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Best podcasts about rtog

Latest podcast episodes about rtog

ScienceLink
TOP 2024: tumores ginecológicos

ScienceLink

Play Episode Listen Later Feb 6, 2025 41:16


El Dr. Luis Alfonso Romero, oncólogo médico de León, Guanajuato junto con el Dr. Raúl Márquez, oncólogo médico de Madrid, España, presentan un resumen de los estudios que consideran más relevantes en el ámbito de los tumores ginecológicos expuestos durante el 2024. CÉRVIX ENGOT-cx11/GOG-3047/KEYNOTE-A18 INTERLACE NRG oncology/RTOG 0724/GOG-0724 innovaTV 301 ENDOMETRIO ENGOT-en11/GOG-3053/KEYNOTE-B21 RUBY DUO-E NRG GY018 SIENDO ENGOT-en9/LEAP-001 TROPHAMET OVARIO PRIMA/ENGOT-OV26/GOG-3012 ATHENA-COMBO PICCOLO BrUOG 354 NEO  Fecha de grabación: 29 de enero de 2025                     Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

QuadShot News Podcast
1.27.2025 - RTOG 0920

QuadShot News Podcast

Play Episode Listen Later Jan 27, 2025 8:38


Check out this week's QuadCast as we highlight the results of RTOG 0920 for adjuvant therapy in H&N cancer, the benefit of bone protective agents in patients receiving radium 223 + enzalutamide, the benefit of incorporating counseling into smoking cessation strategies, and more. Check out the website and subscribe to the newsletter! www.quadshotnews.com Founders & Lead Authors: Laura Dover & Caleb Dulaney Podcast Host: Sam Marcrom

QuadShot News Podcast
1.13.2025 - Cord Constraints

QuadShot News Podcast

Play Episode Listen Later Jan 13, 2025 10:58


Check out this week's QuadCast as we highlight spinal cord constraints for spine SBRT, published results of RTOG 1112 where liver SBRT shines, the role of prophylactic nodal RT in prostate SBRT, and more. Check out the website and subscribe to the newsletter! www.quadshotnews.com Founders & Lead Authors: Laura Dover & Caleb Dulaney Podcast Host: Sam Marcrom

ASCO Guidelines Podcast Series
Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma Guideline

ASCO Guidelines Podcast Series

Play Episode Listen Later Dec 16, 2024 16:14


Dr. Van Morris presents the new evidence-based guideline on systemic therapy for localized anal squamous cell carcinoma. Dr. Morris discusses the key recommendations from the Expert Panel, including recommended radiosensitizing chemotherapy agents, dosing and schedule recommendations, the role of induction chemotherapy and ongoing adjuvant chemotherapy, and considerations for special populations. He emphasizes the importance of this first guideline from ASCO on anal squamous cell carcinoma for both clinicians and patients with stage I-III anal cancer, and ongoing research the panel is looking to for the future. Read the full guideline, “Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma: ASCO Guideline” at www.asco.org/gastrointestinal-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/gastrointestinal-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02120 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts, delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Van Morris from MD Anderson Cancer Center, co-chair on “Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma: ASCO Guideline.” Thank you for being here today, Dr. Morris. Dr. Van Morris: Thank you for having me. On behalf of our committee who put together the guidelines, I'm really excited to be here and talk with you today. Brittany Harvey: Great. Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Morris, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to jump into the content of this guideline, Dr. Morris, can you provide an overview of both the purpose and the scope of this guideline on stage I to III anal squamous cell carcinoma? Dr. Van Morris: So anal cancer is considered a rare malignancy for patients in the United States and across the world as well. Even though it's not something we see as commonly, for example, as the adjacent colorectal cancer, this still is a cancer that is rising in incidence every year in the United States. And really, despite the presence of the preventative HPV vaccines, which we hope will ultimately prevent and eradicate this cancer, we still expect the incidence to continue to rise in the coming decades before we really start seeing numbers begin to decrease as a result of the vaccine. So this is an alarming trend for which oncologists will continue to see likely more and more cases and new diagnoses every year. So we wanted to review the most recent literature and provide oncologists up to date recommendations for how they can best take care of patients with a new diagnosis of localized anal cancer. Brittany Harvey: Absolutely. I appreciate that background and context to set the stage for this guideline. So then next I'd like to review the key recommendations of this guideline. So starting from the first clinical question, what are the recommended radiosensitizing, doublet or single chemotherapy agents for patients with stage I to III anal cancer? Dr. Van Morris: It's true that really the standard treatment for patients with localized anal cancer has not changed over the last literally half century. When the Nigro regimen was first reported back in 1974, 50 years ago, the standard of care for patients with a new diagnosis of localized anal cancer centers around concurrent chemotherapy and radiotherapy. And we looked at the various randomized control trials and the highest level of evidence which has been reported over the past decades, and really for most patients, the standard of care continues to remain doublet cytotoxic chemotherapy in combination with radiation. We reported that the most commonly, and I think most accepted, regimen here is a combination regimen of 5-FU, intravenous 5-fluorouracil with mitomycin C. And this most commonly is given on a week 1 to 5 regimen. The 5-FU, we recommended a dose of 1000 milligrams per meter squared per day on days 1 to 4 and then on days 29 to 32 of the radiation treatment. And then the mitomycin C, looking at various trials, has been given at a dose of 10 milligrams per meter squared on day 1 and day 29, or alternatively a single dose of mitomycin C at 12 milligrams per meter squared on day 1. I think that the thing that's important for clinicians and patients alike to remember is that this chemotherapy can be very toxic in patients who are undergoing a curative-intent therapy for this diagnosis of localized anal cancer. I think it's just important for oncologists to be watching closely the blood counts for the patients to make sure that the myelosuppression doesn't get too bad. And then in select cases, if that is the case, when the oncologist opts to go for the day 1 and day 29 dosing, it may be prudent, if the myelosuppression is too excessive, to consider withholding that day 29 dose. Brittany Harvey: Great. Thank you for providing those recommendations along with some of those dosing and the schedule recommendations from the expert panel. So are there any other alternate dose or schedule recommendations from the expert panel? Dr. Van Morris: Yeah, but I think that we saw with the ACT II data that was a randomized trial that was done out of the UK that compared 5-FU mitomycin with 5-FU cisplatin as two different doublet cytotoxic regimens, that overall outcomes were very similar between the two regimens in terms of curative outcomes for patients treated whether 5-FU mitomycin or 5-FU cisplatin. So certainly there is evidence supporting the use of cisplatin as a second cytotoxic agent with 5-fluorouracil. In the ACT II study that was given at a dose of 60 milligrams per meter squared on days 1 and 29 along with the 5-FU at the regimen I talked about previously. There is other lower level of evidence data suggesting that even the 5-FU and cisplatin can be given on a weekly schedule and that that can be safe. Actually, at my institution at MD Anderson, that is our standard practice pattern as well. There's also the option when we're thinking about giving pelvic radiation for patients with lower GI cancers, many oncologists in the treatment of localized rectal adenocarcinoma are accustomed to using capecitabine as a chemosensitizer in patients with localized rectal cancer. If I'm giving chemoradiation for a patient with localized anal cancer, can I substitute the intravenous 5-FU with oral capecitabine? And although the evidence is not as strong in terms of available data with regards to randomized controlled trials, there certainly is data that suggests that capecitabine may be an acceptable alternative in lieu of intravenous 5-fluorouracil that would be given at a dose of 825 milligrams per meter squared on days of radiation. But certainly, I think that that's a feasible approach as well and maybe even associated with less hematologic toxicity than intravenous 5-FU would be. Brittany Harvey: Great. It's important to understand all the options that are out there for patients with early-stage anal squamous cell carcinoma. So in addition to those chemoradiation recommendations, what is recommended from the expert panel regarding induction chemotherapy or ongoing adjuvant chemotherapy for this patient population? Dr. Van Morris: When we think about treating patients with lower GI cancers with curative intent therapies, when we think about the more common rectal adenocarcinoma, oncologists may be used to giving chemoradiation followed by subsequent cytotoxic chemotherapy. But actually when you look at the data for anal cancer, really there's not any data that strongly supports the use of either induction chemotherapy prior to chemoradiation or adjuvant post-chemoradiation chemotherapy. The RTOG 98-11 study was a trial which evaluated the role of induction 5-fluorouracil prior to chemoradiation and did not show any survival benefit or improved outcomes with the use of induction chemotherapy in a randomized control trial setting. The ACT II trial, which I referenced earlier, was a 2 x 2 design where patients were either randomized to concurrent chemoradiation with 5-FU mitomycin C or concurrent chemoradiation with 5-FU cisplatin. But then there was a second randomization after chemoradiation where half of the study participants received adjuvant cisplatin 5-fluorouracil after completion of their chemo radiation, or the other half were randomized to the standard of care, which of course would be observation. And what that trial showed was that there was no added benefit with the addition of post-chemoradiation cytotoxic chemotherapy. So we look at these data and say that in general, for the general population of patients with localized stages I to III anal cancer, there really is no supporting data suggesting benefit of either induction chemotherapy or adjuvant chemotherapy. And to that end, really it's concurrent chemoradiation remains the standard of care at this time for patients with a new diagnosis of localized anal cancer. Brittany Harvey: Absolutely. It's just as important to know what is not recommended as it is to know what is recommended for these patients. And so I thank you for explaining the evidence behind that decision from the panel as well. So then, are there any other considerations for special populations that oncologists should consider? Dr. Van Morris: I think so. I think that anal cancer is a disease where we don't see that many patients being diagnosed earlier at a younger age, especially in relation to the alarming trend of early onset colorectal cancer that we're currently seeing right now. So there may be patients who come with a new diagnosis of localized anal cancer who are an octogenarian at an advanced age or may have other significant medical comorbidities. And if that is the case, we get called about this quite frequently from outside institutions. I have an 85 year old who is coming to my clinic with this diagnosis. I don't feel comfortable giving this patient doublet cytotoxics, what options do I have? Especially given other organ dysfunction that may precede this diagnosis. And I think that in that case, there are times when it's okay safely to drop the mitomycin C and opt for single agent 5-fluorouracil as a single cytotoxic agent. So I think that that would be something that we've certainly incorporated into our practice at our institution. There's also an association between various autoimmune disorders, patients on immunosuppression, even persons living with HIV being at higher risk for this virally associated cancer. So I think that, again, if the patient is coming with baseline immunosuppression for these reasons prior to treatment, certainly kind of being in tune to the potential for hematologic toxicity. And watching these patients very closely as they're getting chemoradiation remains really important. Brittany Harvey: Definitely. So, you've just discussed some of those comorbidities and patient characteristics that are important for clinicians to consider when deciding which regimens to offer. So in addition to those, in your view, what is the importance of this guideline and how will it impact clinical practice for clinicians who are reading this guideline. Dr. Van Morris: Chemoradiation remains a very effective option and most patients will be cured with this diagnosis and with this treatment. So it's important to make sure that these patients are able to safely get through their treatment, minimizing treatment delays due to toxicities which may come about because of the treatment, and really help to carry them over the finish line so that they have the best likelihood for achieving cure. So we really hope that these data will provide oncologists with a readily available summary of the existing data that they can refer to and continue to help as many patients as possible achieve and experience a cure. Brittany Harvey: Absolutely. So then to build on that, it's great to have this first guideline from ASCO on anal squamous cell carcinoma. But how will these new recommendations affect patients with stage I to III anal cancer? Dr. Van Morris: I certainly hope it will allow patients and oncologists to know what their options are. It certainly is not a one size fits all treatment approach with regards to the options which are available. Depending on the patient, depending on the various medical conditions that may accompany them, these treatments may need to be tailored to most safely get them through their treatment. Brittany Harvey: I appreciate you describing the importance of this guideline for both clinicians and patients. So what other outstanding questions and future research do you anticipate seeing in this field? Dr. Van Morris: It's a really good question and I think that there is a lot coming on the horizon. Even though the standard treatment has really not changed over the last half century, I think it still remains true that not all patients will achieve cure with a chemoradiation treatment. So a recent trial has completed enrollment in the United States, this is the EA2165 trial led by one of our committee members, Dr. Rajdev and Dr. Eng as well, that's looking at the use of nivolumab anti PD-1 immunotherapy after completion of concurrent chemo adiation. So in that trial, patients were randomized to concurrent chemoradiation followed by either observation or six months of adjuvant anti PD-1 therapy. We're really awaiting the results of that. Hopefully if we see an improvement with the addition of nivolumab following concurrent chemoradiation, our hope would be that more patients would be able to achieve a cure. So we're certainly looking forward to the outcomes of that EA2165 study. And then I think one question that we often get from our patients in the clinics is, “What is the role of circulating tumor DNA in the management of my disease?” And really, to date there have been some series which have shown that we can assess patients or circulating tumor DNA after completion of their concurrent chemo radiation that may need to start about three months after to give time for the radiation to wear off and most accurately prognosticate that. But I think that this will be a powerful tool moving forward, hopefully, not only in the surveillance to identify patients who may be at high risk for recurrence, but ultimately to translate that into next generation clinical trials which would treat patients at higher risk for recurrence by virtue of a detectable circulating tumor DNA result. In doing so, hopefully cure even more patients with this diagnosis. Brittany Harvey: Yes, we'll look forward to these developments and hope to add more options for potential treatment and surveillance for patients with anal cancer. So, I want to thank you so much for your work to develop these guidelines and share these recommendations with us and everything that the expert panel did to put this guideline together. Thank you for your time today, Dr. Morris. Dr. Van Morris: Thank you. And thank you to ASCO for helping to keep this information out there and ready for oncologists for this rare cancer. Brittany Harvey: Absolutely. And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have 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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.    

JCO Precision Oncology Conversations
Transcriptomic Profiling of Non-Localized Prostate Cancer

JCO Precision Oncology Conversations

Play Episode Listen Later Oct 16, 2024 27:07


JCO PO author Dr. Amar U. Kishan, Professor, Executive Vice Chair, and Chief of Genitourinary Oncology Service in the Department of Radiation Oncology at the University of California, Los Angeles, shares insights into his JCO PO article, “Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.”  Host Dr. Rafeh Naqash and Dr. Kishan discuss the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) PET/CT-based metastatic spread. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO articles. I'm your host, Dr. Rafeh Naqash, Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today we are joined by Dr. Amar Kishan, Executive Vice Chair of the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and UCLA Jonsson Comprehensive Cancer Center, and also the corresponding and senior author of the JCO Precision Oncology article entitled, “Transcriptomic Profiling of Primary Prostate Cancers and Non Localized Disease on Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.” Dr. Kishan, welcome to our podcast and thank you for joining us today. Dr. Amar Kishan: Thank you so much for that kind introduction and the invitation to be here today. Dr. Rafeh Naqash: Well, it seems to me that there's a theme that people in the GU space, investigators in the GU space, are very interested in trying to understand risk predictors for prostate cancer. We had somebody, I believe from Huntsman Cancer Center a few months back on a previous podcast, where they were trying to do risk prediction modeling as well. Could you tell us why that's something that the GU community is very interested in? What's the background? Is it because there's no risk prediction approaches currently? And would this somehow influence management in the near future? Dr. Amar Kishan: Yeah, that's a great question. So, I think this goes back to the point that we're in the era of precision medicine now, and many cancers have these molecular stratification scores and all that. Prostate cancer has lagged a little bit behind in that regard, despite the fact that it's such a common cancer that affects so many people across the country and across the world. So, we do have risk stratification schemes for prostate cancer. These are based off clinical and pathologic variables, like the level of PSA, the size of the tumor on digital rectal examination, now, we're incorporating MRI imaging as well, and then what the cancer looks like under the microscope, the Gleason score. And now there have been revisions to the Gleason score, but it's really kind of the architecture, what the biopsy looks like. And this was kind of developed many, many years ago by Donald Gleason, a pathologist at the VA. What we're not necessarily taking into account routinely is kind of the biology of the cancer per se. You know, what are the molecular drivers? How could that influence ultimate outcome? And that's very important because we have these risk groups, low risk, very low risk, favorable intermediate risk, unfavorable intermediate risk, high risk, very high risk. But within each of those groups, based on the clinical kind of pathological characteristics, there's a huge heterogeneity in outpatients too, and our treatments are effective, but they can be morbid. Putting someone on hormone therapy for an extended period of time has a lot of side effects. Dose escalating radiotherapy or doing surgery and then radiation afterwards, these are big things that have a big impact on the patient, and I think we really need better risk stratification tools to understand who needs intensification and who we can de-escalate treatment for. Dr. Rafeh Naqash: I think those are absolutely valid points, perhaps not just for prostate cancer, more so for all cancers that we currently treat, especially in the current day and age, where we have a tendency to add more and more therapies, combination therapies for patients, and as you mentioned, risk stratification to help identify high risk versus low risk, where you can de intensify treatment, is of high value from a patient standpoint as well as from a financial toxicity standpoint. So then, going to this next part of the approach that you used, and from what I understand in this paper, you had the radiological aspect, which is the PSMA PET, which we'll talk about. Then you had the genomic aspect, where you did some genomic risk-based stratification. Then you had the transcriptomic score based on the Decipher score. So, could you go into some of the details, first, for the PSMA PET, when is it used? What is the utilization? What is it based on, the science behind the PSMA PET? And then we can talk about some of the other genomic transcriptomic predictors that you use in this study. Dr. Amar Kishan: Sure. Absolutely. So, a PSMA PET is an advanced molecular imaging tool. PSMA stands for prostate specific membrane antigen. It's a membrane protein that is expressed on the surface of prostate cancer cells. It is expressed elsewhere in the body as well. The utilization of this for imaging has been a revolution in the staging of prostate cancer, both upfront and in the recurrent setting. We basically had fairly recent approval for PSMA PET being used more routinely in upfront staging and recurrent staging in 2022. Essentially, what this is it gives us an ability to detect whether prostate cancer has spread at a time of diagnosis or try to localize the recurrence. Now, no imaging test is perfect, of course, and a PET has a resolution of about 3 mm. There are questions about the sensitivity of the PET. You get it on a patient with high-risk disease, the PET is negative; you do surgery, there are positive lymph nodes. That can happen, but it's far superior to the tools that we have had before. For instance, beforehand, all we would have is a contrast enhanced CT, bone scan, and MRI. And the sensitivity of those is far below that of a PSMA PET. And that has actually been shown in a randomized trial called the ProPSMA trial out of Australia, where they compared conventional upfront imaging versus PSMA upfront imaging with a crossover design, and there was better detection of disease with the PSMA PET. So that's been a revolution in how we stage prostate cancer. But I'm sure many of your listeners and others are aware of the concerns. When you get a new test and you're detecting disease that's extra prostatic, for instance, are you seeing truly significant new disease that we do need to change our management for, or are we just seeing stuff that wasn't there before that actually wouldn't impact anything? And what I mean by that is, let's say you're seeing things that would never have made a difference to the patient, but now you're saying they have metastatic disease. You're changing their entire treatment paradigm, all kinds of things like that. There's implications to this that hasn't been fully fleshed out. But very recently, like we're talking in July of 2024, essentially, there was a Lancet Oncology paper that looked at the long-term prognosis of patients who had extra prostatic disease on PSMA PET, judged by something called a PROMISE score, kind of gives a quantification on the volume of disease, the brightness of disease, and they correlated that with long term outcomes. And that was really the first time that we have long term follow up data that this extra prostatic disease on PSMA PET actually is prognostically important. So, we're getting there. I mean, now that it's approved and, in some sense, the cat is out of the bag, patients are coming in asking for a PSMA PET, etc. I'm sure everyone has experienced that, but I think we now do have good evidence that it actually is prognostically important as well. Dr. Rafeh Naqash: Thank you for that explanation. And again, to put this into context for things that I've seen and that might also help the listeners in other tumors, so, for example, melanoma surveillance tends to be or while on treatment, patients tend to have more PET scans than what you see, maybe in individuals with lung cancer, where you get a baseline PET and then you have follow up CT scan based imaging is that something that you guys have shifted from in the prostate cancer space with the approval for PSMA PET, where follow up imaging, whether patient is on treatment or surveillance imaging, is PSMA PET based? Dr. Amar Kishan: Yeah, that's a good question. I think there's actually less robust data to support it as a means of treatment response. But in terms of evaluating a recurrence, then, yes, that has become kind of a standard tool. It's very complicated because all of the metrics that we have for, say, a treatment failing are based on conventionally detected metastases or something that shows up on a CT or bone scan. So, again, that question arises if someone is on systemic therapy and then you see something on a PSMA PET, are you going to abandon the therapy that you're on? It technically would be earlier than you would otherwise have done that, or what are you going to do? So, that hasn't been fully fleshed out, but it is used in that circumstance. So, I'd say less for treatment monitoring and more for evaluation of suspected recurrence. Dr. Rafeh Naqash: Understood. And I'm guessing, as a futuristic approach, somebody out there may perhaps do a trial using PSMA PET based imaging to decide whether treatment change needs to be made or does not need to be made. Dr. Amar Kishan: Yeah. It is being incorporated into trials as we speak, I think. Dr. Rafeh Naqash: Now, going to the second part of this paper is the Decipher score. Could you explain what the score is, what its components are, how it's calculated? Is it DNA, is it RNA, is it both combined? Is it tissue based; is it blood based? Dr. Amar Kishan: Yeah. So, the Decipher is also an approved test now, was approved in 2018. What it is, essentially, and how it's derived is based on the idea originally that patients might have a recurrence after surgery for prostate cancer. And it's just a PSA recurrence. It's this way. It's literally what we call a biochemical recurrence. That patient might not have any problems, whereas other patients with a recurrence might go on to develop metastatic disease. And we didn't have a good way of determining which patient is which. Get back to that prognostic problem that we have. So, some investigators, they looked at men that had radical prostatectomy from 1987 to 2001 at the Mayo Clinic that had archived tissue. They looked at FFPE, or basically paraffin embedded tissue. They extracted the RNA and then did a microarray analysis and looked at transcriptomic signatures and wanted to see, could this discern the patients who had mets, who had clinically significant recurrences from those that didn't? And out of that exercise came the Decipher Genomic Classifier, which basically is based on 22 genes. These are involved with cell proliferation, etc., but it's an RNA-based, tissue-based assay. So, if you wanted to order a Decipher on somebody, you would need to use a biopsy or prostatectomy specimen to do so. Essentially, that the samples, they would take the highest grade, highest Gleason grade specimen, send it to their lab. Their main lab is in California. The company is called Veracyte. And then they will do this RNA express analysis with a microarray and then return a score. The score is 0 to 1. Basically, 0 is the lowest, one is the highest, and it is a way of prognosticating the risk of metastasis. Originally, when you get a Decipher report, it actually will tell you the 5 and 10-year risks of distant metastasis, and we'll quantify that. Dr. Rafeh Naqash: And you said this is approved or has been approved in 2018. So, is this insurance reimbursable at this point? Dr. Amar Kishan: Most insurances do, not all, and the criteria for getting it can vary, so we can talk about it, but it was initially developed in this post-op setting. On the basis of a significant amount of validation studies, it has been moved to being used in the upfront setting as well. So, if you look at some of the ongoing NRG trials, for instance, they are stratifying patients based off the upfront Decipher score. And this is based off of validation studies that have been conducted looking at past RTOG trials and other trials. That said, sometimes it is not approved by commercial insurances in the upfront setting, because that wasn't where it was initially validated and derived. But honestly, here in 2024, that's very uncommon. It's much more common that it's approved. Dr. Rafeh Naqash: Understood. And in your practice, or the medical oncologist practice at your institution or other institutions, is this something that is commonly used for some sort of treatment decision making that you've seen? Dr. Amar Kishan: Yeah. So, as a radiation oncologist, I do think it's a useful test, because my approach is, if we're talking about adding hormone therapy, for instance, which is oftentimes dominating the conversation, we know that it offers a relative benefit to a lot of patients. We've published on this; others have published on it. Let's say it reduces the chance of metastasis by about 40%. 10-year risk of metastasis has a ratio of 0.6. So, 40% reduction. But if your risk of metastasis is 2%, that benefit is not that much in absolute terms. And we don't historically have a great way of saying, what is your absolute risk of metastasis? And I think Decipher is one tool that does tell us that - it literally gives it on the report. Now, is that a holy grail? Is it 100% accurate? Nothing is 100% accurate. But it does give us some quantification. Then I can go back to the patient and say, yes, you will get a benefit from adding hormone therapy, but you're talking about going from 2% to 1%, and so they can decide if that's worth it to them. Conversely, it could be a situation where they really don't want hormone therapy, but it comes back that their risk of metastasis is 20%, and then there's actually a big absolute benefit. So that's how I use it as a radiation oncologist, and we would use it upfront. Now surgeons, and if I was consulting on a post operative patient, maybe it plays more of a role. And do we need to do post operative radiotherapy on this patient, or do we need to add hormone therapy in the postoperative situation? From the medical oncology perspective, there are emerging data that may be useful in the choice of systemic therapy for metastatic disease, but that is a little bit earlier in the investigational stage, I would say. So, when I'm working with medical oncologists, it's often still in this localized setting, and typically, do we add hormone therapy or not, and that type of thing. Dr. Rafeh Naqash: Understood. And from a reporting standpoint, so the Decipher score, I'm guessing it's some sort of a report that comes back to the ordering physician and you basically see the score, it gives you a potential recurrence free survival percentage or a metastasis percentage of what is your risk for having metastasis in the next five years - is that how they generally do it? Because I've personally never seen one, so I'm just curious. Dr. Amar Kishan: Yeah, essentially, it comes back with a score, a numerical score, again, from 0 to 1, and it will basically give you the five-year risk of distant metastasis. The ten-year risk of distant metastasis. You can request an extended report that provides additional, not as well supported signatures that are out there, like ADT response signature, etc. But those maybe may have been published, but are not clinically validated as much, but the actual Decipher report, which goes to patients too, just has this kind of 5,10-year risk of distant metastasis. They have some estimations on prostate cancer specific mortality as well. Dr. Rafeh Naqash: Sure. Now, the third part of this project, and correct me if I'm wrong, the grid database of the 265 genomic signature score. From what I understood, this is a different component than the Decipher score. Is that a fair statement? Dr. Amar Kishan: Yeah. No, that's exactly correct. And that was an exploratory part of this analysis, to be honest. Basically, I think our main focus in the paper was those advances that we've talked about PSMA and Decipher, those happened concurrently. People started developing PSMA PET, people started developing Decipher. And so, what we wanted to understand was, if you have a patient that has extra prosthetic disease on PSMA PET, are those biologically more aggressive cancers, is their Decipher score going to be higher? What can we learn about the biology of this? And we were the first, to my knowledge, where we actually had a large data set of patients that actually received PSMA PETs and Decipher. And that's kind of the gist of the paper. We have patients in the upfront setting, patients in the post radical prostatectomy setting, and we're essentially showing that there is this correlation. In the upfront setting, the odds of extra prosthetic disease are higher for higher Decipher scores, which is kind of maybe validating that this biology is capturing something that's akin to this ability to spread. And in the post-op setting, because we have time to failure, technically, we can calculate a hazard ratio rather than odds ratio. So, we have a hazard ratio that's significantly associated with an increased risk of spread for patients with higher Decipher. The grid portion, which is the genomic resource information database, was more of an exploratory part where I mentioned the Decipher score is based off this microarray, they're looking at 1.4 million transcripts. Only 22 are part of the Decipher, but you can request the rest of the signature data as well. And so, we wanted to look at other pathways, other signatures that have been published, like looking at DNA repair, neuroendocrine pathway, just to see if we could see any correlations there that's not necessarily as clinically actionable. These are more exploratory. But again, we were trying to just look at whether patients who had non localized disease on their PSMA PET, whether their primary had more aggressive biology. We did see that. So that's kind of loosely speaking things like PTEN loss, androgen receptor, DNA repair, metabolism, neuroendocrine signaling, which are thought to be portenders of aggressive disease. Those pathways were upregulated at the RNA level in patients who had non-localized disease. And that's kind of the take home from that. But I wouldn't say any of that is clinically actionable at this point. It's more kind of defining biology. Dr. Rafeh Naqash: Some of the interesting correlations that you make here, at least in the figures that we see, you're looking at different local occurrences, nodal metastases, M1A and M1B disease. And one thing that I'm a little curious about is the Decipher score seems to be lower in pelvic nodal metastasis, that is, PSMA PET positive versus local recurrence, which has a slightly higher Decipher score. Is that just because of a sample size difference, or is there a biologically different explanation for that? Dr. Amar Kishan: Yeah, that's a good point. I would assume that's probably because of a sample size in this case, and it's a little bit complicated. It wasn't statistically different. And it was 0.76 on average for patients with local recurrence and 0.7 for patients with a pelvic nodal metastasis. Well, what I think is interesting is we can maybe think that in this post-op setting the time to failure could have been long in some of these cases. So, it is conceivable that an isolated nodal recurrence 10 years after the surgery, for instance, is not as aggressive a cancer as a local recurrence in a short time after the surgery. And that's not taken into account when you're just looking at median scores like we are in this fox and whiskers plot. But overall, I think what it's suggesting is that there are patients who have more indolent disease. That's actually pretty widespread there. There are pretty indolent cases that have these nodal metastases. So just because you have a nodal metastasis doesn't mean it's an incredibly aggressive cancer, biologically. Dr. Rafeh Naqash: Now, the exploratory component, as you mentioned, is the grid part where you do look at TP53, which is a cell cycle gene, and higher TP53 associated with worse recurrences, from what I understand. Do you see that just from a cell cycle standpoint? Because from what I, again, see in the paper, there's a couple of other cell cycle related signatures that you're using. Is that just a surrogate for potential Gleason score? Have you guys done any correlations where higher Gleason score is associated with maybe higher cell cycle checkpoint, pathway related alterations and replication stress and DNA damage and perhaps more aggressive cancers? Dr. Amar Kishan: Yeah, that's a great question. We haven't done that in this paper, but it has been published before that there is this correlation loosely between grade and some of these parameters - so repair, metabolism, androgen receptor signaling. However, it's a very great point that you bring up, which is that it's pretty heterogeneous and that's why we need something like this as opposed to Gleason score. So, you can have Gleason 10 cancer. I mean, that would be pretty uncommon. But within the Gleason 9, at least, which we have published on and looked at, there's a heterogeneity. There are some that are biologically not that aggressive. And the converse Gleason 7, you can have some that are actually biologically aggressive. That's why it may be useful to move away from just the pathological architecture and get a little bit more into some of these pathways. Dr. Rafeh Naqash: What's the next step here? I know this perhaps isn't ready for primetime. How would you try to emphasize the message in a way that makes it interesting and clinically applicable for your colleagues in the GU community? Dr. Amar Kishan: Yeah. I think for me, what I would try to emphasize here and what I think is the main takeaway is this is kind of a validation that having extra prostatic disease on PSMA PET is likely suggestive of a more aggressive disease biology. And I think what this stresses to me is the importance of getting a PSMA PET, particularly in patients with high-risk prostate cancer. This isn't always happening. And I think if we see things on a PSMA PET, we really need to consider systemic therapy intensification. And what do I mean by that as a practical point? You have a high-risk prostate cancer patient. You get a PSMA PET, you see an isolated pelvic lymph node. If we believe the results of the study, that's a more aggressive biology likely. Whether we have the Decipher or whether we have genomic signatures, which we may or may not have, maybe that patient should get treated with something like an androgen receptor signaling inhibitor in addition to ADT, more akin to a clinically node positive case. So, intensify the systemic therapy, more aggressive disease. That's how I would incorporate it practically into my practice, that really what we're seeing on the PSMA PET is real. It's a reflection of biology that's aggressive. It's not just some Will Rogers effect where you're upstaging stuff needlessly. I think this is telling us some true biology. So that's kind of what my takeaway would be. I think future areas of investigation would be, honestly, to try to have a better idea of what's going on in these metastases. So, if you could design a study potentially, where your biopsy some of these and actually do sequencing and understand a little bit more of that. And so, we're looking into stuff like that. But my takeaway for like the everyday clinician would be to try to get a PSMA PET, if you can, and to intensify therapy on the basis of that, or at least consider it, discuss it in a multidisciplinary setting. Dr. Rafeh Naqash: And I'm guessing somebody out there, perhaps even you, are thinking or planning on doing a ctDNA MRD based correlation here, since that's up and coming in this space. Dr. Amar Kishan: That is up and coming, I think one of the challenges in prostate cancer is the amount of ctDNA can be low. But yes, you're right, that's certainly things that a lot of us are looking at, too. Dr. Rafeh Naqash: Excellent. Well, thank you for the science discussion, Dr. Kishan, could you tell us a little bit about yourself, your career trajectory, where you started, what you're doing, and perhaps some advice for early career junior investigators, trainees, things that might have worked for you, that could also work for them as they are progressing in their careers. Dr. Amar Kishan: Sure. So, yeah, I'm a radiation oncologist at UCLA. I run the prostate cancer radiation program. Clinically. I'm also heavily involved in our research enterprise, so I kind of oversee the clinical and translational research aspect. That's what I do currently. So, I did my residency in radiation oncology at UCLA. Just on a personal note, my wife is from LA, her parents live in LA. We really wanted to stay in LA, so I was fortunate to be able to join the faculty here. I always liked GU oncology, so that was kind of a natural thing for me to kind of go into this position here and try to build the GU program. I've been very fortunate to have great collaborators. My message to students and trainees is to try to reach outside your department for mentorship as well. It's important to have people inside your department who can mentor you. But as a radiation oncologist, I work so closely with urology, so closely with medical oncology that I'm very fortunate to have individuals in those departments who have a vested interest in me and my success as well. I like working with them. It's important to be a team player. If they need help, you help them. If you need help, you ask for help from them. So, I think that's the single biggest thing that I would say to any trainee is don't be intimidated. Please reach outside of your department. Lots of people are willing to help and provide mentorship, and it's helpful to have that perspective. We are in a very multidisciplinary environment and era of practicing medicine. Dr. Rafeh Naqash: Well, thank you again for those personal insights and especially for submitting your work to JCO PO. And we hope to see more of this work perhaps in the subsequent sessions for JCO PO, and maybe we'll bring you back again. And at that point, the Decipher and the PSMA PET scan will have more data, more implementation in the clinically relevant real-world setting. Dr. Amar Kishan: Thank you very much. And if I could just give one quick shout out. The first author of this work, which I presented, was Dr. John Nikitas, who is a trainee that works with me here at UCLA a PGY5 resident. So, I do want to give credit to him as well. Dr. Rafeh Naqash: And John, if you're listening to this hopefully, it's always great to get a shout out from your mentor. Thank you both again for putting in the work and effort to submit this manuscript. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at 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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Disclosures  Dr. Kishan Honoraria Company: Varian Medical Systems, Boston Scientific,  Janssen Oncology  Consulting or Advisory Role Company: Janssen, Boston Scientific, Lantheus  Research Funding Company: Janssen , Point Biopharma

DocPreneur Leadership Podcast
Spotlight: Concierge Oncology, Chad Levitt, MD - Radiation Oncologist

DocPreneur Leadership Podcast

Play Episode Listen Later Apr 25, 2024 81:28


Concierge Medicine is unique in so many ways and impacting the lives of Patients and Physicians in multiple specialties. Today we sit down with Dr. Chad Levitt, a Radiation Oncology and Founder of ONCare. Dr. Levitt strives to put himself “in his patients' shoes” as he considers all aspects of their care plan. Central to his philosophy is the interest in providing care beyond mere treatment, and this passion complements his role within each of his patients' treatment teams.   By Concierge Medicine Today, Editor/The DocPreneur Leadership Podcast   A board-certified radiation oncologist and Atlanta-native, https://onc.care/ completed his doctorate and residency at Emory University's School of Medicine in Atlanta. Dr. Levitt has served as clinical director of oncology practices and departments previously in Colorado, Florida, and Georgia. He is the founder of Radiotherapy Associates of Forsyth as well as ONCare Specialty Consultants.   LEARN MORE, VISIT: https://onc.care/   With over 20 years of experience in the treatment of cancer, Dr. Levitt has, over the years, been at the forefront of radiation treatment techniques, innovations and practices. He is a national speaker and has published clinical studies in multiple peer reviewed oncology journals. He has served on national advisory boards and working groups throughout his career as well as having been the practice liaison and PI for RTOG and USOncology clinical research trials.   Dr. Levitt strives to put himself “in his patients' shoes” as he considers all aspects of their care plan. Central to his philosophy is the interest in providing care beyond mere treatment, and this passion complements his role within each of his patients' treatment teams.   As he has continued to practice within the evolving landscape of system based healthcare, he has now founded the concierge based practice to maximize his ability to help empower and educate patients to navigate and advocate for themselves amidst what has become a guideline based delivery of treatment. Choosing to help clients and their families in a very personal, experienced and detail oriented manner, he strives to remain unincentivised by treatment, but to focus on care for the whole patient and support system in a custom tailored manner. Knowing there's not a one size fits all paradigm for healing, he is now able to focus his energy and time on helping patients to minimize the hurdles unrelated to treatment and well-being and to help clients ensure their focus can be on living while on their health related journeys.   Dr. Levitt has been nominated by his piers and colleagues as a Castle Connolly “Top Doctor” in Atlanta since 2014. He and his wife, Alisha, are fortunate to be able to raise their three children in their native city close to their extended family. In his spare time Dr. Levitt enjoys rock climbing, playing guitar, coaching soccer, camping with his family and woodworking.   © Concierge Medicine Today, LLC. ("CMT") All rights reserved.   Disclaimers: All content presented here is for general information purposes only. It is NOT intended to provide medical, legal, professional, accounting or financial advice. No warranties or guarantees are assumed or implied and user(s) releases Concierge Medicine Today, LLC, its agents, representatives, affiliated brands/companies and/or guests from all damages, liability and/or claims. Be advised, some references, companies, individuals, products, services, resources and/or links may be out-of-date. Concierge Medicine Today, LLC does not update content past its release date. User(s) assume all risk and liability with any use of the content as well as third party links. Concierge Medicine Today, LLC., has no formal peer review and, therefore, cannot guarantee the validity of information and/or content contained on its web sites, podcasts, and/or all content it produces or releases. While some of our speakers may be licensed Physicians, they are not your Physician. Please consult your Physician related to anything you may have read or heard or have questions about or call 911. The views, thoughts, and opinions expressed are the speaker's own and do not necessarily represent the views, thoughts, and/or opinions of Concierge Medicine Today, LLC. The "Concierge Medicine Today, LLC" ("CMT") name and all forms and abbreviations are the property of its owner and its use does not imply endorsement of or opposition to any specific organization, product, or service. Additional disclaimers, releases, terms of use and conditions apply also to the production and/or use of this content, https://conciergemedicinetoday.org/tcpp/.

ASTRO Journals
Red Journal Podcast March 1, 2024: The Evolution of Postprostatectomy CTV Delineation

ASTRO Journals

Play Episode Listen Later Feb 7, 2024 57:42


Editor-in-Chief Sue Yom co-hosts with Dr. Thomas Zilli, Associate Editor at the Red Journal and Professor and Director of the Department of Radiation Oncology at the Oncology Institute of Southern Switzerland. Dr. Zilli was co author on Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy, published in the April 2021 issue of the Red Journal. Guests include Dr. Alan Dal Pra, Associate Professor and Director of Clinical Research in the Department of Radiation Oncology at the University of Miami, who first authored the ESTRO ACROP 2023 guideline and with colleagues at UCLA has worked on patterns of prostate bed recurrence on PSMA-PET in relation to the RTOG guidelines, as well as Dr. Floor Staal, PhD candidate at the University of Groningen, who is focused on the study of salvage radiotherapy treatment and is coordinator of the PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy (or PERYTON) trial. She first authored an article publishing this month, PSMA PET/CT based clinical target volume delineation guideline for postprostatectomy salvage radiation therapy: the PERYTON-Guideline.

Oncology Unscripted
The Insider's Guide to Radiation Therapy: Proton Therapy

Oncology Unscripted

Play Episode Listen Later Oct 16, 2023 47:51


On this episode of Oncology Unscripted, patient advocates Julie Johnson and Katie Coleman and radiation oncologist Dr. Matt Spraker continue The Insider's Guide to Radiation Therapy! Here are the figures/graphics we referenced during the show:The first figure we discussed, demonstrating the Bragg Peak and the difference between proton and photon (x-ray) beams. The second figure we discussed, comparing 3D photon (x-ray) radiation, intensity modulated radiotherapy with photons (x-ray), passive scatter and intensity modulated proton therapy.Here are some other things we discussed during the show:Relative biological effectiveness in radiobiologyA video about "IMRT for proton therapy", or pencil beam scanning proton therapy, from manufacturer IBA.Brada review of proton evidence, questioning whether the US should open so many proton centers so quickly. Goitein and Cox response to Brada, arguing that the benefit of proton therapy is self-evident.Glatstein, Glick, Kaiser, and Hahn, arguing that trials are needed to prove the benefit of proton therapy.Liao et al., randomized phase II trial of proton versus photon (x-ray) radiotherapy for locally advanced non-small cell lung cancer.RTOG 1308, randomized phase III trial of proton versus photon (x-ray) radiotherapy for locally advanced non-small cell lung cancer. Now filled, awaiting results!Lin et al., randomized phase IIB trial of proton versus photon (x-ray) radiotherapy for locally advanced esophageal cancer.NRG GI-006, randomized phase III trial of proton versus photon (x-ray) radiotherapy for locally advanced esophageal cancer, enrolling now!Oncology Unscripted is a Photon Media production. Intro and Outro music by Emmy-award winning artist Lucas Cantor Santiago.Additional content from Katie Coleman can be found at her website, https://www.katiekickscancer.com/. This show and our opinions are meant for general informational purposes and are not medical advice. We encourage you to reach out to your doctors to discuss your individual case. 

JAMA Network
JAMA Oncology : Radiosurgery of Spine Metastasis—NRG/RTOG 0631 RCT Final Results

JAMA Network

Play Episode Listen Later Apr 20, 2023 14:15


Interview with Samuel Ryu, MD, author of Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial. Hosted by Jack West, MD. Related Content: Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine

JAMA Oncology Author Interviews: Covering research, science, & clinical practice in oncology that improves the care of patien

Interview with Samuel Ryu, MD, author of Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial. Hosted by Jack West, MD. Related Content: Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine

The Fellow on Call
Episode 028: Lung Cancer Series, Pt. 6: Radiation Oncology in the Treatment of Lung Cancer

The Fellow on Call

Play Episode Listen Later Sep 7, 2022


Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. An important component of treatment in lung cancer (and many other cancers) is the use of radiation. This week, we continue our discussion about the fundamentals of Radiation Oncology with our guest, Dr. Evan Osmundson. *We hear the terms “hypo-fractioned” and “hyper-fractionated” radiation. What do those mean?- Fractionation, that is breaking up the total dose of radiation into smaller ones, has allowed patients to tolerate the radiation better. The repeat exposure allows the healthy tissue to repair, whereas the tumor is not able to heal as well- Standard fractionation involves keeping the maximum dose per session at 1.8-2Gy/fraction. - Hyper-fractionation is when a patient gets multiple doses per day, each less than 2Gy. This is important in small cell lung cancer, where the standard dose of radiation is 1.5Gy twice daily- Hypo-fractionation os when larger doses are given in each session, typically larger than 2.5-3Gy, often 4-5Gy per fraction. This is analogous to SBRT. *With regards to SBRT, how do you determine the number of sessions? - Typically 3-5 sessions, and this is based on data run through their computer algorithm that allows the dose to be tumoricidal. - More sessions (more likely 5 sessions) if central tumor (

Clinical Papers Podcast
# 113 - RTOG 91-11: Câncer de laringe localmente avançado: comparação de 3 estratégias não operatórias - Resultados de longo prazo

Clinical Papers Podcast

Play Episode Listen Later Jul 28, 2022 30:33


Com o objetivo primário de SLL (sobrevida livre de laringectomia), mais de 500 pacientes com tumores EC III e IV de laringe (regiões glóticas ou supraglóticas) foram randomizados para receber QT de indução com cisplatina/fluorouracil + RT (braço de controle), cisplatina/RT concomitante ou RT isolada.Neste episódio, Renan Lira, Genival B. de Carvalho, Fernando Arruda e Gilberto Castro discutem esse importante paper que trouxe os protocolos de preservação de tumores de laringe para a prática clínica! Sejam bem vindos ao episódio 113 do Clinical Papers Podcast!Para saber mais sobre o paper, acesse:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577950/

ASCO Guidelines Podcast Series
Management of Stage III NSCLC Guideline

ASCO Guidelines Podcast Series

Play Episode Listen Later Dec 22, 2021 11:44


An interview with Dr. Megan Daly from University of California in Davis, California and Dr. Navneet Singh from the Postgraduate Institute of Medical Education & Research in Chandigarh, India, co-chairs on “Management of Stage III Non–Small-Cell Lung Cancer: ASCO Guideline.” They summarize guideline recommendations on five subtopics – evaluation & staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. Read the full guideline at www.asco.org/thoracic-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING]   ANNOUNCER: 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. BRITTANY HARVEY: 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 ASCO.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Megan Daley from University of California in Davis, California, and Dr. Navneet Singh from the Post-Graduate Institute of Medical Education and Research in Chandigarh, India, co-chairs on management of stage III non-small cell lung cancer ASCO guideline. Thank you for being here, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you for having us. NAVNEET SINGH: Thank you for having us, too. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Daley, do you have any relevant disclosures that are directly related to this guideline topic? MEGAN DALEY: I have research funding from EMD Serono, Merck, and Genentech. BRITTANY HARVEY: Thank you for those disclosures. Then Dr. Singh, do you have any relevant disclosures that are directly related to this guideline? NAVNEET SINGH: No, I have no financial conflicts of interest. BRITTANY HARVEY: Thank you. Getting into the content of this guideline, Dr. Singh, can you give us an overview of both the scope and the purpose of this guideline? NAVNEET SINGH: Yes, absolutely. So this guideline has been developed to assist clinicians involved in the management of patients with stage III non-small-cell lung cancer, or NSCLC, as we call it briefly. Now, stage III NSCLC represents one of the most heterogeneous subgroups of lung cancer. Consequently, it is also the subgroup in which the choice of multimodality treatment and the sequence of multimodality treatment varies significantly amongst clinicians, with variations being observed across institutes, as well as within an institute. And we sincerely hope that, with the help of this guideline, clinicians can accurately confirm the presence of stage III disease and offer the most appropriate treatment based on clinical and radiographic characteristics, as well as other medical factors that influence treatment decision-making. This evidence-based guidance also seeks to provide clarification on the common clinical dilemmas that clinicians may have while evaluating a patient with suspected or known stage III NSCLC. BRITTANY HARVEY: Thank you for that background information, Dr. Singh. Then, Dr. Daley, this guideline addresses five main sections, evaluation and staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. So starting with evaluation and staging, what are the key recommendations for workup for patients with suspected stage III non-small cell lung cancer? MEGAN DALEY: Our first recommendation for such patients is that they should undergo a history and physical exam and a CT scan of the chest and upper abdomen with contrast, unless it's contraindicated. If metastatic disease is not identified on CT, those patients should go on to a PET CT scan and MRI of the brain. If the patients are being considered for curative intent treatment, the guideline recommends pathologic mediastinal lymph node assessment. And we recommend that endoscopic techniques should be offered as the initial staging modality, if available. If not available, invasive surgical mediastinal staging should be offered. And finally, for patients who have suspected or confirmed stage III lung cancer, we recommend that multidisciplinary discussion should occur prior to any initiation of a treatment plan. BRITTANY HARVEY: Great, I appreciate your reviewing those recommendations. So following that, Dr. Singh, what does the guideline recommend regarding which patients with stage III non-small-cell lung cancer should be considered for surgical resection? NAVNEET SINGH: So in this guideline, the recommendation which has come forth is that for patients with stage IIIA, basically N2 disease, induction therapy should be followed by surgery with or without adjuvant therapy if several conditions are met. Basically, a complete resection of the primary tumor and the involved lymph nodes is deemed feasible, and three nodes or contralateral lymph nodes are deemed to be not involved, and the expected perioperative 90-day mortality is low, typically 5% or less. Another recommendation is that for selected patients with the P4N0 disease, surgical resection may be offered if medically and surgically feasible following multidisciplinary review. We would like to emphasize here that surgeons should always be involved in decisions regarding the feasibility of surgical resection. And they are an integral part of a multidisciplinary evaluation for surgical resection for stage III NSCLC patients. BRITTANY HARVEY: Great. Then Dr. Singh just reviewed who should be considered for surgical resection. So Dr. Daley, for patients with potentially resectable stage III non-small-cell lung cancer, what are the key recommendations for neoadjuvant therapy? MEGAN DALEY: Our first recommendation is that patients who are planned for a multimodality approach that will incorporate surgery should receive systemic neoadjuvant therapy. Second, that those patients with N2 disease who are planned for surgical resection should receive either neoadjuvant chemotherapy or neoadjuvant concurrent chemoradiation. And finally, for patients with a resectable superior sulcus tumor, neoadjuvant concurrent chemoradiation should be administered. BRITTANY HARVEY: Understood. Then in addition, Dr. Singh, for patients with resected stage III non-small-cell lung cancer, what are the key recommendations for adjuvant therapy? NAVNEET SINGH: So the panel came up with three recommendations for adjuvant treatment. The first is that patients with resected stage III NSCLC who did not receive neoadjuvant systemic therapy should be offered adjuvant platinum-based chemotherapy. The second recommendation which we came up was that for patients with resected stage III disease and presence of a sensitizing EGFR mutation-- classically, exon 19 deletion or the L858R exon 21 point mutation-- they may be offered adjuvant osimertinib, which is an EGFR inhibitor, after platinum-based chemotherapy. And this is based upon the ADAURA trial, which was published last year. And the third recommendation was that for patients with completely resected NSCLC and mediastinal involvement N2 disease, but without extracapsular extension, post-operative radiotherapy should not be routinely offered. BRITTANY HARVEY: OK. And then the last section of recommendations covers unresectable disease. So Dr. Daley, what does the guideline recommend regarding the management of unresectable stage III non-small-cell lung cancer? MEGAN DALEY: The guideline first recommends that these patients who have a good performance status should be offered concurrent, rather than sequential, chemoradiation, that concurrent chemotherapy delivered with radiation should include a platinum-based doublet, preferably cisplatin-etoposide, carboplatin-paclitaxel, or cisplatin-pemetrexed or cisplatin-vinorelbine. The patients who are not candidates for concurrent chemoradiation, but who are potentially candidates for chemotherapy, should be offered sequential chemoradiation, rather than radiation alone, that patients receiving concurrent chemoradiation should be treated to 60 gray. And that's based on the results of RTOG 0617. We also recommend within the guideline that doses higher than 60 gray and up to 70 gray could be considered for selected patients, with careful attention to doses to the heart, lung, and esophagus, among other organs. The guideline also recommends that patients receiving definitive radiation without chemotherapy, that hypofractionation using slightly larger doses could be considered-- over 2 gray per fraction, and up to 4 gray per fraction, and that patients without disease progression during concurrent chemoradiation should be offered consolidation durvalumab, based on the PACIFIC trial. BRITTANY HARVEY: Thank you both, then, for reviewing the key recommendations of this guideline. So, Dr. Singh, in your view, what is the importance of this guideline, and how does it impact clinicians? NAVNEET SINGH: I think this guideline will go a long way in helping clinicians who are involved in the diagnosis and treatment of lung cancer, especially stage III NSCLC. As mentioned earlier, this is a very heterogeneous disease. And there are several challenging situations, both in the context of diagnosis, as well as treatment. And using this guideline, which has an extensive evidence review, as well as the development of two very helpful algorithms, we sincerely hope that clinicians who are both in academic centers as well as in practice in the community are able to accurately diagnose stage III, appropriately stage it, and offer the best treatment, given the patient characteristics and the disease characteristics and available resources. BRITTANY HARVEY: Great. Those are important points. So then, finally, Dr. Daley, how will these guideline recommendations affect patients? MEGAN DALEY: Well, we hope very much that these guidelines will help patients consistently receive high-quality care for their stage III lung cancer. In particular, we're hoping that the recommendation from multidisciplinary assessment of patients prior to treatment is carefully followed. We're hoping that some of the recommendations surrounding the appropriate workup for patients may help ensure that all patients receive a thorough and complete workup prior to initiation of treatment. And the guideline, in particular, is highlighting some of the more recent developments in stage III lung cancer, such as the use of consolidation durvalumab based on the PACIFIC trial, the use of osimertinib in resectable disease based on the ADAURA trial. And we're hoping to make sure that these results are disseminated to practitioners everywhere so that patients can receive the latest and best care for their stage III lung cancer. BRITTANY HARVEY: Understood. Yeah, as you both mentioned, we hope that this has a positive impact for both clinicians and patients. So I want to thank you both for all of your hard work to develop this guideline and the evidence-based recommendations along with it. And thank you for taking the time to speak with me today, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you so much for having us. NAVNEET SINGH: Thank you. BRITTANY HARVEY: 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/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

QuadShot News Podcast
10.25.2021 - Daniel Krauss & RTOG 0815 - ASTRO 2021

QuadShot News Podcast

Play Episode Listen Later Oct 25, 2021 22:07


We get a chance to sit down with Dr. Daniel Krauss to discuss RTOG 0815, modern management of intermediate risk prostate cancer, and much more. Be sure to check out the live content from ASTRO 2021. @QuadShotNews@SamuelMarcromMD@LauraDoverMD@ASTRO_org#ASTRO21

Clinical Papers Podcast
#71 - RTOG 0521 – Docetaxel, radioterapia e supressão androgênica em pacientes com câncer de próstata localizado de alto risco

Clinical Papers Podcast

Play Episode Listen Later Oct 26, 2020 25:38


A RT, juntamente com a supressão androgênica (AS), é uma opção de tratamento padrão para pacientes com câncer de próstata localizado de alto risco. Com a hipótese de que a adição de QT com docetaxel poderia melhorar a sobrevida global dos pacientes este estudo foi criado. Recrutados entre 2005 e 2009, pacientes com doença não metastática de alto risco foram randomizados receber SA mais RT com ou sem docetaxel adjuvante......Ainda que “vintage”, esse esquema melhorou a SG de 89% para 93% em 4 anos, com melhora da sobrevida livre de doença e redução na taxa de metástases à distância. Foi, portanto, um estudo positivo, sugerindo que docetaxel pode ser uma opção de tratamento a ser discutida em pacientes de alto risco. .....Para ler o paper na íntegra, acesse: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506419/

BrainWaves: A Neurology Podcast
#109 Misnomers in medicine: Low grade glioma

BrainWaves: A Neurology Podcast

Play Episode Listen Later Aug 20, 2020 25:19


A lot can happen in two years. You might have matched into residency, graduated from fellowship, had a kid... Or several phase II trials in low grade glioma research could have been published. Since the original airing of this episode in May 2018, there have been a few updates in neuro-oncology. We'll cover some of the major ones this week in the BrainWaves podcast. Produced by James E. Siegler, Brian Nahed and Jorg Dietrich. Music courtesy of Ian Sutherland, Lovira, and Lee Roosevere. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast. REFERENCES McGirt MJ, Chaichana KL, Attenello FJ, Weingart JD, Than K, Burger PC, Olivi A, Brem H and Quinones-Hinojosa A. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery. 2008;63:700-7; author reply 707-8. Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR and Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:3065-70. Schiff D. Low-grade Gliomas. Continuum (Minneap Minn). 2017;23:1564-1579. Wen PY and Huse JT. 2016 World Health Organization Classification of Central Nervous System Tumors. Continuum (Minneap Minn). 2017;23:1531-1547. Bell EH, Zhang P, Fisher BJ, Macdonald DR, McElroy JP, Lesser GJ, Fleming J, Chakraborty AR, Liu Z, Becker AP, Fabian D, Aldape KD, Ashby LS, Werner-Wasik M, Walker EM, Bahary JP, Kwok Y, Yu HM, Laack NN, Schultz CJ, Gray HJ, Robins HI, Mehta MP and Chakravarti A. Association of MGMT Promoter Methylation Status With Survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial. JAMA Oncol. 2018;4:1405-1409. van den Bent MJ, Klein M, Smits M, Reijneveld JC, French PJ, Clement P, de Vos FYF, Wick A, Mulholland PJ, Taphoorn MJB, Lewis J, Weller M, Chinot OL, Kros JM, de Heer I, Verschuere T, Coens C, Golfinopoulos V, Gorlia T and Idbaih A. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol. 2018;19:1170-1179. Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ and Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019;20:1011-1022. Bell EH, Zhang P, Shaw EG, Buckner JC, Barger GR, Bullard DE, Mehta MP, Gilbert MR, Brown PD, Stelzer KJ, McElroy JP, Fleming JL, Timmers CD, Becker AP, Salavaggione AL, Liu Z, Aldape K, Brachman DG, Gertler SZ, Murtha AD, Schultz CJ, Johnson D, Laack NN, Hunter GK, Crocker IR, Won M and Chakravarti A. Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020:JCO1902983. Breen WG, Anderson SK, Carrero XW, Brown PD, Ballman KV, O'Neill BP, Curran WJ, Abrams RA, Laack NN, Levitt R, Galanis E, Buckner JC and Shaw EG. Final report from Intergroup NCCTG 86-72-51 (Alliance): a phase III randomized clinical trial of high-dose versus low-dose radiation for adult low-grade glioma. Neuro Oncol. 2020;22:830-837. Ullrich NJ, Prabhu SP, Reddy AT, Fisher MJ, Packer R, Goldman S, Robison NJ, Gutmann DH, Viskochil DH, Allen JC, Korf B, Cantor A, Cutter G, Thomas C, Perentesis JP, Mizuno T, Vinks AA, Manley PE, Chi SN, Kieran MW and Consortium NFCT. A Phase II Study of Continuous Oral mTOR Inhibitor Everolimus for Recurrent, Radiographic-Progressive Neurofibromatosis Type 1-Associated Pediatric Low-Grade Glioma: A Neurofibromatosis Clinical Trials Consortium Study. Neuro Oncol. 2020.

Clinical Papers Podcast
#54 - Câncer de Próstata - Associação entre PSA prévio a RT de resgate e Sobrevida com a adição de terapia antiandrogênica de longo prazo

Clinical Papers Podcast

Play Episode Listen Later Jun 13, 2020 24:51


Homens com recorrência bioquímica de câncer de próstata são tratados geralmente com RT em associação com terapia anti-androgênica (TAA). “HOWEVER” esse tratamento tem morbidades e não há marcadores bioquímicos que identificam os pacientes que mais se beneficiariam dessa associação.Há cerca de três anos, foi publicado um grande estudo que randomizou mais de 700 pacientes entre receber ou não TAA durante o tratamento com RT. Neste episódio os colegas Carlos Dzik, Fernando Korkes e Rodrigo Hanriot (os mais novos componentes da equipe!) irão discutir um paper publicado na JAMA Oncol agora em março de 2020, derivado do RTOG 9601 (os quatro primeiros números do telefone do Korkes), que examina o papel dos níveis de PSA pré RT/TAA e sua relação com sobrevida.Uma dica: um dos grandes problemas dessa terapia foi a dose utilizada da bicalutamida: 150mg/d durante 2 anos!Sejam muito bem-vindos ao episódio #54 OU episódio #01 do Clinical Papers UROLOGIA!

ASCO Daily News
Dr. S. Lindsay Davis Highlights Key Abstracts on GI Cancers from the #ASCO20 Virtual Scientific Program

ASCO Daily News

Play Episode Listen Later Jun 9, 2020 19:26


Dr. S. Lindsay Davis, medical oncologist and assistant professor at the University of Colorado Cancer Center, highlights key abstracts on GI cancers that were featured at the #ASCO20 Virtual Scientific Program.   Transcript ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carol, a reporter for the ASCO Daily News. I'm delighted to welcome Dr. Lindsay Davis to the podcast today. She's a medical oncologist and assistant professor at the University of Colorado Cancer Center, where her clinical focus is gastrointestinal tract cancers.   She joins me today to discuss key abstracts in the GI field that were featured at the ASCO20 Virtual Scientific Program. Dr. Davis reports no financial conflicts of interest relating to the issues discussed in this podcast. Full disclosures relating to all daily news podcasts can be found on our episode pages. Dr. Davis, it's great to have you on the podcast today.   Dr. Lindsay Davis: Thank you, Geraldine. I am excited for the opportunity to discuss some of the key abstracts related to GI malignancies with you today. I must say the virtual scientific program was a bit of a different ASCO experience than we're accustomed to. However, the high quality of the data and presentations we expect at the annual ASCO meeting was really beautifully maintained in the virtual sessions.   ASCO Daily News: Well, what are the abstracts, Dr. Davis, that really caught your attention in the GI field this year?   Dr. Lindsay Davis: To me, the results from the KEYNOTE-177 study, abstract LBA4, which was presented at the plenary session, is really the standout in terms of GI malignancies from this ASCO meeting. KEYNOTE-177 is a randomized, open label, phase III study, comparing pembrolizumab to standard of care chemotherapy as first-line treatment for microsatellite instability-high and mismatch repair deficient metastatic colorectal cancer.   With a median follow-up of 32 months, the primary progression-free survival endpoint was met, with a median PFS in the pembrolizumab group of 16.5 months, as compared to 8.2 months in the chemotherapy group. So that's a doubling of PFS and a hazard ratio of 0.6.   In addition, and as expected, the toxicity rates were significantly lower in the pembrolizumab versus chemotherapy arms, with grade 3 or higher events occurring in only 22% of patients treated with pembrolizumab. And that's compared to 66% of patients treated with chemotherapy. This, of course, provides us the best case scenario of a treatment that is more effective, but also less toxic.   And though the MSI high population represents a relatively small proportion of our patients with metastatic colorectal cancer, this study is still clearly practice changing, making pembrolizumab the first-line treatment of choice for patients with metastatic MSI high disease.   In addition, I think this object is also important, as it provides further direction toward the biomarker-driven treatment of metastatic colorectal cancer. So I would encourage our listeners to look at abstract 4000, the DESTINY-CRC01 study.   There are a couple of additional biomarker-based trials in colorectal cancer that I wanted to touch on as well. The first is the PANDA study. This is abstract 4002. This is a randomized phase II trial, evaluating 185 patients aged 70 and above. The median age in this study was actually 77.   These patients had untreated RAS and BRAS wild-type metastatic colorectal cancer and were treated with FOLFOX plus the EGFR inhibitor panitumumab, or with 5-fluorouracil plus leucovorin and panitumumab for up to 12 cycles, followed by panitumumab maintenance. So really, the key difference between the arms here is that oxaliplatin was not included in the second arm.   Interestingly, approximately 20% of patients treated in each arm on the PANDA trial had right-sided primary tumors, which we now have data to suggest in a general population, not specific to age, would be less likely to benefit from EGFR inhibitor therapy in the first-line setting.   The primary endpoint for this study was progression-free survival in each arm, with no direct comparison made between the arms in this trial. The median PFS was 9.6 months in the FOLFOX panitumumab arm and very similar at 9.1 months in the 5-fluorouracil leucovorin panitumumab arm.   This was accompanied by a significant decrease in grade 3 and greater toxicity, including, of course, neurotoxicity-related to oxaliplatin as well as neutropenia and diarrhea. In general, these results are promising for our elderly patients with RAS and BRAF wild-type metastatic colorectal cancer and warrant further assessment in a phase III study for formal comparison of the arms.   And importantly, I'll say in clinical practice, we do encounter elderly patients who are not candidates for oxaliplatin or who are unlikely to tolerate intensive chemotherapy due to competing medical risks. So this data provides us some evidence for proceeding with 5FU and EGFR inhibitor therapy in this population.   That said, given the data regarding the decreased benefit of EGFR inhibitor therapy as part of first-line treatment for RAS wild-type right-sided colorectal cancer, I would limit the use of this strategy to elderly patients with left-sided tumors that are RAS and BRAF wild-type.   I would also like to just briefly mention a third biomarker-based abstract for metastatic colon cancer, abstract 4001, which detailed the updated survival results from the phase III BEACON CRC trial. And I wanted to mention this study because these results are the basis for the recent FDA approval of the encorafenib cetuximab doublet for the treatment of BRAF V600E mutant metastatic colorectal cancer beyond first-line.   This subset of metastatic colorectal cancer has historically been associated with a very poor prognosis with minimal response to cytotoxic chemotherapy. The BEACON CRC trial evaluated the doublet of encorafenib plus cetuximab, as well as a triplet of encorafenib plus cetuximab and MEK inhibitor binimetinib, as compared to standard chemotherapy for the treatment of BRAF V600E metastatic colorectal cancer. This was in the second or third-line setting.   The results presented at this ASCO are a post-hoc analysis of the previously published BEACON data, including an additional six months of follow-up. This data demonstrated a median overall survival of 9.3 months for both the encorafenib, cetuximab doublet, as well as the encorafenib, cetuximab, binimetinib triplet. And this was compared to only 5.9 months in the control arm with chemotherapy.   As expected, there was added toxicity in the triplet arm as compared to the doublet arm, consistent with the known toxicity of MEK inhibitor therapy. So as the FDA approval supports, this targeted regimen of encorafenib, cetuximab should be considered the standard of care for this population in the second-line setting and beyond, given improved survival outcomes as compared to standard chemotherapy and improved side effect profile as compared to the triplet combination.   ASCO Daily News:  Dr. Davis, are there any new agents that will potentially change standard of care moving forward?   Dr. Lindsay Davis: Some very promising data was presented on the compound trastuzumab deruxtecan, or T-DXd, an antibody drug conjugate composed of anti-HER2 antibody with a topoisomerase I inhibitor payload. Studies evaluating this compound were presented both for patients with HER2 expressing metastatic colorectal cancer, as well as HER2 expressing gastric cancer. We'll talk about each of these.   In the DESTINY-CRC01 study, T-DXd was evaluated in patients with HER2 expressing RAS wild-type metastatic colorectal cancer in the third line and beyond. 78 patients received T-DXd, of whom about 90% had left colon rectal cancer, which was heavily pre-treated with a median prior lines of therapy of 4, and it ranged from 2 to 11 prior lines.   The primary endpoint in this open label phase II study was objective response rate in patients with HER2 IHC 3+ or HER2 IHC 2+ with a positive ISH test. Confirmed overall response rate in this population was 45% with one complete response, which was quite impressive, given these patients are heavily pretreated with the median of four prior regiments.   Also of note is the overall response rate in patients with prior HER2 treatment, which actually represented 30% of the population. The overall response rate in this group was 44%. In terms of toxicity, grade 3 and greater treatment emergent adverse events were documented in 62% of patients, with the most common being cytopenias, neutropenia, and anemia mostly.   However, in addition, five patients developed interstitial lung disease related to treatment. This is a toxicity that has been seen in other trials of this compound. But in this study, it included two fatal grade 5 events of interstitial lung disease. So in terms of HER2 positive RAS wild-type metastatic colorectal cancer, I think T-DXd represents an encouraging option for treatment of this molecular subgroup, with notable effects in patients pretreated with HER2 targeted agents.   However, given the notable risk of treatment-related interstitial lung disease, this will need to be further vetted in a phase III trial. I think the study further highlights the importance of broad molecular testing in colorectal cancer, as though HER2 positivity is only identified in 2% to 3% of patients with this disease. Effective targets for this and other uncommon molecular alterations are being developed.   Similarly, promising results were presented in the DESTINY-Gastric01 study. This is abstract 4513, an open label, randomized, phase II trial evaluating T-DXd and HER2 expressing advanced gastric or GE junction adenocarcinoma. Patients had centrally confirmed HER2 positive disease, according to the same definition as the CRC01 study with progression on at least two prior lines of therapy.   Patients were randomized 2 to 1 to T-DXd or physician's choice of chemotherapy, which included irinotecan or paclitaxel. All patients in the trial had received prior HER2 therapy, of course, as this is standard of care for HER2 positive gastric and esophageal cancers. The primary endpoint on the study was overall response rate. And in the 187 patients treated, the overall response was 51% in patients treated with T-DXd, as compared to only 14% in those treated with chemotherapy.   With central confirmation of response, this overall response rate was a bit lower at 43% in the T-DXd arm, versus 13% in the control group. In addition, overall survival was prolonged in the T-DXd arm at 12.5 months versus 8.4 months in the chemotherapy group with a hazard ratio of 0.59.   Grade 3 and greater adverse events occurred in 86% of patients treated with T-DXd, as compared to 57% treated with standard chemotherapy, and were similar to those documented in the CRC01 study, including treatment-related interstitial lung disease documented in 12 patients.   Though there were no grade 5 events of ILD documented in this Gastric01 study, one grade 5 occurrence of pneumonia was noted in the treatment arm. These results are important, as they suggest a potential effect of a HER2 targeting therapy beyond trastuzumab, the only HER2 targeted therapy shown to be effective for the treatment of HER2-positive gastroesophageal cancers to date.   However, similar to the CRC01 study, the pulmonary toxicity documented in this trial remains a concern. We will look forward to a phase III study to further expand upon these findings.   ASCO Daily News: Are there any additional biomarker-focused studies of interest presented for GI malignancies outside of metastatic colon cancer?   Dr. Lindsay Davis: Yes, there are two additional studies focused on HER2-positive gastroesophageal cancers that were presented at this meeting. Here, they're evaluating the addition of HER2 targeted agents in the curative setting. The PETRARCA study, which is abstract 4502, evaluated perioperative FLOT, or FLOT with trastuzumab and pertuzumab, followed by nine cycles of trastuzumab plus pertuzumab in patients with resectable HER2-positive gastric or GE junction adenocarcinoma.   The primary endpoint for this study was pathologic complete response rate, which was significantly improved in the trastuzumab pertuzumab arm at 35% versus only 12% in the FLOT alone arm. There's also suggestion of benefit on PFS and OS in this study, though it was not powered for formal analysis.   Important to note is the added toxicity of trastuzumab pertuzumab to the FLOT regimen, which is already associated with a significant burden of adverse effects. Grade 3 or greater adverse events were documented in 85% of patients in the trastuzumab pertuzumab arm versus 75% of patients in the FLOT alone arm. And diarrhea and leukopenia were the most notable in the arm that added trastuzumab and pertuzumab therapy.   It should be noted that this trial was originally designed as a phase II/III study, but it was halted at phase II due to the emerging results from the JACOB trial. The JACOB trial was a phase III study which failed to meet its primary endpoint of improved overall survival for the addition of pertuzumab to trastuzumab and chemotherapy in the metastatic setting.   Despite this, I believe these phase II results from the PETRARCA study suggest there is rationale for proceeding with further assessment of this combination in the phase III setting. In contrast to these promising results for the addition of HER2 targeted therapy to standard chemotherapy and HER2-positive gastric and GE junction adenocarcinoma, the RTOG 1010 study, abstract 4500, did not meet its primary endpoint.   This study evaluated the addition of trastuzumab to tri-modality therapy with carboplatin, paclitaxel chemoradiation, followed by surgery in 571 patients with HER2 overexpressing esophageal or GE junction adenocarcinoma. Patients receiving carboplatin paclitaxel chemoradiation followed by surgery had a median disease free survival of 14.2 months as compared to 19.6 months in the trastuzumab arm.   However, this did not meet the prespecified primary endpoint of increasing disease free survival from 15 to 25 months. These results further confirm that defining the role of anti-HER2 therapies for the treatment of HER2-positive gastroesophageal cancers in the curative setting is complex, though deserving of continued attention and investigation.   ASCO Daily News: Dr. Davis, are there any updates on immuno-oncology therapies for the treatment of GI malignancies beyond colorectal cancer?   Dr. Lindsay Davis: Yes, updated results from the randomized phase III KEYNOTE-061 study were presented at this virtual meeting in abstract 4503. The KEYNOTE-061 study is a randomized phase III trial evaluating pembrolizumab versus paclitaxel as a second-line therapy for advanced gastric or GE junction adenocarcinoma in patients with PDL1 combined positive scores greater than or equal to 1.   In the previously presented primary analysis of this study, the primary overall survival endpoint was not met. However, duration of response was significantly longer at 18 months in the pembrolizumab arm versus 5 months in the paclitaxel arm. Presented in this abstract is data from an additional two years of follow-up, as well as further assessment according to additional combined positive scores of greater than or equal to 5 and greater than or equal to 10.   The survival benefit of pembrolizumab over paclitaxel seemed to increase with increasing combined positive score. In the general cohort of CPS greater than or equal to 1, patients treated with pembrolizumab had an overall survival of 9.1 months versus 8.3 months with paclitaxel. This is a hazard ratio of 0.81.   This is compared to an overall survival of 10.4 months with pembrolizumab versus 8.3 months with paclitaxel, a hazard ratio of 0.72 in the CPS 5 or greater population. And finally, in patients with CPS 10 or greater, the overall survival in the pembrolizumab versus paclitaxel arms was 10.4 versus 8.0 months, with the hazard ratio of 0.69.   In addition, the duration of response numerically increased with increasing CPS score, from 19 months in the CPS 1 group to 33 months in the CPS 5 group. And the duration of response has actually not been reached in the CPS 10 group.   I think the conclusion from these updated results is that a proportion of patients have long-term survival benefit from second-line pembrolizumab, which might be somewhat improved with higher CPS. This calls into question a need to adjust our selection criteria for pembrolizumab in patients with gastroesophageal cancers.   In summary, I think the underlying theme of this group of abstracts focused on GI malignancies is that we are continuing to move toward personalized cancer care for the treatment of gastrointestinal tract cancers. These studies also highlight the importance of broad molecular testing for GI cancers, as well as the importance of involvement of our patients with targetable alterations in clinical trials in order to help us continue to improve the individualized care we provide our patients.   ASCO Daily News: Well, thank you, Dr. Davis, for sharing your valuable insights with us today on these promising developments in the GI field.   Dr. Lindsay Davis: Thank you, Geraldine. It was my pleasure.   ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the podcast, please rate and review us on Apple Podcasts.   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.

QuadShot News Podcast
9.16.2019 - Dan Spratt

QuadShot News Podcast

Play Episode Listen Later Sep 16, 2019 30:03


Dan Spratt talks about RTOG 9601 and his take on prostate cancer treatment. quadshotnews@gmail.com @QuadShotNews

Clinical Papers Podcast
Episódio 16 - RTOG 9410: Terapia sequencial vs. cocomitante com RT/QT para câncer de pulmão

Clinical Papers Podcast

Play Episode Listen Later Aug 15, 2019 20:01


O RTOG 9410 avaliou a sequência de tratamento para câncer de pulmão não pequenas células em pacientes com doença inoperável EC II, IIIa e IIIb. Foram 610 pacientes randomizados para a terapia sequencial com RT/QT vs. concommmitante. Com resultados muito bons, o esquema concomitante foi superior, mas com um preço importante a pagar: toxicidade. Marcos André e Tiago Biachi conversam sobre esse artigo publicado no J Natl Cancer em 2011 e foi decisivo para a mudança e padronização dessa conduta em câncer de pulmão não pequenas células. Não perca mais este episódio! Tenha acesso ao paper GRATUITAMENTE pelo link: https://www.ncbi.nlm.nih.gov/pubmed/21903745

MOC Brasil
#050_ASCO 2019 | Próstata_Tratamento de resgate_Dr. Andrey Soares

MOC Brasil

Play Episode Listen Later Aug 14, 2019 3:49


Dr. Andrey Soares, autor do MOC, fala sobre o abstract 5001 (atualização do estudo fase III GETUG-AFU 16), que avaliou a adição da hormonoterapia curta (HT) associada à radioterapia (RT) como tratamento de resgate para sobrevida livre de metástases após prostatectomia radical. Outro estudo comentado pelo Dr. Andrey é o RTOG 9601, que também avaliou a estratégia de bloqueio hormonal associado à radioterapia de resgate no câncer de próstata.

ASCO eLearning Weekly Podcasts
ASCO Guidelines: Role of Treatment Deintensification in the Management of p16+ Oropharyngeal Cancer PCO

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Jul 31, 2019 14:42


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.

Research To Practice | Oncology Videos
Lung Cancer | Corey J Langer, MD

Research To Practice | Oncology Videos

Play Episode Listen Later Jun 5, 2019 64:06


Lung Cancer for Radiation Oncologists — Part 2: Our interview with Dr Langer highlights the following topics and cases from his practice: Case: A woman in her mid-60s, a never smoker, with locally advanced, unresectable adenocarcinoma of the lung and an EGFR exon 18 tumor mutation receives CRT followed by consolidation durvalumab (00:00) Clinical significance and prognostic relevance of microsatellite instability testing in the management of lung cancer (1:29) Risk of recurrence after concurrent CRT for patients with Stage III NSCLC (3:05) Improvement in progression-free and overall survival with the addition of consolidation durvalumab after CRT for patients with Stage III NSCLC on the PACIFIC trial (5:25) Role of immune checkpoint inhibition in the treatment of locally advanced NSCLC with an EGFR tumor mutation (10:15) Perspective on the use of EGFR tyrosine kinase inhibitors in the adjuvant or neoadjuvant setting for patients with locally advanced NSCLC and EGFR tumor mutations (12:50) Initial diagnostic workup and disease management for patients with locally advanced NSCLC (17:17) RTOG-1308: An ongoing Phase III trial of photon versus proton CRT for patients with inoperable Stage II to Stage IIIB NSCLC (19:27) Role of proton beam RT in the treatment of locally advanced NSCLC (21:44) Rationale for the combination of RT and immune checkpoint inhibitors (24:20) Risk of pneumonitis with CRT (26:07) Design and results of the Phase III PACIFIC trial of durvalumab after CRT for unresectable Stage III NSCLC (27:55) Monitoring and management of the toxicities associated with immune checkpoint inhibitors (32:03) Use of durvalumab for patients with preexisting autoimmune disease and for transplant recipients (35:07) Results from the Phase II Hoosier Cancer Research Network LUN14-179 trial of consolidation pembrolizumab after CRT for unresectable Stage III NSCLC (36:45) Ongoing investigation of anti-PD-1/PD-L1 immune checkpoint inhibitors for locally advanced disease (38:56) Case: A man in his mid-80s, a former heavy smoker with multiple comorbidities, is diagnosed with locally advanced squamous cell carcinoma of the lung with a high PD-L1 TPS (tumor proportion score) (40:54) Use of liquid biopsies to detect targetable tumor mutations in patients with lung cancer (44:37) Case: A man in his mid-50s, a former smoker, is diagnosed with Stage IIIA mixed adenosquamous carcinoma of the lung with TTF-1 and p40 tumor mutations (47:17) Perspective on the use of anti-PD-1/PD-L1 antibodies as neoadjuvant therapy for patients with NSCLC (51:22) Case: A man in his early 70s, a current smoker, with adenosquamous carcinoma of the lung and a KRAS mutation receives SBRT (56:28) Optimal approach to RT for patients with locally advanced NSCLC (59:58) Select publications

Empowered to Empower Others
Trials are not to break you, but designed to make you - Pastor Maxine Winfield

Empowered to Empower Others

Play Episode Listen Later May 27, 2019 43:00


We are excited this week to have as our guest, Pastor Florence Winfield, of Resurrection Temple of God, Petersburg, Virginia.  Pastor Maxine, as she's lovingly known, is a powerful Woman of God who has a heart for God's people.  Her message this week will come from 1 Samuel 1.  Plan now to join us by dialing in at 323-927-3014 or using the attached link.  You will be Empowered!  For more information about The Empowerment Place, visit our website at www.theempowermentplace.org

ASCO Guidelines Podcast Series
Role of Treatment Deintensification in the Management of p16+ Oropharyngeal Cancer PCO

ASCO Guidelines Podcast Series

Play Episode Listen Later Apr 25, 2019 14:42


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.

BrainWaves: A Neurology Podcast
#109 Misnomers in medicine: Low grade glioma

BrainWaves: A Neurology Podcast

Play Episode Listen Later May 17, 2018 21:05


The year 2016 marked the transition in an era of neuro-oncology from histologic-based diagnoses of primary brain tumors to a molecular and genetic classification system. Drs. Jorg Dietrich (neuro-oncology) and Brian Nahed (neurosurgery) of Massachusetts General Hospital discuss what the reclassification of primary glial neoplasms means for their patients. Produced by James E. Siegler. Music by Lee Rosevere, Ian Sutherland, and Lovira. Voiceover by Erika Mejia. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. REFERENCES Schiff D. Low-grade Gliomas. Continuum (Minneap Minn). 2017;23:1564-1579. Wen PY and Huse JT. 2016 World Health Organization Classification of Central Nervous System Tumors. Continuum (Minneap Minn). 2017;23:1531-1547. McGirt MJ, Chaichana KL, Attenello FJ, Weingart JD, Than K, Burger PC, Olivi A, Brem H and Quinones-Hinojosa A. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery. 2008;63:700-7; author reply 707-8. Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, Tihan T, Vandenberg S, McDermott MW and Berger MS. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26:1338-45. Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR and Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:3065-70.

Psykologen i Øret
Kisser Paludan om modet til at være os selv og om nødvendigheden af en jordbunden spiritualitet

Psykologen i Øret

Play Episode Listen Later Sep 11, 2017 49:13


Man skulle tro, at det at være sig selv ville være det nemmeste i verden, men det har du sikkert opdaget, at det ikke altid er. Mange af os bruger uanede mængder af tid og ressourcer på at være alt muligt andet end os selv, og det er mildest talt udmattende. For os selv men faktisk også for andre. Hvorfor er det egentligt så svært? Lyt til dagens episode, som var en fantastisk snak, jeg havde med Kisser Paludan om hvordan vi finder modet til at være os selv, hvorfor det er vigtigt og meget mere. Kisser Paludan er psykolog, og så er hun forfatter til flere bøger, kursusleder og foredragsholder, og så har hun endda også en podcast, der hedder Soultalk, som jeg på det varmeste kan anbefale. Kisser kombinerer psykologien med et spirituelt livssyn og hun har senest skrevet bogen MOD til at være dig, som vi kommer til at tale om i dag. Kisser bor desuden i Hellerup sammen med sin mand og 2 børn. Lyt til denne episode hvor vi kommer ind på: Hvad der har krævet mest mod af Kisser selv som psykolog og som menneskeHvorfor hun har valgt at dele af egne personlige erfaringer i bogenDe særlige mennesker, der har givet Kisser mod i hendes eget livAt det at kunne se hvilke psykologiske mønstre, der forhindrer én i nærvær og kærlighed er vejen hjemForskellen på egoisme og sund selvudviklingOm at sætte grænser, når det gælder salater og flyverdragterAt vi sætter andre mennesker på overarbejde, når vi ikke er i stand til at tage ansvar for os selv (!)En øvelse, du kan bruge til at skabe kærlig kontakt med dig selvHvordan spiritualitet kan bruges som flugtstrategi fra det, der gør ondt og er sværtOg mange andre spændende ting Lyt til episoden her:

GRACEcast
What is V20 and Why Do Radiation Dose & Field Size Matter?

GRACEcast

Play Episode Listen Later Feb 3, 2016 4:09


Dr. Jeffrey Bradley, Radiation Oncologist at Washington University in St. Louis, defines the V20 standard for lung radiation and outlines the advantages of limiting dose and field size in lung radiation therapy.

GRACEcast ALL Subjects audio and video
What is V20 and Why Do Radiation Dose & Field Size Matter?

GRACEcast ALL Subjects audio and video

Play Episode Listen Later Feb 3, 2016 4:09


Dr. Jeffrey Bradley, Radiation Oncologist at Washington University in St. Louis, defines the V20 standard for lung radiation and outlines the advantages of limiting dose and field size in lung radiation therapy.

GRACEcast Lung Cancer Video
What is V20 and Why Do Radiation Dose & Field Size Matter?

GRACEcast Lung Cancer Video

Play Episode Listen Later Feb 3, 2016 4:09


Dr. Jeffrey Bradley, Radiation Oncologist at Washington University in St. Louis, defines the V20 standard for lung radiation and outlines the advantages of limiting dose and field size in lung radiation therapy.

Journal of Clinical Oncology (JCO) Podcast
Better Outcome of Chemo-Irradiation of Head and Neck Cancer in High-Patient-Volume Institutions

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Dec 8, 2014 8:41


In a randomized RTOG study of chemotherapy concurrent with accelerated vs standard fractionated radiotherapy for head and neck cancer, it was found that patients treated in institutions who accrued a large number of patients had better outcomes compared with those treated at low-volume institutions, highlighting the importance of referring patients with advanced cancer to high-volume centers.

Journal of Clinical Oncology (JCO) Podcast
Recurrent/Metastatic Human Papillomavirus-Associated Oropharynx Cancer: What Happens When This Good Prognostic Cancer Misbehaves?

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Jun 23, 2014 13:09


This podcast describes the rising epidemic of HPV-associated oropharynx cancer, its unique demographic profile and natural history, and comments on new findings from Carole Fakhry et al. regarding patterns of disease recurrence seen in patients enrolled on RTOG 0129 and 0522.

Journal of Clinical Oncology (JCO) Podcast
Functional Imaging as a Biomarker for Survival in Locoregionally Advanced Non-Small Cell Lung Cancer Patients

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Sep 16, 2013 10:34


ACRIN 6668/RTOG 0235 demonstrates that a post chemoradiotherapy PET scan for locoregionally advanced non-small cell lung cancer can be used as an early indicator for long-term outcome.

GRACEcast
ASCO Lung Cancer Highlights, Part 2: Optimizing Radiation for Stage III NSCLC (audio)

GRACEcast

Play Episode Listen Later Aug 11, 2013 8:45


Dr. David Gerber, University of Texas-Southwestern, reviews results from RTOG 0617 that help clarify the optimal dose of radiation for stage III unresectable NSCLC.

GRACEcast
ASCO Lung Cancer Highlights, Part 2: Optimizing Radiation for Stage III NSCLC (video)

GRACEcast

Play Episode Listen Later Aug 11, 2013 8:45


Dr. David Gerber, University of Texas-Southwestern, reviews results from RTOG 0617 that help clarify the optimal dose of radiation for stage III unresectable NSCLC.

GRACEcast Lung Cancer Video
ASCO Lung Cancer Highlights, Part 2: Optimizing Radiation for Stage III NSCLC (video)

GRACEcast Lung Cancer Video

Play Episode Listen Later Aug 11, 2013 8:45


Dr. David Gerber, University of Texas-Southwestern, reviews results from RTOG 0617 that help clarify the optimal dose of radiation for stage III unresectable NSCLC.

GRACEcast ALL Subjects audio and video
ASCO Lung Cancer Highlights, Part 2: Optimizing Radiation for Stage III NSCLC (audio)

GRACEcast ALL Subjects audio and video

Play Episode Listen Later Aug 11, 2013 8:45


Dr. David Gerber, University of Texas-Southwestern, reviews results from RTOG 0617 that help clarify the optimal dose of radiation for stage III unresectable NSCLC.

GRACEcast ALL Subjects audio and video
ASCO Lung Cancer Highlights, Part 2: Optimizing Radiation for Stage III NSCLC (video)

GRACEcast ALL Subjects audio and video

Play Episode Listen Later Aug 11, 2013 8:45


Dr. David Gerber, University of Texas-Southwestern, reviews results from RTOG 0617 that help clarify the optimal dose of radiation for stage III unresectable NSCLC.

GRACEcast Lung Cancer Audio
ASCO Lung Cancer Highlights, Part 2: Optimizing Radiation for Stage III NSCLC (audio)

GRACEcast Lung Cancer Audio

Play Episode Listen Later Aug 10, 2013 8:45


Dr. David Gerber, University of Texas-Southwestern, reviews results from RTOG 0617 that help clarify the optimal dose of radiation for stage III unresectable NSCLC.

Journal of Clinical Oncology (JCO) Podcast
Evolution of Concurrent Chemoradiation Treatment Approaches in Head and Neck Cancer

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Mar 5, 2013 8:56


This podcast provides commentary and observations on the long term results summary of RTOG 91-11 in which concurrent chemoradiation was shown to provide superior outcome over induction chemotherapy or radiation alone to achieve larynx preservation and locoregional tumor control.

ASTRO Journals
Memantine for the Prevention of Cognitive Dysfunction in Patients Receiving WBRT: First Report of RTOG 0614, a Placebo-controlled, Double-blind, Randomized Trial

ASTRO Journals

Play Episode Listen Later Dec 27, 2012 3:11


Anthony Zietman talks with author Nadia Laack about this game-changing research

ESMO Congress 2012
Chemotherapy and radiotherapy in advanced local non-small cell lung cancer: Dr Dirk De Ruysscher – University of Leuven

ESMO Congress 2012

Play Episode Listen Later Oct 17, 2012 6:02


Dr Dirk De Ruysscher talks to ecancer at ESMO 2012 in Vienna about the treatment of non-small cell lung cancer and current and previous clinical trial results. The difficulty in choosing a treatment stems from the fact that not all patients react the same to combination chemotherapy and radiation treatment. While the majority of patients react better to concurrent radiotherapy, rather than sequential, there is a minority that does not. Currently these topics are being investigated in on going trials. Previous trials, such as the RTOG trial, showed an example of this when a high dose of chemotherapy is actually less effective than smaller doses.

Medizin - Open Access LMU - Teil 17/22
Impact of Radiotherapy, Chemotherapy and Surgery in Multimodal Treatment of Locally Advanced Esophageal Cancer

Medizin - Open Access LMU - Teil 17/22

Play Episode Listen Later Jan 1, 2011


Objectives: It was the aim of this study to assess our institutional experience with definitive chemoradiation (CRT) versus induction chemotherapy followed by CRT with or without surgery (C-CRT/S) in esophageal cancer. Methods: We retrospectively analyzed 129 institutional patients with locally advanced esophageal cancer who had been treated by either CRT in analogy to the RTOG 8501 trial (n = 78) or C-CRT/S (n = 51). Results: The median, 2-and 5-year overall survival (OS) of the entire collective was 17.6 months, 42 and 24%, respectively, without a significant difference between the CRT and C-CRT/S groups. In C-CRT/S patients, surgery statistically improved the locoregional control (LRC) rates (2-year LRC 73.6 vs. 21.2%; p = 0.003); however, this was translated only into a trend towards improved OS (p = 0.084). The impact of escalated radiation doses (>= 60.0 vs.