic complications, in the last eight years, there's been a myriad of new treatments that may potential increase the risk of these complications, specifically and most importantly in patients with myeloma in whom the use of immunomodulators such as lenalidomide or thalidomide does increase the risk of thromboembolic events per se. And in those patients, if they were to be considered for treatment with erythropoietin-stimluating agents, that should be done in a very, very careful fashion. The risk of thrombosis is significantly high in these patients, and the concurrent use of erythropoietin-stimluating agents is probably not a very good idea. So if one were to summarize the guidelines, I would say that, one, consider very carefully whether your patient actually needs these agents, and if they do need the agents, whether they should be receiving them, specifically if they are only being given chemotherapy with palliative intent with a short time life expectancy. Some patients would be considered to be in palliative. However, in conditions such as myeloma, for instance, although they are not curable, the patients may go on living for many years. So that's probably not a very good idea to use these agents if they increase the risk of complications. And if one is going to be considering these, they should consider also the concurrent use of iron to improve the efficacy of these agents. And finally, how will these guideline recommendations affect patients? Well, the guideline recommendations won't have a particularly high impact on patients. The most important thing is that, if patients require ongoing transfusional support due to the palliative chemotherapy or the nature of the disease they have, the use of erythropoietin-stimluating agents might decrease the need for these transfusions at the cost of increasing the risk of complications. The new updated guidelines are probably going to result in-- if they are considered when a clinician is using these agents, they are probably going to result in lower complications for patients due to the more restrictive nature of the recommendations. And in general, the only other consideration would be that under special circumstances related to, for instance, access to transfusional support or other personal considerations from certain patients and groups, these guidelines might actually help to overcome those barriers for transfusional support. But those were the two major impact points that would be considered based on this updated guideline. Great. Thank you for your work on this important guideline and thank you for your time today, Dr. Lazo-Langner. Thank you for the invitation. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. 

An interview with Dr. Lynn Henry from University of Utah Huntsman Cancer Institute on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." This guideline update includes data from the MINDACT and TAILORx trials to clarify the recommendations for patients with hormone receptor-positive, HER2 not overexpressed, axillary node-negative early breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines  TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin. And today, I'm interviewing Dr. Lynn Henry from the University of Utah Huntsman Cancer Institute, lead author on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you for being here today, Dr. Henry. Thank you very much for the invitation. So this guideline was updated to incorporate new data from the TAILORx and the MINDACT trials. So can you give us an overview of these trials and their results? Sure. So patients with hormone receptor-positive, HER2 negative breast cancer, are generally treated with anti-estrogen treatment and are sometimes also recommended to have chemotherapy. Since these tumors don't always respond well to chemotherapy, tests have been developed that provide more information about how much benefit, in terms of reduction of the likelihood of cancer coming back, an individual patient is likely to get from treatment with chemotherapy. It is important that the benefit of a treatment outweighs the risk of toxicity from the treatment. Two of those tests are called Oncotype DX and MammaPrint. And they have recently been tested in large clinical trials. So TAILORx is a large prospective trial that tested the Oncotype DX assay. In the Oncotype DX assay, a tumor is tested to get more information about how likely a cancer is to return and how much benefit the patient is likely to get from chemotherapy. Scores on this assay can range from 0 to 100. Previously, a study showed that patients whose tumors had scores of 10 or less, and who received five years of anti-estrogen treatment, were very unlikely to have their tumors return. So chemotherapy is not recommended for them. For patients with higher scores, above 30, we also already knew that chemotherapy is likely to decrease the chance of cancers in those patients, and, so, therefore, we generally recommend chemotherapy for women with higher scores. In the TAILORx trial, the recently reported trial, more than 6,700 women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer had their tumors tested and were found to have Oncotype DX recurrent scores between 11 and 25, which is in that intermediate range or at the higher end of the low range. Before this trial was conducted, many people with tumors like these, in the intermediate range, were treated with both chemotherapy and endocrine therapy because we weren't sure how much benefit they would obtain from chemotherapy, and we didn't want to leave out a potentially helpful treatment. In this trial, patients were randomized, or randomly assigned by a computer, to treatment with chemotherapy followed by endocrine therapy or to treatment with endocrine therapy alone. The trial was mainly looking at whether leaving out chemotherapy would increase the likelihood of invasive cancer returning. And, luckily, overall, the trial showed that the likelihood of cancer returning in those patients who got endocrine therapy alone, without chemotherapy, wasn't significantly different compared to those who were treated with chemotherapy followed by endocrine therapy. They also looked, specifically, at the group of women who were 50 years of age or younger. So mostly premenopausal women. Now, this was an exploratory question, meaning it provides information that may be correct, but it hasn't been as fully tested as the main question about what do we do for all women? In these younger women, there appeared to be some benefit from chemotherapy in those whose tumors had scores from 21 to 25, and, also possibly, in those whose tumors had scores from 16 to 20. Therefore, we still consider giving chemotherapy to younger women with Oncotype DX scores in the middle range, from 16 to 25, but not to women over age 50. So that was the TAILORx trial. The MINDACT trial was a bit different. It was testing the MammaPrint assay and the trial also included primarily women with hormone receptor-positive, HER2 negative breast cancer. But in this case, most women's sorry lymph nodes were negative, although a few women had up to three lymph nodes involved. In that trial, patient's risk of disease recurrence was assessed in two ways. First, it was assessed based on clinical factors. So the size of the tumor, how many lymph nodes were involved, and the estrogen receptor, progesterone receptor, and HER2 receptors. Second, it was assessed based on genomic factors-- that was using the MammaPrint test. So if patients were low for both clinical factors and genomic factors, they only were treated with anti-estrogen therapy. If they were high for both clinical factors and genomic factors, then they were treated with chemotherapy followed by anti-estrogen therapy. However, if they were high for one and low for the other, then they were randomized to either endocrine therapy alone or chemotherapy followed by endocrine therapy. So it was a little bit of a confusing trial. In the MINDACT trial, those patients who were thought to be high risk based on their clinical risk, so the size of the tumor, the number of lymph nodes, but then found to be low risk on the MammaPrint assay. They found that there was no benefit to treatment with chemotherapy in terms of how likely a woman was to develop distant metastatic disease. And if they were low risk, based on the clinical assessment, then there didn't appear to be a benefit of actually doing the test, the assay, because chemotherapy wouldn't be recommended for the patient, regardless of the results. So that was the MINDACT trial. So what are the new and updated recommendations for the guideline? Yes, so in this guideline, we, based on the TAILORx trial, we made new recommendations for use of the Oncotype DX results. All of these results apply to women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer. So for women older than age 50, if they have an Oncotype score of 25 or lower, then clinicians may offer endocrine therapy and no chemotherapy. However, for women age 50 or under, if they have an Oncotype score of 15 or lower, 15, then, clinicians may offer endocrine therapy and no chemotherapy. But if the score is 16 to 25, then chemotherapy can be considered in addition to endocrine therapy. So it made a difference in that gray area in the middle. For all women with score 26 to 30, chemotherapy may be considered. And for scores above 30, chemotherapy should definitely be considered. The data from the MammaPrint trial actually aren't that new. Results from that trial were originally published in 2016. However, that was after the original guideline was published, so we wanted to add these results to these updated guidelines for completeness. For a patient with hormone receptor-positive, HER2 negative, node-negative breast cancer, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then treatment with chemotherapy can be avoided. If a patient is thought to be at low clinical risk, the MammaPrint should not be used as chemotherapy can be avoided regardless. And for a patient with hormone receptor-positive, HER2 negative breast cancer, but who has one to three positive lymph nodes, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then it is possible that chemotherapy could be avoided, especially if only one lymph node is involved. So I think the bottom line for this part is that both of these tests-- there are now women who previously would have been recommended to have chemotherapy that maybe now we can avoid chemotherapy based on using these assays on their tumors. So why are these changes so important and how will they affect practice? Yes, that's a good question. Before the publication of the TAILORx trial, we had good information about how to treat patients who had either very low or very high Oncotype scores. But we really weren't sure how best to treat those patients who scores fell in the middle. Now, we have important information to guide decisions about chemotherapy for patients with intermediate scores. For many patients with scores in this range, these new results mean they will be able to avoid chemotherapy and just get endocrine therapy. While these results don't give us answers for every patient, they do provide more information that oncologists can use when having discussions with patients about the benefits and risks of chemotherapy. And what does this mean for patients with early-stage invasive breast cancer? And what should they talk to their doctors about? So as a result of both of these trials, we now have additional tools that can help oncologists provide more individualized treatment recommendations for patients and really assess whether or not chemotherapy, in addition to endocrine therapy, is likely to provide benefits. Knowing which patients' tumors will respond to chemotherapy can help some patients avoid unwanted side effects from a treatment that's not likely to actually give them much benefit. Now, these tests aren't appropriate for everyone and don't provide all the answers, but they are an important step in the right direction for providing more personalized treatment for women newly-diagnosed with certain types of breast cancer. Patients should talk with their doctors about whether these tests are right for them when they're making important decisions about whether or not they should receive treatment with chemotherapy. Great. Thank you, Dr. Henry, for this informative overview of the guideline. Keeping these clinical practice guidelines updated is really crucial and it takes a lot of careful thought to ensure these recommendations represent the evidence. So thank you for coming on the podcast to discuss the "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you very much for the opportunity to talk with you today. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. AloK Khorana from Cleveland Clinic on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." This guideline update adds another treatment regimen to the options for patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy.  Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines  See all of ASCO's podcasts at www.asco.org/podcasts  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Alok Khorana from The Cleveland Clinic, lead author on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." Thank you for being here today, Dr. Khorana. Thank you for having me. So this guideline was first published in 2016. And then we saw an update in 2017. And now we've just updated it again. So can you tell the listeners what has prompted these updates? In the world of pancreatic cancer, this has been an evolution in adjuvant treatment, which is sort of a surprise, because we've been treating pancreatic cancer in a very similar fashion over the past several decades. And between the 1990s and until just a few years ago, there hasn't really been much progress in terms of what to do with pancreatic cancer patients after they've had their cancer resected. It's pretty clear that these patients should not have just the surgery, that they should have additional treatment after the surgery. And for decades, the standard treatment after surgery was either 5-fluorouracil or gemcitabine, but most oncologists are opting for gemcitabine. The two recent updates of the ASCO Guidelines reflect two large randomized trials that have been published in this area. The first changed-- added a new standard of care, which was a doublet adjuvant therapy with gemcitabine and capecitabine. And the reason for this most recent update is the publication of a large randomized trial of adjuvant FOLFIRINOX for patients with pancreatic cancer that was published in December 2018 in "The New England." And we felt that the results were so compelling that we needed to update the guidelines so oncologists and practitioners would have the most current data to help them make decisions for patients. So for our listeners who may not now, can you tell us what changes have been made to the recommendations in this newest version of the guideline? So this is a guideline on a potentially curable pancreatic adenocarcinoma, which is we are saying these are resectable pancreatic cancer patients. And the guideline update changes primarily one recommendation, recommendation 4.1, which is a listing of additional adjuvant therapy options. As I mentioned earlier, the most common monotherapy option used to be the gemcitabine 5-fluorouracil. And that recently changed to doublet therapy. And we've kept those recommendations, but we've added the modified combination regimen of 5-fluorouracil, oxaliplatin, and irinotecan, which is known as the FOLFIRINOX regimen. And we are making this the preferred regimen for patients in the absence of concerns for toxicity or tolerance. We are still keeping the recommendations for the doublet therapy with gemcitabine capecitabine as well as monotherapy with gemcitabine alone or fluorouracil with cholanic acid. But those are not the preferred regimens, because the data for FOLFIRINOX is much better than prior regimens. Having said that, there are concerns about using such an aggressive regimen and in patients who have undergone a major surgery. So patients have not recovered from operation, then it's reasonable to consider one of the other regimens. But the update primarily focuses on adding adjuvant FOLFIRINOX as the preferred option in the adjuvant setting. And how has this guideline and its updates affected care for patients with pancreatic adenocarcinoma? I think since the results of this trial, the PRODIGY 24 trial came out of post-operative FOLFIRINOX. Almost every oncologist I know that focuses on treating patients with pancreatic cancer has suddenly added its use in patients that respected pancreatic cancer who are healthy enough to tolerate adjuvant FOLFIRINOX therapy. So it's definitely a practice-changing landmark paper. The results of the study were really quite impressive. The use of adjuvant therapy with FOLFIRINOX led to much longer survival than we've seen in any trial of adjuvant therapy of pancreatic cancer, almost 54 months-- or actually just over 54 months, almost 55 months-- in patients who are randomized to the modified FOLFIRINOX group and about 35 months in the gemcitabine alone group. The overall survival at three years was 63% in FOLFIRINOX and nearly 49% in the gemcitabine group. So that's a big difference at three-year survival as well. The one thing clinicians should be aware of is that this adjuvant therapy trial used a modified dose of FOLFIRINOX. They initially started off at the full those, which is 85 milligrams per meter squared of oxaliplatin, 400 mg per meter squared of leucovorin, and 180 milligrams per meter square of irinotecan. But the dose of iriniotecan was reduced part way through the study to 150 milligrams per meter squared, along with, of course, the conventional 2.4 grams or 5-fluorouracil over 46 hours. This modification of the irinotecan dose from 180 down to 150 is what many patients on the study received and was the more tolerable regimen and allowed the study to be completed. So the Guidelines Panel felt quite strongly that when using FOLFIRINOX in the adjuvant setting, we should stick with this modified dose, which is a lower dose of irinotecan at 150 milligrams per meter squared. And I think it's important that clinicians be aware of this distinction. And so taking this into account, many of us have made this recommendation to patients who are healthy enough to tolerate adjuvant FOLFIRINOX. And the hope is that this guideline will inform this ongoing practice as it changes in response to new data. And finally, what trials or new research are you keeping an eye on that may prompt an update for this guideline in the future? The results of another large adjuvant therapy trial are expected, hopefully at ASCO this year. This trial is the APAC trial that utilizes gemcitabine and nab-paclitaxel or Abraxane. This doublet combination is quite widely used in patients with metastatic pancreas cancer, particularly those patients for whom we feel FOLFIRINOX may not be appropriate because of their performance status or functional status. And the hope was that the doublet combination would also have good success in the adjuvant therapy setting and perhaps be a better option than the gem-cape doublet. There has been a press release from the sponsor of that trial, and it looks like the trial was not successful, although the way the press release is worded is rather confusing. So we wait for the full results of that trial to be presented at ASCO before we have an understanding of whether that is an appropriate regimen to use or not in the adjuvant setting. So that's certainly one large trial that many of us have been looking forward to complete sort of the set of ongoing adjuvant therapy trials in this setting. Great. It sounds like there's some really exciting things happening in pancreatic cancer right now. And I look forward to seeing this guideline evolve with the research. So Dr. Khorana, thank you so much for coming on the podcast today and summarizing the Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. Thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Fabrice Andre from Institute Gustave Roussy, Paris Sud University, in Paris, France on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." This update provides updated recommendations on chemoendocrine therapy for patients who present with a hormone receptor positive, HER2 not overexpressed, axillary node negative early breast cancer. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Fabrice André from the Institute Gustave Roussy in Paris, France, lead author on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early Stage Invasive Breast Cancer. ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." Thank you for being here today, Dr. André. Thank you. So based on the title of this guideline, we know that this update was prompted by the results of the TAILORx trial. So can you tell us more about that trial and what its results were? Yes. So the TAILORx trial was a trial that randomized two treatment modalities, endocrine therapy versus chemotherapy endocrine therapy in patients who presented what we call an intermediate recurrence cohort. So before moving to the results, maybe we can discuss a little bit the background. What we knew from the past is the fact that patients who present a recurrence score below 11 should be treated with endocrine therapy alone, because they have the good outcomes. And patients who present recurrence score that is high, 31 but also can be more on 25, should receive chemotherapy. And we are talking about patients with hormone-receptor receptor positive, HER2-negative early breast cancer without lymph node involvement. And this is extremely important. So to summarize, it's a clinical trial that includes patients with hormone-receptor positive HER2-negative lymph node negative in early breast cancer, who present with recurrence score between 11 and 25. And the question is whether we can avoid adjuvant chemotherapy in these patients who present this intermediate score. So this is the general design and the question. In terms of research, what we have learned. We have learned that for patients above 50 years old, there is no difference between endocrine therapy and chemotherapy followed by endocrine therapy. So it means that this patient or these patients, we would consider endocrine therapy alone. Then, for patients below 50 years old, there was some difference. And I think we go further into the detail. There was some difference favoring the use of chemotherapy in the group of patients who presented with recurrence score from 16 to 25. And so what changes were made to the recommendations in this update of the guideline? So first, what were [INAUDIBLE] the previous guidelines. The previous guidelines were telling the clinician which genetic tests they could use in patients with hormone-receptor positive, HER2-negative early breast cancer. Now, the big change is that we are making guideline to explain how to use the test. And what is new is that we have made three important decisions. So first, for the patient is at the age above 50, now it is recommended clinician may recommend endocrine therapy alone for women older than 50 who present a recurrence score below 26. Before, the recommendation to use endocrine therapy alone was for patient's who present with low recurrence score. So it means now we have broadened-- we have increased the number of patients who could receive endocrine therapy alone and not receive chemotherapy. Then, for patients who present a recurrence score between 16 to 25 and who are below 50 years old, the clinician may offer chemotherapy followed by endocrine therapy, meaning that we are moving from [INAUDIBLE]. This intermediate score between 11 to 25 was what we call a [INAUDIBLE]. There was no recommendation on how to use the recurrence score. So right now, the update from the ASCO guideline is to provide recommendation on which treatment to administer in case a patient presents with intermediate recurrence score, and there are two different situations above 50 years old and below 50 years old. So why are these changes so important and how will they affect practice? So they will affect practice because for many reasons, I will say. In the US, they would affect practice because they increase the number of patients who will not receive adjuvant chemotherapy, because right now, we have an answer from randomized trial that we can avoid chemotherapy in women above 50 and from 11 to 25 recurrence score. So the impact in terms of public health would be that we could have a decrease in the use of chemotherapy or at least a better precision about who should receive adjuvant chemotherapy. Globally, this trial is going to provide an incentive and increase the level of evidence supporting the use of genetic tests. So it's important to remember that in a large number of countries, genetic tests are not reimbursed. But now, because lack of evidence, and here we have a randomized trial showing a level 1 evidence supporting the use of genetic tests. So we have two direct impacts of this trial. The first, inside US, where [INAUDIBLE] colleagues already use genetic tests, it provides better precision on who will receive adjuvant chemotherapy. And it's going to broaden the number of patients who will not receive. And globally, it's prospective randomized trial that we hope is going to incite payers to reimburse the genetic test in patients with early breast cancer. And so what does this all mean for patients with early stage invasive breast cancer? And what should they talk to their doctors about? So for patients with early breast cancer, so what are the messages for the patient? I think for the patient, the key message is that we are moving to precision medicine. We need a medicine that is extremely precise in terms of who should receive which treatments. And now, thanks to this trial, we are going to decrease the number of patients who receive chemotherapy, but also for the ones who will receive adjuvant chemotherapy, the value of the treatment, we need what the treatment provides to the patient is going to be very, very high. So what is important for patients is to understand that because of this trial, when we give them chemotherapy, we will know that the value of this treatment and the expected benefit is going to be higher than what we used to do in the past. So it's really fast forward and more precise medicine that consists in using molecular tests in order to provide or administer treatment with very high value. Great. Thank you Dr. André for your overview of this guideline update. This has been very informative. It's really good to hear that the expert panel has incorporated the latest research into the guideline and has carefully considered the implications for the patients. So thank you for coming on the podcast to discuss the "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx" Thank you. What people don't realize is we did hard work that ASCO doing with all these guidelines, and people are very committed, and they are [INAUDIBLE]. I mean, it's very reassuring for ASCO member to know that there are highly professional people who provide guidelines and it is also reassuring for the patients, for everyone. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

An interview with Dr. David Adelstein of the Cleveland Clinic on the ASCO PCO which provides statements on the role of treatment deintensification in the management of p16+ oropharyngeal cancer. Read the full PCO at www.asco.org/head-neck-cancer-guidelines The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. David Adelstein from the Cleveland Clinic Taussig Cancer Institute. Lead author on "Role of Treatment Deintensification in the Management of p16 Positive Oropharyngeal Cancer: ASCO Provisional Clinical Opinion."  Thank you for being here today, Dr. Adelstein. Thank you, Shannon. Before we get started, I'd like to first note the contributions of my panel co-chair, Drew Ridge, and those of all of the other panel members. And I'd like to extend a special thank you to ASCO for their support in allowing us to put this together and specifically Nofisat Ismaila who did a tremendous amount of work in allowing us to complete this provisional clinical opinion. First, can you give us an overview of the clinical issue for this PCO? Sure. So this really came out of the implications of human papillomavirus mediated oropharynx cancer. I think as most of the listeners know, over the last several decades we've recognized the fact that oropharynx cancer has a second ideology, that not all of it is caused by tobacco use, but that the human papillomavirus is now the major ideologic factor in North American and northern Europe. The importance of this is that the human papillomavirus-induced oropharynx cancer is a different disease. It has a number of different characteristics from the kinds of head and neck cancer we've seen in the past. It's a disease that tends to occur in younger patients, patients who are otherwise generally more healthy. It is unassociated with smoking, although it can occur in smokers. But it's much more frequent in nonsmokers. And I think most importantly, it's a disease that has a dramatically better prognosis than the tobacco related disease. Now over the last several decades, our ability to treat advanced head and neck cancer has improved significantly, because we've begun to incorporate non-operative treatments-- chemotherapy and radiation-- and have been more aggressive in our utilization of chemotherapy and radiation with significantly greater success than we had in the past. The problem with this kind of treatment is that it is quite rigorous. And there's a good deal of acute and, more importantly, late toxicity that patients experience from these kinds of approaches. Now as we became more familiar with the importance of HPV associated oropharynx cancer, we realized that there are subgroups of these patients who have cure rates that are in excess of 90%. And the question arose whether the kinds of rigorous chemotherapy and radiation therapy treatments that we were utilizing were really necessary. Was it necessary to cause this much acute and late toxicity in patients who in vast majority of cases were going to be cured of the disease. And it's important, because these are younger patients. And the late toxicities are going to have a major impact on their quality of life for a number of years. What came about was the notion of treatment deintensification, the idea that perhaps it would be possible to deintensify the kinds of treatments we were giving in select patients. It's a very compelling hypothesis for medical oncologists and radiation oncologists. But there are a number of problems as we try to test this hypothesis. The first problem is how do we identify the good risk patients? There are patients with HPV-positive disease who do not do so well-- the heavy smokers and patients with very advanced tumors. And we need to be careful if we're going to be talking about giving less treatment that we don't give less treatment to the patients who have a worse prognosis. We pick the best prognosis patients. There have been a number of what we call risk stratification schemes that have been developed looking at trying to identify the very good prognosis patients-- those patients who are HPV positive who don't smoke and who have relatively limited disease extent. There's not universal agreement on how best to define these patients. All we know is that they do exist, that you can look at patients with these characteristics and see very good outcomes. One of the issues that has come up is how do we utilize the American Joint Committee staging system-- AJCC the 8th edition. One of the things that AJCC 8 did which is new is that it defined a separate staging system for patients with HPV-positive oropharynx cancer, a system which is entirely different than the staging system that we've used for head and neck cancers for many years. This was based on the recognition that the prognosis of patients with HPV-positive disease is so good so that many patients who we would previously have considered to have stage 4 disease are now classified as having stage 1 tumors, because their prognosis is so good. And that can be confusing, because the typical thought process for an oncologist is that a patient with stage 1 disease should be treated with single modality therapy. The reason that the HPV-positive patients have such a good prognosis, however, is that many of them have been treated with combined modality therapies. And to make the assumption that because now they're classified as stage 1 is incorrect. It is they shouldn't be treated with less intensive treatments and can be confusing. AJCC 8th edition is a prognostic robust staging system, but it really doesn't help us in defining treatment. First problem is how best to define patients who are appropriate for deintensification. Second problem is, what do you do to deintensify? What constitutes meaningful deintensification? Well, over the last 10 or 20 years there have been some significant advances in our standard treatments for all head and neck cancers that weren't developed the idea of deintensification. We now have tremendous experience using transoral surgical techniques, which are generally minimally morbid, much less morbid than the former open techniques that previously were used, which allows consideration of surgery for many of these patients where we wouldn't have considered it before. Similarly, intensity modulated radiation therapy has been widely adopted, and d clearly an approach using radiation, which is far less difficult, far less toxic than the former 2D or 3D radiation planning techniques that used to be used. But if we talk about intensification, what kinds of things can we do to deintensify our treatments? Well, one thought is to reduce the radiation dose. Then the question is, how much reduction is reasonable? And how much reduction is going to actually impact on this toxicity? And are our toxicity measuring tools adequate to even detect the difference in reduction of a radiation dose? Many of our toxicity tools are very crude. Perhaps we should be using some of the patient-reported outcome quality of life instruments that are available. Other thoughts are, perhaps one can reduce the size of the radiation therapy field. Can we reduce the dose of the chemotherapy? Can we eliminate chemotherapy? Can we even use less intensive chemotherapy? Generally, the other treatments for this disease have employed high doses of cisplatin, which is a toxic agent. And then there the question has been asked as to whether we can reincorporate minimally morbid transoral surgical techniques in an effort to better pathologically stage patients and define more appropriate adjuvant treatment. Perhaps not all patients need adjuvant radiation or chemotherapy and radiation. All of these approaches are interesting. They're exciting. They're being tested. But all of the experiences is preliminary. And that really brings us to the third and the biggest problem in any deintensification approach. And that's the need to be certain that if we deintensify our therapy, we're not going to compromise outcomes. It would not be acceptable to give less treatment or less intensive treatment if our survival were compromised. And we have to be certain that we don't do this. So what has evolved over the past decade is a whole number of treatment approaches that have some very enthusiastic early results. But these are generally single arm phase 2 reports where there is no comparison to conventional treatment. And they become difficult to interpret, because the results in general are very good. I think what really raised a red flag for us and that really caused us to take notice was the results of the RTOG 1016 trial that we reported last year. And at the same time, the European de-escalate trial, both of which had a similar design. These were studies that were designed in an effort to see if treatment deintensification would be possible by randomly comparing the standard treatment radiation and cisplatin with what was felt to be a less intensive approach-- radiation and concurrent cetuximab. And cetuximab is an accepted agent in the United States for treating head and neck cancer. The assumption here is that the survival would be equivalent when these two arms were compared, but that the toxicity would be improved by giving the less intensive systemic agent-- the cetuximab. The surprise when the study was analyzed was that that assumption was incorrect, that the radiation and cetuximab arm-- the deintensified arm-- actually proved inferior in terms of survival. And this was in both trials-- both the RTOG trial and the trial from Europe. And that was a big note of caution, because it was somewhat unexpected. I think we learned from that kind of a study, from a good randomized-- a large randomized trial-- that even though the outcomes may appear to be good, we need to be very careful about deintensifying our treatment until we're sure that the survival is equivalent. So although it's tempting for the clinician to see these very exciting reports about administering less treatment with the idea of producing less toxicity, the guideline advisory committee for ASCO really thought it was important that we get the message out that this kind of approach is not a treatment standard. This remains an investigational approach, and that the treatment standards for this disease really haven't changed. So what are the provisional clinical opinions that were made by the expert panel? They made several statements. The first was to acknowledge that the idea of treatment deintensification is a very compelling hypothesis, and it does require careful and appropriate testing. The second was that even though we are now better at identifying good prognosis patients, and we've seen some very promising early results, and even though we're now reclassifying patients with previously advanced stage HPV-positive disease as stage 1 or stage 2 tumors, the treatment recommendations for this disease have not changed. And they're based on the results achieved using AJCC 6 and 7. Standard of non-operated management to patients who are eligible to receive cisplatin remains high concurrent radiation and high dose cisplatin given every three weeks. If patients undergoing a surgical resection, then adjuvant chemotherapy and radiation with radiation and high dose cisplatin every three weeks is recommended in those patients with high risk factors of positive surgical margins or external tumor extension. And most importantly, deintensification, though it's a compelling hypothesis, is something that should only be undertaken on a clinical trial. Why is this guidance so important? And how will it affect practice? Well, I think the important thing about this guideline is that it shouldn't affect practice. The practice shouldn't change. The standards of care are not altered. And that for the clinician, this remains something that is exciting, something that should encourage enrollment on a clinical trial, but that we haven't changed treatment standards. And finally, how will this guidance affect patients? So from a patient's point of view, I think there is continued reason for optimism. A patient with the diagnosis of an HPV-positive oropharynx cancer is a patient with a very good prognosis. Patients are increasingly sophisticated. They read about the potential for treatment deintensification, and recognize that this is not something which is an accepted standard. But it should encourage their participation in clinical trials if [INAUDIBLE] is offered. I think ultimately it's a remarkable thing when oncologists can consider the possibility of reducing treatment intensity because the treatment results have been so good. Great. Thank you for your overview of this PCO. And thank you for your time today, Dr. Adelstein. And thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full PCO, go to www.asco.org/head-neck-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Paul Celano from the greater Baltimore Medical Center, lead author on "Safe Handling of Hazardous Drugs: ASCO Standards." TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Paul Celano from the greater Baltimore Medical Center, lead author on "Safe Handling of Hazardous Drugs: ASCO Standards." Thank you for being here today, Dr. Celano. Thank you for having me. I'm certainly glad to talk about these standards. They're very important to our employees and our patients. So first I want to make the distinction that this publication is not a guideline like we usually cover on this podcast. So can you tell us what standards are and how they differ from guidelines? Well, guidelines really are intended to guide practitioners around recommended care options. They give obviously a lot of latitude to clinical judgment and circumstances. Standards, on the other hand, are really meant primarily for the organization of care and are intended to have a higher level of obligation to help drive either practice or policy or even legislative efforts. So that's really the distinction. And what are the standard statements that are made by ASCO in this publication? The publication really is about safe handling of hazardous drugs. This all came about is because recently there have been a number of national guidelines or standards that have been offered by other organizations, but not specifically oncology or certainly ASCO or the ASCO organization. We felt a need to address the standards that have been put out on the basis of the evidence, so that best practices can be offered. Initially, we did collaborate with other societies, such as the Oncology Nursing Society and the Hematology Oncology Pharmacy Association. That was really the impetus behind making sure that we are, in a sense, congruent with standards that are already being published and discussed, but also to also place in our interpretation of these standards so that they're based on the best evidence that's available. And what qualifying statements are there to note about these standards? Well, I think the best way to look at these standards is there has been recently published or offered what's been called the UST 800 standards, which really incorporate other previous standards by the Pharmacy Association as well as OSHA, the Occupational Safety and Health Association, as well as NIOSH, the American Society of Hospital Pharmacists, Oncology Nursing, etc. So there's a lot of standards that have been offered. And in fact, the ASCO review of this really in a sense agrees with many of the standards that have already been published and offered-- types of exposures, the responsibilities of personnel handling the drugs, the personal protective equipment, how we communicate the hazardous drugs, the training of compounding personnel, how the drugs are dispensed and even transported. So there's lots of things that we really do agree with. I think it's also important to understand that the objectives of this is really to protect personnel and the environment to make sure the standards apply to all personnel who compound hazardous drugs and preparations, all places where hazardous drugs are prepared and stored, transported and administered. So that's really a key part of this. These are a comprehensive program really to prevent worker environmental exposure and to provide the most practical safety environment for all involved. So finally, why are these standards so important? And how will they affect practice? Well, they effect practice in many ways. I mean, the key thing is making sure that our employees, meaning the nurses, pharmacy, the technicians, really everyone involved that they're not unduly exposed to these hazardous drugs. And so that's really the key thing that we're all trying to achieve by this. Now, what really makes the sort of ASCO standards somewhat different or the things that we came into a contention with has to do with the differences that ASCO has come up with in contrast to some of the other standards. And these have to do with really four main areas within these standards. They have to do with medical surveillance, external ventilation, closed system transfer devices, and also proper assignment of our personnel while they may have either trying to conceive or pregnant or nursing. So those areas that in our review, the ASCO review, have come under some question. As an example, medical surveillance, there in some of the standards offered-- not ASCO's-- that there's a number of medical surveillance procedures that have been elucidated, that really we find, number one, have really not any proven value for our employees and generate a lot of confusion in terms of how this process is supposed to be done. Obviously, if one of our employees has some undue exposure, such as a spill of chemotherapy or even just have flat out a concern, then obviously those things will be clearly investigated. But to have general medical surveillance of all employees, really we did not feel was of great value. But also further, we really feel that this is an area where more research needs to be done to better elucidate really what should this process look like and what value are we providing to our employees. Another aspect of this is the use of what are called closed system transfer devices. Currently, there are a number of these devices available that there is interestingly no standard way that these devices have been evaluated. And so it's hard to recommend one device over another, because there is no standards for which they're really being compared. And there certainly have been no studies looking at really any form of health outcome that really help us to direct this to how best to use these devices. And so really, a lot of these objections are more around let's do things in an evidence-based way so we can better know how to best direct our practices. Another area of concern in terms of ASCO standards have been the implementation of external ventilation in either containment secondary engineering controls or other situations. And the challenges is that HEPA filters are probably appropriate for collecting solid or aerosolized particles, but don't capture vaporized drugs. But there's little data available on the ability of hazardous drugs to vaporize within the workplace environment and what those hazards really are. And so again, it's is a call for more research to have an optimal environment for preparing these drugs and without having to place undue burdens in terms of external ventilation. Another area is options for alternative duties for workers who are actively trying to conceive or are pregnant or breastfeeding. And these we recognize can be special burdens to small practices looking to implement alternative duty programs. There is a lot of controversy regarding the potential level of risk that really these workers really have. And basically our stance has been that we should have a policy that identifies alternative work options for workers who are trying to conceive, are pregnant or are breastfeeding, and that this information needs to be conveyed to these employees at the time of their hire so they understand what their risks are and what their options are within the workplace. Again, trying to make sure everyone is well informed and aware of what the work environment they're in and as their life circumstances change what they can do to change with this. I think the key is that we all feel that this is an area that we should have continued research on. And our standard, certainly ASCO's standards will continue to evolve as more and more research and evidence becomes available. Thank you so much for taking the time to explain these standards to us today, Dr. Celano. You're welcome. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Nancy Baxter from St. Michael's Hospital in Toronto, senior author on "Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Baxter. Thanks very much, Shannon, for speaking with me. I'm happy to share our work developing this guideline. So first, can you give us a general overview of what this guideline covers and the studies which provide the evidence? Absolutely. So use of adjuvant therapy for patients with stage III colon cancer is common, and it's effective. We know that these patients are at substantial risk of recurrence of their disease and that adjuvant therapy can reduce that risk. But we also know that comes with a cost. The most effective adjuvant therapy is FOLFOX or oxaliplatin-containing chemotherapy regimens. And we know that a really substantial number of people will end up with neurotoxicity, with peripheral sensory neurotoxicity, that can be long lasting and certainly affects their quality of life. So the whole question was whether the duration of oxaliplatin-containing chemotherapeutic regimens could be shortened when they're used for adjuvant therapy, so if we could give three months instead of six months. Because we know that if we give three months of therapy, the risk of neurotoxicity is much lower. So if we had the same effectiveness with the shorter duration, then we could spare patients the negative consequences of the agent given for a longer period of time. So in developing these guidelines, we looked at the results of international group of trials, the six trials from the IDEA collaboration. So these were six randomized trials in various jurisdictions that tried to look at this question, so three months of an oxaliplatin-based chemotherapeutic regimen for adjuvant therapy for stage III cancer versus six months duration of therapy. And so there was a planned analysis to bring all of these data together to develop the evidence base to make this recommendation. So our guideline and our systematic review basically identified this is the key piece of literature to base our recommendations and guidelines on. That's essentially the main study, so the meta-analysis of these six randomized controlled trials that formed the basis of the IDEA collaboration. So the IDEA collaboration studies-- there were six individual randomized trials that formed part of the IDEA collaboration. And they were conducted in Italy, Greece, Japan, North America, through CALGB/SWOG, the UK, Denmark, Spain, Australia, Sweden, and New Zealand, as well as France. So data came from, really, around the world. The median age of people in the studies was 64 years of age. And these people had a really good performance status, so almost all of these patients had an ECOG performance status of 0 or 1. So they were healthy patients that were in the study. And so some patients received CAPOX, and some received FOLFOX. That wasn't part of the randomization scheme. Other than the CALGB/SWOG study, this was up to the discretion of the investigator or patient. In the SWOG/CALGB study, only FOLFOX was given. And the authors planned a prespecified subgroup analysis to look at differences between CAPOX and FOLFOX. There was also a prespecified analysis to look at differences based on stage. What they found when they looked at the results was that, overall, the difference between groups in terms of the three months versus six months was that the hazard ratio between these two was 1.07, meaning a small difference between the groups in terms of recurrence or death between three months and six months overall. But because the prespecified confidence interval, noninferiority interval, for the difference in outcome was 1.12, the 95% confidence interval for the hazard ratio was above this. So it was 1.15, indicating that this prespecified noninferiority margin was exceeded. And so the study did not prove noninferiority of the three-month regimen. So we're left with an inconclusive result. So that's why our guidelines don't have a strong recommendation for the three months, because we can't rule out a small but potentially important difference between the two groups in terms of recurrence or death. Now, interestingly, when they looked at the prespecified subgroup analysis, which was looking at CAPOX versus FOLFOX, a difference was found. So they actually found that for FOLFOX chemotherapy, three months of therapy was inferior to six months of therapy, while for CAPOX, actually, three months and six months were the same. So it met the criteria of noninferiority. So these are kind of two different conclusions based on which type of chemotherapy was used. This was surprising to the investigators and was not expected. And certainly, it was not consistent with the randomized trials that we have comparing these regimens. So we therefore did not make any conclusions in our recommendations about CAPOX versus FOLFOX. But this is certainly something that requires further investigation in the future. In terms of stage, we did not find that there was an interaction between T stage or end stage when you looked at the differences between the three and the six month. And that was the prespecified analysis. But in non-prespecified analysis, which was the higher risk versus lower risk categories, you did find this difference where the patients with high-risk disease had inferior disease-free survival with three months versus six months of therapy, while those at low risk of disease, it seemed quite safe to give three months versus six months. So that's a long story. But essentially, because the high risk versus low risk analysis was not prespecified, there's a limitation to how strong our recommendations can be to have three months of therapy. However, given that the hazard ratio associated with three months versus six months of therapy for this lower risk group was only 1.01, indicating they were the same, and the risk of neuropathy was substantially higher with six months, this has led to us making recommendations that the three months of therapy is adequate for patients with low-risk disease after discussion with patients about the possible pros and cons. And what are the key recommendations of this guideline? Well, so the recommendations of this guideline do depend on the pathology, so how high risk the patient is. So based on the evidence from the IDEA collaboration, the researchers found that patients who had a high risk of recurrence-- so had T4 disease or heavily node-positive disease, N2 disease-- the six-month duration of therapy was better than the three-month duration of therapy. These studies and the meta-analysis were designed as noninferiority meta-analyses. But it was clear from the results that the three-month duration was inferior when compared to three months for these high-risk patients. So that seems clear, although we know that those patients will also be at more risk of neuropathy. And so that needs to be discussed with patients, as well. So for the second group, which are patients who are at lower risk of recurrence, what we found was there was less of a clear benefit of six months of therapy. The recommendation was that patients who are in this low-risk category-- so T1, T2, or T3 cancers that are N1, so not heavily node-positive-- clinicians can offer three months versus six months of therapy after having a discussion with their patients about the pros and cons of that. So the clinicians can go ahead and offer that to patients and still be within the common guidelines based on evidence for treatment of stage III colon cancer. So because there's some uncertainty after analysis of the IDEA collaboration, one of the really important recommendations that we make is about this shared decision-making approach. So the third recommendation that we make is that oncologists should discuss these factors with their patients who have stage III resected colon cancer and that the duration of therapy needs to take into account the tumor characteristics-- the surgical resection, the number of lymph nodes examined, the comorbidities, the patient functional status, all of these various things-- and there needs to be a discussion of the potential for benefit and the risk of harm based on the duration of therapy. And oncologists definitely discuss these things with their patients. And this just emphasizes how this is yet another component of the discussion that needs to be included, particularly when speaking with low-risk patients who are at substantial risk of harm from neuropathy and are unlikely to benefit greatly by extending chemotherapy to six months. So why is this guideline so important? And how will it change practice? Well, I think, until now, the standard recommendation has been six months of FOLFOX or six months of oxaliplatin-based chemotherapy. And again, there are many patients who have quality of life-affecting neuropathy because of this. So for a substantial proportion of patients who present to us with stage III cancer-- so those that are low risk-- I think this provides some options to them. So they can opt for a shorter duration of chemotherapy with a lower risk of toxicity. This saves time. This saves cost to the patient and to the system and potentially improves their quality of life without a great impact on outcome in terms of disease recurrence. So that's a substantial number, a substantial proportion of our patients, who can be treated in this way. So I think that this is a real benefit. Again, oncologists need to have a conversation with their patients about the pros and cons. But this is an option for their patients, whereas from an evidence-based perspective, it wasn't before the publication of the IDEA collaboration. Finally, how will these guideline recommendations affect patients? So for patients who have heavily node-positive disease-- so high-risk patients with T4 or N2 disease-- it's not going to affect care. So the expectation would be those patients would be treated with six months of therapy, similar to previous recommendations. So this will be for people who are at lower risk of disease recurrence, so patients with T1 to 3 tumors that are N1 positive, so not heavily node positive. So these patients will have the opportunity to opt for a shorter duration of therapy. So that's a major benefit to patients. Again, it's important that there's a discussion and that patients understand the pros and cons. But this is now an option for them, which is excellent. Thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Alejandro Lazo-Langner from Western University in London, Ontario, senior author on Management of Cancer-Associated Anemia with Erythropoeiesis-stimulating Agents, ASCO/ASH Clinical Practice Guidelines Update. Thank you for being here today, Dr. Lazo-Langner. Thank you very much for the invitation to present the new guidelines. So this guideline has been updated now three times since its original publication in 2002. So how has this guideline changed over time? Since initial publication in 2002, this guideline has undergone a number of different changes. If you look at the initial series of recommendations in the 2002 guideline, it was really limited and it was fairly upfront recommending the use of erythropoiesis-stimulating agents in this setting. But during the last two updates in 2007 and 2010, that has changed significantly. And in the current guidelines, we have added some additional evidence that has been published in the last eight years. And now, in general, what we can tell is that the use of erythropoiesis-stimulating agents is now more restrictive than in the original guideline and is basically recommended for only one or two situations. There has been some other updates in the last iteration of the guideline that I can certainly discuss in more detail later. But basically, in general, the guideline has now, in the last iterations, restricted the recommendations that were much more general during the first edition of this guideline, almost all of them based on available and emerging evidence regarding the onset of their side effects with these medications. And can you give us a general overview of what this new guideline update covers, especially that new evidence that's emerged? Yeah. So the new guideline has changed a few items. And indeed, we-- the committee did a little bit of an overhaul in the recommendations that are not in the same order as they were in the previous editions. We can say that there is a couple of important updates. The first one would be addressing the use of biosimilars, which were not available in the previous guidelines. And we have addressed that in the current edition. The biosimilars have not been extensively studied in cancer, but they have. And so far, the committee considered that they were equivalent in terms of effectiveness and safety to the originator agents, both epoetin and erythropoietin. And the second most important update on the guideline is the recommendation of the concurrent use of iron supplementation in patients who are receiving erythropoietin-stimulating agents. The previous versions of the guideline just recommended the use of iron supplementation in patients with documented iron deficiency. However, in the last eight years, there's been a number of studies that have suggested that the concurrent use of iron supplementation, irrespective of the baseline iron status, does increase the efficacy of the agents. Third point is that, although this is not new, there's been more emerging evidence supporting the notion that all of the erythropoietin-stimluating agents increase the risk of thromboembolism. And this has been very consistent across all studies, and in particular derive from Julia Bohlius's systematic review and meta-analysis that was published a few years ago. And she's the lead author on these guidelines now. This has been confirmed, and I think that at this point this is probably the main limiting factor on the use of these medications. And the final minor update was that regarding the use of erythropoietin in patients with myelodysplastic syndrome. This guideline now suggests baseline serum erythropoietin level cut-off that might actually increase the chances of the erythropoietin-stimluating agents of being effective. This has been updated from the previous guidelines based on recent research. And what are the key takeaways of this guideline update? Well, the key takeaways is that if a clinician is deciding to use erythropoietin-stimluating agents, in agreement with the previous guidelines, the first thing that you have to consider is that you should not use these agents in patients that are receiving chemotherapy with a curative intent. And it should be reserved to patients in whom the chemotherapy is being given with a palliative intent. It should be only used to decrease the use of red blood cell transfusions. And if a clinician is to make a decision as to whether to use these agents or not, they should consider concurrent use of iron supplementation. But basically, the other consideration that needs to be made is that because of the confirmed increase in the risk of thromboembolic complications, in the last eight years, there's been a myriad of new treatments that may potential increase the risk of these complications, specifically and most importantly in patients with myeloma in whom the use of immunomodulators such as lenalidomide or thalidomide does increase the risk of thromboembolic events per se. And in those patients, if they were to be considered for treatment with erythropoietin-stimluating agents, that should be done in a very, very careful fashion. The risk of thrombosis is significantly high in these patients, and the concurrent use of erythropoietin-stimluating agents is probably not a very good idea. So if one were to summarize the guidelines, I would say that, one, consider very carefully whether your patient actually needs these agents, and if they do need the agents, whether they should be receiving them, specifically if they are only being given chemotherapy with palliative intent with a short time life expectancy. Some patients would be considered to be in palliative. However, in conditions such as myeloma, for instance, although they are not curable, the patients may go on living for many years. So that's probably not a very good idea to use these agents if they increase the risk of complications. And if one is going to be considering these, they should consider also the concurrent use of iron to improve the efficacy of these agents. And finally, how will these guideline recommendations affect patients? Well, the guideline recommendations won't have a particularly high impact on patients. The most important thing is that, if patients require ongoing transfusional support due to the palliative chemotherapy or the nature of the disease they have, the use of erythropoietin-stimluating agents might decrease the need for these transfusions at the cost of increasing the risk of complications. The new updated guidelines are probably going to result in-- if they are considered when a clinician is using these agents, they are probably going to result in lower complications for patients due to the more restrictive nature of the recommendations. And in general, the only other consideration would be that under special circumstances related to, for instance, access to transfusional support or other personal considerations from certain patients and groups, these guidelines might actually help to overcome those barriers for transfusional support. But those were the two major impact points that would be considered based on this updated guideline. Great. Thank you for your work on this important guideline and thank you for your time today, Dr. Lazo-Langner. Thank you for the invitation. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. 

TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and I'm interviewing Dr. Joe Mikhael from the City of Hope Cancer Center and International Myeloma Foundation, lead author on "Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline." Thank you for being here today, Dr. Mikhael. It's a pleasure to be with you. So first, can you give us some context as to why this guideline was developed? Well, we had a lot of ideas when we put together this guideline, but most importantly, multiple myeloma continues to be a rare disease in the cancer world. It really only accounts for about 1% to 2% of cancers. So for the practicing oncologist, they spend perhaps 3-ish percent of their time doing multiple myeloma. And when you add to that there has been really a revolution in myeloma with new drugs approved, new treatments, new approaches, it really leaves the general oncologist with a complexity of how to treat this disease. And so we wanted to create a very practical guideline that would give very precise advice to walk through how one would care for a multiple myeloma patient, right from their diagnosis to indeed relapse disease. We felt this approach was so important now, more than ever, because of the fact that myeloma has really changed so much, and now, thankfully, we're seeing our patients live so much longer that the treatment options can become a little bit more complicated over time. Furthermore, we partnered with Cancer Care Ontario, because this was really felt to be not just an American phenomenon, but really a full North American phenomenon of how we could work together to really give practical advice as to how to treat this disease. So what are the key recommendations of this guideline? In this guideline, we focused really on the treatment of the disease itself. There have been other guidelines that have focused on supportive care and bone disease and multiple myeloma, but we really focused on the treatment of patients really from induction therapy through to relapse. So we spend time helping guide the decision around whether or not a patient is transplant eligible or ineligible, because that's really the first dividing marker in myeloma, because we know that transplant still has a role in myeloma, and eligible patients should have a transplant, or at least have access to a transplant. And historically, this was really done on the basis of age. But the guidelines helps the clinician see that it's really not just an age phenomena. It's really a decision based on comorbidities and really what's best for the patient. So we spend time helping making that decision, and then provide very practical advice as to how to treat a patient who's going to transplant versus a patient who's not going to transplant. We also, then, after the transplant, or in lieu of a transplant, we discuss the importance of continuous therapy, or sometimes called, maintenance therapy in myeloma. Again, we've seen maintenance therapy, now, have an impact on both progression free and overall survival. And so we felt it was really important to be very practical in giving advice as to what maintenance therapy agents to use and how to use them. And then lastly, the guideline provides a lot of practical advice as to a patient who has relapsed with multiple myeloma. We have so many choices now with three major classes of drugs of proteasome inhibitors, immuno-modulatory drugs, and now newer monoclonal antibodies, it can be difficult sometimes to know which combination to use. We know that triplet combinations tend to be preferred. So we walk through a number of those triplets and provide advice as how to explicitly use them. We do emphasize the importance of supportive care and of risk factor analysis throughout the guideline, so that we can understand the difference between high risk and low risk myeloma, so that we can understand how important a patient's comorbidities, especially in a disease that primarily affects older patients, can be managed. And so we try to do so in a comprehensive way, but one that really distills down to the critical pieces to allow the practicing clinician some real advice. So why is this guideline so important, and how will it change practice? There are several kinds of guidelines for multiple myeloma, but I really think this is a critical guideline because it is so clinical and practical in its essence. It's really designed to not just give the utopian view or the clinical trial view of a disease, but practically in the trenches, how do we use the drugs that we know are going to benefit our patients. Myeloma is one of the few cancers where we have seen a doubling, if not a tripling of survival in the last decade, because of so many of these new agents. And so making sure that our patients are treated optimally really is important. And we want to be able to ensure that they receive the best therapy possible, so they can live a longer life, but also live it with a greater quality of life. And so finally, how will these guideline recommendations affect patients? Well, we really hope that this is going to help patients all across North America and the whole world, because it will give very concrete advice to the practicing clinician in how to approach the disease. And one of the things I think will directly impact patients, if you will, right away is one of the themes of these guidelines, which is that you don't treat a patient simply based on the biopsy or simply based on their age, but that it is really a complex network of comorbidities, risk factors from the disease itself, the potential side effects of certain drugs, and a patient's own very personal history. It really fits in with the ASCO modality that we have of ensuring that we bring personalized medicine to our patients. And so this will allow the person who's reading it and who's applying it to their patient to recognize the importance of general guidelines, but also of applying it to the specific patient they care for. Because as I like to say, we don't treat multiple myeloma, we treat people. And so hopefully, this will allow the clinician to have that precision to care for their patient in the best way possible. Great. Thank you for that overview of this guideline, and thank you for your time today Dr. Mikhael. It's been a real pleasure. Thank you very much. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/hematologic-malignancies-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and I'm interviewing Dr. Joe Mikhael from the City of Hope Cancer Center and International Myeloma Foundation, lead author on "Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline." Thank you for being here today, Dr. Mikhael. It's a pleasure to be with you. So first, can you give us some context as to why this guideline was developed? Well, we had a lot of ideas when we put together this guideline, but most importantly, multiple myeloma continues to be a rare disease in the cancer world. It really only accounts for about 1% to 2% of cancers. So for the practicing oncologist, they spend perhaps 3-ish percent of their time doing multiple myeloma. And when you add to that there has been really a revolution in myeloma with new drugs approved, new treatments, new approaches, it really leaves the general oncologist with a complexity of how to treat this disease. And so we wanted to create a very practical guideline that would give very precise advice to walk through how one would care for a multiple myeloma patient, right from their diagnosis to indeed relapse disease. We felt this approach was so important now, more than ever, because of the fact that myeloma has really changed so much, and now, thankfully, we're seeing our patients live so much longer that the treatment options can become a little bit more complicated over time. Furthermore, we partnered with Cancer Care Ontario, because this was really felt to be not just an American phenomenon, but really a full North American phenomenon of how we could work together to really give practical advice as to how to treat this disease. So what are the key recommendations of this guideline? In this guideline, we focused really on the treatment of the disease itself. There have been other guidelines that have focused on supportive care and bone disease and multiple myeloma, but we really focused on the treatment of patients really from induction therapy through to relapse. So we spend time helping guide the decision around whether or not a patient is transplant eligible or ineligible, because that's really the first dividing marker in myeloma, because we know that transplant still has a role in myeloma, and eligible patients should have a transplant, or at least have access to a transplant. And historically, this was really done on the basis of age. But the guidelines helps the clinician see that it's really not just an age phenomena. It's really a decision based on comorbidities and really what's best for the patient. So we spend time helping making that decision, and then provide very practical advice as to how to treat a patient who's going to transplant versus a patient who's not going to transplant. We also, then, after the transplant, or in lieu of a transplant, we discuss the importance of continuous therapy, or sometimes called, maintenance therapy in myeloma. Again, we've seen maintenance therapy, now, have an impact on both progression free and overall survival. And so we felt it was really important to be very practical in giving advice as to what maintenance therapy agents to use and how to use them. And then lastly, the guideline provides a lot of practical advice as to a patient who has relapsed with multiple myeloma. We have so many choices now with three major classes of drugs of proteasome inhibitors, immuno-modulatory drugs, and now newer monoclonal antibodies, it can be difficult sometimes to know which combination to use. We know that triplet combinations tend to be preferred. So we walk through a number of those triplets and provide advice as how to explicitly use them. We do emphasize the importance of supportive care and of risk factor analysis throughout the guideline, so that we can understand the difference between high risk and low risk myeloma, so that we can understand how important a patient's comorbidities, especially in a disease that primarily affects older patients, can be managed. And so we try to do so in a comprehensive way, but one that really distills down to the critical pieces to allow the practicing clinician some real advice. So why is this guideline so important, and how will it change practice? There are several kinds of guidelines for multiple myeloma, but I really think this is a critical guideline because it is so clinical and practical in its essence. It's really designed to not just give the utopian view or the clinical trial view of a disease, but practically in the trenches, how do we use the drugs that we know are going to benefit our patients. Myeloma is one of the few cancers where we have seen a doubling, if not a tripling of survival in the last decade, because of so many of these new agents. And so making sure that our patients are treated optimally really is important. And we want to be able to ensure that they receive the best therapy possible, so they can live a longer life, but also live it with a greater quality of life. And so finally, how will these guideline recommendations affect patients? Well, we really hope that this is going to help patients all across North America and the whole world, because it will give very concrete advice to the practicing clinician in how to approach the disease. And one of the things I think will directly impact patients, if you will, right away is one of the themes of these guidelines, which is that you don't treat a patient simply based on the biopsy or simply based on their age, but that it is really a complex network of comorbidities, risk factors from the disease itself, the potential side effects of certain drugs, and a patient's own very personal history. It really fits in with the ASCO modality that we have of ensuring that we bring personalized medicine to our patients. And so this will allow the person who's reading it and who's applying it to their patient to recognize the importance of general guidelines, but also of applying it to the specific patient they care for. Because as I like to say, we don't treat multiple myeloma, we treat people. And so hopefully, this will allow the clinician to have that precision to care for their patient in the best way possible. Great. Thank you for that overview of this guideline, and thank you for your time today Dr. Mikhael. It's been a real pleasure. Thank you very much. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/hematologic-malignancies-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Susan Chang from the University of California San Francisco, lead author on "Anticonvulsant Prophylaxis and Steroid Use in Adults with Metastatic Brain Tumors: ASCO and SNO Joint Endorsement of the CNS Guidelines." Thank you for being here today, Dr. Chang. Thank you so much for this opportunity. So first, can you give us the general overview of what this guideline covers and about the endorsement process? Absolutely. So one of the things we've noticed, of course, is that the incidence of newly diagnosed adult patients with brain metastases is now estimated to be in the range of about 20,000 to 40,000 per year. And this has really been increasing because of several factors. This includes improved imaging tools, the fact that there's an increase in the number of cancers that are prone to spread to the brain, and the improved survival of patients with cancer. And so the Congress of Neurological Surgeons have developed a series of guidelines on the treatment of adults with metastatic brain tumors. That includes systemic therapy, as well as supportive care. There are two guidelines that address the role of anti-convulsant abuse and steroids in the care of patients with brain tumors. Specifically, the guideline questions were do prophylactic anti-epileptic drugs decrease the risk of seizures in both non-surgical and post-surgical patients, who are otherwise seizure free? So these are patients who have never had a seizure, does it make any sense to use these drugs? The second is do steroids, which are commonly used in patients when there is increased mass effect and cerebral edema, could that help to improve neurological functioning or quality of life, compared to supportive care or other treatments? And if they are used, what sort of dose should be used? So the process of endorsing these guidelines included an initial assessment by content evaluators from ASCO and members of the Society of Neuro Oncology, or SNO guidelines committee. And subsequently, it was determined that a detailed review of the guidelines should be pursued. So in this joint effort of both ASCO and SNO, a multidisciplinary expert panel of medical and radiation oncologists and neurosurgeons, neurologists, and others providing care for adults with metastatic brain tumors reviewed the content to determine the appropriateness for endorsement by the two professional societies. So what are the key recommendations of this guideline? The key recommendations of this guidelines include the fact that routine use of prophylactic anti-epileptic drugs is not recommended for patients who are seizure free, either in the non-surgical and post-surgical settings, and that steroids could be used when patients had mild, moderate, or severe symptoms that were related to mass effect in the brain. This choice of steroids that was recommended was dexamethasone, and the doses was about 4 to 16 milligrams, depending on the severity of the symptoms. Now, what they found was that there was insufficient evidence to recommend steroid use in asymptomatic patients, when they didn't have any mass effect. And one of the additional aspects that the panel provided was that the minimal effective dose should be used, and that nighttime doses should be avoided. And this is because of the known side effect of insomnia that a lot of our patients experience when taking this medication right before they go to sleep. So why is this guideline so important, and how will it change practice? Well, these guidelines provide a basis for oncologists to avoid the over prescription of anti-epileptics and steroids in patients with brain metastases, particularly in those who are asymptomatic and those without signs of mass effect. It also highlights that if steroids are going to be administered, that clinicians should be very familiar with both the short and long term sequelae of steroid therapy, and they should have a plan to taper the steroids as fast as can be clinically tolerated. So finally, how will these guideline recommendations affect patients? Well, both anti-epileptics and steroids have a wide range of toxicities that can adversely affect a patient's quality of life. And so the routine use of these drugs in patients with incidentally discovered or asymptomatic brain metastases is not supported by the available medical literature. For patients with symptoms related to mass effect, the best evidence supports the temporary use of steroids are the lowest effective dose with the intent to taper them off, and if tolerated, and after a definitive treatment of brain metastases has been initiated. And because of the well known side effects of insomnia and agitation, nighttime doses of steroids should be avoided. So the hope is that this will have a direct effect on how we care for our patients. Great. Thank you for your work on these important guidelines, and thank you for your time today, Dr. Chang. You're very welcome. It's such a pleasure to be able to provide this for patients and families. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/neurooncology-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Rachna Shroff from the University of Arizona Cancer Center, lead author on "Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Shroff. Thank you so much for having me. So what does this guideline recommend? This is a guideline that is basically looking at the role of post-operative therapy in patients who undergo surgical resection for biliary tract cancers. Biliary tract cancers are a somewhat heterogeneous group of malignancies that include intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancer. And so the question always in most cancers are, if you are able to undergo surgical and curative treatment, is there a role for post-operative chemotherapy or radiation therapy to help improve the chance of cure and decrease the risk of recurrence? So that is exactly what we investigated as an expert panel. So our recommendations are actually twofold. The first one is that we are clearly recommending that patients with resected biliary tract cancer should be offered adjuvant chemotherapy with capecitabine for a total of six months. Within that recommendation, we do acknowledge that this is based on the BILCAP phase III randomized controlled trial and that there was a specific dosing and treatment schedule that was done in that study, but that we are allowing for institutional and regional variances that we've noted in terms of dosing of capecitabine. And so as a result, we're recommending adjuvant capecitabine, and we're allowing practitioners to determine what the best and safest dosing would be, based on their experience. The second recommendation is more specifically for patients with extrahepatic cholangiocarcinoma or gallbladder cancer who undergo resection and have a microscopically positive surgical margin, which is an R1 resection. And in those patients, we are recommending that we could consider offering these patients chemoradiation therapy. Now, again, this is not as strong of a recommendation, because we do not have prospective randomized phase III data to support it. This was based more on a prospective single-arm study out of the Southwest Oncology Group, as well as some other retrospective studies. And so we do go on to qualify that that recommendation should really be made in a shared decision-making approach, with a multidisciplinary conversation to decide the risks and benefits of radiation in these patients-- and that we acknowledge that a prospective study would really help clarify that question a little bit more. So can you tell us about the research that informed these recommendations? There have been a number of studies that have looked at the role of adjuvant therapy in biliary cancers. And up until very recently, a lot of these studies were small retrospective series, single-institution or multi-institution, but everything in retrospect-- no prospective or randomized data. And so I think a lot of the reasons that we decided to have these guidelines come out now is that in the last two to three years we do finally have prospective randomized data that helps guide the recommendations. And the majority of the recommendations that we made are based on one randomized phase III, which is BILCAP study. This was a study that was done in the UK and was presented at ASCO in 2018 and is currently in press. And it is basically a randomized controlled trial that compares adjuvant capecitabine by itself versus surveillance alone in patients who undergo surgery for biliary tract cancers. And so our recommendations, which include that study as well as a couple others, is primarily hinged on that, since that is the largest prospective data we have so far. And based on that study, we did in fact recommend that there was a role for adjuvant chemotherapy with capecitabine after complete resection for biliary tract cancers. And based on that research that was done in that trial that was completed, we do believe that the role for capecitabine for six months is pretty strong and that the data supports that now. So why is this guideline so important, and how will it change practice? Well, I think it's going to be practice-changing because up until now there has not been a clear consensus on how we approach these patients. And I will say that even now, it's really just this one study that has helped guiding these recommendations. There were a number of other studies that we looked at as part of the expert panel. And these were all prospective studies as well that looked at things like gemcitabine and oxaliplatin in the adjuvant setting, or single-arm phase II studies that came out of the Southwest Oncology Group that also explored the role of radiation. But really, nothing was a positive study other than the BILCAP study. And so up until now, I would say it was a little bit all over the place in terms of how medical oncologists approached resected biliary cancers. I think the majority of us felt that there was probably a role for adjuvant chemotherapy or perhaps chemoradiation. But there was no rules that we could follow, and there was no clear study that we could turn to that would tell us what we should give, how long we should give it for, and whether it should be a combination of chemotherapy or chemoradiation. And so I think it will be practice-changing because now, as part of the expert panel, we are making a very clear recommendation that patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy for a total of six months, hopefully eliminating that kind of regional or specialist-based variation that has been happening up until this point. And finally, how will these guideline recommendations affect patients? Again, I think that the main way it's going to affect them is that there's going to be a little bit less gray area, in terms of medical oncologists having conversations with the patients and saying, well, you know, I think that there's probably a role for agent therapy here, but I can't show you the data that supports why I think that. And as a result, I would hope that patients will have a little bit more faith and confidence in knowing that there is a large study that has looked at and proven the benefit of adjuvant capecitabine and that that decreases the chance of recurrence and improves overall survival. The improvement in overall survival was dramatic in this study. And we had not seen a survival of 51 months, which is what we saw in this study, in a very long time. So for patients, not only does it make clear what they should be doing after surgery, but I would hope it also gives them additional hope that we have really changed the bar by doing this adjuvant capecitabine, and that the chance for cure is even higher when we can offer adjuvant chemotherapy. I think the only other thing that may still be a gray area, and that is kind of what we allude to in our second recommendation, and that is in patients who undergo resection and have a microscopically positive margin or an R1 resection. And that's typically patients with extrahepatic cholangiocarcinoma or gall bladder cancer. In those patients, we suggest that they could be offered chemoradiation therapy, but the evidence is not as strong there. Again, it's more retrospective studies that we looked at. There is no prospective study that answers the question of whether or not there's a role for radiation. And so as a result for patients, I think that is still the one area that's a little bit of a gray zone in terms of knowing whether chemoradiation would benefit them if they undergo surgery and have a microscopically positive resection. But I do think that there is a definitive benefit to giving adjuvant chemotherapy, and that, hopefully, will clarify things not only from the physician perspective but also from the patient perspective. Great. Thank you for your work on these important guidelines, and thank you for your time today, Dr. Shroff. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Susan Chang from the University of California San Francisco, lead author on "Anticonvulsant Prophylaxis and Steroid Use in Adults with Metastatic Brain Tumors: ASCO and SNO Joint Endorsement of the CNS Guidelines." Thank you for being here today, Dr. Chang. Thank you so much for this opportunity. So first, can you give us the general overview of what this guideline covers and about the endorsement process? Absolutely. So one of the things we've noticed, of course, is that the incidence of newly diagnosed adult patients with brain metastases is now estimated to be in the range of about 20,000 to 40,000 per year. And this has really been increasing because of several factors. This includes improved imaging tools, the fact that there's an increase in the number of cancers that are prone to spread to the brain, and the improved survival of patients with cancer. And so the Congress of Neurological Surgeons have developed a series of guidelines on the treatment of adults with metastatic brain tumors. That includes systemic therapy, as well as supportive care. There are two guidelines that address the role of anti-convulsant abuse and steroids in the care of patients with brain tumors. Specifically, the guideline questions were do prophylactic anti-epileptic drugs decrease the risk of seizures in both non-surgical and post-surgical patients, who are otherwise seizure free? So these are patients who have never had a seizure, does it make any sense to use these drugs? The second is do steroids, which are commonly used in patients when there is increased mass effect and cerebral edema, could that help to improve neurological functioning or quality of life, compared to supportive care or other treatments? And if they are used, what sort of dose should be used? So the process of endorsing these guidelines included an initial assessment by content evaluators from ASCO and members of the Society of Neuro Oncology, or SNO guidelines committee. And subsequently, it was determined that a detailed review of the guidelines should be pursued. So in this joint effort of both ASCO and SNO, a multidisciplinary expert panel of medical and radiation oncologists and neurosurgeons, neurologists, and others providing care for adults with metastatic brain tumors reviewed the content to determine the appropriateness for endorsement by the two professional societies. So what are the key recommendations of this guideline? The key recommendations of this guidelines include the fact that routine use of prophylactic anti-epileptic drugs is not recommended for patients who are seizure free, either in the non-surgical and post-surgical settings, and that steroids could be used when patients had mild, moderate, or severe symptoms that were related to mass effect in the brain. This choice of steroids that was recommended was dexamethasone, and the doses was about 4 to 16 milligrams, depending on the severity of the symptoms. Now, what they found was that there was insufficient evidence to recommend steroid use in asymptomatic patients, when they didn't have any mass effect. And one of the additional aspects that the panel provided was that the minimal effective dose should be used, and that nighttime doses should be avoided. And this is because of the known side effect of insomnia that a lot of our patients experience when taking this medication right before they go to sleep. So why is this guideline so important, and how will it change practice? Well, these guidelines provide a basis for oncologists to avoid the over prescription of anti-epileptics and steroids in patients with brain metastases, particularly in those who are asymptomatic and those without signs of mass effect. It also highlights that if steroids are going to be administered, that clinicians should be very familiar with both the short and long term sequelae of steroid therapy, and they should have a plan to taper the steroids as fast as can be clinically tolerated. So finally, how will these guideline recommendations affect patients? Well, both anti-epileptics and steroids have a wide range of toxicities that can adversely affect a patient's quality of life. And so the routine use of these drugs in patients with incidentally discovered or asymptomatic brain metastases is not supported by the available medical literature. For patients with symptoms related to mass effect, the best evidence supports the temporary use of steroids are the lowest effective dose with the intent to taper them off, and if tolerated, and after a definitive treatment of brain metastases has been initiated. And because of the well known side effects of insomnia and agitation, nighttime doses of steroids should be avoided. So the hope is that this will have a direct effect on how we care for our patients. Great. Thank you for your work on these important guidelines, and thank you for your time today, Dr. Chang. You're very welcome. It's such a pleasure to be able to provide this for patients and families. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/neurooncology-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Rachna Shroff from the University of Arizona Cancer Center, lead author on "Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Shroff. Thank you so much for having me. So what does this guideline recommend? This is a guideline that is basically looking at the role of post-operative therapy in patients who undergo surgical resection for biliary tract cancers. Biliary tract cancers are a somewhat heterogeneous group of malignancies that include intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancer. And so the question always in most cancers are, if you are able to undergo surgical and curative treatment, is there a role for post-operative chemotherapy or radiation therapy to help improve the chance of cure and decrease the risk of recurrence? So that is exactly what we investigated as an expert panel. So our recommendations are actually twofold. The first one is that we are clearly recommending that patients with resected biliary tract cancer should be offered adjuvant chemotherapy with capecitabine for a total of six months. Within that recommendation, we do acknowledge that this is based on the BILCAP phase III randomized controlled trial and that there was a specific dosing and treatment schedule that was done in that study, but that we are allowing for institutional and regional variances that we've noted in terms of dosing of capecitabine. And so as a result, we're recommending adjuvant capecitabine, and we're allowing practitioners to determine what the best and safest dosing would be, based on their experience. The second recommendation is more specifically for patients with extrahepatic cholangiocarcinoma or gallbladder cancer who undergo resection and have a microscopically positive surgical margin, which is an R1 resection. And in those patients, we are recommending that we could consider offering these patients chemoradiation therapy. Now, again, this is not as strong of a recommendation, because we do not have prospective randomized phase III data to support it. This was based more on a prospective single-arm study out of the Southwest Oncology Group, as well as some other retrospective studies. And so we do go on to qualify that that recommendation should really be made in a shared decision-making approach, with a multidisciplinary conversation to decide the risks and benefits of radiation in these patients-- and that we acknowledge that a prospective study would really help clarify that question a little bit more. So can you tell us about the research that informed these recommendations? There have been a number of studies that have looked at the role of adjuvant therapy in biliary cancers. And up until very recently, a lot of these studies were small retrospective series, single-institution or multi-institution, but everything in retrospect-- no prospective or randomized data. And so I think a lot of the reasons that we decided to have these guidelines come out now is that in the last two to three years we do finally have prospective randomized data that helps guide the recommendations. And the majority of the recommendations that we made are based on one randomized phase III, which is BILCAP study. This was a study that was done in the UK and was presented at ASCO in 2018 and is currently in press. And it is basically a randomized controlled trial that compares adjuvant capecitabine by itself versus surveillance alone in patients who undergo surgery for biliary tract cancers. And so our recommendations, which include that study as well as a couple others, is primarily hinged on that, since that is the largest prospective data we have so far. And based on that study, we did in fact recommend that there was a role for adjuvant chemotherapy with capecitabine after complete resection for biliary tract cancers. And based on that research that was done in that trial that was completed, we do believe that the role for capecitabine for six months is pretty strong and that the data supports that now. So why is this guideline so important, and how will it change practice? Well, I think it's going to be practice-changing because up until now there has not been a clear consensus on how we approach these patients. And I will say that even now, it's really just this one study that has helped guiding these recommendations. There were a number of other studies that we looked at as part of the expert panel. And these were all prospective studies as well that looked at things like gemcitabine and oxaliplatin in the adjuvant setting, or single-arm phase II studies that came out of the Southwest Oncology Group that also explored the role of radiation. But really, nothing was a positive study other than the BILCAP study. And so up until now, I would say it was a little bit all over the place in terms of how medical oncologists approached resected biliary cancers. I think the majority of us felt that there was probably a role for adjuvant chemotherapy or perhaps chemoradiation. But there was no rules that we could follow, and there was no clear study that we could turn to that would tell us what we should give, how long we should give it for, and whether it should be a combination of chemotherapy or chemoradiation. And so I think it will be practice-changing because now, as part of the expert panel, we are making a very clear recommendation that patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy for a total of six months, hopefully eliminating that kind of regional or specialist-based variation that has been happening up until this point. And finally, how will these guideline recommendations affect patients? Again, I think that the main way it's going to affect them is that there's going to be a little bit less gray area, in terms of medical oncologists having conversations with the patients and saying, well, you know, I think that there's probably a role for agent therapy here, but I can't show you the data that supports why I think that. And as a result, I would hope that patients will have a little bit more faith and confidence in knowing that there is a large study that has looked at and proven the benefit of adjuvant capecitabine and that that decreases the chance of recurrence and improves overall survival. The improvement in overall survival was dramatic in this study. And we had not seen a survival of 51 months, which is what we saw in this study, in a very long time. So for patients, not only does it make clear what they should be doing after surgery, but I would hope it also gives them additional hope that we have really changed the bar by doing this adjuvant capecitabine, and that the chance for cure is even higher when we can offer adjuvant chemotherapy. I think the only other thing that may still be a gray area, and that is kind of what we allude to in our second recommendation, and that is in patients who undergo resection and have a microscopically positive margin or an R1 resection. And that's typically patients with extrahepatic cholangiocarcinoma or gall bladder cancer. In those patients, we suggest that they could be offered chemoradiation therapy, but the evidence is not as strong there. Again, it's more retrospective studies that we looked at. There is no prospective study that answers the question of whether or not there's a role for radiation. And so as a result for patients, I think that is still the one area that's a little bit of a gray zone in terms of knowing whether chemoradiation would benefit them if they undergo surgery and have a microscopically positive resection. But I do think that there is a definitive benefit to giving adjuvant chemotherapy, and that, hopefully, will clarify things not only from the physician perspective but also from the patient perspective. Great. Thank you for your work on these important guidelines, and thank you for your time today, Dr. Shroff. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Shlomo Koyfman from the Cleveland Clinic, lead author on "Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Koyfman. It's a pleasure. So first, can you give us a general overview of what this guideline covers? Yeah, so this is an exciting guideline because it covers a topic that we don't usually think about in head and neck cancer in a formal way, and that is management of the neck in squamous cell cancer of the oral cavity and the oropharynx. So there's a lot of literature and guidelines out there on how to manage oropharynx cancer, which is becoming a more and more common cancer, especially in the HPV-positive era, less so on oral cavity. But a lot of times it's focused on people who don't get surgery, chemoradiation, or people who do get surgery and TORS, Transoral Robotic Surgery, and different approaches. But rarely do we have something focus on management of the neck per se, which is really, really important in these cancers and often overlooked in favor of the primary tumor itself. So these guidelines really take us through some salient questions in how to manage the neck in these two cancers. And what are the key recommendations of this guideline? The recommendations came off of six fundamental questions, three in oral cavity and three in oropharynx. There are some commonalities between the two and some differences. A lot of the fundamental questions revolve around surgical quality, and neck dissection is the standard surgical approach for management of the neck in these patients. And as we enter the quality era, how do we define benchmarks of surgical quality, which is one thing that it deals with. The other is when to do adjuvant therapy like adjuvant radiation or chemoradiation. We also deal with when to do surgery for the neck or to do nonoperative approaches like radiation or chemoradiation. And then lastly, how do you follow patients after you've treated them? So those are kind of the salient issues that we dealt with. And what we came out with was nothing earth shatteringly new, but I think the way it was organized and systematically put together, I think it's going to be really, really helpful for people. So some of the most important findings that this recommendation does, I think this is the first that incorporates surgical quality, as I mentioned before. So specifically neck dissection should have 18 or more nodes as multiple studies have shown that that's associated with better outcomes. And similarly we define for different diseases of oral cavity and oropharynx, and depending on what kind of tumor it is and where, what nodal levels should be dissected or treated, whether surgically or nonsurgically, and when to do just one side of the neck versus both sides of the neck. So I think there's a lot of good guidance there in terms of the surgical quality. From a standpoint of adjuvant therapy, we define pretty clearly indications for when after surgery for oral cavity cancer, for example, when radiation should be added and when chemoradiation should be added, and I think that's very helpful. And especially for the neck itself, there's been confusion about what happens if I have 30 nodes taken out and they're all negative but I have a big, large primary tumor. What do I do with the neck? Do I radiate it? Do I not radiate it at one side, both sides? And this guideline gives some pretty clear guidance in different scenarios about how to think about that, which is pretty novel and really important, I think. I get questions about this all the time. It comes up in tumor boards all the time, and it's pretty practical. And mostly what we say is if you have a primary tumor that's like a T3 or T4 oral cavity cancer or it approaches midline, either a contralateral neck dissection should be done or radiation should be done to the contralateral neck. And even if you have a lot of lymph nodes taken out and they're negative, if you have very high-risk primary tumor features like very large tumor or multifocal perineural invasion, those kinds of things, even with a negative neck dissection we still typically do treat the neck. So the next recommendation that's really helpful is who can be observed after surgery? And specifically low-volume N1 you can consider observing in oral cavity cancer, whereas N2 or N3 patients all need radiation or chemoradiation in the setting of extranodal extension and positive margins. We did come out pretty firmly advocating for bolus cisplatin 100 milligrams per meter squared every three weeks as recent studies suggest that weekly cisplatin or other regimens are not as effective, and we were pretty clear about that. We were pretty synchronized with recent ASCO-endorsed guidelines in oropharynx cancer that say similar things. In addition, one of the very important questions that comes up is a surgeon will say, well, I'm cutting out the neck tumor, and I know it comes to midline and he's got a bunch of nodes on the right side, but do I really need to do a left neck dissection? Aren't you going to radiate it anyway? And that comes up all the time. Is radiation adequate to manage a clinically negative neck in oral cavity cancer and oropharynx cancer? I think in oropharynx cancer everybody feels pretty comfortably yes. I think in oral cavity cancer it's been somewhat controversial. We favor neck dissections when possible, but if radiation is known to be happening, especially to an elective contralateral neck, that that is adequate therapy. However, we're pretty strong in the fact that neck dissections are the tried and true way to treat oral cavity cancer and that in a T2 or above tumor where a neck dissection is indicated, just resecting the primary and leaving the neck to elective radiation is not something that we thought there was enough evidence for to advocate, and we still advocate classic neck dissection first followed by adjuvant radiotherapy as indicated. One area of controversy that we did touch on is the issue of early stage tongue cancers and whether they need a neck dissection at all. And we came down pretty consistently with all of the co-authors on the guideline that we advocated for a neck dissection for all patients with oral cavity cancer unless it is a very small tumor that we define with very compliant patient who is amenable to very rigorous follow-up that has been done in Europe and in some other places with, specifically, people trained in careful neck ultrasound techniques. So all of those really help guide, both in early stage and more advanced stage, how to manage the neck and oral cavity cancer. And in oropharynx cancer, again, many of the same quality metrics apply. We have some guidance about when doing transoral robotic surgery how to reduce bleeding risk by ligating feeding blood vessels, which is an important addition. We also discuss the fact that, as opposed to lateralized oral cavity patients where a unilateral either neck dissection of radiation is often indicated, in oropharynx cancer the group felt very strongly that bilateral neck should be treated. And typically if tumors extend to midline or involve the posterior oropharyngeal wall, which has bilateral drainage, that either bilateral neck dissection should be performed in those cases or a unilateral neck dissection can be done as long as adjuvant radiation is planned to both necks. Finally, a couple of very important questions of who should not be treated surgically and who should be treated with a nonoperative chemoradiation based approach. In oral cavity cancer, as long as they were not metastatic, we felt people should be resected as long as they were surgically resectable and medically operable. In oropharynx cancer, however, anybody who had unequivocal extranodal extension of nodes into soft tissues or involvement to the carotid artery or extensive cranial-nerve involvement or skull-based involvement by extensive nodal disease are not good candidates for surgery and should be preferentially treated with chemoradiation. That was pretty strong. And finally, the other thing we gave clarity on is when we treat oropharynx cancer with chemoradiation, how do we follow them and when do we decide to do a neck dissection or not? And essentially we recommended a PET CT scan at 12 weeks. And as long as that was negative, a neck dissection should not be done. If you don't have a PET scan and you just have high quality CT or MRI but all of the neck disease has resolved, similarly there should be no neck dissection. And then most importantly, the situation we all face which is very complex is what happens when you have a PET CT done three to four months after treatment and you have small nodes that are still there? You have a little bit of uptake. The FDG avidity is much less than it was. There still is a lesion there, but it's much better and the patient is feeling well. And we felt pretty comfortable not doing a standard neck dissection on those patients but rather following them closely with a follow-up CT scan two to three months later and continual assessment and reserving surgery for obvious progressive disease. So why is this guideline so important, and how will it change practice? So this guideline is really important because head and neck cancer being not the most common cancer, and especially because head and neck cancer is not really one disease-- there's so many different diseases. Even oral cavity and oropharynx, there's quite a bit of variability in how we think about it. There's not a one size fits all recipe for how to manage people properly, and that leads to a lot of confusion and sometimes doubt as to what the best thing to do is in these patients. And that is a very common thing. So I think the most important reason why these guidelines are helpful is they're really clear. They give really clear guidelines of if you're going to do surgery, here's the expectations of what nodal levels to take out and how many nodes to take out. Here's when you should do adjuvant radiation. Here's when you should do adjuvant chemoradiation. Here's when you should treat one side of the neck. Here's when you should treat both sides of the neck. If you're not going to do surgery, here's when you do radiation. And for oropharynx cancer, here's when you can consider surgery. Here's where surgery is not the best idea. And when you treat them and if you do surgically, here's how you do it. If you do with radiation, here are the nodes that should be treated, the nodal levels. And finally, after you do that, how do you watch and act to make sure that people don't fail? So I feel like all of those things lend a lot of clarity to some complicated decision-making processes for these patients, and this really lends clarity to that, which should help kind of lend consistency of practice. That's really our goal. Our goal was there a lot of great docs taking care of these patients out there, but patients are treated in very different ways depending on who they're seeing and where you go. Our goal was to try to increase the consistency of how people are treated no matter where they are. And if practitioners, surgeons, radiation oncologists, medical oncologists see this guideline and kind of follow it and, of course, reach out with any questions at any time, then what we'll be able to do is kind of harmonize the way patients are treated in this country, which should help, I think, the quality of care. And finally, how will these guideline recommendations affect patients? They're going to affect patients because right now a lot of patients get great care, but there are some patients that are not getting ideal care either because maybe they're in parts of the country that don't have the same access to resources or they're in places where the volume of these kind of very complicated and yet not so common diseases aren't seen as high and there's confusion about how to manage them or what the quality metrics are. I think patients are going to be affected knowing, hey, if I'm going to have a neck dissection, here's what I should be asking to make sure my surgeon knows to do and does consistently to make sure it's of high quality. Here's where I think I should be treated with surgery, maybe I shouldn't be treated with surgery, and here's how to follow me. Because there is a lot of variability in how patients are treated, and sometimes there's too many surgeries being done, not enough surgeries being done. If they're being done, maybe they're not the best quality. Even if we don't treat with surgery and we do chemoradiation, we're watching them and we may not be following them as closely, and then people may be recurring and we're not picking it up closely enough. So I think it's going to harmonize, for patients, the way they're ultimately treated. If everybody in the country is treated relatively compatible with this guideline, I think the standard of care will go up across the board. Great. Thank you so much for your work on this important guideline, and thank you for your time today, Dr. Koyfman. Thank you so much. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Marcia Cruz-Correa from the University of Puerto Rico and MD Anderson Cancer Center, senior author on "Early Detection for Colorectal Cance: ASCO Resource-Stratified Guideline." Thank you for being here today, Dr. Cruz-Correa. Well, thank you very much for the opportunity to speak with you today. So first, can you give us a general overview of what this guideline covers? Absolutely, Shannon. Well, we are very excited to review the content of the guideline. And we put together a summary of the current guidelines out there for patients that are undergoing colorectal cancer screening. With these particular resource, a certified guideline takes, for the first time, into account the place where the colorectal cancer screening is being delivered, which is different from when you read any other colorectal cancer screening guidelines, where normally we assume that all available methodologies are equally distributed regardless of the country or the setting. So in our particular guideline, we really emphasize the fact that, depending on where our clinicians are, they might have differing technologies available. And that's why it's called resource-stratified-guidelines, to help our clinicians and our practicing physicians to understand what would be the best method to be able to implement screening in their own settings. So what are the key recommendations of this guideline? I think that the most important recommendation is that colorectal cancer is a prevalent disease, not only affecting very highly developed countries, but a disease that we're seeing more and more in low-to-middle-income countries. As ASCO is an organization that has members from around the world, being cognizant of the fact that colorectal cancer affects many individuals across different settings, and countries, and continents, for that matter, allows us to provide the most important information which is to consider colorectal cancer screening across the different settings, so not only in the industrialized well-developed first-world country, but also in the low-to-middle-income, or those that are becoming more and more industrialized. So our main recommendation-- it's number one-- that we need consider colorectal cancer screening even in settings where, for many years, the burden of disease was really focused in infectious-driven diseases. Nowadays, we're seeing more and more low-to-middle-income countries where the number one cause of death, it's not an infectious-driven disease, but rather a cancer. And colorectal cancer, it's one of the top cancers that we're seeing in many of the settings. So our number one recommendation is to be cognizant about that so that different countries and different settings, the practitioners consider screening. And our second and most important recommendation is that, the important thing is to consider what you have available in your setting, in your clinical practice. And depending on what you have available, then you can offer the method that could be given to your patient. So it's almost like thinking differently. It's not a one size fits all, but rather it's more or less of a personalized recommendation based on your setting, based on your clinical practice methods available to you. So why is this guideline so important? And how will it change practice? We believe that it's very important, because when you look at guidelines in any published article out there, we read it. And it looks as if everyone had every resource available. And when you're practicing in a low-to-middle-income country, or a place-- it could be a rural area where you have more basic settings or more limited settings-- you might not have that new machine or that new equipment. So then, as a practitioner, you feel that you're not equipped to be able to provide the best care to your patients. So this guideline, it's mirrored after a previous guideline that was put together by the ASCO Clinical Practice Group, where we stratify the type of practice for our-- where our practitioners are providing care. There are four main practice settings. The first one is what we call the basic setting, which is where you have the minimal necessary facilities to be able to evaluate patients and provide first primary care services. The second tier, it's called the limited setting, where you have more clinical facilities, but yet you don't have all the elements, like imaging, for instance, or the specialized surgeon, or the third- or fourth-level specialized technology. Then you have something, the next level would be the enhanced, where you, again, you see more methods and more availability of more clinical instrumentation and facilities. And then final one, which is the fourth level, will be the maximal setting. So in a maximal setting is when you go to a city, a cancer center, for instance, where you have all the specialists, all the imaging, all the endoscopy, and experts that are able to use those equipments and provide the best care. So using that four-level approach, from basic-- and think about, when you think about basic, it's in a rural community maybe in-a-low-to-middle income or developing country, places where you have a general surgeon. And you may have a primary physician. You may have nurse practitioners or nurses that actually provide that first care, first-level care. And then you keep going from there all the way to the maximal setting. So depending where you are, these resource-stratified guidelines will provide the physician and the clinical practitioner with methods that they can implement now. So to give you an example, when you think about colorectal cancer screening, you think about individuals that come to see you because they have no symptoms or they might have some symptoms. Most of the time, they would be asymptomatic individuals that come for a general screening, general visit. So this resource-stratified allows the physician that is practicing at a basic or a limited setting to provide, for the case of colorectal cancer, screening to provide fecal or cold-blood testing. This is a test that has been shown to be effective, that when used in the adequate setting for a patient that is 50 years of age or older, will provide enough sensitivity to diagnose an individual that might have either colorectal cancer or advanced colonic polyps so that that patient can then undergo a confirmatory test such as a barium enema, if you are in a basic setting. Very different, Shannon, when you are in a setting where you have all the instrumentation there-- you as a physician, you could either do a fecal immunological testing to look for, or cold blood. Or you could decide to refer a patient to a colonoscopy. And I think, when you practice in the US, I mean, large or industrialized places like Europe or Australia, you think that everyone has access to endoscopy. And believe it or not, one of the things that we realized when we were looking at all these data, is that in basic settings, setups for colonoscopy for removal of polyps with polypectomy during a colonoscopy are not available. So we took all those factors of clinical facilities, and availability of equipment, and expert physicians to be able to provide adequate care for the patients that are receiving care by our practitioners in the different settings, from basic all the way to enhanced and maximal settings. And finally, how will these guideline recommendations affect the patients? You have asked the most important question. The reason that we put guidelines out there is to guide our physicians, our practitioners to provide the best care that they can regardless of where they are. By providing this information, the ultimate and most important beneficiary of these guidelines is the patients. Right now, in many settings, especially in low-to-middle-income or developing countries, they are not receiving screening or preventive testing. In fact, there are many countries that do not have standardized or institutionalized programs for colorectal cancer screening. So if you don't have a program in place, you can imagine that then a patient would not even be considered for preventive care. So the ultimate and most important beneficiary of this resource-stratified colorectal cancer screening guideline is the patients that we serve. So as countries continue to evolve, and even in a country that is industrialized but where you have limited resources, only access to a basic laboratory, there we can still provide screening. And then the guidelines are written in a way that you can identify the type of practice where you're at. And you can choose between the different methods. And then it guides you as to decide when to refer a patient to a higher level with regards to clinical facilities. So if you're in a basic setting and you get a positive screening test, what do you do with that patient? Are you able to refer to the second level, which will be the limited? Or do you have to refer it all the way to enhanced? So it's almost like it's a guideline, but it's very practical in nature. So our hope is that this will allow our practitioners to feel empowered, to understand that this is a disease that will be affecting their population, the patients that they are taking care of, but furthermore, that they feel empowered to provide the best care, because that's why we practice medicine. And that's the bottom line, the most important reason why this was put together. Great, thank you so much for your work on this important guideline. And thank you for your time today, Dr. Cruz-Correa. Thank you very much for the opportunity, Shannon. And you know, hopefully we'll get many comments from across the different members of the organization across the globe. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Manish Shah from New York Presbyterian Weill Cornell Medical Center, senior author on "Treatment of Patients with Early-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline." Thank you for being here today, Dr. Shah. Thank you, it's a pleasure and honor to be here. So first, can you give us a general overview of what this guideline covers? Yes, absolutely. So the "Treatment of Patients with Early-Stage Colorectal Cancer" is a resource-stratified guideline. And it focuses on the management of patients with early-stage colon cancer. It's different than the surveillance and screening guideline that was written simultaneously for ASCO as another resource-stratified guideline. We felt that this was a big enough topic that we should keep it separate. So it really talks about the management of pre-malignant lesions, as well as early-stage colon cancers, as well as rectal cancers. And the other aspect of this is that we really focused on how the guideline may apply in settings where there-- they don't have maximal resources, so basic or limited settings as well. So I would like to talk a little bit about how the guideline was created, because I think that's an important aspect. And it distinguishes it from typical other ASCO Guidelines. So the management of colon cancer or colorectal cancer, there's a lot of literature on this. And there are several guidelines that have been produced by colorectal cancer societies, or surgical societies, or from other countries like the EORTC, or Japan, or Korea, or even the UK. So in fact, there were, I think, 30 to 40 different guidelines that we reviewed. And we felt that, instead of doing a new literature search to kind of rehash much of the same information, we reviewed all the guidelines for certain quality measures to then select a handful of guidelines that we would use as the reference for each of our key questions or key points. And this was done in a formal process, the first by ASCO and Sarah, who was the ASCO staff who wrote the guideline, along with the members of the guideline panel. And in this process, I think that we have a pretty comprehensive guideline that covers the questions with the best evidence available. So what are the key recommendations of this guideline? Yeah, so we addressed some several questions with regard to key recommendations. The first question, for example, was, what's the optimal treatment for patients with colon cancer that would be clinical stage 1 through 3c? And we distinguish that from a non-obstructing cancer to obstructing cancers as well, because the management would be very different. And what we really sort of focused on is that these patients should have resection following oncologic principles. Then ideally, they should have an en bloc resection by a surgical oncologist to give the patients the best chance of care. But I think what's unique to resource-stratified guidelines, and what we have to do is sort of highlight the care that would be achieved in settings that have less resources. So a non-obstructing colon cancer in a basic setting should still have surgery and should still undergo an en bloc resection following standard oncologic principles. So that was, for example, one of the key points that was uniform across all the settings. Other things were how to manage [INAUDIBLE] colon cancer. So in more enhanced and maximal settings, sometimes there might be opportunity to place a colonic stent, for example, by either a colorectal surgeon or by someone who has specialized training in the placement of these stents. And that would be a preferred approach in both the enhanced and maximal guidelines, whereas in a more basic setting, the recommendation was to perform a resection and possibly, if required, if a resection was not possible, a diversion to overcome the obstruction in that localized setting. There were other recommendations that were also important. So for example, in early-stage rectal cancer, so clinical stage 1, T1 and 0 rectal cancer, in a maximal setting, these are sort of low-risk cancers without adverse features like high-grade or involvement of lymphovascular structures. The surgical oncologist and/or colorectal surgeon might consider a local excision such as the TEM procedure, which is a transendomucoscal resection. And in basic or limited settings, we would still recommend surgery in that setting following TME principles to achieve clear margins and a good surgical outcome, because we felt that, in basic-limited settings, the skill and the equipment necessary to do a local excision may not be available. Another recommendation that might highlight the differences between basic and limited settings versus a more maximal setting is the optimal strategy for post-treatment surveillance. So this is after resection of the stage 1 to 3 colorectal cancer. What would be the best way to monitor and surveil patients? And this is the recognition that the purpose of surveillance is to identify recurrence early at a time point where the patient may still be amenable to having local regional resection or resection of the metastatic lesion to change the outcome. So the current ASCO guidelines are to perform a medical history, and physical examination, and a CEA every six months for three to five years, have an abdominal and chest CT scan, in high-risk patients, every 6 to 12 months for three years, and a colonoscopy one year after the surgery, and then every five years or so after that, as indicated, up to age of 75. And that's what we recommended in the maximal and enhanced settings. But in a more basic setting, the recommendation was similarly medical history and physical exam every six months for three years, a CEA every six months for three years, a chest X-ray and abdominal ultrasound twice in the first three years, and a colonoscopy once i the first two years. And then if a colonoscopy is not available, we recommended a double-contrast barium enema or, for left-side tumors, a sigmoidoscopy to try to surveil the local regional extent of the the disease. So I think what we're trying to highlight is that we think that we can help patients for the management of localized early-stage colon cancer, both for treatment as well as for surveillance, and that these recommendations may vary a little bit in more limited settings, but with these recommendations, we can provide the best care for patients overall. And so why is this guideline so important? And how will it change practice? I think that the guideline is really important, because we recognize that we're practicing medicine in the United States, or in Europe, or wherever you practice, but the levels of resources that are available to us are not uniform. And so we really are getting to the aspect that cancer care is a global proposition. And ASCO should reflect that. And so the intention of these resource-stratified guidelines is to try to provide guidance into the best management for the indication across the spectrum of resources that are available. Interestingly, we've also heard from many people who practice in more resource-limited settings that they can use these guidelines to sort of advocate for their own area, to say that, based on our availability, we fit in a criteria that's basic or limited, but we really want to be an enhanced setting, and lobby their governments or their local officials to say, these are areas that we can improve on to take us to the next level, literally. And finally, how will these guideline recommendations affect patients? Yeah, at the end of the day, I think it's very important that we remind ourselves that we're doing this to improve patient care overall. I think, in maximal and enhanced settings, the guidelines kind of reiterate the best practices across [INAUDIBLE] of guidelines that were reviewed. So I think that's a very important thing. And they unify the treatment plan across different practices. But I think most importantly, in basic and limited settings, it provides a benchmark for what should be done. I think, for me, one key thing was that, even in basic and limited settings, we don't want to compromise oncology principles for a surgical resection. You know, it's not appropriate to just resect the tumor but leave some tumor behind to relieve an obstruction. We still need to manage that appropriately. And that is the expectation in a basic setting, for example. So I think that, overall, wherever you are, this guideline provides recommendations to help manage the patient across the resources that are available to you. I think that's very important, because we live in a heterogeneous environment where resources are not uniform across the world. Great, thank you for your discussion of this important guideline. And thank you for your time today, Dr. Shah. Oh, it's my pleasure. Thanks for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Jennifer Griggs from the University of Michigan, senior author on "Adjuvant Endocrine Therapy for Women with Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update." Thank you for being here, Dr. Griggs. And thank you for the opportunity to talk about this focused update to the guidelines on extended adjuvant therapy. I would, of course, like to thank all my co-authors in the ASCO guidelines team for their contribution to this effort. So first, can you give us a general overview of what this guideline covers and their research which informed this focus update? Yes. First of all, the goal of the guideline was to give an update to the previous guidelines on this topic. And we specifically focused on extended adjuvant therapy. In particular, the aromatase inhibitors in women who had completed five years of adjuvant endocrine therapy. And it goes without saying, but it's worth reminding our listeners that the guideline is restricted only to post-menopausal women with hormone receptor-positive breast cancer. And, of course, our guidelines are only as good as the data upon which we rely. So for this guideline, six phase III randomized controlled trials met the pre-specified eligibility criteria for the updated systematic review and provide the evidence base for the guideline recommendations on the duration of aromatase inhibitor therapy. Each of the trials used the standard doses of the drugs that we use in practice today. So I'm not going to say the doses of each of the medications. So I'm going to go briefly over those six trials and just describe them so everybody's up to date with how the studies were designed. So briefly, the first trial I'll describe is MA17R, which compares letrozole to placebo for five years in over 1,900 women who had already received 4.5 to six years of adjuvant therapy with an AI, proceeded in most women by treatment with tamoxifen. The second study is NSABP B-42. And this also compares letrozole to placebo in nearly 4,000 women who'd completed five years of endocrine therapy with either five years of an aromatase inhibitor or up to three years of tamoxifen followed by an aromatase inhibitor, for a total of five years. The third study that we looked at is the DATA trial, which stands for the Different Durations of Adjuvant Anastrozole Therapy. This trial compared six years of adjuvant anastrozole with three years of adjuvant anastrozole in over 1,600 women after two to three years of adjuvant tamoxifen. The fourth trial out of the six is the IDEAL trial, the Investigation on the Duration of Extended Adjuvant Letrozole. This study randomized over 1,800 women to either 2 and 1/2 or five years of letrazole after five years of tamoxifen, an AI, or a combination in sequence of tamoxifen and an AI. So very similar study designs. The fifth study is the ABCSG-16 trial, the Austrian Breast Cancer Study Group Trial 16, which randomized nearly 3,500 women following four to six years of adjuvant therapy with tamoxifen and AI or a sequence of tamoxifen and then an AI, to either two or five years of anastrozole as extended therapy. And finally, the study of letrozole extension, or the SOLE trial, randomized over 4,800 women with node-positive breast cancer who had completed five years of adjuvant endocrine therapy to receive either continuous letrozole for five years or five years of an intermittent schedule of letrozole given nine months on and three months off in years one to four and on continuously for a year or five. So I know that's a lot to take in, but I do think it was important for our audience to understand the six trials that were included. These were all large studies, randomized, and patients had completed five years of adjuvant endocrine therapy. And then, were randomized either to placebo or different durations of an aromatase inhibitor or a placebo. For all of these studies, it's important to know that the primary outcome was disease-free survival. Overall survival and adverse events where secondary outcome. Great. So given that research and those trials, what are the key recommendations for this guideline update? Five key recommendations are included in this focused update to the previous guidelines. And they are for women with node-negative breast cancer, extended adjuvant aromatase inhibitor therapy can be offered for up to a total of five years of adjuvant therapy. Recommendations are based on considerations of recurrence risk using our usual established prognostic factors. However, since the recurrence risk is lower, the benefits are likely narrower in node-negative patients. The guidelines panel recommends that women with low-risk, node-negative tumors should not routinely be offered extended adjuvant therapy. Now, that might sound vague. We did not make recommendations using genomic profiling results because we don't have sound data to support such views that we felt were strong enough to integrate genomic testing results. Our second recommendation is that women with node-positive breast cancer should be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine therapy. And that means combined tamoxifen and aromatase endocrine therapy. That's the total that we meant to recommend. Third recommendation is that women receiving extended adjuvant endocrine therapy should receive no more than 10 years of total treatment. The fourth recommendation is when given as prevention of secondary or contralateral breast cancer, the risk of second breast cancers based on prior therapy should inform the decision to pursue extended therapy. So what this means is specifically, a woman who has had a bilateral mastectomy will not reap the benefit of preventative therapy with endocrine therapy. The fifth recommendation is that extended therapy carries ongoing risks and side effects, and these should be weighed against the potential absolute benefits of longer treatment in a shared decision-making process between the clinical team and the patient. Specifically, to date, none of the studies have shown improvement in overall survival with longer duration aromatase inhibitor therapy. As such, the recommendations, therefore, an extended adjuvant AI therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers. So why is this guideline so important and how will it change practice? The importance of this guideline rests in the fact that it supports what many clinicians and patients are already doing in practice. The second is it recommends against durations of endocrine therapy longer than 10 years in the absence of data supporting such a practice. So it's our thought that doctors and patients and other care providers, nurse practitioners, physician assistants, primary care doctors, are already practicing what we're recommending, and it supports doing so. And the second is that for those providers and patients who aren't sure that 10 years is enough, this guideline suggests that 10 years is sufficient. We don't have any data supporting giving more than 10 years. And the third recommendation is that this guideline really supports the need for shared decision-making, given the absence of data supporting an improvement in overall survival. So finally, since you did mention shared decision-making, how does this guideline recommendation affect patients? Well, the panel strongly believes that the tailored decision-making process is key in the decision to recommend extended adjuvant therapy. So tailoring on disease factors plays a role in the recommended duration of therapy. Obviously, since we stratified by high-risk and low-risk and what treatment's been received specifically. And if a woman's had bilateral mastectomy, she's not going to benefit from the risk reduction that's achieved with giving somebody extended therapy. But in addition to disease factors, patient preferences and tolerance of therapy should inform clinician and patient decision-making. Again, since none of the studies have shown improvement in overall survival with longer duration of AI therapy, patients and their medical providers need to make decisions based on an awareness that the benefits include, specifically prevention of distant recurrence and prevention of second breast cancers. And the importance of those benefits is going to vary according to a patient and how she views her life going forward and how bad her side effects have been, how well she tolerates the therapy. From my own personal point of view, as a breast oncologist, I believe two things. Number one, we should provide aggressive support for managing symptoms in patients who are most likely to benefit from extended therapy. That is, we should not stop therapy early if she is very likely to benefit if we haven't maximized control of her symptoms. There are many things we can do to improve symptoms and we shouldn't just stop therapy because she's not tolerating treatment if we haven't done the most that we can to improve her quality of life and her symptoms. Conversely, my hope is that we are not doggedly persisting in recommending prolonged therapy in a patient who has a fear of recurrence but who has little to gain from extended therapy. In the latter case, high quality information support is more therapeutic than extended therapy with a medication that's proven, in randomized controlled trials and in her own personal experience, to decrease her quality of life with marginal, if any, medical benefit. Thank you so much for the overview of this guideline today and thank you for your time. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast Series. Is my name Shannon McKernin and today, I'm interviewing Dr. Elena Stoffel from the University of Michigan, lead author of "Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion.” Thank you for being here today, Dr. Stoffel. I'm delighted to join you. So first, can you tell us what a professional clinical opinion is and why this topic is so important to ASCO? Well, a provisional clinical opinion is a statement that ASCO puts out when we are seeing trends that are relevant to the care of our patients but that may not necessarily have the level of evidence needed to include in a true clinical guideline. This particular provisional clinical opinion that deals with the management of patients with pancreatic cancer and their families is based on some new data that has been published regarding the prevalence of inherited factors influencing pancreatic cancer risk. So what are the key statements of this Provisional Clinical Opinion or also known as a PCO? This particular provisional clinical opinion, which is about just the inherited susceptibility to pancreatic cancer, was prompted by several recent publications, which found that the prevalence of genetic predisposition among patients with pancreatic cancer was much higher than we had originally anticipated. And this is relevant because in talking about pancreatic cancer as one of the deadliest cancers in both in the United States and worldwide, we are very interested in finding ways to reduce the morbidity from this cancer to patients and their families. And this particular provisional clinical opinion addresses the role that genetic risk assessment should have in the care of pancreatic cancer patients and also the role for clinical genetic testing, as well as the risks and benefits of pancreatic cancer screening for at risk family members. What considerations are there for having these conversations with patients and their families? Well, many times when we see families affected with cancer, one of the questions they have is what is the likelihood that this will happen to other individuals in our family and what can we do to prevent cancers in other family members. And I think what's important here is that review of the data from multi-gene panel genetic testing in unselected individuals diagnosed with pancreatic cancer identified pathogenic germline variants in 1 out of every 10 individuals. And this is really important because when you think about it, if 1 out of every 10 patients with pancreatic cancer develop their cancer in the setting of a genetic predisposition syndrome, this has tremendous implications for management both for them as well as for their family members. One of the most common inherited cancer syndromes identified in families affected with pancreatic cancer is hereditary breast ovarian cancer associated with mutations of BRCA1 and BRCA2. As you know, there are definite screening recommendations we make for individuals who carry these genetic alterations. And certainly if a family member is diagnosed with a genetic alteration, then that has an impact for cancer screening and management. Furthermore, there are emerging data about the utility of pancreatic cancer screening in high risk individuals. And while there's still some controversy about how to screen individuals at risk for pancreatic cancer, certainly there are some emerging data suggesting that this may have a role for early detection. And finally, the panel included a discussion section on the limitations of the research and future directions. So what are the key points of this section? I think that what we're learning is with genetic testing, and particularly with multi-gene panel testing, we are we often find unexpected results. Certainly variants of uncertain significance are not uncommon when multi-gene panel tests are used. And being able to interpret the clinical significance of some of these genetic test results can pose some challenges, especially for clinicians who don't have specific expertise in genetics. Certainly being able to deal with the volumes of patients who need genetic testing who are also battling pancreatic cancer, we want to make sure that we have the resources to be able to offer genetic testing to everyone who needs it. And finally, in talking about screening for pancreas cancer, while there are some studies that have demonstrated that screening with MRIs and/or endoscopic ultrasounds has led to early detection and down staging of cancers in some cases, larger studies are needed to be able to refine more specifically who and how to screen individuals at risk for pancreas cancer. Great. Thank you so much for taking your time today to discuss this PCO with us, Dr. Stoffel. Thank you very much for having me. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer the show to a colleague.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Scott Morgan from the Ottawa Hospital and University of Ottawa, lead author on "Hypofractionated Radiation Therapy for Localized Prostate Cancer: an ASTRO, ASCO, and AUA Evidence-Based Guideline.” Thank you so much for being here today, Dr. Morgan. It's my pleasure, Shannon. I'm happy to take part in the podcast and hopefully share the highlights of the guideline with your listeners. So first, can you give us a general overview of what this guideline covers? Yeah. So the guideline covers really hypofractionated external beam radiation therapy, which is a treatment for localized prostate cancer, and for the non-radiation oncology folks in your audience, I think it's important to begin by placing the guideline sort of in its context and going over some of the terminology that we use as radiation oncologists. So external beam radiotherapy, it's a standard treatment-- standard local treatment option for men with localized prostate cancer. It gives outcomes which are really equivalent to those of radical prostatectomy or brachytherapy, which are the other two standard local treatment options. And traditionally, it's given in small daily fractions over several weeks and the usual daily fraction size is 1.8 to 2 Gray per day. And this is called conventional fractionation. And that really translates into a course of about seven and a half to nine weeks of treatment. And so that total dose which is delivered in those daily treatments, five days a week, is about 76 to 80 Gray. And that's what we call conventional or standard fractionation. And there's a theoretical framework in radiation medicine and there's some evidence to accompany that that suggests that prostate cancer is quite sensitive to radiation fraction size. And just to give a brief primer, for any tissue, cancerous or non-cancerous, there's a sensitivity to fraction size and it's characterized by something called the alpha-beta ratio. And for prostate cancer, that's felt to be low compared to most other cancers, the alpha-beta ratio, and indeed, it's thought to be lower than the adjacent dose-limiting normal structure, which is the rectum. And so an implication of that is that hypofractionation, and by that we mean daily fraction size of more than 2 Gray, might improve the therapeutic ratio of radiation therapy in localized prostate cancer. Now the guideline-- and I think it's important to emphasize this-- it draws a distinction between what we call moderate hypofractionation and ultra-hypofractionation. Clearly, fraction size is a continuous variable, so any subdivision that we might make is necessarily a bit arbitrary, but it turns out that at least in clinical practice, there's been really two distinct approaches to hypofractionation that have arisen. And one of these is moderate hypofractionation and that's an approach where the fraction size is modestly higher than 2 Gray per fraction, and in the guideline, it's been defined as a fraction size between 2.4 and 3.4 Gray, whereas ultra-hypofractionation, this is defined in the guideline as a fraction size greater than 5 Gray. And it's also been referred to in the literature as extreme hypofractionation or Stereotactic Body Radiation Therapy, SBRT, or SABR, Stereotactic Ablative Radiation Therapy. But in any case, we are talking here about, with ultra-hypofractionation, with radical courses of treatment that are often delivered over as few as five fractions, often on an alternate day approach over two or two and a half weeks. And so the guideline really was largely motivated by the publication of a number of randomized trials, including four large-scale trials in the past two years that have compared conventionally fractioned radiation therapy and moderately hypofractionated radiation therapy. So that is really what stimulated the guideline, which was the evidence concerning moderately hypofractionated radiation therapy. But at the same time, there has been an increasing use in routine clinical practice that's been observed of ultra-hypofractionated radiotherapy, so the decision was made to make recommendations on it as well. So ASTRO, American Society for Radiation Oncology, in collaboration with ASCO and the AUA, convened a panel of radiation oncologists, medical physicists, urologists, radiation oncology resident, patient representative, and a systematic review of the literature was conducted and their recommendations have been made on the basis of this systematic review. So the aim was to provide recommendations on use of both moderate hypofractionation and ultra-hypofractionation, in particular with reference to oncologic outcomes, toxicity, and quality of life. So we didn't directly consider health economic endpoints, though clearly the very nature of hypofractionation is such that there are potential advantages in terms of cost and convenience for patients. And what are the key recommendations of this guideline? We separated the key recommendations into three main groups and the first set of recommendations pertains to moderate hypofractionation, and these are generally based on the highest-quality evidence. So they could be viewed as the strongest recommendations in the guideline. And the second set of recommendations concern ultra-hypofractionation. They're somewhat less strong given they're based on somewhat weaker evidence. And then the third set of recommendations relate to some of the technical aspects of the planning and delivery of hypofractionated radiation therapy. So, dealing with the moderate hypofractionation recommendations first, arguably the most important recommendation of the guideline is that the panel has recommended that in patients with localized prostate cancer who are candidates for external beam radiation therapy, moderate hypofractionation should be offered. And this is graded as a strong recommendation. It's based on high-quality evidence and it applies to patients across all risk groups. So it applies to patients with low-risk prostate cancer who require active treatment or who have declined active surveillance and it also applies to patients with intermediate-risk or high-risk localized prostate cancer. And why really does it apply to all these groups? It's essentially because these groups are well-represented in the trials of moderate hypofractionation. And the trials have shown that moderate hypofractionation really gives similar outcomes in terms of efficacy to conventional fractionation. Now one caveat I guess that I should say is that the trials generally only looked at radiation therapy to the prostate rather than radiation therapy to the prostate as well as the pelvic lymph nodes. So the panel's recommendations regarding moderate hypofractionation don't apply to the scenario where the clinician has decided to include the pelvic lymph nodes in the radiation therapy volume. The panel also made recommendations with respect to toxicity and quality of life, and specifically, they did recommend that men should be counseled about a small increased risk of acute gastrointestinal toxicity, typically rectal toxicity, with moderately hypofractionated radiation therapy. And they should also be counseled that moderately hypofractionated radiation therapy has a similar risk of late GI toxicity and also has a similar risk of both acute and late GU toxicity compared to conventional fractionation. The only difference was seen in acute GI toxicity. And I think it's probably worth dwelling on this a little bit more. Probably the most granular data on acute GI toxicity comes from the CHHiP trial. This was a trial from the UK. It was far and away the largest randomized trial of moderate hypofractionation versus conventional fractionation. And they followed the amplitude of GI toxicity very carefully over the short and long term and what they did found was that in the early weeks, there was greater peak acute GI toxicity with moderate hypofractionation, but this difference had really disappeared by about 18 weeks after the start of radiotherapy. So within a few months, there was no difference, and afterwards, there was no consistent difference in long-term GU or GI toxicity across these trials. Now I guess I should mention that, at the current time, that the median follow-up of most of these trials is between five and six years, so arguably, the last word hasn't been written. The panel also offered conditional recommendations on particular moderate hypofractionation regimens. There were multiple different regimens that were evaluated but most were not compared head-to-head. And the panel preferred two particular regimens-- 60 Gray and 20 fractions over four weeks or 70 Gray and 28 fractions over five and a half weeks, as these were the two regimens that were evaluated in the largest populations. And of these two, likely the strongest evidence supports 60 Gray and 20 fractions, given it was used in two different trials and it was used across all risk groups and with or without concomitant hormonal therapy. So those were the recommendations regarding moderate hypofractionation. So moving to ultra-hypofractionation, again, this is talking about fraction size of at least 5 Gray, typically a course of as few as five fractions over perhaps two or two and a half weeks. I think it's important to say that, at the time we were preparing this guideline, there were no published efficacy or toxicity data from randomized trials comparing ultra-hypofractionation and conventional fractionation. So the strengths of the recommendations made by the panel is correspondingly lower than was the case for moderate hypofractionation. But having said that, there are several prospective non-randomized studies that have been published and have documented safe delivery of ultra-hypofractionation for appropriately-selected patients and pretty good biochemical control and low toxicities have been observed in these studies. But again, relatively few have follow-up beyond five years. So what the panel recommended was that in men with low-risk prostate cancer-- and the bulk of the data to date for ultra-hypofractionation has been in this group-- panel conditionally recommended that in those who decline active surveillance and choose active treatment with radiation therapy, that ultra-hypofractionation may be offered as an alternative to conventional fractionation. Again, this is a conditional recommendation. In men with intermediate-risk prostate cancer, the panel has conditionally recommended that ultra-hypofractionation may be offered as an alternative to conventional fractionation but it's strongly recommended in this group that these patients be treated as a part of a clinical trial-- and there are several clinical trials ongoing-- or as part of the multi-institutional registry. And then finally, in patients with high-risk localized prostate cancer, there was really insufficient comparative evidence for the panel to suggest offering this outside of a clinical trial or outside of a registry. Regarding particular regimens, that the panel again made a conditional recommendation that a schedule of 35 Gray to 36.25 Gray and five fractions delivered to the planning target volume could be offered and that it recommended against consecutive daily treatments for this schedule. So I think it's again important to note that compared to moderate hypofractionation, the ultra-hypofractionation literature is really substantially less mature and it is evolving rapidly. And therefore, a short-term update of this guideline to address new data pertaining specifically to ultra-hypofractionation is likely going to be necessary. And then I mentioned there was a third set of recommendations and these pertain to the technical aspects of planning and delivering radiation therapy. And these probably are not of core interest to your audience, but briefly, the guideline recommends that in the planning of hypofractionated radiotherapy, that normal tissue constraints and target volumes derive from published reference standards the use and that image guidance and intensity modulation at one form or another are recommended in delivering hypofractionated radiotherapy. Great. Thank you for the overview of those guideline recommendations. So why is this guideline so important and how will it change practice? Yeah. I guess the first point to make is that the guideline potentially can inform the care of a very large number of patients. Across North America, about 200,000 patients a year are diagnosed with prostate cancer and its far and away that the most prevalent non-dermatologic cancer in men and it's the third-leading cause of cancer death in men, at least in North America. So the vast majority of those 200,000 men are diagnosed with localized disease at the time of presentation and therefore they're potentially treatable with radiation therapy and therefore the guideline is relevant to these patients. Prior to the publication of the trials that motivated this guideline, the overwhelming majority of these men who chose external beam radiotherapy as their primary treatment have been treated with conventionally fractionated therapy. In other words, seven and a half to nine weeks of treatment. And already, since the publication of these trials-- the trials of moderate hypofractionation-- we're talking really about moderate hypofractionation because I think that is where the guideline will have its impact, at least in the short term. In the jurisdiction where I practice in Canada, practice has already substantially changed in light of these trials, and I think a large majority of patients with localized prostate cancer choosing external beam radiation therapy are now typically being treated with a moderately hypofractionated approach, typically a four-week schedule. So it will be interesting to see if a similar change is occurring or will occur over time in the United States, particularly informed or potentially informed in part by this guideline. And then finally, with respect to ultra-hypofractionation, I think again I have to note that this is a very dynamic space in terms of evidence and there are a number of large-scale trials looking at ultra-hypofractionation and comparing it to either conventional fractionation or moderate hypofractionation that are in progress or near to reporting. And so again, an update of the guideline in the short-term as data emerges from these studies will likely be important and it may ultimately influence practice as well on a large scale. And finally, how will these guideline recommendations affect patients? So I think in the short term, that the recommendation that has the potential to impact patients in the greatest way is the recommendation regarding moderate hypofractionation. And the guideline really recommends that this is a management approach that substantially reduces the treatment burden without compromising treatment efficacy and without increasing the risk of long-term side effects. So in my view, the move to moderately hypofractionated radiation therapy is a win for patients with localized prostate cancer who choose radiation therapy as their primary treatment modality. And so moderate hypofractionation really represents about a halving of the overall treatment time in some patients. And those who live, for example, in rural or remote areas and who need to travel considerable distance to have their treatment, a halving of treatment time is significant. But I think even more generally, halving of treatment time is significant for patients regardless of where they live. And clearly there are also benefits potentially in terms of cost and also benefits in terms of for the health care system but those really weren't specifically studied in the guideline. Great. Thank you so much for your time today, Dr. Morgan, and thank you for your work on this important guideline. My pleasure, Shannon, and thank you for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Paul Celano from the greater Baltimore Medical Center, lead author on "Safe Handling of Hazardous Drugs: ASCO Standards." Thank you for being here today, Dr. Celano. Thank you for having me. I'm certainly glad to talk about these standards. They're very important to our employees and our patients. So first I want to make the distinction that this publication is not a guideline like we usually cover on this podcast. So can you tell us what standards are and how they differ from guidelines? Well, guidelines really are intended to guide practitioners around recommended care options. They give obviously a lot of latitude to clinical judgment and circumstances. Standards, on the other hand, are really meant primarily for the organization of care and are intended to have a higher level of obligation to help drive either practice or policy or even legislative efforts. So that's really the distinction. And what are the standard statements that are made by ASCO in this publication? The publication really is about safe handling of hazardous drugs. This all came about is because recently there have been a number of national guidelines or standards that have been offered by other organizations, but not specifically oncology or certainly ASCO or the ASCO organization. We felt a need to address the standards that have been put out on the basis of the evidence, so that best practices can be offered. Initially, we did collaborate with other societies, such as the Oncology Nursing Society and the Hematology Oncology Pharmacy Association. That was really the impetus behind making sure that we are, in a sense, congruent with standards that are already being published and discussed, but also to also place in our interpretation of these standards so that they're based on the best evidence that's available. And what qualifying statements are there to note about these standards? Well, I think the best way to look at these standards is there has been recently published or offered what's been called the UST 800 standards, which really incorporate other previous standards by the Pharmacy Association as well as OSHA, the Occupational Safety and Health Association, as well as NIOSH, the American Society of Hospital Pharmacists, Oncology Nursing, etc. So there's a lot of standards that have been offered. And in fact, the ASCO review of this really in a sense agrees with many of the standards that have already been published and offered-- types of exposures, the responsibilities of personnel handling the drugs, the personal protective equipment, how we communicate the hazardous drugs, the training of compounding personnel, how the drugs are dispensed and even transported. So there's lots of things that we really do agree with. I think it's also important to understand that the objectives of this is really to protect personnel and the environment to make sure the standards apply to all personnel who compound hazardous drugs and preparations, all places where hazardous drugs are prepared and stored, transported and administered. So that's really a key part of this. These are a comprehensive program really to prevent worker environmental exposure and to provide the most practical safety environment for all involved. So finally, why are these standards so important? And how will they affect practice? Well, they effect practice in many ways. I mean, the key thing is making sure that our employees, meaning the nurses, pharmacy, the technicians, really everyone involved that they're not unduly exposed to these hazardous drugs. And so that's really the key thing that we're all trying to achieve by this. Now, what really makes the sort of ASCO standards somewhat different or the things that we came into a contention with has to do with the differences that ASCO has come up with in contrast to some of the other standards. And these have to do with really four main areas within these standards. They have to do with medical surveillance, external ventilation, closed system transfer devices, and also proper assignment of our personnel while they may have either trying to conceive or pregnant or nursing. So those areas that in our review, the ASCO review, have come under some question. As an example, medical surveillance, there in some of the standards offered-- not ASCO's-- that there's a number of medical surveillance procedures that have been elucidated, that really we find, number one, have really not any proven value for our employees and generate a lot of confusion in terms of how this process is supposed to be done. Obviously, if one of our employees has some undue exposure, such as a spill of chemotherapy or even just have flat out a concern, then obviously those things will be clearly investigated. But to have general medical surveillance of all employees, really we did not feel was of great value. But also further, we really feel that this is an area where more research needs to be done to better elucidate really what should this process look like and what value are we providing to our employees. Another aspect of this is the use of what are called closed system transfer devices. Currently, there are a number of these devices available that there is interestingly no standard way that these devices have been evaluated. And so it's hard to recommend one device over another, because there is no standards for which they're really being compared. And there certainly have been no studies looking at really any form of health outcome that really help us to direct this to how best to use these devices. And so really, a lot of these objections are more around let's do things in an evidence-based way so we can better know how to best direct our practices. Another area of concern in terms of ASCO standards have been the implementation of external ventilation in either containment secondary engineering controls or other situations. And the challenges is that HEPA filters are probably appropriate for collecting solid or aerosolized particles, but don't capture vaporized drugs. But there's little data available on the ability of hazardous drugs to vaporize within the workplace environment and what those hazards really are. And so again, it's is a call for more research to have an optimal environment for preparing these drugs and without having to place undue burdens in terms of external ventilation. Another area is options for alternative duties for workers who are actively trying to conceive or are pregnant or breastfeeding. And these we recognize can be special burdens to small practices looking to implement alternative duty programs. There is a lot of controversy regarding the potential level of risk that really these workers really have. And basically our stance has been that we should have a policy that identifies alternative work options for workers who are trying to conceive, are pregnant or are breastfeeding, and that this information needs to be conveyed to these employees at the time of their hire so they understand what their risks are and what their options are within the workplace. Again, trying to make sure everyone is well informed and aware of what the work environment they're in and as their life circumstances change what they can do to change with this. I think the key is that we all feel that this is an area that we should have continued research on. And our standard, certainly ASCO's standards will continue to evolve as more and more research and evidence becomes available. Thank you so much for taking the time to explain these standards to us today, Dr. Celano. You're welcome. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a moment to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Valerie de Haas from Princess Máxima Center for Pediatric Oncology in the Netherlands, lead author on "Initial Diagnostic Workup of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the CAP and ASH Guideline.” Thank you for being here today, Dr. de Haas. Thank you. So first, can you give us a general overview of what this guideline covers? Well, yes. The laboratory evaluation of patients who are suspected of having acute leukemia is very complex, and it has evolved significantly with the incorporation of advanced laboratory techniques. The traditional backbone of initial workup of AL, of acute leukemia, is composed of ctyomorphology, cytochemistry, immunophenotyping, and molecular cytogenetics. These techniques are the backbone of the initial diagnostic workup of acute leukemia. This is leading to risk stratification and fine tuning of the therapy by molecular signatures. The advanced molecular diagnostics, such as next-generation sequencing, has become more important in the diagnosis and in the risk stratification of acute leukemia. This guideline is meant for both pediatric and adult patients, and it was initially published in 2017. This year, we reviewed this guideline, and we have taken into account two important developments. First, since 2017, we've seen that there are major advances in molecular techniques and also that we can identify and validate new molecular markers. And those two events have contribute to a better risk stratification. And the second development is the effect that the WHO classification was revised in 2017 which also has led to new risk recoveries and refined subclassifications. So what are the key recommendations of this guideline? Well, in total, we have reviewed 27 guideline statements by the ASCO endorsement expert panelists. And discussion points are used to summarize issues that were identified from the updated literature. The ASCO expert panel determined that the recommendations from the guideline as published in 2016 are clear, thorough, and they are based upon the most relevant scientific evidences. We fully endorse the CAP-ASH guideline on initial diagnostic workup of acute leukemia. And we decided to include some discussion points according to clinical practice and according to the updated literature. In fact, we identified four categories of key recommendations. The first one is the initial diagnostics focusing on basic diagnostics and determination of risk parameters. This concerns, in total, about 11 guideline recommendations, and they give an overview of the initial workup varying from the collection of the clinical history of the patient to initial basic diagnostics by cytomorphology, flow cytometry and molecular cytogenetic analysis of peripheral blood, bone marrow, and cerebrospinal fluids. Secondly, the second category were molecular markers and MRD detection, and they were addressed by 10 of the recommendations. And these recommendations give a structural overview of the molecular and cytogenetic workup for acute lymphoblastic leukemia versus acute myeloid leukemia identifying different prognostic markers. Also, the detection of MRD is taken into account in this recommendation. There is a major difference between children and adults, and this part is given most attention in the discussion part as the developments have been major during the past few years. The third one is the context of referral to another institution with expertise in the management of acute leukemia. This is addressed by four recommendations, emphasizing the point that referral to an institution with specific expertise is of major importance for the central workup of acute leukemia. And finally, the final reporting and report keeping is reflected in three recommendations, mainly supporting conclusions from 2017 which were describing the fact that the complete report with basic diagnostics in one central report should be available within 48 to 72 hours. And this should be followed by complete, final, comprehensive report in one or two weeks. So can you tell us about those discussion points that were made and why the panel decided to include these? The discussion points include mostly issues regarding diagnostics that involve flow cytometry and molecular techniques as addressed in part one and two of the guidelines. We think that the cytomorphologic assessment is essential for initial diagnosis of acute leukemia. Multicolor flow cytometry using 8 to 10 colors has led to a better distinction between myeloids, lymphoid, and mixed lineage blast origin. Even when the number of cells are limited, for instance in CNS involvement, fine needle aspirate of extramedullary leukemic infiltration, or skin biopsy for leukemic cutis. Also, it was suggested to better assess the central nervous system involved in leukemia. The expert panel recommends the immunophenotyping studies as an additional detection technique next to the cytomorphological examination of cytospins and particularly for those with a low level involvement of acute leukemia that cannot be well addressed by a morphologic examination only. The TDT immunohistochemistry staining of cytospins has alternatively been used for detection of CNS disease in AML and evaluation of CSF by multicolor flow cytometry has been recently adopted in some centers. Flow cytometry, using at least six, but we now use in some laboratories, even 8 to 10 colors has led to a much more specific in tentative diagnosis. And this has improved the detection of CNS involvement. The use of molecular tools, for instance, polymerase change reaction, PCR, NGS for low-level CSF involvement is still under study, and therefore, we did not recommend this in our discussion. Regarding the molecular markers and MRD detection, the discussion here was mainly based upon the results of translational research supported by better molecular detection techniques. And those molecular diagnoses have been developing in the past few years with the inclusion of many more molecular markers. And they included one of the key diagnostic criteria in the revised WHO classification, which was revised in 2017. And we made substantial changes that have been made in the ASH-CAP guidelines concerning molecular diagnostics. Those newly identified targets by advanced molecular techniques give possibilities for better risk stratification. Some examples of better molecular characterization of acute lymphoblastic leukemia are, for instance, additional testing for MLL translocations. Furthermore, we can look in patients with T-ALL for NOTCH1, and FBXW7 mutations. The Ikaros family zinc finger gene, the IKZF1 gene is frequently deleted in adults as well in children with B-ALL. And it was shown to have an independent prognostic significance and was also associated with poor clinical outcome. In the current text of the current risk that the protocols IKZF1 should be regularly included in the screening panels for all ALL patients. If we look for examples for better characterization of AML, acute myeloid leukemia, we have found an increasing number of additional cytogenetic aberrations, like for instance FLT3 ITD which is associated with poor outcome. Another example is appropriate mutational analysis for kids, which can be detected both in adult patient as pediatric patients with a confirmed core binding factor acute myeloid leukemia. So this is myeloid leukemia with a translocation A21, RUNX1, or inversion 16. This recommendation is very strong in adults, whereas in children, this prognostic fact impact remains unclear. So there have been proven several publications which refer to a similar prognosis for children and others who refer to a poor prognosis in comparison to known mutated genes. So we suggest to test for this mutation in adults, especially, but also in children to learn from it. Finally, emerging evidence supports molecular studies as principle test for monitoring minimal residual disease of acute leukemia. And there are several key molecular markers that are included in the initial workup, which will be carried on for monitoring MRD, for instance, PML- RAR-alpha, RUNX1-RUNXT1, CBFB-MYH11, and NPM1, CEBP-alpha and others. Beside those aforementioned markers, it's very important to screen for other molecular markers that have predictive or prognostic value in the individual. And it is possible to use them for MRD. We have found a recent consensus from the European Leukemia Net MRD Working Group, who was proposing that for detection of molecular MRD, and they refer the RT PCR platform to NGS and digital PCR platforms. Although all those molecular techniques have been developed very quickly and it is very tempting to use them for initial diagnostics, currently, not all laboratories will have all those techniques available. So the expert panel strongly advises understanding to make distinction between diagnostic that are needed in the first phase to start treatment and subsequently, treatment stratification, in contrast to the usual dose findings in a broader research. For instance, available karyotyping, FISH, PCR techniques, if possible, NGS can be used in the initial start of treatment, whereas techniques like whole exome sequencing, whole genome sequencing, RNA sequencing, and epigenomic studies are meant for a broader research. And finally, how will these guideline recommendations affect patients? Well, in the end, the patients will receive better and especially, more personalized treatment. If we have results available within two weeks from diagnosis, it will be possible to better identify which basis will better benefit from more intensified and more personalized treatment, whereas others may need less intensive treatment with less toxicity. If you use traditional techniques to do this supported by molecular techniques like karyotyping, FISH, and PCR techniques, and in the end, following MRD to see which patients are responding to treatment, MRD detection will help to identify these patients and stratify them finally to the best treatment. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. de Haas. OK. Thanks a lot. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Valerie de Haas from Princess Máxima Center for Pediatric Oncology in the Netherlands, lead author on "Initial Diagnostic Workup of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the CAP and ASH Guideline.” Thank you for being here today, Dr. de Haas. Thank you. So first, can you give us a general overview of what this guideline covers? Well, yes. The laboratory evaluation of patients who are suspected of having acute leukemia is very complex, and it has evolved significantly with the incorporation of advanced laboratory techniques. The traditional backbone of initial workup of AL, of acute leukemia, is composed of ctyomorphology, cytochemistry, immunophenotyping, and molecular cytogenetics. These techniques are the backbone of the initial diagnostic workup of acute leukemia. This is leading to risk stratification and fine tuning of the therapy by molecular signatures. The advanced molecular diagnostics, such as next-generation sequencing, has become more important in the diagnosis and in the risk stratification of acute leukemia. This guideline is meant for both pediatric and adult patients, and it was initially published in 2017. This year, we reviewed this guideline, and we have taken into account two important developments. First, since 2017, we've seen that there are major advances in molecular techniques and also that we can identify and validate new molecular markers. And those two events have contribute to a better risk stratification. And the second development is the effect that the WHO classification was revised in 2017 which also has led to new risk recoveries and refined subclassifications. So what are the key recommendations of this guideline? Well, in total, we have reviewed 27 guideline statements by the ASCO endorsement expert panelists. And discussion points are used to summarize issues that were identified from the updated literature. The ASCO expert panel determined that the recommendations from the guideline as published in 2016 are clear, thorough, and they are based upon the most relevant scientific evidences. We fully endorse the CAP-ASH guideline on initial diagnostic workup of acute leukemia. And we decided to include some discussion points according to clinical practice and according to the updated literature. In fact, we identified four categories of key recommendations. The first one is the initial diagnostics focusing on basic diagnostics and determination of risk parameters. This concerns, in total, about 11 guideline recommendations, and they give an overview of the initial workup varying from the collection of the clinical history of the patient to initial basic diagnostics by cytomorphology, flow cytometry and molecular cytogenetic analysis of peripheral blood, bone marrow, and cerebrospinal fluids. Secondly, the second category were molecular markers and MRD detection, and they were addressed by 10 of the recommendations. And these recommendations give a structural overview of the molecular and cytogenetic workup for acute lymphoblastic leukemia versus acute myeloid leukemia identifying different prognostic markers. Also, the detection of MRD is taken into account in this recommendation. There is a major difference between children and adults, and this part is given most attention in the discussion part as the developments have been major during the past few years. The third one is the context of referral to another institution with expertise in the management of acute leukemia. This is addressed by four recommendations, emphasizing the point that referral to an institution with specific expertise is of major importance for the central workup of acute leukemia. And finally, the final reporting and report keeping is reflected in three recommendations, mainly supporting conclusions from 2017 which were describing the fact that the complete report with basic diagnostics in one central report should be available within 48 to 72 hours. And this should be followed by complete, final, comprehensive report in one or two weeks. So can you tell us about those discussion points that were made and why the panel decided to include these? The discussion points include mostly issues regarding diagnostics that involve flow cytometry and molecular techniques as addressed in part one and two of the guidelines. We think that the cytomorphologic assessment is essential for initial diagnosis of acute leukemia. Multicolor flow cytometry using 8 to 10 colors has led to a better distinction between myeloids, lymphoid, and mixed lineage blast origin. Even when the number of cells are limited, for instance in CNS involvement, fine needle aspirate of extramedullary leukemic infiltration, or skin biopsy for leukemic cutis. Also, it was suggested to better assess the central nervous system involved in leukemia. The expert panel recommends the immunophenotyping studies as an additional detection technique next to the cytomorphological examination of cytospins and particularly for those with a low level involvement of acute leukemia that cannot be well addressed by a morphologic examination only. The TDT immunohistochemistry staining of cytospins has alternatively been used for detection of CNS disease in AML and evaluation of CSF by multicolor flow cytometry has been recently adopted in some centers. Flow cytometry, using at least six, but we now use in some laboratories, even 8 to 10 colors has led to a much more specific in tentative diagnosis. And this has improved the detection of CNS involvement. The use of molecular tools, for instance, polymerase change reaction, PCR, NGS for low-level CSF involvement is still under study, and therefore, we did not recommend this in our discussion. Regarding the molecular markers and MRD detection, the discussion here was mainly based upon the results of translational research supported by better molecular detection techniques. And those molecular diagnoses have been developing in the past few years with the inclusion of many more molecular markers. And they included one of the key diagnostic criteria in the revised WHO classification, which was revised in 2017. And we made substantial changes that have been made in the ASH-CAP guidelines concerning molecular diagnostics. Those newly identified targets by advanced molecular techniques give possibilities for better risk stratification. Some examples of better molecular characterization of acute lymphoblastic leukemia are, for instance, additional testing for MLL translocations. Furthermore, we can look in patients with T-ALL for NOTCH1, and FBXW7 mutations. The Ikaros family zinc finger gene, the IKZF1 gene is frequently deleted in adults as well in children with B-ALL. And it was shown to have an independent prognostic significance and was also associated with poor clinical outcome. In the current text of the current risk that the protocols IKZF1 should be regularly included in the screening panels for all ALL patients. If we look for examples for better characterization of AML, acute myeloid leukemia, we have found an increasing number of additional cytogenetic aberrations, like for instance FLT3 ITD which is associated with poor outcome. Another example is appropriate mutational analysis for kids, which can be detected both in adult patient as pediatric patients with a confirmed core binding factor acute myeloid leukemia. So this is myeloid leukemia with a translocation A21, RUNX1, or inversion 16. This recommendation is very strong in adults, whereas in children, this prognostic fact impact remains unclear. So there have been proven several publications which refer to a similar prognosis for children and others who refer to a poor prognosis in comparison to known mutated genes. So we suggest to test for this mutation in adults, especially, but also in children to learn from it. Finally, emerging evidence supports molecular studies as principle test for monitoring minimal residual disease of acute leukemia. And there are several key molecular markers that are included in the initial workup, which will be carried on for monitoring MRD, for instance, PML- RAR-alpha, RUNX1-RUNXT1, CBFB-MYH11, and NPM1, CEBP-alpha and others. Beside those aforementioned markers, it's very important to screen for other molecular markers that have predictive or prognostic value in the individual. And it is possible to use them for MRD. We have found a recent consensus from the European Leukemia Net MRD Working Group, who was proposing that for detection of molecular MRD, and they refer the RT PCR platform to NGS and digital PCR platforms. Although all those molecular techniques have been developed very quickly and it is very tempting to use them for initial diagnostics, currently, not all laboratories will have all those techniques available. So the expert panel strongly advises understanding to make distinction between diagnostic that are needed in the first phase to start treatment and subsequently, treatment stratification, in contrast to the usual dose findings in a broader research. For instance, available karyotyping, FISH, PCR techniques, if possible, NGS can be used in the initial start of treatment, whereas techniques like whole exome sequencing, whole genome sequencing, RNA sequencing, and epigenomic studies are meant for a broader research. And finally, how will these guideline recommendations affect patients? Well, in the end, the patients will receive better and especially, more personalized treatment. If we have results available within two weeks from diagnosis, it will be possible to better identify which basis will better benefit from more intensified and more personalized treatment, whereas others may need less intensive treatment with less toxicity. If you use traditional techniques to do this supported by molecular techniques like karyotyping, FISH, and PCR techniques, and in the end, following MRD to see which patients are responding to treatment, MRD detection will help to identify these patients and stratify them finally to the best treatment. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. de Haas. OK. Thanks a lot. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast Series. Is my name Shannon McKernin and today, I'm interviewing Dr. Elena Stoffel from the University of Michigan, lead author of "Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion.” Thank you for being here today, Dr. Stoffel. I'm delighted to join you. So first, can you tell us what a professional clinical opinion is and why this topic is so important to ASCO? Well, a provisional clinical opinion is a statement that ASCO puts out when we are seeing trends that are relevant to the care of our patients but that may not necessarily have the level of evidence needed to include in a true clinical guideline. This particular provisional clinical opinion that deals with the management of patients with pancreatic cancer and their families is based on some new data that has been published regarding the prevalence of inherited factors influencing pancreatic cancer risk. So what are the key statements of this Provisional Clinical Opinion or also known as a PCO? This particular provisional clinical opinion, which is about just the inherited susceptibility to pancreatic cancer, was prompted by several recent publications, which found that the prevalence of genetic predisposition among patients with pancreatic cancer was much higher than we had originally anticipated. And this is relevant because in talking about pancreatic cancer as one of the deadliest cancers in both in the United States and worldwide, we are very interested in finding ways to reduce the morbidity from this cancer to patients and their families. And this particular provisional clinical opinion addresses the role that genetic risk assessment should have in the care of pancreatic cancer patients and also the role for clinical genetic testing, as well as the risks and benefits of pancreatic cancer screening for at risk family members. What considerations are there for having these conversations with patients and their families? Well, many times when we see families affected with cancer, one of the questions they have is what is the likelihood that this will happen to other individuals in our family and what can we do to prevent cancers in other family members. And I think what's important here is that review of the data from multi-gene panel genetic testing in unselected individuals diagnosed with pancreatic cancer identified pathogenic germline variants in 1 out of every 10 individuals. And this is really important because when you think about it, if 1 out of every 10 patients with pancreatic cancer develop their cancer in the setting of a genetic predisposition syndrome, this has tremendous implications for management both for them as well as for their family members. One of the most common inherited cancer syndromes identified in families affected with pancreatic cancer is hereditary breast ovarian cancer associated with mutations of BRCA1 and BRCA2. As you know, there are definite screening recommendations we make for individuals who carry these genetic alterations. And certainly if a family member is diagnosed with a genetic alteration, then that has an impact for cancer screening and management. Furthermore, there are emerging data about the utility of pancreatic cancer screening in high risk individuals. And while there's still some controversy about how to screen individuals at risk for pancreatic cancer, certainly there are some emerging data suggesting that this may have a role for early detection. And finally, the panel included a discussion section on the limitations of the research and future directions. So what are the key points of this section? I think that what we're learning is with genetic testing, and particularly with multi-gene panel testing, we are we often find unexpected results. Certainly variants of uncertain significance are not uncommon when multi-gene panel tests are used. And being able to interpret the clinical significance of some of these genetic test results can pose some challenges, especially for clinicians who don't have specific expertise in genetics. Certainly being able to deal with the volumes of patients who need genetic testing who are also battling pancreatic cancer, we want to make sure that we have the resources to be able to offer genetic testing to everyone who needs it. And finally, in talking about screening for pancreas cancer, while there are some studies that have demonstrated that screening with MRIs and/or endoscopic ultrasounds has led to early detection and down staging of cancers in some cases, larger studies are needed to be able to refine more specifically who and how to screen individuals at risk for pancreas cancer. Great. Thank you so much for taking your time today to discuss this PCO with us, Dr. Stoffel. Thank you very much for having me. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Jennifer Griggs from the University of Michigan, senior author on "Adjuvant Endocrine Therapy for Women with Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update." Thank you for being here, Dr. Griggs. And thank you for the opportunity to talk about this focused update to the guidelines on extended adjuvant therapy. I would, of course, like to thank all my co-authors in the ASCO guidelines team for their contribution to this effort. So first, can you give us a general overview of what this guideline covers and their research which informed this focus update? Yes. First of all, the goal of the guideline was to give an update to the previous guidelines on this topic. And we specifically focused on extended adjuvant therapy. In particular, the aromatase inhibitors in women who had completed five years of adjuvant endocrine therapy. And it goes without saying, but it's worth reminding our listeners that the guideline is restricted only to post-menopausal women with hormone receptor-positive breast cancer. And, of course, our guidelines are only as good as the data upon which we rely. So for this guideline, six phase III randomized controlled trials met the pre-specified eligibility criteria for the updated systematic review and provide the evidence base for the guideline recommendations on the duration of aromatase inhibitor therapy. Each of the trials used the standard doses of the drugs that we use in practice today. So I'm not going to say the doses of each of the medications. So I'm going to go briefly over those six trials and just describe them so everybody's up to date with how the studies were designed. So briefly, the first trial I'll describe is MA17R, which compares letrozole to placebo for five years in over 1,900 women who had already received 4.5 to six years of adjuvant therapy with an AI, proceeded in most women by treatment with tamoxifen. The second study is NSABP B-42. And this also compares letrozole to placebo in nearly 4,000 women who'd completed five years of endocrine therapy with either five years of an aromatase inhibitor or up to three years of tamoxifen followed by an aromatase inhibitor, for a total of five years. The third study that we looked at is the DATA trial, which stands for the Different Durations of Adjuvant Anastrozole Therapy. This trial compared six years of adjuvant anastrozole with three years of adjuvant anastrozole in over 1,600 women after two to three years of adjuvant tamoxifen. The fourth trial out of the six is the IDEAL trial, the Investigation on the Duration of Extended Adjuvant Letrozole. This study randomized over 1,800 women to either 2 and 1/2 or five years of letrazole after five years of tamoxifen, an AI, or a combination in sequence of tamoxifen and an AI. So very similar study designs. The fifth study is the ABCSG-16 trial, the Austrian Breast Cancer Study Group Trial 16, which randomized nearly 3,500 women following four to six years of adjuvant therapy with tamoxifen and AI or a sequence of tamoxifen and then an AI, to either two or five years of anastrozole as extended therapy. And finally, the study of letrozole extension, or the SOLE trial, randomized over 4,800 women with node-positive breast cancer who had completed five years of adjuvant endocrine therapy to receive either continuous letrozole for five years or five years of an intermittent schedule of letrozole given nine months on and three months off in years one to four and on continuously for a year or five. So I know that's a lot to take in, but I do think it was important for our audience to understand the six trials that were included. These were all large studies, randomized, and patients had completed five years of adjuvant endocrine therapy. And then, were randomized either to placebo or different durations of an aromatase inhibitor or a placebo. For all of these studies, it's important to know that the primary outcome was disease-free survival. Overall survival and adverse events where secondary outcome. Great. So given that research and those trials, what are the key recommendations for this guideline update? Five key recommendations are included in this focused update to the previous guidelines. And they are for women with node-negative breast cancer, extended adjuvant aromatase inhibitor therapy can be offered for up to a total of five years of adjuvant therapy. Recommendations are based on considerations of recurrence risk using our usual established prognostic factors. However, since the recurrence risk is lower, the benefits are likely narrower in node-negative patients. The guidelines panel recommends that women with low-risk, node-negative tumors should not routinely be offered extended adjuvant therapy. Now, that might sound vague. We did not make recommendations using genomic profiling results because we don't have sound data to support such views that we felt were strong enough to integrate genomic testing results. Our second recommendation is that women with node-positive breast cancer should be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine therapy. And that means combined tamoxifen and aromatase endocrine therapy. That's the total that we meant to recommend. Third recommendation is that women receiving extended adjuvant endocrine therapy should receive no more than 10 years of total treatment. The fourth recommendation is when given as prevention of secondary or contralateral breast cancer, the risk of second breast cancers based on prior therapy should inform the decision to pursue extended therapy. So what this means is specifically, a woman who has had a bilateral mastectomy will not reap the benefit of preventative therapy with endocrine therapy. The fifth recommendation is that extended therapy carries ongoing risks and side effects, and these should be weighed against the potential absolute benefits of longer treatment in a shared decision-making process between the clinical team and the patient. Specifically, to date, none of the studies have shown improvement in overall survival with longer duration aromatase inhibitor therapy. As such, the recommendations, therefore, an extended adjuvant AI therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers. So why is this guideline so important and how will it change practice? The importance of this guideline rests in the fact that it supports what many clinicians and patients are already doing in practice. The second is it recommends against durations of endocrine therapy longer than 10 years in the absence of data supporting such a practice. So it's our thought that doctors and patients and other care providers, nurse practitioners, physician assistants, primary care doctors, are already practicing what we're recommending, and it supports doing so. And the second is that for those providers and patients who aren't sure that 10 years is enough, this guideline suggests that 10 years is sufficient. We don't have any data supporting giving more than 10 years. And the third recommendation is that this guideline really supports the need for shared decision-making, given the absence of data supporting an improvement in overall survival. So finally, since you did mention shared decision-making, how does this guideline recommendation affect patients? Well, the panel strongly believes that the tailored decision-making process is key in the decision to recommend extended adjuvant therapy. So tailoring on disease factors plays a role in the recommended duration of therapy. Obviously, since we stratified by high-risk and low-risk and what treatment's been received specifically. And if a woman's had bilateral mastectomy, she's not going to benefit from the risk reduction that's achieved with giving somebody extended therapy. But in addition to disease factors, patient preferences and tolerance of therapy should inform clinician and patient decision-making. Again, since none of the studies have shown improvement in overall survival with longer duration of AI therapy, patients and their medical providers need to make decisions based on an awareness that the benefits include, specifically prevention of distant recurrence and prevention of second breast cancers. And the importance of those benefits is going to vary according to a patient and how she views her life going forward and how bad her side effects have been, how well she tolerates the therapy. From my own personal point of view, as a breast oncologist, I believe two things. Number one, we should provide aggressive support for managing symptoms in patients who are most likely to benefit from extended therapy. That is, we should not stop therapy early if she is very likely to benefit if we haven't maximized control of her symptoms. There are many things we can do to improve symptoms and we shouldn't just stop therapy because she's not tolerating treatment if we haven't done the most that we can to improve her quality of life and her symptoms. Conversely, my hope is that we are not doggedly persisting in recommending prolonged therapy in a patient who has a fear of recurrence but who has little to gain from extended therapy. In the latter case, high quality information support is more therapeutic than extended therapy with a medication that's proven, in randomized controlled trials and in her own personal experience, to decrease her quality of life with marginal, if any, medical benefit. Thank you so much for the overview of this guideline today and thank you for your time. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

TRANSCRIPT [MUSIC PLAYING] Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University. Today we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Davendra Sohal from Cleveland Clinic, lead author on Metastatic Pancreatic Cancer American Society of Clinical Oncology Clinical Practice Guideline update. Thank you for being here today, Dr. Sohal. Thanks for having me. It's a pleasure. So this update is focused on revising the recommendations on second line treatment for metastatic pancreatic cancer. Can you tell us about the studies that informed this update? Certainly. The first study is a paper published in Science on PD-1 inhibition and solid tumors. This study included 86 patients with mismatch repair deficient tumors, also known as microsatellite instability high tumors. In this study, 53% of the patients had an objective response with a disease control rate of 71% across multiple histologies. The study also included eight patients with pancreatic cancer, two of whom had complete responses with a disease control rate of 75%. This is the study that informed our recommendation for checkpoint inhibitor therapy in the second line setting. The second study is the PANCREOX trial published in JCO, which randomized patients to 5-fluorouracil or FOLFOX. With 108 patients, the primary outcome of overall survival was 9.9 months in the control 5-fluorouracil arm, and surprisingly, only 6.1 months in the FOLFOX arm. This study informed our recommendation for chemotherapy regimens in the second line setting. And what are the new and updated recommendations for second line treatment? For second line treatment of metastatic pancreatic cancer, our first recommendation now is to consider testing for mismatch repair deficiency or microsatellite instability in patients who are candidates for checkpoint inhibitors therapy. Any standard form of testing is acceptable, whether IHC or PCR or next-gen sequencing. Patients who have mismatch repair deficient or microsatellite instability high tumors should be treated with pembrolizumab given the excellent responses noted in the study we just discussed. For patients who do not meet these criteria for checkpoint inhibitor therapy, second line therapy with gemcitabine plus nab-paclitaxel can be offered to those who received FOLFIRINOX in the first line and meet other criteria for aggressive chemotherapy as detailed in the guideline. Now, for patients who receive gemcitabine plus nab-paclitaxel in the first line, fluorouracil plus nanoliposomal irinotecan is the preferred second line therapy. Where nanoliposomal irinotecan is not accessible, fluorouracil plus regular irinotecan is an acceptable alternative. As I mentioned the combination, of 5-fluorouracil plus oxaliplatin can be considered as an option in this setting, but we have noted a qualifying statement about the PANCREOX study whose results are inconsistent with the CONCORD-3 study using the same agents as the off regimen. Given these conflicting results from different studies of 5-fluorouracil plus oxaliplatin, the recommendation for its use in the second line setting has been softened. Can you also give us an overview of the recommendations from the original 2016 version that the expert panel decided were still valid? Sure. In 2016, the expert panel made recommendations which span from initial assessment through to follow up and surveillance. For every patient with metastatic pancreatic cancer, a multi-phase CT scan should be performed and baseline performance datas and comorbidities should be evaluated. Goals of care should be discussed with a multidisciplinary team, and all patients should be offered information about clinical trials. Outside of a clinical trial, standard first line treatment options include FOLFIRINOX, gemcitabine plus nab-paclitaxel, or gemcitabine alone. And the full guideline provides details on which treatment is appropriate for which patients. The panel also recommended that every patient should be offered palliative care early in their treatment. These recommendations were endorsed in the update and are reprinted in totality in the bottom line box on the second page of the article. And finally, what are some important things to note about communicating with patients with pancreatic cancer, especially in the metastatic setting? Excellent point. It is important to communicate that participation in clinical studies is strongly encouraged. These studies could include new treatments, or supportive care measures, or collection of blood and tumor samples for further research, et cetera. While chemotherapy forms the backbone of treatment, it is only one component, and that is an important point to make. The use of supportive care or palliative care is strongly encouraged for all patients with metastatic pancreatic cancer in order to maximize not just the quantity, but also the quality of life. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Sohal. Sure. Thank you very much. I'd like to thank our panel for diligent data review and dedicated discussions and the ASCO staff for all their support in producing the update. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Scott Morgan from the Ottawa Hospital and University of Ottawa, lead author on "Hypofractionated Radiation Therapy for Localized Prostate Cancer: an ASTRO, ASCO, and AUA Evidence-Based Guideline.” Thank you so much for being here today, Dr. Morgan. It's my pleasure, Shannon. I'm happy to take part in the podcast and hopefully share the highlights of the guideline with your listeners. So first, can you give us a general overview of what this guideline covers? Yeah. So the guideline covers really hypofractionated external beam radiation therapy, which is a treatment for localized prostate cancer, and for the non-radiation oncology folks in your audience, I think it's important to begin by placing the guideline sort of in its context and going over some of the terminology that we use as radiation oncologists. So external beam radiotherapy, it's a standard treatment-- standard local treatment option for men with localized prostate cancer. It gives outcomes which are really equivalent to those of radical prostatectomy or brachytherapy, which are the other two standard local treatment options. And traditionally, it's given in small daily fractions over several weeks and the usual daily fraction size is 1.8 to 2 Gray per day. And this is called conventional fractionation. And that really translates into a course of about seven and a half to nine weeks of treatment. And so that total dose which is delivered in those daily treatments, five days a week, is about 76 to 80 Gray. And that's what we call conventional or standard fractionation. And there's a theoretical framework in radiation medicine and there's some evidence to accompany that that suggests that prostate cancer is quite sensitive to radiation fraction size. And just to give a brief primer, for any tissue, cancerous or non-cancerous, there's a sensitivity to fraction size and it's characterized by something called the alpha-beta ratio. And for prostate cancer, that's felt to be low compared to most other cancers, the alpha-beta ratio, and indeed, it's thought to be lower than the adjacent dose-limiting normal structure, which is the rectum. And so an implication of that is that hypofractionation, and by that we mean daily fraction size of more than 2 Gray, might improve the therapeutic ratio of radiation therapy in localized prostate cancer. Now the guideline-- and I think it's important to emphasize this-- it draws a distinction between what we call moderate hypofractionation and ultra-hypofractionation. Clearly, fraction size is a continuous variable, so any subdivision that we might make is necessarily a bit arbitrary, but it turns out that at least in clinical practice, there's been really two distinct approaches to hypofractionation that have arisen. And one of these is moderate hypofractionation and that's an approach where the fraction size is modestly higher than 2 Gray per fraction, and in the guideline, it's been defined as a fraction size between 2.4 and 3.4 Gray, whereas ultra-hypofractionation, this is defined in the guideline as a fraction size greater than 5 Gray. And it's also been referred to in the literature as extreme hypofractionation or Stereotactic Body Radiation Therapy, SBRT, or SABR, Stereotactic Ablative Radiation Therapy. But in any case, we are talking here about, with ultra-hypofractionation, with radical courses of treatment that are often delivered over as few as five fractions, often on an alternate day approach over two or two and a half weeks. And so the guideline really was largely motivated by the publication of a number of randomized trials, including four large-scale trials in the past two years that have compared conventionally fractioned radiation therapy and moderately hypofractionated radiation therapy. So that is really what stimulated the guideline, which was the evidence concerning moderately hypofractionated radiation therapy. But at the same time, there has been an increasing use in routine clinical practice that's been observed of ultra-hypofractionated radiotherapy, so the decision was made to make recommendations on it as well. So ASTRO, American Society for Radiation Oncology, in collaboration with ASCO and the AUA, convened a panel of radiation oncologists, medical physicists, urologists, radiation oncology resident, patient representative, and a systematic review of the literature was conducted and their recommendations have been made on the basis of this systematic review. So the aim was to provide recommendations on use of both moderate hypofractionation and ultra-hypofractionation, in particular with reference to oncologic outcomes, toxicity, and quality of life. So we didn't directly consider health economic endpoints, though clearly the very nature of hypofractionation is such that there are potential advantages in terms of cost and convenience for patients. And what are the key recommendations of this guideline? We separated the key recommendations into three main groups and the first set of recommendations pertains to moderate hypofractionation, and these are generally based on the highest-quality evidence. So they could be viewed as the strongest recommendations in the guideline. And the second set of recommendations concern ultra-hypofractionation. They're somewhat less strong given they're based on somewhat weaker evidence. And then the third set of recommendations relate to some of the technical aspects of the planning and delivery of hypofractionated radiation therapy. So, dealing with the moderate hypofractionation recommendations first, arguably the most important recommendation of the guideline is that the panel has recommended that in patients with localized prostate cancer who are candidates for external beam radiation therapy, moderate hypofractionation should be offered. And this is graded as a strong recommendation. It's based on high-quality evidence and it applies to patients across all risk groups. So it applies to patients with low-risk prostate cancer who require active treatment or who have declined active surveillance and it also applies to patients with intermediate-risk or high-risk localized prostate cancer. And why really does it apply to all these groups? It's essentially because these groups are well-represented in the trials of moderate hypofractionation. And the trials have shown that moderate hypofractionation really gives similar outcomes in terms of efficacy to conventional fractionation. Now one caveat I guess that I should say is that the trials generally only looked at radiation therapy to the prostate rather than radiation therapy to the prostate as well as the pelvic lymph nodes. So the panel's recommendations regarding moderate hypofractionation don't apply to the scenario where the clinician has decided to include the pelvic lymph nodes in the radiation therapy volume. The panel also made recommendations with respect to toxicity and quality of life, and specifically, they did recommend that men should be counseled about a small increased risk of acute gastrointestinal toxicity, typically rectal toxicity, with moderately hypofractionated radiation therapy. And they should also be counseled that moderately hypofractionated radiation therapy has a similar risk of late GI toxicity and also has a similar risk of both acute and late GU toxicity compared to conventional fractionation. The only difference was seen in acute GI toxicity. And I think it's probably worth dwelling on this a little bit more. Probably the most granular data on acute GI toxicity comes from the CHHiP trial. This was a trial from the UK. It was far and away the largest randomized trial of moderate hypofractionation versus conventional fractionation. And they followed the amplitude of GI toxicity very carefully over the short and long term and what they did found was that in the early weeks, there was greater peak acute GI toxicity with moderate hypofractionation, but this difference had really disappeared by about 18 weeks after the start of radiotherapy. So within a few months, there was no difference, and afterwards, there was no consistent difference in long-term GU or GI toxicity across these trials. Now I guess I should mention that, at the current time, that the median follow-up of most of these trials is between five and six years, so arguably, the last word hasn't been written. The panel also offered conditional recommendations on particular moderate hypofractionation regimens. There were multiple different regimens that were evaluated but most were not compared head-to-head. And the panel preferred two particular regimens-- 60 Gray and 20 fractions over four weeks or 70 Gray and 28 fractions over five and a half weeks, as these were the two regimens that were evaluated in the largest populations. And of these two, likely the strongest evidence supports 60 Gray and 20 fractions, given it was used in two different trials and it was used across all risk groups and with or without concomitant hormonal therapy. So those were the recommendations regarding moderate hypofractionation. So moving to ultra-hypofractionation, again, this is talking about fraction size of at least 5 Gray, typically a course of as few as five fractions over perhaps two or two and a half weeks. I think it's important to say that, at the time we were preparing this guideline, there were no published efficacy or toxicity data from randomized trials comparing ultra-hypofractionation and conventional fractionation. So the strengths of the recommendations made by the panel is correspondingly lower than was the case for moderate hypofractionation. But having said that, there are several prospective non-randomized studies that have been published and have documented safe delivery of ultra-hypofractionation for appropriately-selected patients and pretty good biochemical control and low toxicities have been observed in these studies. But again, relatively few have follow-up beyond five years. So what the panel recommended was that in men with low-risk prostate cancer-- and the bulk of the data to date for ultra-hypofractionation has been in this group-- panel conditionally recommended that in those who decline active surveillance and choose active treatment with radiation therapy, that ultra-hypofractionation may be offered as an alternative to conventional fractionation. Again, this is a conditional recommendation. In men with intermediate-risk prostate cancer, the panel has conditionally recommended that ultra-hypofractionation may be offered as an alternative to conventional fractionation but it's strongly recommended in this group that these patients be treated as a part of a clinical trial-- and there are several clinical trials ongoing-- or as part of the multi-institutional registry. And then finally, in patients with high-risk localized prostate cancer, there was really insufficient comparative evidence for the panel to suggest offering this outside of a clinical trial or outside of a registry. Regarding particular regimens, that the panel again made a conditional recommendation that a schedule of 35 Gray to 36.25 Gray and five fractions delivered to the planning target volume could be offered and that it recommended against consecutive daily treatments for this schedule. So I think it's again important to note that compared to moderate hypofractionation, the ultra-hypofractionation literature is really substantially less mature and it is evolving rapidly. And therefore, a short-term update of this guideline to address new data pertaining specifically to ultra-hypofractionation is likely going to be necessary. And then I mentioned there was a third set of recommendations and these pertain to the technical aspects of planning and delivering radiation therapy. And these probably are not of core interest to your audience, but briefly, the guideline recommends that in the planning of hypofractionated radiotherapy, that normal tissue constraints and target volumes derive from published reference standards the use and that image guidance and intensity modulation at one form or another are recommended in delivering hypofractionated radiotherapy. Great. Thank you for the overview of those guideline recommendations. So why is this guideline so important and how will it change practice? Yeah. I guess the first point to make is that the guideline potentially can inform the care of a very large number of patients. Across North America, about 200,000 patients a year are diagnosed with prostate cancer and its far and away that the most prevalent non-dermatologic cancer in men and it's the third-leading cause of cancer death in men, at least in North America. So the vast majority of those 200,000 men are diagnosed with localized disease at the time of presentation and therefore they're potentially treatable with radiation therapy and therefore the guideline is relevant to these patients. Prior to the publication of the trials that motivated this guideline, the overwhelming majority of these men who chose external beam radiotherapy as their primary treatment have been treated with conventionally fractionated therapy. In other words, seven and a half to nine weeks of treatment. And already, since the publication of these trials-- the trials of moderate hypofractionation-- we're talking really about moderate hypofractionation because I think that is where the guideline will have its impact, at least in the short term. In the jurisdiction where I practice in Canada, practice has already substantially changed in light of these trials, and I think a large majority of patients with localized prostate cancer choosing external beam radiation therapy are now typically being treated with a moderately hypofractionated approach, typically a four-week schedule. So it will be interesting to see if a similar change is occurring or will occur over time in the United States, particularly informed or potentially informed in part by this guideline. And then finally, with respect to ultra-hypofractionation, I think again I have to note that this is a very dynamic space in terms of evidence and there are a number of large-scale trials looking at ultra-hypofractionation and comparing it to either conventional fractionation or moderate hypofractionation that are in progress or near to reporting. And so again, an update of the guideline in the short-term as data emerges from these studies will likely be important and it may ultimately influence practice as well on a large scale. And finally, how will these guideline recommendations affect patients? So I think in the short term, that the recommendation that has the potential to impact patients in the greatest way is the recommendation regarding moderate hypofractionation. And the guideline really recommends that this is a management approach that substantially reduces the treatment burden without compromising treatment efficacy and without increasing the risk of long-term side effects. So in my view, the move to moderately hypofractionated radiation therapy is a win for patients with localized prostate cancer who choose radiation therapy as their primary treatment modality. And so moderate hypofractionation really represents about a halving of the overall treatment time in some patients. And those who live, for example, in rural or remote areas and who need to travel considerable distance to have their treatment, a halving of treatment time is significant. But I think even more generally, halving of treatment time is significant for patients regardless of where they live. And clearly there are also benefits potentially in terms of cost and also benefits in terms of for the health care system but those really weren't specifically studied in the guideline. Great. Thank you so much for your time today, Dr. Morgan, and thank you for your work on this important guideline. My pleasure, Shannon, and thank you for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

[MUSIC PLAYING] Welcome to the ASCO Guidelines episode of the ASCO University Weekly Podcast. My name is Alexander Drilon, and I'm the Clinical Director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University. Today, we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines Podcast Series. The ASCO Guidelines Podcast Series features interviews with panelists of recently-published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin and today, I'm interviewing Dr. Supriya Mohile from University of Rochester Medical Center, lead author on "Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy-- American Society of Clinical Oncology Guideline for Geriatric Oncology." Thank you for being here today, Dr. Mohile. Thank you very much. First, what is the purpose of this guideline, and can you tell us about the research that was reviewed to inform the recommendations? Sure. So we know that our population is aging. So currently, there are an incredible number of patients who are age 65 and over with cancer. The statistics are showing that more and more older adults are developing cancer. And this was really informed by our movement in geriatric oncology that ASCO has supported over the last 10 to 15 years. When I started my fellowship, which was now close to 15 years ago, there was very little knowledge about how to treat older patients with cancer. We know that clinical trials include fewer older adults and that the older adults that are enrolled tend to be more fit than those older adults seen in community practices and being cared for by, really, community oncologists. Therefore, there is a large gap in knowledge in terms of what might be safe and effective in a phase III clinical trial that provides our evidence for cancer treatment and what might be safe and effective for an older patient-- say 75-plus-- who's being seen in community who has medical conditions such as cognitive impairment or significant comorbidities that may limit their life expectancy. So the guideline really strives to address how older patients should be evaluated and managed in oncology clinics specifically. And this guideline is geared towards older patients with cancer who are undergoing a decision or who are receiving chemotherapy because that's really where the data and the evidence for geriatric oncology practices supports at this point. There's less data for evaluating patients who are going to undergo targeted agents or immunotherapy. But we have, now, a robust level of evidence for older patients who are undergoing chemotherapy. And so this guideline could help clinicians with how to best manage and evaluate and make decisions for older patients with cancer who they're seeing in their clinic. And it can also help support other guidelines that ASCO and others put forth. For example, I sat on the ASCO Guidelines Committee, and we were looking at a guideline for bladder cancer. And some of the guidelines were related to life expectancy. So a intervention is appropriate, for example, for patients who have a 10- or more-year life expectancy. However, there's very limited information for how physicians should estimate life expectancy in our guidelines. And so this guideline includes that kind of information that could help really support other guidelines when we're talking about things like life expectancy, underlying health status, comorbidities, that might influence outcomes for older patients with cancer. In terms of what research was reviewed to inform the recommendations, well, we in the geriatric oncology field-- and many of the co-authors are geriatric oncologies-- worked with others in specific fields, such as cognition, physical health, and community oncologists and primary care doctors, to develop a very comprehensive yet practical way for oncologists to really assess older patients. As I mentioned, our field is small, and it started about 10 to 15 years ago, really focusing on this toolkit called geriatric assessment. Geriatric assessment is a compilation of, really, patient-reported outcomes that can assess health status for older patients. And we sort those pieces in the geriatric assessment into domains. And each domain is known to predict morbidity and mortality in older adults. So those domains include things like cognition, function, psychological status, comorbidities, polypharmacy, social support. And we know from the evidence in community-dwelling older adults without cancer that each of those domains are predictive of outcome. So it made sense to us, having been trained in both geriatrics and oncology, to think about this tool as a way to evaluate underlying health status in older patients with cancer. And the field started by looking at feasibility of geriatric assessment in oncology clinics. These efforts were led by Arti Hurria and the Cancer and Aging Research Group and others. And over time, there has been a lot of data showing that geriatric assessment is feasible in oncology clinics. They can be incorporated in both academic settings and community oncology clinics. In addition, there's been data to support that geriatric assessment is feasible in clinical trials. And so, as we started to grow that data in the field, then there have been large studies looking at prediction of outcomes and looking to see if geriatric assessment and the domains within geriatric assessment can help clinicians identify older patients who are at most risk from adverse outcomes from chemotherapy. And that data has grown significantly. So when that data grew, we paused as a community and really partnered with ASCO, who's been incredibly supportive, to think about a guideline to really summarize the literature-- and not only summarize the literature but to communicate it to clinicians as the audience to really communicate a way that geriatric assessment can be practically incorporated and integrated into routine clinical care for older adults with cancer. And so those are the studies we looked to. We worked with ASCO. ASCO, as you know, has a very rigorous methodology for looking at research. And in our field, the research is less RCT-based-- although randomized controlled trials are forthcoming-- but more based on large, robust, very well-done prospective observational studies. And we reviewed the literature for that in a systematic way and summarized that in the guidelines. And what are those key recommendations for this guideline? So the guideline breaks down into four important components. So the first component really focuses on the value added by geriatric assessment to routine oncology clinical care. And so that recommendation was based on data that shows geriatric assessment identifies factors that can be routinely missed in routine oncology care and are not captured by our routine oncology assessments like ECOG Performance Status or Karnofsky Performance Status assessments. So there is a very robust data that shows those domains that I spoke about earlier-- functional status, physical performance and falls, comorbid medical conditions, depression, social activity and support, nutritional status and cognition-- add value by identifying vulnerabilities or impairments that are not routinely captured in oncology assessments. And that's a very high level, or strong level, of evidence. The second component of the guideline really focuses on how to practically incorporate, or integrate, geriatric assessment into routine oncology care. And so we took a step back and looked at the literature, at what was feasible-- not for academic, robust groups that have a ton of support but really for community oncologists who are seeing many patients in their clinic, really getting their feedback on what might be practical and the quickest way, and the most high-priority tools to assess these domains. And so the tools that were identified were pulled out of the literature in that each of these tools captures an important domain that's predictive of outcomes. So we know that these tools can help identify older patients at high risk for adverse outcome. And they are practically able to be incorporated in the clinic and do not need to be done by a physician. They can be done by a technician, a staff member, a nurse. And so we thought about that in terms of selection of the tools. And so the second recommendation is that the evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. And we recommended, as a panel, the Instrumental Activities of Daily Living-- which is a short, very well-validated patient-reported outcome with a few questions to assess function; a thorough history or validated tool to assess comorbidity-- so this can happen as part of a routine history and physical exam that physicians are often already doing as part of their assessment; a single question for falls-- so have you fallen in the last six months, or have you fallen since the last visit?; the Geriatric Depression Scale as a screen for depression; the Mini-Cog or Blessed Orientation-Memory-Concentration test-- they're both very short, less than two minute type assessments of cognition-- they're administered to the patient by a staff member to screen cognitive issues; and an assessment of unintentional weight loss to evaluate nutrition. And in addition to those tools, if these are being used to evaluate an older patient who's starting chemotherapy, using a validated tool that assesses the risk of chemotherapy toxicity can be informative in helping with the discussion about risk in the informed consent process. And there are two tools that do that-- the Cancer and Aging Research Group tool, and the CRASH tool out of Moffitt, which is called the Chemotherapy Risk Assessment Scale for High-Age Patients-- CRASH tool. Both of those help predict or estimate risk of chemotherapy toxicity. There are, in addition, two additional tools that are short screening tools that can help identify patients at risk for early mortality. Those are called G8 or the Vulnerable Elders Survey-13. So this can form a sort of minimal data set to a basic geriatric assessment. There are options for each of those domains in terms of the tools to be used. So these are our recommendations, but they're not set in stone. In fact, which recommendation to use doesn't have a super high level of evidence. It's a moderate level. Because we don't know, necessarily, which one tool is better than another. We do know that these domains should be captured-- so function, cognition, depression, et cetera-- but which tool to use can be more flexible. So in the guideline, there is the main tool, sort of the recommended tool, but also options for other tools so that practices and physicians can pick what works best for them. In terms of the third recommendation, the third recommendation is focused on estimation of life expectancy. As I mentioned earlier, estimating life expectancy is often part of our guidelines when we're thinking about high-risk interventions. We want to be able to identify as best as we can, with the tools that we have available, patients who are likely to live long enough to benefit from high-risk interventions like chemotherapy, like adjuvant treatment, like high-risk surgeries-- for example, cystectomy for bladder cancer. You know, those kinds of approaches deserve a thoughtful approach to life expectancy estimation. A lot of what we do in clinical practice is Gestalt, so it's sort of the eyeball test-- well, I think my patient might live five years. I think my patient might live 10 years. And we know from the literature that the eyeball test is very subjective, and every individual physician has their different perspective on how long someone might live. And we are, as a medical community, not very good at estimating prognosis. They're all tools that could help this approach and they're all available on the web. And we recommended the Schonberg Lee Index, which is part of ePrognosis, where, as part of the assessment process, there are easy-to-capture variables that can be included. And it creates a very standardized, validated approach to life expectancy estimation that can be shared with a patient. Of note, as part of that recommendation, they do ask about cancer because cancer influences life expectancy. And our recommendation is to say no to that question. Because we're looking at life expectancy from the perspective of outside of cancer-- so in other words, other medical problems that might influence life expectancy, not the cancer, in order to inform decisions for treatment of cancer. The last recommendation really focuses on management. And here's where there are randomized controlled trials in progress. There are consensus studies that are from experts in geriatric oncology that have developed algorithms to incorporate management options for each domain impairment. So for example, one finds that a patient may be falling. That's a domain impairment we assess with the question-- that's the tool-- so have you been falling? and perhaps another type of test-- an objective physical performance test, for an example. And then, we institute, or implement, geriatric-relevant management interventions such as physical therapy, an evaluation for assistive device, a safety evaluation at home, making sure that the patient is not alone at home, looking at medications to make sure their blood pressure medicines aren't too strong and they're going to become orthostatic. So there are these algorithmic approaches to each domain. And these are outlined in several papers that have looked at these Delphi consensus approaches to these algorithms. And these algorithms are now being tested in randomized controlled trials both in the United States and in Europe. And so that's the summary for the recommendations for this guideline. So you mentioned some of those assessment tools, like the CARG tool and the CRASH tool. So how do you implement those in practice? So in the guideline, we have several examples of how a practitioner can use this toolkit to really help with clinical decision-making in a very practical way. So embedded in the guideline is an older patient being considered for adjuvant chemotherapy and the approach-- all the way from the patient is sitting in the clinical setting outside and is filling out the surveys to the plan where they come into the clinic office, someone administers the cognition tool, the nurse or the physician captures the correct information, they go online, and they plug in the information, and they print out the tools. So all of the tools will be made available on relevant ASCO websites-- so the main ASCO website, the educational ASCO websites-- and also the tools themselves, plus the guideline recommendations, and also cases. So we have one case embedded in the actual guideline, but we also, in the supplement, have several additional cases that can be reviewed to really show how to incorporate this in clinical practice. So as part of ASCO, the panel members plus the ASCO geriatric oncology task force that works out of the Health Disparities Committee are going to do our best to make the translation of these guidelines into implementation as easy as possible and have everything available. The three tools that I mentioned-- the CARG toxicity tool, the CRASH tool, and the ePrognosis tool-- are all already available online. And so those links are available in the guideline and can be used right away. The other tools will be available on the ASCO website. We will put that on so that people can download them and use them in the clinic setting. Great. And what interventions can be informed by the results of geriatric assessment? I know you mentioned physical therapy. What else can you tell us about that? So as part of those Delphi consensus process there, we developed sort of an algorithmic approach to the different interventions for each of the domains. So there is a table in the guideline that summarizes the high-priority interventions that the experts use in their clinic when they identify patients with impairments. So as I mentioned, there are things like physical therapy for people with physical performance problems or people who have functional issues, strength and balance training, assistive device evaluation, exercise programs, fall prevention. For comorbidities, thinking about communication aspects of talking to patients and caregivers about how to use multiple medications, talking to other important members of the team like the primary care doctor or pharmacist to help decrease risk from medications. For cognition, for people who have impaired cognitive status, we have very limited data about the safety of chemotherapy in this population. It's under-recognized. Even me, who have many years of working with older patients, cannot tell just by looking or talking to an older adult that they have cognitive impairment. And so screening tools are absolutely necessary. If someone has impairment on a validated cognitive screen like the Mini-Cog or Blessed that I mentioned earlier, thinking about a formal assessment of decision-making capacity and ability to consent for treatment is important. And as we start implementing practices in the clinics to really capture consent processes, even for routine chemotherapy-- off-clinical trials-- this is an important aspect to consider. Delirium risk counseling, medication review, again, are all important things to consider for somebody who has cognitive impairment. For depression, with screening for depression, there is already an ASCO guideline in place for management of patients in general who have depression. And we incorporated some of those management recommendations-- so considering cognitive behavioral therapy, if that's available, social work involvement, counseling. We do consider medications but try the other mechanisms first before medication use in an older adult because medications may have more side effects. And for nutrition, thinking about nutritional interventions, a need for extra support and availability of caregiver to provide extra support for meal preparation. So there is a table, and there's also references to other papers that have Delphi guidelines in place of how to utilize management recommendations. There is also a table that summarizes the ongoing clinical trials. And as we learn more about incorporating this as an evaluation of management plan in terms of improving outcomes for older adults with cancer, we'll be able to expand the guideline to incorporate that information, in addition. So finally, what difference does it make to patients, performing these assessments? How are they impacted by these recommendations? So we truly believe that the evidence shows that assessing older patients with a standardized validated geriatric assessment measure can improve the identification process and discussion surrounding chemotherapy risk. And that is important for this population. Because this population is less included in clinical trials and, therefore, the safety and efficacy of treatments are often uncertain for older adults who are 75-plus because just that population itself is underrepresented in clinical trials-- but also those who are older who have other medical issues. And so that discussion itself, as part of communication for informed consent, is very important. And that's outlined in the communications section of the guideline. In addition, the guideline stresses that factors that identify patients as vulnerable are captured by geriatric assessment. We have standardized tools to assess risk through toxicity tools and mortality. We have standardized tools to help assess life expectancy when one is considering an older adult for adjuvant treatment, which may be six months, a year long. If the older adult you're seeing has a life expectancy of one year based on their comorbid conditions, does it make sense to put them through a one-year program of adjuvant treatment or a big surgery? In addition, it also helps identify those older patients who are fit-- so not just identifying patients who may be at risk, but the other side of the coin is you're 80, but you're healthy. You're fit. You don't have a high risk of toxicity or higher risk than maybe those patients that were included in the clinical trial because your health status is good. And you should get treatment, right? So that conversation is also very important. And again, as I mentioned, there is an example in the guideline where we take an older adult who has some medical issues, and we take them through the process by which these tools can be used to help with the decision-making process. And also, we compare that to a patient that's 10 years older that doesn't have those same health conditions and show the comparison and the contrast between the recommendations. So the older adult, in our example, who is actually, chronologically, 10 years older is actually probably less likely to have harm from treatment than the person that was in their 70s who has other medical problems. And that just goes to show how important underlying health status is when we're making our clinical decisions for treatment. We still need to know more about direct decision-making. We know that geriatric assessment influences oncology decision-making. That data has been shown. In other words, when our oncologists get this information from geriatricians at a tumor board, or it's provided to them through a summary, they utilize that, and they change what they're going to do on average 30% to 50% of the time. Because they value that information, and that information adds value to what their plan is. But what we're still waiting for with these randomized trials is, does geriatric assessment and management approach decrease harm overall, improve survival, decrease toxicity, et cetera? There has been some data in geriatric assessment incorporated into therapeutic trials that shows that when a geriatric assessment plan is used that that might lower toxicity. But we still need more data in that area. And that was recommendation four. And so that recommendation will be more robust as the data matures from these randomized controlled trials. But just to summarize, the panel feels, and ASCO feels, based on this guideline, that there is enough data to support using the tools that we recommend to help assess and manage older adults receiving chemotherapy. Great. Thank you so much for your work on this important and very comprehensive guideline. And thank you for your time today, Dr. Mohile. Thank you very much for inviting me. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Carole Fakhry from Johns Hopkins School of Medicine, lead author on Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the CAP Guideline. Thank you for being here today, Dr. Fakhry. Thanks for having me. So first, can you give us a general overview of what this guideline covers? Sure. This guideline serves to guide multi-disciplinary clinicians in the evaluation of head and neck cancers. And it really starts to clarify which HPV tests to order and when. Also discusses some of the imitations of using surrogate HPV testing in specific situations. The College of American Pathology Guidelines were recently published and we are providing an endorsement with certain classifications and discussions of nuances that we as a committee felt were important and clinically significant, specifically, aspects that could alter clinical care. So what are the key recommendations of this guideline? So first and foremost, the key recommendation is that HPV tumor detection should be performed in oropharynx tumors and not for non-oropharynx tumors. An important aspect of that is that HPV tumor testing should not be altered based on sex, race, age, or smoking history. Another important recommendation is that the term "high-risk" only be used when HPV-specific testing is performed. That would establish the tumor is ideologically related to the infection human papillomavirus. In the absence of HPV-specific testing, we recommend that the term HPV-related tumors be used, and that p16 deserving for oropharynx tumors only. And can you tell us a little bit about the qualifying statements made on some of these recommendations, and why the expert panel decided to include these? Sure. So one of the qualifying statements that we did make was a generalized one, and the one that I kind of just touched upon, that the term "high-risk HPV" should only be used in situations when HPV-specific testing was performed. And that's because sometimes things are p16 positive but not necessarily HPV-related or etiologically related to the infections. So as a committee, we wanted to make sure that that was clear. In light of that, one of the recommendations from the CAP Guidelines was that for tissue specimens presenting with medistatic squamma cell carcinoma of unknown primary and cervical upper, or mid-jugular, chain lymph nodes, pathologists should perform p16 in situ hybridisation. They also had added a note saying that additional high-risk HPV testing on p16-positive cases should be performed for tumors located outside of level two or three in the neck, and/or for tumors with keratinizing morphology. So in the qualifying statement, our committee felt that p16 immunohistochemistry alone was not sufficient in the scenario of an unknown primary cancer. We can get false positives and tumors that are p16-positive but not related to HPV. Can arise in situations of metastasis from the skin cancers, salivary gland malignancies, or even lung primaries. Therefore, in the case of an unknown primary, we would recommend HPV-specific testing. What other important consideration that our committee felt was important to clarify was that in the unknown primary, whether or not a tumor is felt to have keratinizing or non-keratinizing morphology, that HPV-specific testing should be done. And the reason for that is that the pathologists acknowledge that considering a tumor keratinizing or non-keratinizing may be a difficult distinction for most pathologists, and that discerning HPV status may actually be easier and may help hone in on the diagnosis. And as part of this, what we did was we created an algorithm which simplified the College of American Pathologists algorithm for HPV detection. So there are fewer nodes in terms of HPV detection. And in general, for oropharynx tumors, we recommend starting a p16 immunohistochemistry. We endorse the 70% cutoff used on immunohistochemistry for p16. And if it's an oropharynx tumor with greater than 70% p16 staining, then that can be considered an HPV-related squama cell carcinoma. For non-oropharynx tumors, we don't ever recommend HPV tumor status evaluation. And then for unknown primary, whether or not it's a level 2 or 3, starting with p16 is adequate, but if it is p16-positive, that needs to be followed up with HPV-specific testing to be deemed HPV-related. In the College of American Pathology algorithm, acknowledging that determining HPV status can be complex, there are more nodes and more decisions that could be made in terms of discerning what's HPV-related and what's not. And so our committee tried to distill it down and simplify the algorithm. And finally, how will these guideline recommendations affect patients? So it is recommended that patients with oropharynx cancer be tested for HPV. And so this really helps their clinicians determine how to best test their tumors. In cases that are not so clear that are not oropharynx tumors, it also helps to guide their clinicians in terms of the when and how to test their tumors. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Fakhry. Thanks for having me. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Justin Bekelman from University of Pennsylvania Perelman School of Medicine, lead author on "Clinically Localized Prostate Cancer: ASCO Clinical Practice Guideline Endorsement of an AUA/ASTRO/SUO Guideline.” Thank you for being here today, Dr. Bekelman. Thanks for having me. First, can you give us a general overview of what this guideline covers? Sure. So this guideline addresses the key question about what is the current best practice available for the management of localized prostate cancer. It's an endorsement guideline, which means it reinforces the recommendations offered by the American Urologic Association, ASTRO, SUO, which is the Society of Urologic Oncology. In April of 2017, these three groups got together to release a joint evidence-based practice guideline on clinically localized prostate cancer. And then, now more recently, in 2018 ASCO assembled a panel to review those policies, update them, and endorse them as appropriate. So this guideline has over 60 recommendations. So I'm not going to ask you to read through all of them. But can you talk about some of the key topics and discussion points that was added by the ASCO expert panel? Yeah, absolutely. I'd like to highlight four areas. The first area-- panel endorsed guideline recommendations on active surveillance for men with low risk Gleason 6 prostate cancer, what's called grade 1 prostate cancer now. The panel also felt it reasonable to add that ASCO has also produced a guideline on active surveillance which provides more context and counsel for clinicians and patients. It also includes a discussion of how surveillance might be considered for men with low volume Gleason 3+4, or what's called grade 2 cancers. And so I would reference that ASCO guideline on active surveillance for folks who are interested in that. Second, panel updated the recommendation regarding the length of androgen deprivation therapy or hormone therapy for men with higher risk clinically localized prostate cancer. Prior recommendations considered 24 to 36 months to be appropriate. And that's what's captured in the 2017 guidelines from the AUA, ASTRO, and SUO. But new evidence released after those guidelines were published from two trials-- one called RADAR and one called PCS IV trial-- shows that 18 months may be equivalent and permissible, and thus these trials should be followed really closely. But that's really interesting, provocative information for patients as they consider adjuvant hormone therapy for high risk cancers when they're receiving radiation. Third, the panel describes two really high impact quality of life studies comparing surgery, external beam radiation, and brachytherapy that were published in JAMA in 2017, again, after the AUA guideline was published. These two studies are actually summarized in the discussion of the panel findings. And they are an excellent reference for both clinicians and patients as they consider the potential benefits and harms of the various treatments for prostate cancer. The last one I'd want to highlight to the audience is the panel's recommendations regarding cryosurgery. And even though the original guidelines stated that selected patients are candidates for cryosurgery, the panel found that there was insufficient evidence to support the use of cryosurgery for clinically localized prostate cancer. So those are four highlights from the evidence based review. And why is this guideline so important? And how will it change practice? This guideline represents the most up to date consensus recommendations from the major professional societies that represent clinicians-- the surgeons, the radiation oncologists, the medical oncologists-- who counsel and treat men with prostate cancer. So it's a really important initial original guideline and then a really important endorsement. I think it will change practice by highlighting what the current best practice standards of care are for clinically localized prostate cancer. And finally, how will these guideline recommendations affect patients? I think this guideline will have an immediate impact on important questions that patients and their clinicians want answered. I think that's how the panel actually took its role, is thinking, how can we both endorse and provide further evidence that would be patient centered as we considered these guidelines. So this endorsement and the guidelines, they ask questions like, how should we conduct shared decision making with our patients to offer the highest chance that treatment decisions will be concordant with our patient goals of care? That's number one and so crucial. Who is appropriate for active surveillance? A top topic for men facing clinically localized prostate cancer. What are the differences and side effects among the major treatments for clinically localized prostate cancer, mostly focused on surgery and radiation? The endorsement updates the latest data through 2017 and even in 2018 with really patient-centric information about what patients might expect with each of these treatments. Even what are the aspects of prostate cancer care that represent the highest quality? And how might patients assess that? What are the most important aspects of survivorship? So the endorsement and recommendations from the original guidelines themselves hit on each of these. And I think that patients will find them very interesting and insightful. Great. Thank you so much for your time today. And thank you for your work on this important guideline, Dr. Bekelman. Oh, my pleasure. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Randy Taplitz from UC San Diego Health, lead author on Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. Thank you for being here, Dr. Taplitz. Thank you. So first, can you give us a general overview of what this guideline covers? Yes. I mean, I think we're all aware that infection in the setting of neutropenia associated with cancer chemotherapy is really a major cause of morbidity in these patients. And it's also important to be aware that prevention and appropriate management of febrile neutropenia and infection should thus be a critical focus in cancer care. So the focus of this particular guideline was to evaluate the risk and benefits of antimicrobial prophylaxis in these patients and really to determine evidence-based best practices for prevention of infection and how to go about doing that. So In this guideline, what we do is we identify the groups at risk for febrile neutropenia and really recommend settings for which prophylaxis with antibacterial, antifungal, antiviral medications are indicated. And then as well make recommendations for consideration of vaccination and other measures such as respiratory etiquette, and hand hygiene, and the like that will help reduce the risk of infection in these vulnerable patients. So since this is an update of a 2013 guideline, what are the major changes? And can you tell us a little bit about the research that informed this update? Yes. Really, when you update a guideline, one is informed by review of articles that encompass, in this setting, randomized clinical trials as well as meta analysis of interventions to prevent microbial infections in patients with neutropenia or other types of immunosuppression. And one example of this-- I think one of the better examples-- is we reviewed a large meta analysis of antibiotic prophylaxis in neutropenic patients after chemotherapy that showed that for fluoroquinolone prophylaxis resulted in really significant reductions in all cause mortality and febrile episodes, particularly in patients who were high risk, meaning the hematologic malignancy population and stem cell transplant population. And in that particular population, in fact, the number needed to treat to prevent one death was 29. So therefore, in that high risk population, really as with prior guidelines, the fluoroquinolone prophylaxis is recommended. However, we also reviewed other articles that include emerging data on some of the risks of fluoroquinolone prophylaxis. So for instance, the effect of fluoroquinolone on the intestinal microbiome and its association with selection of fluoroquinolone-resistant bacteria such as Gram-negative rods, as well as selection of organisms such as Clostridium difficile and enterococcus. And then we also reviewed fluoroquinolone toxicities. So what is added to this guideline are some qualifying statements alerting clinicians to really be aware for these concerns and to consider what the clinical spectrum of things like Clostridium difficile infection, et cetera, look like. In terms of antifungal prevention, including pneumocystis prevention, we really haven't made any major changes to this guideline with the exception that in this new guideline, the panel has also started looking at complications associated with immunotherapy and actually makes a suggestion that people consider pneumocystis prophylaxis in the setting of prolonged steroid use when it's used to treat immune-related adverse events that we've begun to see in increasing numbers associated with agents like checkpoint inhibitors and other immunotherapies. In terms of viral infections, the updated guidelines recommend risk assessment for hepatitis B reactivation and then treatment in accordance with other ASCO guidelines and yearly influenza vaccine, as well as really endorsing other vaccines as described in the Infectious Disease Society of America Guideline for Vaccination in Immunocompromised Hosts. So really, those are the main new events since 2013. And what are the key recommendations of this guideline? So the key recommendations-- the first thing is what we call a risk assessment. So after-- what one does is carefully assess, really, what the risk of febrile neutropenia is. And that includes assessment of patient, what the cancer is, and what the treatment-related factors are. And then after they're risk adjusted and risk assessed, then we take, in turn, different forms of prophylaxis that we consider. And so the first one that we always consider is antibiotic prophylaxis against bacterial infections. And the recommendation is still with the fluoroquinolone. And that's recommended for most patients who are at high risk for febrile neutropenia or profound, really prolonged neutropenia, such as those getting therapy for AML, or myelodysplastic syndrome, or stem cell transplant recipients, particularly with myeloablative regimens. In the lower risk groups, such as those with most solid tumors, fluoroquinolone prophylaxis is not recommend. In terms of antifungal prophylaxis, what is recommended is an oral triazole or Micafungin-- for patients, again, at risk for profound protracted neutropenia such as that AML, MDS, stem cell transplant group during that period of neutropenia. When the risk of invasive aspergillus is high, such as in patients with AML or MDS during the neutropenia period while getting chemotherapy, then the consideration of a mold-active triazole is recommended and in addition should be considered in the context of stem cell transplant recipients with graft versus host disease. In terms of PCP prophylaxis, PCP preventive therapies are recommended for those at high risk for PCP, which include those on greater than what we say 20 milligrams of prednisone equivalent a day for over a month, or based on purine analog use. Viral prophylaxis for HSV is recommended for seropositive patients undergoing allogeneic stem cell transplant or leukemia induction. And then as I mentioned before, patients at risk for hepatitis B reactivation are recommended treatment with a nucleoside reverse transcriptase inhibitor. And this is more carefully discussed in the ASCO Provisional Clinical Opinion on Hepatitis-B Virus Screening for Patients With Cancer Before Therapy. It's also recommended that a yearly flu vaccine is given to patients as well as given to family, household contacts, and health care workers. Other vaccination recommendations are as per the Infectious Disease Society of America Guidelines for Vaccination of Immunocompromised Hosts. And then the other things that are recommended are really review and repeat recommendation of adherence with hand hygiene, with respiratory etiquette, which is recommended and really required for all health care workers. And that out patients with neutropenia from cancer chemotherapy should avoid high risk activities, which include really contact with environments that have high concentration of fungal spores such as construction and demolition, high intensity gardening, et cetera. So those are really a summary of the key recommendations of this guideline. And finally, how will these guideline recommendations affect patients? I think it's important to remember that to ensure best practices on infection prevention, the literature needs to be reviewed frequently and guidelines need to be updated. I don't think that these current guidelines will dramatically change the preventive strategies that are used for patients, with the exception of perhaps a few extra vaccines-- some newer indications for pneumocystis prevention, hepatitis B reactivation prevention, those kinds of things. However, I think in reviewing the literature, it becomes clear what will we will need to be thinking about in the coming years, what we will need to be assessing. And a couple of those things are the dramatic increase in the use of immune-based therapies and how that will affect infection risk in patients with or without neutropenia. We need to be considering the effects of routine antibiotic prophylaxis on the microbiome and the risks that that might incur. And we need to really understand how new vaccines can be utilized. So yeah, I think these areas are really ripe for research and need to be followed closely to ensure optimization of these preventive strategies for our patients in the future. Thank you for your time today, Dr. Taplitz. You're quite welcome. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer this show to a colleague.