POPULARITY
Dr. Ko Un “Clara” Park and Dr. Mylin Torres present the latest evidence-based changes to the SLNB in early-stage breast cancer guideline. They discuss the practice-changing trials that led to the updated recommendations and topics such as when SLNB can be omitted, when ALND is indicated, radiation and systemic treatment decisions after SLNB omission, and the role of SLNB in special circumstances. We discuss the importance of shared decision-making and other ongoing and future de-escalation trials that will expand knowledge in this space. Read the full guideline update, “Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update” at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/breast-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-25-00099 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. Ko Un "Clara" Park from Brigham and Women's Hospital, Dana-Farber Cancer Institute, and Dr. Mylin Torres from Glenn Family Breast Center at Winship Cancer Institute of Emory University, co-chairs on “Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update.” Thank you for being here today, Dr. Park and Dr. Torres. Dr. Mylin Torres: Thank you, it's a pleasure to be here. Brittany Harvey: And 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. Torres and Dr. Park, who have 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. To start us off, Dr. Torres, what is the scope and purpose of this guideline update on the use of sentinel lymph node biopsy in early-stage breast cancer? Dr. Mylin Torres: The update includes recommendations incorporating findings from trials released since our last published guideline in 2017. It includes data from nine randomized trials comparing sentinel lymph node biopsy alone versus sentinel lymph node biopsy with a completion axillary lymph node dissection. And notably, and probably the primary reason for motivating this update, are two trials comparing sentinel lymph node biopsy with no axillary surgery, all of which were published from 2016 to 2024. We believe these latter two trials are practice changing and are important for our community to know about so that it can be implemented and essentially represent a change in treatment paradigms. Brittany Harvey: It's great to hear about these practice changing trials and how that will impact these recommendation updates. So Dr. Park, I'd like to start by reviewing the key recommendations across all of these six overarching clinical questions that the guideline addressed. So first, are there patients where sentinel lymph node biopsy can be omitted? Dr. Ko Un "Clara" Park: Yes. The key change in the current management of early-stage breast cancer is the inclusion of omission of sentinel lymph node biopsy in patients with small, less than 2 cm breast cancer and a negative finding on preoperative axillary ultrasound. The patients who are eligible for omission of sentinel lymph node biopsy according to the SOUND and INSEMA trial are patients with invasive ductal carcinoma that is size smaller than 2 cm, Nottingham grades 1 and 2, hormone receptor-positive, HER2-negative in patients intending to receive adjuvant endocrine therapy, and no suspicious lymph nodes on axillary ultrasound or if they have only one suspicious lymph node, then the biopsy of that lymph node is benign and concordant according to the axillary ultrasound findings. The patients who are eligible for sentinel lymph node biopsy omission according to the SOUND and INSEMA trials were patients who are undergoing lumpectomy followed by whole breast radiation, especially in patients who are younger than 65 years of age. For patients who are 65 years or older, they also qualify for omission of sentinel lymph node biopsy in addition to consideration for radiation therapy omission according to the PRIME II and CALGB 9343 clinical trials. And so in those patients, a more shared decision-making approach with the radiation oncologist is encouraged. Brittany Harvey: Understood. I appreciate you outlining that criteria for when sentinel lymph node biopsy can be omitted and when shared decision making is appropriate as well. So then, Dr. Torres, in those patients where sentinel lymph node biopsy is omitted, how are radiation and systemic treatment decisions impacted? Dr. Mylin Torres: Thank you for that question. I think there will be a lot of consternation brought up as far as sentinel lymph node biopsy and the value it could provide in terms of knowing whether that lymph node is involved or not. But as stated, sentinel lymph node biopsy actually can be safely omitted in patients with low risk disease and therefore the reason we state this is that in both SOUND and INSEMA trial, 85% of patients who had a preoperative axillary ultrasound that did not show any signs of a suspicious lymph node also had no lymph nodes involved at the time of sentinel node biopsy. So 85% of the time the preoperative ultrasound is correct. So given the number of patients where preoperative ultrasound predicts for no sentinel node involvement, we have stated within the guideline that radiation and systemic treatment decisions should not be altered in the select patients with low risk disease where sentinel lymph node biopsy can be omitted. Those are the patients who are postmenopausal and age 50 or older who have negative findings on preoperative ultrasound with grade 1 or 2 disease, small tumors less than or equal to 2 cm, hormone receptor-positive, HER2-negative breast cancer who undergo breast conserving therapy. Now, it's important to note in both the INSEMA and SOUND trials, the vast majority of patients received whole breast radiation. In fact, within the INSEMA trial, partial breast irradiation was not allowed. The SOUND trial did allow partial breast irradiation, but in that study, 80% of patients still received whole breast treatment. Therefore, the preponderance of data does support whole breast irradiation when you go strictly by the way the SOUND and INSEMA trials were conducted. Notably, however, most of the patients in these studies had node-negative disease and had low risk features to their primary tumors and would have been eligible for partial breast irradiation by the ASTRO Guidelines for partial breast treatment. So, given the fact that 85% of patients will have node-negative disease after a preoperative ultrasound, essentially what we're saying is that partial breast irradiation may be offered in these patients where omission of sentinel node biopsy is felt to be safe, which is in these low risk patients. Additionally, regional nodal irradiation is something that is not indicated in the vast majority of patients where omission of sentinel lymph node biopsy is prescribed and recommended, and that is because very few of these patients will actually end up having pathologic N2 disease, which is four or more positive lymph nodes. If you look at the numbers from both the INSEMA and the SOUND trial, the number of patients with pathologic N2 disease who did have their axilla surgically staged, it was less than 1% in both trials. So, in these patients, regional nodal irradiation, there would be no clear indication for that more aggressive and more extensive radiation treatment. The same principles apply to systemic therapy. As the vast majority of these patients are going to have node-negative disease with a low risk primary tumor, we know that postmenopausal women, even if they're found to have one to three positive lymph nodes, a lot of the systemic cytotoxic chemotherapy decisions are driven by genomic assay score which is taken from the primary tumor. And therefore nodal information in patients who have N1 disease may not be gained in patients where omission of sentinel lymph node biopsy is indicated in these low risk patients. 14% of patients have 1 to 3 positive lymph nodes in the SOUND trial and that number is about 15% in the INSEMA trial. Really only the clinically actionable information to be gained is if a patient has four or more lymph nodes or N2 disease in this low risk patient population. So, essentially when that occurs it's less than 1% of the time in these patients with very favorable primary tumors. And therefore we thought it was acceptable to stand by a recommendation of not altering systemic therapy or radiation recommendations based on omission of sentinel nodes because the likelihood of having four more lymph nodes is so low. Dr. Ko Un "Clara" Park: I think one thing to add is the use of CDK4/6 inhibitors to that and when we look at the NATALEE criteria for ribociclib in particular, where node-negative patients were included, the bulk majority of the patients who were actually represented in the NATALEE study were stage III disease. And for stage I disease to upstage into anatomic stage III, that patient would need to have pathologic N2 disease. And as Dr. Torres stated, the rate of having pathologic N2 disease in both SOUND and INSEMA studies were less than 1%. And therefore it would be highly unlikely that these patients would be eligible just based on tumor size and characteristics for ribociclib. So we think that it is still safe to omit sentinel lymph node biopsy and they would not miss out, if you will, on the opportunity for CDK4/6 inhibitors. Brittany Harvey: Absolutely. I appreciate you describing those recommendations and then also the nuances of the evidence that's underpinning those recommendations, I think that's important for listeners. So Dr. Park, the next clinical question addresses patients with clinically node negative early stage breast cancer who have 1 or 2 sentinel lymph node metastases and who will receive breast conserving surgery with whole breast radiation therapy. For these patients, is axillary lymph node dissection needed? Dr. Ko Un "Clara" Park: No. And this is confirmed based on the ACOSOG Z0011 study that demonstrated in patients with 1 to 3 positive sentinel lymph node biopsy when the study compared completion axillary lymph node dissection to no completion axillary lymph node dissection, there was no difference. And actually, the 10-year overall survival as reported out in 2017 and at a median follow up of 9.3 years, the overall survival again for patients treated with sentinel lymph node biopsy alone versus those who were treated with axillary lymph node dissection was no different. It was 86.3% in sentinel lymph node biopsy versus 83.6% and the p-value was non-inferior at 0.02. And so we believe that it is safe for the select patients who are early stage with 1 to 2 positive lymph nodes on sentinel lymph node biopsy, undergoing whole breast radiation therapy to omit completion of axillary lymph node dissection. Brittany Harvey: Great, I appreciate you detailing what's recommended there as well. So then, to continue our discussion of axillary lymph node dissection, Dr. Torres, for patients with nodal metastases who will undergo mastectomy, is axillary lymph node dissection indicated? Dr. Mylin Torres: It's actually not and this is confirmed by two trials, the AMAROS study as well as the SENOMAC trial. And in both studies, they compared a full lymph node dissection versus sentinel lymph node biopsy alone in patients who are found to have 1 to 2 positive lymph nodes and confirmed that there was no difference in axillary recurrence rates, overall survival or disease-free survival. What was shown is that with more aggressive surgery completion axillary lymph node dissection, there were higher rates of morbidity including lymphedema, shoulder pain and paresthesias and arm numbness, decreased functioning of the arm and so there was only downside to doing a full lymph node dissection. Importantly, in both trials, if a full lymph node dissection was not done in the arm that where sentinel lymph node biopsy was done alone, all patients were prescribed post mastectomy radiation and regional nodal treatment and therefore both studies currently support the use of post mastectomy radiation and regional nodal treatment when a full lymph node dissection is not performed in these patients who are found to have N1 disease after a sentinel node biopsy. Brittany Harvey: Thank you. And then Dr. Park, for patients with early-stage breast cancer who do not have nodal metastases, can completion axillary lymph node dissection be omitted? Dr. Ko Un "Clara" Park: Yes, and this is an unchanged recommendation from the earlier ASCO Guidelines from 2017 as well as the 2021 joint guideline with Ontario Health, wherein patients with clinically node-negative early stage breast cancer, the staging of the axilla can be performed through sentinel lymph nodal biopsy and not completion axillary lymph node dissection. Brittany Harvey: Understood. So then, to wrap us up on the clinical questions here, Dr. Park, what is recommended regarding sentinel lymph node biopsy in special circumstances in populations? Dr. Ko Un "Clara" Park: One key highlight of the special populations is the use of sentinel lymph node biopsy for evaluation of the axilla in clinically node negative multicentric tumors. While there are no randomized clinical trials evaluating specifically the role of sentinel lymph nodal biopsy in multicentric tumors, in the guideline, we highlight this as one of the safe options for staging of the axilla and also for pregnant patients, these special circumstances, it is safe to perform sentinel lymph node biopsy in pregnant patients with the use of technetium - blue dye should be avoided in this population. In particular, I want to highlight where sentinel lymph node biopsy should not be used for staging of the axilla and that is in the population with inflammatory breast cancer. There are currently no studies demonstrating that sentinel lymph node biopsy is oncologically safe or accurate in patients with inflammatory breast cancer. And so, unfortunately, in this population, even after neoadjuvant systemic therapy, if they have a great response, the current guideline recommends mastectomy with axillary lymph node dissection. Brittany Harvey: Absolutely. I appreciate your viewing both where sentinel lymph node can be offered in these special circumstances in populations and where it really should not be used. So then, Dr. Torres, you talked at the beginning about how there's been these new practice changing trials that really impacted these recommendations. So in your view, what is the importance of this guideline update and how does it impact both clinicians and patients? Dr. Mylin Torres: Thank you for that question. This update and these trials that inform the update represent a significant shift in the treatment paradigm and standard of care for breast cancer patients with early-stage breast cancer. When you think about it, it seems almost counterintuitive that physicians and patients would not want to know if a lymph node is involved with cancer or not through sentinel lymph node biopsy procedure. But what these studies show is that preoperative axillary ultrasound, 85% of the time when it's negative, will correctly predict whether a sentinel lymph node is involved with cancer or not and will also be negative. So if you have imaging that's negative, your surgery is likely going to be negative. Some people might ask, what's the harm in doing a sentinel lymph node biopsy? It's important to recognize that upwards of 10% of patients, even after sentinel lymph node biopsy will develop lymphedema, chronic arm pain, shoulder immobility and arm immobility. And these can have a profound impact on quality of life. And if there is not a significant benefit to assessing lymph nodes, particularly in someone who has a preoperative axillary ultrasound that's negative, then why put a patient at risk for these morbidities that can impact them lifelong? Ideally, the adoption of omission of sentinel lymph node biopsy will lead to more multidisciplinary discussion and collaboration in the preoperative setting especially with our diagnostic physicians, radiology to assure that these patients are getting an axillary ultrasound and determine how omission of sentinel lymph node biopsy may impact the downstream treatments after surgery, particularly radiation and systemic therapy decisions, and will be adopted in real world patients, and how clinically we can develop a workflow where together we can make the best decisions for our patients in collaboration with them through shared decision making. Brittany Harvey: Absolutely. It's great to have these evidence-based updates for clinicians and patients to review and refer back to. So then finally, Dr. Park, looking to the future, what are the outstanding questions and ongoing trials regarding sentinel lymph node biopsy in early-stage breast cancer? Dr. Ko Un "Clara" Park: I think to toggle on Dr. Torres's comment about shared decision making, the emphasis on that I think will become even more evident in the future as we incorporate different types of de-escalation clinical studies. In particular, because as you saw in the SOUND and INSEMA studies, when we de-escalate one modality of the multimodality therapy, i.e., surgery, the other modalities such as radiation therapy and systemic therapy were “controlled” where we were not de-escalating multiple different modalities. However, as the audience may be familiar with, there are other types of de-escalation studies in particular radiation therapy, partial breast irradiation or omission of radiation therapy, and in those studies, the surgery is now controlled where oftentimes the patients are undergoing surgical axillary staging. And conversely when we're looking at endocrine therapy versus radiation therapy clinical trials, in those studies also the majority of the patients are undergoing surgical axillary staging. And so now as those studies demonstrate the oncologic safety of omission of a particular therapy, we will be in a position of more balancing of the data of trying to select which patients are the safe patients for omission of certain types of modality, and how do we balance whether it's surgery, radiation therapy, systemic therapy, endocrine therapy. And that's where as Dr. Torres stated, the shared decision making will become critically important. I'm a surgeon and so as a surgeon, I get to see the patients oftentimes first, especially when they have early-stage breast cancer. And so I could I guess be “selfish” and just do whatever I think is correct. But whatever the surgeon does, the decision does have consequences in the downstream decision making. And so the field really needs to, as Dr. Torres stated earlier, rethink the workflow of how early-stage breast cancer patients are brought forth and managed as a multidisciplinary team. I also think in future studies the expansion of the data to larger tumors, T3, in particular,reater than 5 cm and also how do we incorporate omission in that population will become more evident as we learn more about the oncologic safety of omitting sentinel lymph node biopsy. Dr. Mylin Torres: In addition, there are other outstanding ongoing clinical trials that are accruing patients right now. They include the BOOG 2013-08 study, SOAPET, NAUTILUS and the VENUS trials, all looking at patients with clinical T1, T2N0 disease and whether omission of sentinel lymph node biopsy is safe with various endpoints including regional recurrence, invasive disease-free survival and distant disease-free survival. I expect in addition to these studies there will be more studies ongoing even looking at the omission of sentinel lymph node biopsy in the post-neoadjuvant chemotherapy setting. And as our imaging improves in the future, there will be more studies improving other imaging modalities, probably in addition to axillary ultrasound in an attempt to accurately characterize whether lymph nodes within axilla contain cancer or not, and in that context whether omission of sentinel lymph node biopsy even in patients with larger tumors post-neoadjuvant chemotherapy may be done safely and could eventually become another shift in our treatment paradigm. Brittany Harvey: Yes. The shared decision making is key as we think about these updates to improve quality of life and we'll await data from these ongoing trials to inform future updates to this guideline. So I want to thank you both so much for your extensive work to update this guideline and thank you for your time today. Dr. Park and Dr. Torres. Dr. Mylin Torres: Thank you. Dr. Ko Un "Clara" Park: Thank you. Brittany Harvey: And 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/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app 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.
In this episode, we dive into the data on maintenance therapy in multiple myeloma with Dr. Hira Mian and Dr. Manni Mohyuddin. Here are the key studies we discussed:1. Meta-analysis of individual patient-level data from CALGB, IFM, and Italian maintenance RCTs (lenalidomide vs placebo or observation): https://pubmed.ncbi.nlm.nih.gov/28742454/ 2. Myeloma XI RCT (lenalidomide vs observation): https://pubmed.ncbi.nlm.nih.gov/30559051/ 3. Outcomes of lenalidomide maintenance stratified by cytogenetic subgroups (Secondary analysis of Myeloma XI): https://pubmed.ncbi.nlm.nih.gov/36564045/ 4. Canadian real-world data on lenalidomide maintenance: https://pubmed.ncbi.nlm.nih.gov/33054120/ 5. FORTE trial (Carfilzomib-Lenalidomide vs Lenalidomide): https://pubmed.ncbi.nlm.nih.gov/34774221/ 6. ATLAS trial (Carfilzomib-Lenalidomide-Dexamethasone vs Lenalidomide): https://pubmed.ncbi.nlm.nih.gov/36642080/ 7. Differential censoring and potential impact on PFS in ATLAS trial: https://pubmed.ncbi.nlm.nih.gov/37433885/ 8. GEM2014 (Ixazomib-Lenalidomide-Dexamethasone vs Lenalidomide-Dexamethasone): https://ashpublications.org/blood/article-abstract/142/18/1518/497188 9. MASTER trial (MRD-guided treatment de-escalation): https://pubmed.ncbi.nlm.nih.gov/37776872/ 10. Outcomes after MRD-guided treatment discontinuation (Secondary analysis of GEM2014MAIN trial): https://pubmed.ncbi.nlm.nih.gov/37506339/
Dr. Shannon Westin and her guest, Dr. Reshma Jagsi, discuss the paper "Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA" recently published in the JCO. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth with manuscripts that were published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN Oncologist and Social Media Editor for the JCO. It is my pleasure to speak with Dr. Reshma Jagsi. Hello, Dr. Jagsi. Dr. Reshma Jagsi: Hello. Thanks for having me. Shannon Westin: I am so excited that you're here. Dr. Jagsi is the Lawrence W. Davis Professor and Chair of the Department of Radiation Oncology at Emory University School of Medicine, Winship Cancer Institute. She is going to be talking about her incredible work, "The Omission of Radiotherapy After Breast Conserving Surgery for Women with Breast Cancer with Low Clinical and Genomic Risk: Five-year Outcomes of IDEA," which was published in JCO in February 2024. All right, let's get right to it. First, I want to levelset. Can you run us through some brief facts and figures about breast cancer just to make sure that all the listeners are on the same page? Dr. Reshma Jagsi: Breast cancer is the most common cancer in the world. It's 12.5% of all new annual cancer cases worldwide and is the most commonly diagnosed cancer among US women. About a third of all newly diagnosed cancers in women are breast cancer, and about 13% of US women develop invasive breast cancer over their lifetime. In 2023, there were nearly 300,000 new cases of invasive breast cancer. The median age of breast cancer diagnosis is 62, meaning an awful lot of people are getting diagnosed with breast cancer in the population that we specifically chose to study. Shannon Westin: Wow, you're really good at this. That's like the perfect transition to move to the next piece. So, first, I think I'd love to hear about the standard of care for the population that you were studying and how we got to this point. Dr. Reshma Jagsi: We offer women who are diagnosed with early-stage invasive breast cancer the option of breast conservation, and we encourage breast conservation because, of course, it is a better-tolerated surgery than mastectomy. Many women are eligible for breast-conserving therapy. And years ago, we as radiation oncologists encouraged our surgical colleagues to refer to breast-conserving therapy as lumpectomy plus radiation, just as one set. Because the studies that have been done in the 1970s and 1980s to establish that breast conversation was equally safe and effective in treating breast cancer relied on radiation therapy to minimize in-breast tumor recurrence rate, which one of those trials independently showed that there was no difference in survival. But the ones that compared lumpectomy surgery alone to lumpectomy followed by radiation therapy did show a pretty substantial improvement in local control with the addition of radiation treatment. And so radiation treatment became a part of a parcel of breast conservation in the early 1990s when consensus statements came out favoring breast conservation as a treatment approach. And so the net analysis has combined all of these studies together and showed that overall, without radiation treatment, a patient treatment with a lumpectomy had a 30% risk of in-breast tumor occurrence in those historical studies. And it was reduced by about two thirds to about 10% when that lumpectomy was followed by radiation in those historical randomized trials. But of course, we've made many advances in our understanding since that time, and so that's what this study is seeking to build on. Shannon Westin: It makes sense. We all know that radiotherapy can lead to other issues, acute and chronic morbidities, as well as cost and having to do the treatment itself. So we're all interested in de-escalation of therapy. Tell me, prior to your study, what data were out there potentially supporting the de-escalation and avoiding radiotherapy in that specific population? Dr. Reshma Jagsi: In the ‘90s, after those landmark foundational historical trials have been completed, there was a lot of interest in seeing if we could identify a population of patients in whom the risk of local recurrence was sufficiently low that they might safely choose to omit radiation therapy. All of these randomized trials have shown very consistently that there is a relative risk reduction. Whatever your risk is without radiation, radiation reduces that risk. The overall disease recurrence risk is cut in half with the addition of radiation treatment. But, if I told you that your overall risk was 1%, and I could cut that in half with radiation, you might say, “I might be willing to tolerate the 1%.” At least some women might be willing to tolerate that. So can we find a population in whom the risk is low enough that at least some of those women say, "Look, I want to go without radiation." And of course, the balance of where that number should be changes as we get better and better at delivering radiation. So you mentioned, radiation comes with toxicity, comes with burden and yet, there have been some tremendous advances, and particularly in recent years, to shorten the course of radiation. We have evidence that we can treat partial breast radiation safely in five treatment fractions. We have five-year data that we can treat the whole breast in five-treatment fraction. We certainly have long term evidence that we can the whole breast with 15 fractions from many patients diagnosed with breast cancer. So the burden has decreased. We've also found that with hypo fractionated shorter courses of radiation, the toxicities are much lower, patients tend to tolerate radiation treatment both in terms of acute side effects and long term side effects extremely well. So that balance of what is low enough is changing with time. But the trials that were started in the 1990s included the CALGB 9343 trial, a landmark trial published in the New England Journal of Medicine, with its five-year results showing only a 4% risk of recurrence at five years in patients who were 70 or older with clinical stage one disease that was hormone receptor-positive if they received a lumpectomy and tamoxifen alone, not receiving radiation - that risk, if we added radiation in this randomized trial, was only 1%. So there was still a substantial relative risk reduction with radiation treatment. This was published in 2004 in the New England Journal of Medicine. At the same time, there was a Canadian trial that was published, and in that trial that included women who were 50 years of age and older, there were more concerning results with, even in a very favorable prespecified subgroup of patients who had node-negative breast cancer and T1 hormone receptor-positive tumors, the risk of ipsilateral breast tumor recurrence was 15% at eight years. So that started to feel excessive for women 50 and older. Meanwhile, we went on to get the update of the CALGB trial, and the 10 -year results showed that the risk was, in the women 70 and older, was only about 10% without radiation. It was 2% with radiation. So again, there was a benefit from radiation, and it's up to each individual woman to decide whether they'd prefer to proceed and minimize their risk, or would be willing to tolerate something like a 10% risk. More recently, just this past year in the New England Journal, the PRIME 2 study from the United Kingdom, looking at women 65 and older, again, early-stage node-negative hormone receptor-positive tumors, and very similar results - 10% versus 1% local control at 10 years. So you get an improvement with radiation. But there are some women who are 65 or 70 and older who say, I'm willing to tolerate the 10% risk. And so the question was, could we identify some patients who are younger than 65 to 70, but still postmenopausal, like in that Canadian trial, who might actually have similar outcomes - low risks at five and ten years - such that they might want to entertain the option of omitting radiation therapy, which right now is not standard or in any guidelines? So we have some promising information from some retrospective analysis of that Canadian trial that suggested that looking at biology might help. And in fact, the LUMINA trial, published just this year from Canada, did a prospective cohort study selecting patients based on immunohistochemistry, and suggested very low risks, five years in patients who were somewhat younger, although it ended up that the median age of the patients in that study was 67. So we still sort of had this question of what about the younger postmenopausal patients? And that's what took us to IDEA. Shannon Westin: And just for my education and for the education of the listeners, when you have an in-breast recurrence, how likely are you to be able to cure that? Is that tough to cure, or can you usually get control again? Dr. Reshma Jagsi: It's an excellent question. And so often these recurrences are caught early and are still completely curable with additional intervention. Now, there can be an impact, of course. You can talk to any survivor about the devastating impact of being diagnosed with breast cancer recurrence, and no one wants to go through that. And so there are reasons that people will want to reduce that, and there are implications for breast conservation because it may be that the remaining breast tissue is insufficient to allow a second breast conserving surgical procedure. It may also be that when one experiences recurrence, one decides, "I'm done with this. I'm having a mastectomy at this point." So, in-breast recurrences are very meaningful to patients and something that we should not take lightly. Shannon Westin: It seems, though, the majority of the studies that you were talking about, aside from the LUMINA study, were predominantly based on those clinical features like stage and things like that. So, can you talk a little bit about the role of molecular features, genomic testing, things like that, to select patients? Dr. Reshma Jagsi: Yeah. So, we have seen a tremendous change in the way we think about breast cancer in recent years, with a real focus on tumor biology, rather than classic clinical pathologic features alone to help us make decisions about systemic therapy. And so, there is a body of work that suggests that genomic assays, including the 21-gene recurrence score, that's commonly used for treatment decision making already ordered in many of these patients and available to us, that it may be useful in understanding patients' risk of local recurrence, both when they are treated with radiation and when they are treated without radiation. So, Terry Mamounas did some wonderful work looking at NSABP data where you know that the mastectomy patients at the time of the studies that were included were not receiving radiation treatment. And it did appear that the 21-gene recurrence score was helping to discriminate for local regional recurrence risk, suggesting it might be useful to use that to select patients who might be at lower risk. Shannon Westin: All right, perfect. So, that leads us to your study. So, let's talk a little bit about the design and the population and kind of how you put it together. Dr. Reshma Jagsi: This was really a true collaboration, a partnership across multiple 13 collaborating sites, where my colleagues, the lead investigators at each site, were extremely committed to this question. And we sought to do a preliminary cohort trial, really involving 200 patients. And over the course of three years, we enrolled those 200 patients who were aged 50 to 69 years old and had unicentric invasive breast cancer and lumpectomy surgery that led to negative margins of 2 mm or greater. And their disease needed to be PR positive, HER2 negative, it needed to be node negative, pathologically node negative, and the Oncotype DX 21-gene recurrence score needed to be less than or equal to 18. And then these patients were offered the opportunity to consent and register on a trial to receive five years of endocrine therapy as standard of care alone, and 10 years of surveillance on study, or to proceed with the standard of care treatment off trial, which would have been a recommendation to receive radiation treatment. And so, we ended up with patients with a mean age of 62 years, which, as I said, that's really more mapping the overall population of patients in the country. And we were able to report our results at the San Antonio Breast Cancer Symposium and with simultaneous publication in JCO, with a median follow up of 5.2 years. Shannon Westin: Okay, and let's talk about a little bit about your major findings. Tell us what your good work demonstrated. Dr. Reshma Jagsi: So, the overall and breast cancer-specific survival rates at five years were both 100%, and the five-year freedom from any recurrence was 99%, with a 95% confidence interval that went from 96% to 100%. But I want to emphasize that these are five-year data in a younger postmenopausal population, where five-year data are not typically sufficient to guide decision making. So, I really want to emphasize that these are very early results. But really, what happened here was we only had a couple of patients who had recurrences before five years, two patients, and that was one isolated ipsilateral axillary recurrence, and one ipsilateral breast event. But we also did see six additional patients who recurred later than five years after breast conserving surgery. And because we don't have much long-term follow-up, it makes it incredibly important for us to continue to follow this cohort over time before people make any Monday morning practice implications of offering this cohort of patients, or patients like this cohort of patients, omission off trial. The good news is that there are ongoing trials that are building on this work, including NRG-BR007, the DEBRA ,that includes a population of patients really similar to those enrolled on IDEA and randomizes them to radiation or no radiation, which is actually incredibly important. Because what we want to understand is also the quality of life effects of omitting radiation therapy because what we don't want is to inadvertently cause an increase in worry about recurrence. Or, you could imagine that patients who omit radiation treatment then feel really stuck with their endocrine therapy. Now, endocrine therapy is the standard of care, but if they're experiencing terrible endocrine therapy side effects and they didn't get radiation treatment, are they more likely to persist with that endocrine therapy and to be miserable because they omitted a treatment that, as I mentioned earlier, can be administered now in five days or less? And one of the questions that keeps coming up from older patients that I treat, where we already offer the option of omitting radiation, those CALGB and PRIME II patients, those patients will often say to me, "I've got to say, Doc, that whole experience of radiation that you described for five days, and the toxicity, and that doesn't sound so bad to me. What sounds bad to me is multiple years of endocrine therapy." And so, there are also ongoing trials in Europe, and I hope one day in the United States, also looking at older women and offering them a de-escalation of a different sort. Now that we have made so many advances in radiation treatment, maybe the optimal monotherapy for an older adult is actually, for many patients, given their values and preferences, going to involve omission of endocrine therapy. And we need to find out if that's safe. And again, Europa in Europe is investigating that question, and I hope that the American cooperative groups take up something similar. Shannon Westin: That's awesome! And what else is going on in this space? Any other trials? That was like, such a great review of ongoing trials, and I'm sure our listeners would love to have your expertise. Anything else that you're looking forward to that might impact the treatment landscape here? Dr. Reshma Jagsi: Absolutely, and if there are listeners in other parts of the world, there are trials going on also looking at this. There is PRIMETIME, which is a cohort study designed, but with a much larger cohort that's going on in the United Kingdom. There's the EXPERT trial that is randomizing patients to radiation treatment or not in Australia and New Zealand. So, there are many trials that are ongoing, again, looking at de-escalation of radiation therapy. And I want us all, regardless of our specialty, to think about ways that we can de-escalate and optimize the options that are offered to our patients. And I think there's a tendency for patients to be very scared of radiation, sometimes, for our colleagues to be very scared of radiation. I mean, we are the only specialty that has a special “danger radiation sign” that comes to mind when you hear the word radiation therapy. So, it can be this very frightening thing that we often leap to efforts to avoid. And what I don't want to be the conclusion of this is, “Isn't it great? Radiation oncologists themselves recognize that radiation is terrible and that you should avoid it.” That's not the case. What I hope people will say is, “Isn't it great that radiation therapists are trying to offer as many options to patients as possible?” Because it means a lot to a patient who's had the sense of power and control and autonomy ripped away from them by a breast cancer diagnosis, to be given many options to articulate their values and their preferences and to decide what treatment makes most sense for them. I think, for a lot of patients, that involves radiation treatment. And I think what we need to do as physicians is think about what other things are our patients really concerned about. Our medical oncology colleagues have done tremendous work to de-escalate systemic therapy in the form of chemotherapy. Our colleagues in surgery have, again, de-escalated mastectomies, axillary dissection. So, there are these ongoing efforts, and I do honestly believe that the next frontier is endocrine therapy and optimization of endocrine therapy. It is so powerful. It is why we have such wonderful outcomes. We know that we should have a healthy respect for ER-positive cancer, which can recur in the long term. We don't want to throw out the baby with the bathwater, but baby steps towards understanding what happens if we peel back our treatments is our obligation. Shannon Westin: I think this is a perfect place to end/ I agree - less is more is really becoming a resonant statement across all of our different subtypes. We're certainly seeing it in GYN oncology, and just like you said, systemically or even surgically. So I agree. I think we have a call to action to really assess what we've always done and make sure that we're not over-treating patients for whom it's inappropriate. So I think this is great. And I just want to commend you again on your work. These types of multicenter trials are really hard to do, and getting it done in such a short period of time and really getting the data out to patients is so important. And I appreciate what you're saying about needing more follow-up, but it is certainly very reassuring and very in line with what we've seen. So congratulations on your work. Dr. Reshma Jagsi: Thank you. And I just again want to thank all the patients who enrolled, the Coleman Foundation for their support, the University of Michigan for doing the multi-site coordination and the biostatistic support, and all of the collaborating investigators. I mean, this was a labor of love for everyone involved. Shannon Westin: Yeah, these types of trials definitely take a village. Well, great work. Thank you for taking the time. I know how busy you are. So again, we are so honored and so excited to talk about "The Omission of Radiotherapy After Breast Conserving Surgery for Women with Breast Cancer with Low Clinical and Genomic Risk: Five-year Outcomes of IDEA,” just published in print, February 2024 in the JCO. Definitely check it out. And please check out our other episodes of JCO After Hours. We'd love to have your feedback. Take care. The purpose of this podcast is to educate and 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. Dr. Jagsi: Stock and Other Ownership Interests Company name: Equity Quotient Research Funding Company name: Genentech"
In this episode our team reviews the two groundbreaking RCTs which challenged the long-held dogma that a lobectomy is the only acceptable oncologic procedure for NSCLC. Listen as we compare and contrast the North American CALGB trial and Japanese JCOG trial which were both designed to investigate survival and recurrence outcomes by randomizing stage 1A patients to lobectomy versus a sublobar resection. Learning Objectives: -Compare and contrast the patient characteristics of the CALGB and JCOG trials -Understand the methodology each trial and be able to explain their nuanced differences -Analyze the results of the CALGB and JCOG trials and how they apply to patients today Hosts: Kelly Daus MD, Peter White MD, Eric Vallieres, MD and Brian Louie MD Referenced Material https://pubmed.ncbi.nlm.nih.gov/36780674/ Altorki N, et al. Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Feb 9;388(6):489-498. doi: 10.1056/NEJMoa2212083. PMID: 36780674; PMCID: PMC10036605. https://pubmed.ncbi.nlm.nih.gov/35461558/' Saji H, et al. West Japan Oncology Group and Japan Clinical Oncology Group. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet. 2022 Apr 23;399(10335):1607-1617. doi: 10.1016/S0140-6736(21)02333-3. PMID: 35461558. https://pubmed.ncbi.nlm.nih.gov/37473998/ Altorki N, et al. Lobectomy, segmentectomy, or wedge resection for peripheral clinical T1aN0 non-small cell lung cancer: A post hoc analysis of CALGB 140503 (Alliance). J Thorac Cardiovasc Surg. 2023 Jul 18:S0022-5223(23)00612-8. doi: 10.1016/j.jtcvs.2023.07.008. Epub ahead of print. PMID: 37473998. Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more. If you liked this episode, check out our other Cardiothoracic episodes: https://behindtheknife.org/podcast-category/cardiothoracic/
Join experts Drs Kevin Kalinsky and Priyanka Sharma as they discuss their current approach to neoadjuvant therapy in triple negative breast cancer and how the SCARLET trial might change that. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/991256). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Pembrolizumab for Early Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/32101663/ Clinical and Biomarker Results of Neoadjuvant Phase II Study of Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer (TNBC) (NeoPACT) https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.513 CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/35044810/ NCCN Guidelines® Insights: Breast Cancer, Version 4.2023 https://pubmed.ncbi.nlm.nih.gov/37308117/ Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab https://classic.clinicaltrials.gov/ct2/show/NCT05812807 Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer https://clinicaltrials.gov/study/NCT05929768 Neoadjuvant Atezolizumab in Combination With Sequential Nab-Paclitaxel and Anthracycline-Based Chemotherapy Versus Placebo and Chemotherapy in Patients With Early-Stage Triple-Negative Breast Cancer (IMpassion031): A Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32966830/ Adjuvant Capecitabine for Breast Cancer After Preoperative Chemotherapy https://pubmed.ncbi.nlm.nih.gov/28564564/ Impact of Neoadjuvant Chemotherapy on Axillary Nodal Involvement in Patients With Clinically Node Negative Triple Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/25266871/ Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual HER2 Blockade for HER2-Positive Breast Cancer (TRAIN-2): A Multicentre, Open-Label, Randomised, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/30413379/
Age is a main factor when determining cancer care. In this ASCO Education podcast we speak to one of the top leaders in treatment for older patients who has also credited mentorship as a foundation for his career. Dr. Hyman Muss describes his childhood in Brooklyn, serving as a general physician for troops in Vietnam (6:18), the doctor who influenced his choice of hematology and oncology (7:48) and creating one of the first geriatric oncology fellowships in in the country (21:58). Speaker Disclosures Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Dr. Hyman Muss: None More Podcasts with Oncology Leaders Oncology, Etc. – Devising Medical Standards and Training Master Clinicians with Dr. John Glick Oncology, Etc. – Rediscovering the Joy in Medicine with Dr. Deborah Schrag (Part 1) Oncology, Etc. – In Conversation with Dr. Richard Pazdur (Part 1) If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT Pat Loehrer: Welcome to Oncology, Etc., an ASCO Education Podcast. I'm Pat Loehrer, director of Global Oncology and Health Equity at Indiana University. Dave Johnson: And I'm Dave Johnson of Medical Oncology at the University of Texas Southwestern in Dallas, Texas. If you're a regular listener to our podcast, welcome back. If you're new to Oncology, Etc., the purpose of our podcast is to introduce listeners to interesting and inspirational people and topics in and outside the world of Oncology. We have an inspirational guest today. Pat? Pat Loehrer: If you ask anyone who's achieved any level of success and how they've achieved it, most likely they'll mention a number of people who've influenced them along the way. Quite often, these people reflect on their mentors, and after a certain time of accomplishment and reflection, they begin to mentor others. This is very much what our next guest has done. Dr. Hyman Muss has been a mentor to me and to Dave, and he's one of the most outstanding, wonderful people in the world, and we're so excited to have him today. Dr. Hyman Muss served in the US Army in Vietnam, where he was awarded the Bronze Star Medal. He's an experienced Clinician Scientist, the Mary Jones Hudson Distinguished Professor of Geriatric Oncology at the University of North Carolina School of Medicine, and the Director of Geriatric Oncology Program at the UNC Lineberger Comprehensive Cancer Center Program. His interest in education and research is focused on cancer and older patients, and he is internationally recognized in this area. He's been the co-chair of the Alliance Committee on Cancer and Older Adults and won the BJ Kennedy Award from ASCO in Geriatric Care. His particular interest in research expertise is in the care of breast cancer patients, with a focus on the management of women who are of older ages. He's had a major interest in breast cancer survivorship and long-term toxicity of treatment and also served as the co-chair of the Breast Committee for the Alliance Group. He serves as a mentor for medical students, medical residents, junior faculty, and more recently, his Geriatric Oncology fellows. He served on the Board of Directors of the ASCO Foundation and on the ABIM, the American Board of Internal Medicine, where both Dave and I were privileged to work with him and witness his leadership and his deep breadth of knowledge. Dr. Muss, thanks for joining us today. Dr. Hyman Muss: What a pleasure to be here. Thank you so much for inviting me. My mother would have loved the introduction. Pat Loehrer: Well, speaking of that, tell us a little bit. You grew up in Brooklyn, so tell us a little bit about your parents. Your father was a dentist, I think, and your uncle was a general practitioner. So give us a little bit of the early life of Hy Muss. Dr. Hyman Muss: So I grew up in Brooklyn, New York. I was born and bred there. I went to Brooklyn Technical High School. I almost went to Brooklyn College, but I came back and went to Downstate Medical Center, which was just terrific. My tuition was $600 a year, but that's another story. My parents lived in the same neighborhood. My dad was a dentist, so we knew all the people. My uncle was the GP. You came into their office, sat down, and they saw you anytime, day or night, almost 24/7, something we're probably not going back to, but they had a profound influence on me. My uncle, as a GP, used to take me on house calls in Brooklyn when they were done, and he had an old Buick with MD plates. And I would go into these families, and they loved him, and they would give me ice cream and things. Maybe that's what made me a doctor. But it was a terrific and indelible experience. I had terrific parents. In those days, doctors and medical people usually lived in the same neighborhoods as their patients, so they really knew their people well. It was a terrific upbringing. I got to love medicine and have never had a look back. Dave Johnson: So your inspiration for a career in medicine obviously started at home. Tell us more about your formal education. You mentioned your high school education. What about college? And shortly thereafter? Dr. Hyman Muss: Yeah, well, I went to Lafayette College. I was not the best high school student, but I had good college board scores or whatever they called them then. And I went to Lafayette and I thought I was going to be a chemist, a chemistry major. But I took enough premed courses and I spent a summer in a lab building cyclic ketones. And everybody was outside sitting on the lawn of the campus. And I was in there with all these distillation apparatus, and I said, “I don't think I can do this the rest of my life.” So I applied to medical school, and I got into several medical schools. But my father at that time was dying of metastatic bladder cancer. He had been a heavy smoker, and he was still working as a dentist. He worked until the day he unfortunately died. But I got into Downstate. We lived in Brooklyn, and my uncle, the GP, said, "Hy, you need to come home and help take care of your dad." I'm an only child, so I did. And I had a wonderful experience at Downstate. Several years ago, I was listening to NPR and heard that one of my professors had won the Nobel Prize. Dr. Furchgott in physiology, one would have never thought. And I had a wonderful education and subsequently got into what was then Peter Bent Brigham in Boston, did my internship and residency there, joined the army and medical school, so I wasn't drafted, it was a program then. And then after first year of residency, I went to Vietnam, worked with an artillery battalion, a mystical experience, but no regrets. And then subsequently came back and did hematology and oncology at Brigham and at what was then the Jimmy Fund and Sidney Farber Cancer Center. And Tom Frei had just come. And I did hematology with a guy named Bill Moloney in Boston at Harvard. I'll tell you, a wonderful man. He was like a surrogate father. My dad had died by then, and I just feel I've had every opportunity to have a wonderful education and terrific mentors along the way. Dave Johnson: So we want to ask you about both of those gentlemen, but I would like to just, if I may, drop back to your experience in Vietnam. What was that like? Dr. Hyman Muss: Well, I was 27 years old and I was put as the doctor for 500 men in artillery. My job was to take care of the general health of the troops. Fortunately, we didn't have many casualties. It wasn't a front war like my uncle, who was a GP actually in World War II, landed in Normandy about a week later and went all through World War II as a doctor. But Vietnam was an unusual war, there wasn't really a front. So my experience was I would go out to fire bases, which were units of about 100 men in the jungle, go out three days in a week in a helicopter, do sick call, check people. I dealt with really alcohol problems, unfortunately, a lot of drug problems. You had young people with really not a lot to do during the day, nothing much to do, and no real goal of being there. I did that for a while, and actually, the reason I got the Bronze Star was because I set up– It was nothing like standing in front of a machine gun. I'm not that kind of brave guy, but I set up a drug amnesty program so I got a lot of support from our regular field people to do this, so we didn't have to keep sending kids home with dishonorable discharges. And I learned a lot. I think we were reasonably successful. I learned a lot about artillery. I think overall it was a great experience in my life. Dave Johnson: Tell us how your interest in hematology and oncology originated. Where did that come from? Dr. Hyman Muss: When I was an intern at the Brigham, Dr. Moloney was a very famous Harvard professor. He had studied war casualties after Hiroshima, he was one of the people that found the Philadelphia chromosome in CML. He was a guy that rounded on every single one of his leukemia patients every day. So I was an intern. So in those days I would go and see all the hematology people rounding because all the acute leukemia patients and all the serious cancer patients were right on the floors, right on the wards. We had 17-bed wards, and then we had some private rooms. And he loved what he did. And before I left for Vietnam, we didn't have Ara C and daunomycin. So every leukemia patient I saw died. This is '68 to '70. Yet we tried all these different regimens. Occasionally you got someone who did well for six months, a year. But his bedside manner was absolutely wonderful to me. He knew all the patients. He'd ask them about where they lived in Boston. His humanism was terrific, and yet I loved the diseases he treated. The stakes were high. We didn't have good treatment, and I decided that that's probably what I want to do. So when I was in Vietnam, I applied and got back in the Hematology Fellowship and came back and did that. I saw Ara C and daunomycin. I gave the chemotherapy to them, and he'd say, "Go up and treat Harry Smith with Ara C and daunomycin." I had the syringes in my pocket, guys. Forget about hoods and mixing. And I'd go up and treat them and the marrow would be gone within four or five days. I did a bone marrow. They published their regimen in the New England Journal called COD, C-O-D because they also gave vincristine. So it was cytarabine, vincristine, and daunomycin, the COD regimen. It fit Boston. And I saw it was like the emergence of cisplatin after Larry Einhorn. You saw people that never survived going into remission and I saw some remissions in AML and it cemented it. About my second year of residency, we had a child. I was running out of money. I was being paid $6,000 a year and I had the GI Bill. I went into Dr. Moloney and he talked with Dr. Franny Moore, who was head of surgery at the Brigham, and they made me the Sidney Farber Research Fellow, doubled my salary and I had to go to the Jimmy Fund and see cancer patients. And it so happened that was when Tom Frei came to Dana-Farber. And so I started rounding with Dr. Frei and seeing those patients. And I think the first day I walked in, I knew I wanted to do more than just leukemia because I saw groups of patients with every disease. We treated everybody with CMFEP, it didn't matter what cancer they had. And I just loved it and said, "My God, there's so much we can learn. What a great career." And so that got me into the oncology portion. And then I was offered to stay at Harvard. They were going to make me an assistant professor, but they wanted me to do lab work. And I knew my personality, it just wasn't for me. I worked with a lovely guy named Frank Bunn, one of the world's great hem guys in his lab, and he's still a close friend in his 80s. And he told me one day, he said, "Hy, I don't think the lab is for you." And he actually helped me get my first job at Wake Forest University, which turned out to be wonderful. So that's how I ended up with my circuitous in HemOnc. And it's really from great mentors, it's from Bill Moloney, it's from Tom Frei, Dave Rosenthal, tons of wonderful people along the way that not only taught me a lot, but they seemed to love what they do, which is a gift in life to love what you do and love the people you're doing it with. They instilled that in me. Pat Loehrer: From there you went to Wake Forest and there's a couple of colleagues down there, I believe, that inspired you, Charlie Spurr and Bill Hazzard, who was the founding founder of geriatrics. Tell us about that experience and how'd that shape your life. Dr. Hyman Muss: I was looking for a clinical job and I looked at Rochester, and I got snowed in one night in Wake Forest, and I said, “Where's the contract?” And I signed it. And my mother, who was living in New York City, didn't know where North Carolina was. My mother was from a family, was born over a candy store in Greenwich Village, and said, “Where are you going?” And then I showed her where it was, and she says, “They're going to kill you down there.” And it turned out to be one of the best decisions of my life. My wife Loretta, who both of you know so well, we got out of our VW with our dog and our daughter when we moved here, and VW bug, by the way, not a van, and she cried. It turned out it was one of the best opportunities. Charlie Spurr was an iconic oncology leader. He actually did some of the early work on nitrogen mustard in Chicago during the war, the first chemotherapy drug. He was a terrific leader. He had patients programmed in on those IBM punch cards. He had little cards for the protocols, CMFEP, CMF, AC on little laminated index cards. I learned so much from him, and he was to me, great leaders and great mentors morph from things they do themselves to teaching other people, and whose brains have the ability of having the same dopamine shot when you see one of your fellows or young faculty present a wonderful study as you do. And your brain isn't saying, “I wish I was up there.” It's saying, “Isn't this so cool that this young man or woman or fellow or medical student is doing such a wonderful job?” And I had something to do with providing the soil for this seed to grow. That's the kind of guy he was. And so it was wonderful there. And as I moved on, we got a new Chief of Medicine, Bill Hazzard. And I still hear from Bill on rare occasions, but Bill was one of the first geriatricians in the United States. He wrote the textbook, and his wish was that all the faculty and all the specialties get involved in a geriatric project. And so I had all those little index cards, and I looked and saw how many older people with metastatic breast cancer we'd given chemotherapy to. And these were little protocols, nothing like the protocols today, no 50-page consent forms, 50 pages of where your data is stored. They were like, here's the treatment, here's the dose mods. And I looked at those 70 patients with one of our residents, Kathy Christman, she may be retired now, but in any event, we wrote a paper and showed the old people did as well as the young with breast cancer. And we published it in JAMA. And it's one of the few papers in my career, I got no reviewers. They accepted the paper. I got no reviewers. So because I'm from Brooklyn, and my English is not what it should be, I had my friends read it to just make sure I didn't say anything egregious. But it got published and the next thing I know, my friends in medical oncology in the state were calling me. They said, “I got a 75-year-old woman here.” I'm saying, “Guys, I just wrote this paper. I really don't know anything about older people.” But slowly, with Bill Hazzard and others, I got more and more interested. I started reading about Geriatrics and I ended up making it a focal point of my career. It was kind of happenstance. And Bill was a wonderful mentor. And then as I subsequently moved on, I worked with terrific people like Harvey Cohen, Lodovico Balducci, and Martine Extermann, all of them heavily involved with ASCO over the years as well, and B.J. Kennedy. They were wonderful to work with. And BJ was inspirational because BJ would get up at an ASCO meeting and he'd say when he saw the age cut off, he'd say, “How come you didn't let old people on that study? There'd be 1000 people in the audience.” And so he really was a great mentor. And I had the bittersweet opportunity of writing his obit for JCO years ago and kept up with his family a few years, but he was a wonderful man. Dave Johnson: I'm just reflecting on the fact that today, patient registries are sort of mainstream, but certainly in the ‘70s, ‘80s, even into the ‘90s, having a list of patients with a particular disorder seemed almost novel in many respects. And to have that was a godsend. Dr. Hyman Muss: It was a godsend. I still remember those little file cards. And he called it the Oncology Research Center and it was a godsend. And you've got to remember, this is like ‘74, ‘75, it's a long time ago. Dave Johnson: So many of our listeners may not be as familiar with Wake Forest as they are with Duke and North Carolina, the other medical schools located there. But you were at right at a point where I mean, it was one of the top oncology programs in the country at that time. Still is, I don't mean to diminish it, but there was a who's who of people there at the time. And you were also involved in creating, I think, one of the first cooperative groups of sorts. It was the Piedmont Oncology Group. Tell us about that. Dr. Hyman Muss: Oh, yeah, well, that brings back memories. So the NCI at that time wanted to get more, I think, rural and other smaller places involved in research. And they put out an RFA to form like regional cooperative groups. And we formed the Piedmont Oncology Association, the POA. We actually did well for a few years. We wrote some really good studies. We got one or two New England Journal articles. I worked with all the people, mainly in the community, community docs who would go on, and put people on the protocol. I mean, I looked at all the X-rays and scans in a lot of these patients myself as part of the studies we did. And it turned out to be a wonderful organization and it's still run today by Bayard Powell, who is one of our terrific fellows who's the head of Oncology at Wake Forest. But after a while, we just couldn't compete with CALGB, of which I was a member of also, and ECOG and SWOG, even North Central Group, which was kind of formed in a similar venue, eventually merged. So we did a wonderful job for a while but the truth is we just didn't have the manpower to write studies for every disease site. So eventually we kind of petered out as a clinical trials group. But it's been maintained for educational programs and it's really served as a good resource for a lot of good education for the community oncologists who give most of the care in this country in the state. So it's been good. I think Pat kind of exceeded us with HOG, the Hoosier Oncology Group, which was in a similar vein. But it was a great experience and it was all Dr. Spurr, who thought of doing this and built it. Dave Johnson: Certainly, it was inspirational in many people in and outside of Wake Forest. So with such an idyllic life, what in the world possessed you to move north to Vermont? Dr. Hyman Muss: Well, you get this urgent life. You want to be a leader, you want to be a chief. Now, I tell younger people, if they love what they do, don't do it. So I got a wonderful opportunity at the University of Vermont to go up there and be Head of HemOnc. Chief of Medicine was a terrific guy, Burt Sobel. The university at that time, at one time it had a wonderful Oncology program. It had a federally funded cancer center with Irwin Krakoff and Jerry Yates, two other iconic guys. I don't know what the politics were but it had lost a tremendous amount of faculty, especially its clinical faculty, and they needed to rebuild it. And I went up and I thought, “Well, I'm in my 50s. This is going to be a great opportunity. If I don't do it now, I may never get the chance.” So I went up there and actually, it was a great opportunity. We hired terrific people. We got CALGB and we participated. We had actually a very good accrual for a small place and we had a very small but very effective cancer center. So it turned out to be a really good experience. I worked with wonderful people. I recruited some wonderful people. But over time, the issues of the business of medicine, all the issues that happened, I'm saying I'm kind of losing my focus on clinical care and clinical trials, which I love to do. I don't need to tell either of you. I mean, Dave, you've been chief and department chair and Pat has run cancer centers. After a while, the administrative tasks just were so overwhelming and I didn't enjoy them, that I said, “I've got to get back in some type of more clinical focus.” And that's when I decided to look around and fortunately found what's turned out to be a dream job at UNC. But it was a time of life. Maybe my ego got in the way of my logic. I don't regret it. I met and I think we rebuilt a wonderful clinical program. But you realize some of the resources of big places with- we never had the research infrastructure to hire a lot of people and get big programs going on and great translational programs, just didn't have the funding. But it was great, and I have no regrets. And I learned how to tolerate the cold weather. And I have a lovely daughter, Sarah, who still lives up there. So we get back occasionally. And I've kept up with a lot of the people there. There are some wonderful people at UVM. Pat Loehrer: From there, though, you were pulled down to North Carolina, where you've, again, built an incredible breast program there is outstanding. But you've created a Geriatric Oncology program, one of the first geriatric fellowships in oncology in the country. So tell us a little bit about that and what you feel may be your legacy is there at North Carolina. Dr. Hyman Muss: Well, I had the opportunity over the years when I was at Wake, really, I got to know Shelley Earp, who's our cancer center director. I think maybe you were close to him, Pat. The longest surviving cancer center director on the planet, or among them. And we were good friends. And North Carolina's legislature actually gave the University of North Carolina substantial funding to improve cancer care in North Carolina, not just research. And so I had talked with Shelley about maybe moving, and because of the generosity of the state, really, he was able to really get me going, start a Geriatric Oncology program. And what I wanted to do was develop trials. As Dave says, I built a registry in 2009 here for older cancer patients using geriatric assessment. I have 2000 patients, which has been a resource for all types of faculty and fellows, and students to write papers. But I was able, with the support, to do things like this right from the get-go. And plus, I joined probably one of the best breast groups on the planet with Lisa Carey and Chuck Perou, and Larry, terrific people, Claire Dees. I had great luck in doing this, so I was able to really focus, get great support from my colleagues to build studies focusing on older people. And then I had the great fortune of meeting Ned Sharpless, our prior NCI director. And Ned is one of the world's great aging biologists. And I don't mean aging as an adjective, he's really been a master on why we age, the biology of aging, cell senescence. So Ned taught me all about cell senescence and the mechanisms, especially the gene expression p16, which is like our own CDK inhibitor. And so I was able to start using his lab, collect samples, treat people with chemotherapy, follow them off with geriatric assessment. It was a great opportunity to do that here, and we got a lot of studies going and we showed what the pediatricians have known for years, that chemotherapy dramatically ages people, not just children, but adults. But it also allowed me to work with my colleagues in lymphoma and lung cancer to do little studies along the way. And we eventually then built a T32 program. We got a T32, which we're kind of completing now our first five years to train oncology specialists in geriatrics. So the way we do it is they can be surgical oncologists, GU, we had a GYN oncologist, medical. With their HemOnc training, they do a year where they work with the geriatricians, so they go on geriatric inpatient service for a month and they really learn about older people. And part of it is a project. So we've been able to build that and develop a lot of programs with that. And I should say we've been very successful with mentorship and with ASCO support for things like YIAs, the late and great Arti Hurria, who absolutely an amazing woman. Some of her legacy at ASCO, the YIAs, and things. We've been successful in applying for some. So we've been able to build a whole spectrum of med and hematologists. We have an interest in Myeloma and AML focusing on older people. We've been able to build a whole team approach, including translational projects related to older people. And it's just been a great opportunity, and hopefully, my legacy here will be, too, and I'm working on it. We have a wonderful guy, Bill Wood, who is very effective and has built this incredible coaching program to continue this legacy. Like many of us in this field, we are bothered because we all know the stats, we all know that first slide of the demographics of cancer, and yet it's been very hard in our culture to provide a lot of the services and build the clinical trials we need to best care for older people. It's still a major problem in this country. So as I cut back on my clinical care, I'm going to still advocate to try to improve the care of older people. Do geriatric assessment, build it into your clinical programs, get your hospitals to support you, convince them, build business plans, et cetera. And hopefully, that'll be my ultimate legacy, that we've made greater awareness of the older people, other than the usual stats, and we're really trying to care for them in a much more global sense, in a much more holistic sense than we've done. I hope we'll be successful. It's a slow haul, but we've got lots of great young people coming up through the pipelines, ASCO has been a great player in this. Many of you know people like Supriya Mohile and William Dale, Heidi Klepin, people, the next generation that's going to keep building this. So I hope the legacy will be that we get more buy-in, more interest, more trained people in other oncology-related subspecialties RadOnc, SurgOnc that will really focus on the care of older people. Dave Johnson: I don't think there's any doubt that that will be a part of your legacy Hy, but I think your legacy will be much broader than the world of geriatric oncology. Your mentorship leadership, your clinical skills, your educational capabilities, all of that will certainly last for many, many years in the future. Well, I don't want to bring up a touchy topic, but you yourself are geriatric and we're wondering what your plans are for your semi-retirement. I recognize you're not retiring, but what do you like to do outside of medicine? Dr. Hyman Muss: I'll tell everybody who's interested in hearing this. On Tuesday, I had my 80th birthday. Dave Johnson: Congratulations. Dr. Hyman Muss: And I think I'm one of the most blessed guys. I'm pretty healthy. I married up - my wife Loretta, who both of you, Pat Loehrer and Dave Johnson, know well. Dave Johnson: Yeah, you definitely married up. Dr. Hyman Muss: Yes. It's really carried me most of my life. She's great and so she flew up our three kids and we celebrated and I'm very fortunate. I have the enthusiasm and strength to do more clinical medicine. But I think the time has come for me to cut back my clinical medicine, so I'm going to do that in June. The hardest thing I've done is say goodbye to so many of my patients here. We've been blessed. We have a lovely family. We're pretty close. I'm never bored, probably you two know well, I love to do things like fishing, outdoor stuff. I've really gotten into woodworking, so I'm not going to be bored. But there will be a small piece out of me when I walk out of that clinic in June. I know that and my two close psychiatry friends think it's going to really be a hard fall, but I don't think so. I still have some grants. In fact, I'm working with a fellow in City of Hope, Mina Sedrak, who's been very involved in ASCO, too. We are hoping to get an R01 looking at senolytic drugs that may prevent aging, and exercise in older women with breast cancer to see if we can reverse the trends of chemo. So my brain is still on that stuff, but the clinical care is going to be tough. I had a note and for some reason, we talked about so many things. I wanted to mention that one of my great opportunities was joining the CALGB and then the Alliance and getting the support of Dr. Schilsky, Rich Schilsky, who's been one of the icons of ASCO to build cancer in the elderly working group with Dr. Harvey Cohen at Duke. And Harvey is one of the world's great geriatricians. And using that to get studies done, to incorporate studies with Arti Hurria on geriatric assessment, and really have it as a place where a lot of younger investigators could get started on a career in geriatric oncology. And that was really a great opportunity. It was kept on by Dr. Bertagnolli, who now is our NCI director, and I think was really the first group to really give good support for this. Dave Johnson: So we want to thank you very much for being our guest today. We also want to thank our listeners of Oncology, Etc. This is an ASCO Educational Podcast where we talk about oncology medicine and much more. So if any of our listeners have an idea or a guest they would like for us to interview, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, visit ASCO's website at education.asco.org. Thanks again for being our guest, Hy. Dr. Hyman Muss: My pleasure. Thank you so much. 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.
Drs. Vamsi Velcheti and Jack West discuss key abstracts in advanced SCLC and NSCLC, along with highlighting the largest known data set correlating ctDNA levels and efficacy outcomes in the EMPOWER-Lung 1 trial, in advance of the 2023 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsidhar Velcheti: Hello, I am Dr. Vamsidhar Velcheti, your guest host of the ASCO Daily News Podcast today. I am a professor of medicine at NYU Grossman School of Medicine and the director of thoracic oncology at Perlmutter Cancer Center at NYU Langone Health. I am delighted to welcome Dr. Jack West, a thoracic oncologist and associate professor in medicine at the City of Hope Comprehensive Cancer Center. Today, we'll be discussing key posters and oral abstracts in lung cancer that will be featured at the 2023 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/DNpod. Jack, it's great to have you on the podcast today. Dr. Jack West: Well, thank you so much, it's my pleasure to be here. Dr. Vamsidhar Velcheti: Let's begin with Abstract 8512. This is the follow-up of the Gronberg trial, the Danish trial of BID thoracic radiation for limited-stage small cell lung cancer. What are your key takeaways from this trial? Dr. Jack West: Well, as you noted, this has been presented before a few years ago. It's a trial for limited-stage small cell lung cancer and it directly compared chemotherapy with either 45 Gray or 60 Gray of chest radiation delivered twice daily. It's not an enormous study, it's 170 eligible patients. And years ago, we saw that the efficacy endpoints looked very promising for the patients who received a higher dose of 60 Gray on a BID schedule, which is above our standard. We generally either give 45 Gray BID or probably more commonly in the US and I think globally give maybe 60 Gray on a once-a-day schedule. But the efficacy looked quite promising and without any clear increase in the toxicity of it. And really, despite the impressive results, this hasn't changed practice. It is not a large study and I think that I would say that most of the radiation oncology world has been reserving judgment until potentially seeing a larger study. But what's being presented at ASCO are the longer-term results that continue to look excellent. You have a progression-free survival median of 18.6 months versus 10.9 months. That's not statistically significant but has a hazard ratio of 0.76 associated with it. And the median overall survival is even more pronounced of 43.5 months favoring the 60 Gray arm compared to 22.6 months in 45 Gray on a BID schedule that has a hazard ratio of 0.69. And this is statistically significant. The authors note that they will be presenting five-year overall survival as well. And there's also just passing mention that, as was seen previously, there was no increase in toxicity, no prohibitive toxicity. So I don't think it's necessarily going to change practice because the numbers of patients, which I think are really the leading concern, hasn't changed. But these very promising results still hold up over time and I think should compel us to carefully assess this as an option to potentially increase outcomes for this challenging setting where progress is slow to come. Dr. Vamsidhar Velcheti: Yeah, I completely agree, Jack. And I think one of the things that we have seen, at least in the non-small cell setting, like the higher dose of conventional radiation is not superior to the 45 Gray, BID dosing. I think there were some studies with CALGB and the Gronberg trial, but I think at the end of the day, it comes down to patient conveniencer. It's not often feasible for patients to come in twice a day for radiation. That might be something that might limit utilization here. Dr. Jack West: I think that's a very good point. It's just difficult when you have the potential for higher cure rates, but it is at least challenging, if not completely infeasible. But I really agree with you that that's a big part of why it's underutilized relative to the strength of the data for BID. But we have to be able to actually administer these. Dr. Vamsidhar Velcheti: So let's move on to another trial. And again, we've seen the data before. This is Abstract 8521, the CheckMate-816 trial. They reported the three-year results of the neoadjuvant nivolumab chemotherapy versus chemotherapy by definitive surgery in patients with resected non-smoker lung cancer. What is the data that's being presented at ASCO this year? Dr. Jack West: So yes, as you mentioned, we've seen data on CheckMate-816 for a few years now. It's been published in the New England Journal of Medicine and it's FDA-approved and has become a standard of care, if not the standard of care, but there are many dimensions to this. And one of the questions has been what happens to the patients who did not undergo surgery, which was about 17% of patients on the chemoimmunotherapy arm, a full quarter of patients on the chemo arm. What happened to these folks? And that's what is being presented by Dr. Jonathan Spicer, a thoracic surgeon in Montreal who's been heavily involved with this trial. And I think that's going to be the overwhelming focus of this. And what is reported in the abstract, and I'm sure we'll see more interesting results, is that the outcomes are superior in the patients who received chemoimmunotherapy with nivolumab, in the patients who did not undergo surgery as well as those who did. Specifically, they report on the median time before death or distant metastases, and that was 24.8 months as a median for the chemoimmunotherapy arm versus 15.6 months for the patients who receive neoadjuvant chemo alone. The hazard ratio for that's 0.63. There was also a striking difference in the three-year survival rates, 36% versus 13% also favoring chemo and nivolumab. They also talked about the actual treatments that patients received when they didn't have surgery, and about 60% in both of those arms received radiation instead of surgery, and about half the patients also received additional systemic therapy. So we will see more. But I think it helps to address one lingering question of what happens to the patients who did not end up pursuing surgery and showing that the results were more favorable for the recipients of chemo nivolumab, even in that subset. Dr. Vamsidhar Velcheti: It's simply fascinating how the field is evolving in the perioperative space, Jack. And there are more unanswered questions here and up for debate for years with the recent agent trials we had seen at AACR. We've seen the same kind of trend even with the agent, I think it was 20%, who did not make it to surgery. A lot of them are like stage 3 patients. So it begs the question, are we kind of just being more aggressive with induction therapy? Maybe some of these patients are biologically or anatomically not bound to have surgery. I mean, it's hard to really tell. Dr. Jack West: It really is important for us to still select appropriate patients for this, rather than become overly ambitious and try to shoehorn patients who are really not ideal or appropriate candidates for surgery and anticipate or have kind of aspirational resectability if they aren't de novo great candidates for surgery. We, of course, need to remember that chemoradiation followed by consolidation durvalumab on the PACIFIC trial is not some terrible consolation prize. We've done remarkably better with this over the years, and it's a very strong option. Dr. Vamsidhar Velcheti: Exactly. The other open question, but of course this abstract doesn't really address is, what do you do with all the patients who perhaps have major pathologic responses and what do you do after surgery? That's kind of an open question, and we probably need a better way to determine who might need adjuvant therapy or surgery. I don't know if you have any thoughts on that. Dr. Jack West: As you say, I think that's a big question, a gaping hole in our knowledge base, but it's not addressed here. I think we are going to be struggling with that in the coming years. Dr. Vamsidhar Velcheti: Right. So let's move on to Abstract 9002. This is a report of the first pivotal study results of DZD9008 sunvozertinib in patients with exon 20 EGFR mutation. What are your key takeaways from the study? Dr. Jack West: So I would say obviously we have a couple of agents that target EGFR exon 20 mutations, but unfortunately, neither of the agents that are commercially available is especially active. And they certainly have toxicity challenges, whether it's amivantinab or mobocertinib, they both share some challenges and they're not as efficacious as some of the other targeted therapies we use in different molecular settings. So I would say there's still some unmet need here. And these results with sunvozertinib DZD9008 selective irreversible EGFRexon20 insertion inhibitor really got my attention as very impressive. These are patients who were heavily pretreated. The median was two prior lines of therapy. This is not de novo first line, and that's a setting where it's pretty hard to see response rates that are over 30 or 40%, but what they actually report is about 60.8% response rate and nearly 100 patients assessed. They also looked at patients who had brain metastases and 31 patients in their sample had de novo metastases and the intracranial response rate was 48.5%, so nearly half. This is, of course, something that we hope to see as a pattern when we have a targeted therapy that's very effective for the right target, not just overall extracranial, but intracranial efficacy. And we're going to need to see the details on the tolerability because, as I mentioned, the available agents now have the dual challenge of just modest efficacy and really quite challenging, particularly GI toxicities and amivantamab has issues also with infusion reactions. So some work there and I think there's room to improve on that. This looks to me very promising and I would welcome having the opportunity to use it in my patients who have an exon20 mutation. Dr. Vamsidhar Velcheti: Yeah, I think certainly the brain intracranial activity is perhaps going to be the differentiator here. Given that mobocertinib has limited intracranial activity, I think that's very encouraging to see. So let's move on to the next abstract, the SCARLET trial, Abstract 9006. So this is a clinical trial of sotorasib plus chemotherapy in KRAS G12C-positive patients. Can you tell us a little bit more about this study, Dr. West? Dr. Jack West: Sure. So this was a single-arm phase II trial. It's not large, it's 30 patients, but we really have yet to see results that would compel me to move sotorasib into the first-line setting. I was a little underwhelmed with the CodeBreaK 200 results that didn't beat docetaxel for survival in the second-line setting. But here it's a combination of carboplatin pemetrexed with sodorasib in the first-line setting in patients, of course, with a KRAS G12C mutation and nonsquamous histology. And the reported response rate by independent review is 88.9%, which is quite impressive. The median PFS is not reached yet. The PFS at six months is 61.2%. So I think we'll need to see the full data set, but that really impresses me as a very relevant finding. So I would love to learn more about this. And I think that if it is anything close to holding up with these response rates, close to 90%, I mean, even if it's 70 or 80%, I think that is compelling enough to really want to study this further in the first line setting and maybe a path to getting KRAS inhibitors used in the front line. Dr. Vamsidhar Velcheti: Yeah, I completely agree. And I think with all the issues around the combination with checkpoint inhibitors, especially with sotorasib high liver toxicity, so I think the only way this could move into the frontline is with combination with chemotherapy, especially in certain subsets like KEAP1 CUL drug patients, STK11/KEAP1 patients where immunotherapy historically underperforms. So it'll be interesting to see how this can evolve. So, moving on to Abstract 9012, this is a clinical trial evaluating a often very neglected patient population. This is a retrospective study of chemo without immunotherapy in the elderly population of patients with PD-L1-positive tumors. So what is your takeaway from this study? Dr. Jack West: I would say that it really complements in my mind the presentation by Dr. Akinboro and colleagues from the FDA last year at ASCO, which was looking at the data for the trials of immunotherapy or chemoimmunotherapy in patients with high PD-L1 50% or higher. And what they found was that there was an improvement in response rate and progression-free survival and a trend, but not a significant difference in overall survival favoring chemoimmunotherapy in those patients. But they also noted that patients who were 75 or older did not seem to benefit from chemoimmunotherapy relative to immunotherapy alone. Now, that is in patients with high tumor PD-L1. This is looking specifically at patients who are 75 and older in Japan, 58 centers, and we're talking about over 1,200 patients, 1,245. And they looked at patients with any PD-L1. So the full spectrum, about 22% had PD-L1 less than 1%,31%, one to 49%, and just over a third, 34% with PD-L1 over 50%. I would presume the balance, that missing 13%, was not tested. But these are real-world data and they have strengths and limitations relative to controlled clinical trials. But I think that there is some power in numbers and real-world data. And what they saw was that the patients who received chemoimmunotherapy had a median overall survival of 20 months. It was 19.8 months with a checkpoint inhibitor alone. And those data for both of those conditions are far better than a platinum doublet alone with a median overall survival of 12.8 months. Single-agent chemo just median overall survival of 9.5 months. And then when they looked at toxicities, saw that the grade three or higher immune-related adverse events was clearly higher in the patients who had chemoimmunotherapy, they had a greater need for steroids and a greater probability of pneumonitis than the patients over 75 who received a checkpoint inhibitor alone. And so I would say it's not randomized data. You can only take this so far, but the fact is that it, I think, complements what we saw from the FDA. And that would help me in a situation where we need to make a nuanced decision, there's competing potential standards of care. I think this is informative along with the IPSOS trial that has been presented in some other settings and shows a benefit for in that setting was atezolizumab, I believe, first as the immunotherapy for older patients and PS2. So I think that we're seeing converging evidence to support this concept. Dr. Vamsidhar Velcheti: Yeah, and I completely agree. And I think sometimes the clinical nuances at the individual patient level, I think there are so many other factors that we can actually look at the real-world data, like, for example, tumor burden and medical tomographies. There's so many things that we need to factor into while making those decisions. Let's move on to the next abstract. This is Abstract 9022. This is an abstract looking at correlations of ctDNA levels and efficacy outcomes in the EMPOWER-Lung 1 trial. What are your key takeaways from this study? Dr. Jack West: I would love to use ctDNA for clinical decision-making in a few years. I think it could be as pivotal as PET scans, but we don't have the data yet to show that you can use the results to improve outcomes. But this is looking at ctDNA in a different setting, as you mentioned, it's looking at the EMPOWER-Lung 1 trial, which was cemiplimab versus chemotherapy in patients with PD-L1 over 50% and did not have a driver mutation. They had ctDNA samples available from 175 patients who were pretty evenly split between chemo and checkpoint inhibitor cemiplimab. What they found was that molecular response, or particularly complete molecular response, if it was seen as in complete eradication of ctDNA at week nine, so after three cycles, was highly correlated with imaging-based response for patients who got cemiplimab. It was not correlated for the patients who got chemotherapy and, perhaps not surprisingly, the patients who had a complete molecular response that was associated with the best overall survival, an immediate overall survival of 29 months compared to the rather dismal results for patients who had no drop in their ctDNA, where the median overall survival was just eight months. So, I think that it would be wonderful to be able to use this as a help. We know that sometimes patients have ambiguous imaging. There is the possibility of pseudoprogression and just potentially pneumonitis, making it difficult to interpret. I think that ctDNA could be helpful in that situation, but also for early feedback on who might benefit from intensification and adding chemotherapy, who we should cut our losses and switch to something else other than cemiplimab. And in the best-case scenarios, we do have a subset of patients who are doing extraordinarily well, potentially one or a couple of years later, and we just don't know if or whether to stop it and whether patients can do just as well after stopping after a prolonged period on treatment compared to staying on it. And we don't want to give this for years longer at the expense of cumulative toxicities and requiring a patient to come in for ongoing treatments month after month, year after year, for any longer than they would need. I think that there's great potential utility for this as a concept. But again, at some point, what we'll really need is not to just apply this retrospectively, but prospectively to guide therapeutic decisions, to see if we can have patients do better by intensifying for those patients who need it or de-intensifying for patients who don't. Dr. Vamsidhar Velcheti: It's great, Jack. And I completely agree. I think those kinds of de-escalation trials are very much needed. I'm hoping that we'll get there very soon. Thank you so much, Dr. West, for sharing your valuable insights with us today on the ASCO Daily News Podcast. We really appreciate your time. Thank you so much. Look forward to seeing you in Chicago. Dr. Jack West: Awesome. Great. Dr. Vamsidhar Velcheti: And I'd like to thank all the listeners for joining us today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you so much. 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, experiences, 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. Follow today's speakers: Dr. Vamsidhar Velcheti @VamsiVelcheti Dr. H. Jack West @JackWestMD Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Vamsidhar Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline Dr. Jack West: Honoraria: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati, Regneron, Amgen, Abbvie Consulting or Advisory Role: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati Therapeutics, Regneron, Amgen, Abbvie, Summit Therapeutics Speakers' Bureau: Takeda, Merck, AstraZeneca
Gastrointestinal cancer experts Dr. Aparna Parikh and Dr. Kristin Ciombor discuss the treatment implications of the phase 3 PARADIGM trial and other advances in colorectal cancer with guest host and ASCO Daily News Associate Editor, Dr. Shaalan Beg. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the ASCO Daily News Podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Center and vice president of Oncology at Science 37. I'm delighted to welcome Dr. Aparna Parikh, and Dr. Kristen Ciombor to the podcast today. Dr. Parikh is an assistant professor of Medicine at Harvard University and a GI medical oncologist at the Mass General Hospital Cancer Center. Dr. Ciombor is an associate professor of Medicine and GI medical oncologist at the Vanderbilt University Medical Center. Today, we'll be discussing exciting new approaches using EGFR inhibitors as frontline therapy in colorectal cancer, and promising advances with immune therapy in the treatment of rectal cancer. Our full disclosures are available in the show notes, and disclosures of all guests on the podcast can be found in our transcripts at: asco.org/podcasts. Dr. Parikh, and Dr. Ciombor, it's great to have you on the podcast today. Dr. Aparna Parikh: Thanks so much. Dr. Kristen Ciombor: Thanks so much for having us. Dr. Shaalan Beg: We've seen some exciting advances in GI oncology this year. Let's start with colorectal cancer. Dr. Parikh, there have been many trials looking to compare EGFR and VEGF inhibitors in colorectal cancer. We've heard about the IDEA studies, the FIRE trials, and CALGB 80405. At the 2022 ASCO Annual Meeting, we heard the results of the PARADIGM trial. Have we finally answered the question of when to use EGFR inhibitors as frontline therapy for colorectal cancer? Dr. Aparna Parikh: Thanks so much, Dr. Beg, for this great question. It has been a really exciting year for colorectal cancer across the board. So, the anti-EGFR story is really interesting and has evolved. And maybe just for a little bit of background, we know that colorectal cancer originating from both the right and left side of the colon differ. So, they differ embryologically, and epidemiologically; there are different genetic and molecular aspects to right and left sides of colon cancers. And we have learned over time that in the era of targeted therapy, the primary tumor location has been found to play a very important role, not only in the prognosis of patients but to predict treatment response. We know that patients that have left-sided colon cancers-- and when we think about left-sided colon cancers, we think about cancers that originate from the splenic flexure and descending colon, sigmoid colon, rectosigmoid junction, and sometimes include the rectum in this as well. The rectals have slightly different molecular features than distal colons. And we know that these left-sided patients, overall, have better survival benefits than patients that have right-sided CRC. And that includes again, cecum, ascending colon, hepatic flexure, and transverse colon. So, we know that that had prognostic implications, but what about the predictive implications? And with ASCO, we saw some really exciting data with the PARADIGM study, as Dr. Beg highlighted. We have seen many examples in the past showing the predictive power of anti-EGFR therapy, and anti-EGFR therapy showing a detriment for patients on the right side of the colon. But all these results historically have been obtained by retrospective analysis. So, retrospective analysis of the pivotal CALGB 80405 study, which is the first-line biologic trial. FIRE-3, which is a similar study, but done out of Europe, and KRYSTAL. So all these studies show the same finding but were all obtained basically by retrospective analysis. And what we saw with PARADIGM this year, which is exciting to see, is that this was the first prospective trial to test the superiority of an anti-EGFR inhibitor panitumumab versus bevacizumab in combination with standard doublet first-line chemotherapy for patients that were RAS-wild type. I guess I forgot to mention that again, anti-EGFR therapies are only eligible for patients that are RAS-wild type. We know that RAS-mutant patients and RAS, KRAS HRAS patients don't respond to anti-EGFR therapy. So, the study was looking at RAS-wild type patients, and again, asking the question “was panitumumab better than bevacizumab in combination with chemotherapy for these RAS-wild type patients and for left-sided tumors?” It was a multicenter trial done in Japan-- and I always commend the Japanese on their work and their designs and ability to do these studies that ask really important questions. And, overall survival was the primary endpoint of the study in patients with left-sided tumors, but they also did a full set analysis including patients that didn't have left-sided tumors. They had 823 randomized patients. Many patients, a handful did not receive per-protocol treatment, and some were excluded for other reasons relating to inclusion criteria. And they had 400 patients that ultimately received panitumumab and 402 patients that received bevacizumab in the full set analysis. And of those patients, there were 312 and 292 respectively had left-sided tumors. And although the PFS was comparable between the treatment group, we saw that panitumumab in the left-sided patients actually did improve the OS in both patient populations. But when you looked at the left-sided tumors, the difference was 37.9 versus 34.3 months meeting statistical significance. So, this was an exciting study because it confirmed prospectively what we have seen time and time again, and really behooves us to do early biomarker testing and know RAS status early for these patients with right-sided tumors, as they do derive benefit from anti-EGFR. Maybe I'll just pause there and open it up for more questions or comments from Dr. Ciombor as well. Dr. Kristen Ciombor: Yeah, Dr. Parikh, I thought these data were encouraging. And as you mentioned, the first prospective data that we have in this setting now that we know this primary tumor sidedness matters. Just on a practical note, what do you do in practice? Do you give a lot of anti-EGFR in the first-line? I find that the toxicity can be challenging sometimes and patients may not want to do that. So, it leaves us in a quandary sometimes. Dr. Aparna Parikh: Yeah. So, what's interesting and I don't think we have this data clearly answered yet is, I had, especially for kind of a fit patient-- with the previous data that we've seen with TRIBE and others showing a survival benefit with triplet chemotherapy for first-line therapy, my inclination had actually been to prefer triplet-- and we know that triplet and anti-EGFR toxicity-wise is really, really tough to manage, and really no benefit there that we've seen with OS or PFS, even though you maybe do get a little bit of a better response rate with that. And so where I have sort of struggled is triplet versus just doing first-line doublet plus anti-EGFR. You know, we are not having a discussion about triplet today, but we also saw some data at ASCO showing that perhaps the benefit of the triplet, with the triplet study, is not as much as we had hoped it would've been too. So, it's a good question. I do tend to prefer triplet, I guess, overall, for the healthy, good performance status patient. And then, if not, then doublet. And we, unfortunately, don't have kind of rapid EGFR testing, we're pushing for that. In practice, I think having RAS/RAF status up front would be entirely helpful. It's lumped into our pan-tumor profiling, comprehensive genomic panels. We get microsatellite instability (MSI) status, which I know we'll talk about here next right away. But I think another reason that oftentimes we don't add it right away, is because we don't have the RAS status right away. So, you just start with a doublet and you may end up sneaking it on later. And then, I'd love to, maybe in another podcast, where we can discuss second-line anti-EGFR therapies and what people do in practice for those right-sided patients should they never get anti-EGFR and later-lines of therapy too. And I would argue, perhaps not, because we do see some patients that do benefit, but it can be challenging sometimes with a fresh new patient to make these decisions. But at least, feel encouraged that we're doing the right thing by adding anti-EGFR therapy if they can tolerate it for the left-sided RAS-wild type patient. How about you? What do you do? Dr. Kristen Ciombor: Yeah. Largely, it's a great question. And I don't love giving anti-EGFR therapy. We have an additional issue where I am geographically in that we don't ever give cetuximab because of the high rates of an infusion reaction. So, we pretty much stick to panitumumab and are glad to have that option. But I have started to talk to patients about toxicity and I'm really upfront with the survival data. And it's interesting how people choose differently in terms of what's important to them. And whereas a few extra months in the overall survival may be overshadowed by the toxicity that they have to go through to accomplish that. So, it's good to have many options though, and that's the important thing, and I think the takeaway, as well. Dr. Shaalan Beg: So, kind of brings it back to the fundamentals of practicing medicine, right? Bringing our patients and giving them the options that are most available to them. But I'm going to ask both of you one by one: So, if we have our patient with left-sided colorectal cancer, known as KRAS RAS-wild type, do you recommend EGFR therapy and VEGF therapy and allow the patients to decide, or do you feel that we decide if their profile is such that we should continue with VEGF therapy instead? Dr. Ciombor, do you want to go first? Dr. Kristen Ciombor: Yeah, I think both are good options. I don't only do bevacizumab in the first-line by any means because we do have that survival data. It mostly comes down to a discussion with the patient in terms of toxicities and survival and how well those balance out. Dr. Aparna Parikh: Yeah, very similar. I think we have also gotten a little bit more adept at managing toxicity. I'm pretty aggressive about prophylaxis with even doxy and topicals for managing the rash. And so, for some of my younger patients who are wanting to be "aggressive" and want the exposure to anti-EGFR early but are still very mindful of how it's impacting their day-to-day semblance of self, especially for the younger patients, try to be very proactive about side effect management. And then, of course, we have the patients that have the electrolyte wasting and things too that sometimes if it's bad, we are stuck with infusions frequently and you may end up dropping for those patients. But I think the rash at least I feel like for most patients we can manage if you're aggressive about it too. And I think we have gotten better at that than we were many years ago. Dr. Kristen Ciombor: Never thought we'd be dermatologists, did we? In training, that was definitely not a path I was good at. Dr. Shaalan Beg: Dermato-Oncology, rapidly growing field. So, Dr. Ciombor, the rectal cancer space has evolved very rapidly in recent years, especially when we hear about total neoadjuvant therapy, short-course radiation, watch-and-wait, for those with complete clinical responses. So at ASCO this year, we heard results on immune therapy and rectal cancer. Can you summarize where we are with immune therapy and rectal cancer? Dr. Kristen Ciombor: So, yes. We heard a lot this year at ASCO; both at ASCO GI and ASCO, from the Memorial group and Dr. Cercek's group. And this has been a really exciting advance that we're starting to see and potentially paradigm-shifting data. So, we know-- as you mentioned, that our treatment of rectal cancer, specifically, locally advanced rectal cancer has changed a lot in the last few years with a shift to more Total Neoadjuvant Therapy. And what the Memorial data showed was that for the patients who have microsatellite instability or mismatch repair deficiency, which admittedly, is a small group, but certainly ones that we see in clinic, those patients, on their trial were treated with six months of dostarlimab as neoadjuvant therapy prior to any other treatment; before radiation, surgery, et cetera, and no chemotherapy. And what they found was that actually, six months of dostarlimab in the first 14 evaluable patients actually induced a 100% clinical complete response rate. So, it's really unheard of in most of our trials to see 100%. And I think that caught everyone's attention for sure. I think we have to keep in mind who these patients were and are because they are currently being followed. So, for instance, these were patients that had pretty bulky node-positive disease, almost all these patients did. These were not really early-stage tumors. We did see that 100% were BRAF-wild type, so it does tell us maybe this is not completely the population that we're all seeing when we do see microsatellite instability since we see a lot of sporadic tumors with BRAF mutations. But on the whole, I mean, these were all MSI-high patients and treated with dostarlimab; the six months, that was the total amount of treatment that they received, though a few patients achieved that clinical complete response earlier at about three months, at the three-month reassessment. And what the clinical complete response rate was, was looking both radiographically, as well as endoscopically, and not seeing any sign of residual tumor. I think the important thing here is that median follow-up is still pretty short. There are a few patients who are approaching now two years past that dostarlimab therapy and have not had tumor recurrence, but overall, the median follow-up is still quite short. So, I think we do need to continue to follow these patients. We don't have overall survival data yet either. I think we still have a lot to learn, but this is a very encouraging start and certainly, something that could be really treatment-changing for these patients, which again, as Dr. Parikh was saying, we need this molecular profiling early to make treatment decisions right off the bat, not even only for metastatic now, but even for these locally-advanced rectal cancer patients. Because if you think about it, we've all taken care of patients who have to go through chemoradiation, and chemo, and surgery, and have a lot of morbidity from those treatments so that even if you cure them, they're left with a lot of toxicity. So, if we could avoid some of that, even potentially, surgery, that would be wonderful. But I do caution that this is not the standard of care yet. This is only based on 14 patients with short follow-ups at the current time. But the trial is ongoing, and there are other trials open in this space for patients who don't live in New York or can't get to New York. And for instance, ECOG-ACRIN study 2201 is treating these same patients with nivo and ipi, as opposed to dostarlimab. And that trial is open in about 80 sites now across the US. So hopefully, geographically near all of these patients. Dr. Shaalan Beg: I think a lot of us and a lot of our listeners, that Monday after the results were announced on ASCO had our phone lines and our patient secure messaging lines blowing up. Dr. Kristen Ciombor: We should have warned our nurses and our treatment teams that they would be fielding these questions, yes. On one hand, it's wonderful that our data and the science is getting out to patients. But I think we also have to be really careful as to what is reaching them because many of them didn't realize it was for this subset of patient populations. But great that they're asking those questions and wondering-- being advocates for themselves too. Dr. Shaalan Beg: You use the term clinical complete response. Can you talk about how we determine someone has a complete clinical response and what their follow-up looks like? Dr. Kristen Ciombor: Yeah. In the context of this study, it was actually, as I mentioned, it was both radiographic complete response, as well as endoscopic. So that's one thing that is a little bit tricky when you think about surveillance of these patients. So, it requires a lot, both in frequent surveillance, MRIs, FLEX SIGs often, digital rectal exams, sometimes doing PET scans or CTs, and patients who-- not only on this kind of study but also in non-operative management; watch-and-wait - really have to commit to very close, very frequent follow-up because if the cancer recurs, we don't want to miss that and lose our chance to cure them. So I think that's a little bit different everywhere, how that watch-and-wait approach really manifests, but I think we're learning how to do that, and working in a multidisciplinary group to make sure that patients get the surveillance that they need. Dr. Aparna Parikh: Yeah. I totally agree. If we offer, for the MSI-high patients, if we ultimately end up offering neoadjuvant immunotherapy-- and actually, I'm looking forward to your study, Dr. Ciombor, too, I think the monotherapy versus doublet, too, is going to come up for these patients. But I had a patient just a week or two ago that was starting on this approach with neoadjuvant immunotherapy, but for now, as a group, if we're proceeding down that and they do get a clinical complete response, we're deciding to forego even the radiation and surgery. We're following what they did in the OPRA study, which was pretty aggressive surveillance on the backend, both with direct visualization and MRIs, and you're seeing these patients every three months or so. Dr. Shaalan Beg: Well, thank you Dr. Ciombor and Dr. Parikh for sharing some valuable insights with us on the podcast today. Dr. Aparna Parikh: Thanks so much for having us. It was a lot of fun. Dr. Kristen Ciombor: Thanks for having us on. Dr. Shaalan Beg: And thank you to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review and subscribe, wherever you get your 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. 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. Follow today's speakers: Dr. Kristen Ciombor @KristenCiombor Dr. Aparna Parikh @aparna1024 Dr. Shaalan Beg @ShaalanBeg Listen to additional episodes on advances in GI oncology: Novel Therapies in GI Oncology at ASCO22 ASCO22: Key Posters on Advances in GI Oncology Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Kristen Ciombor: Consulting or Advisory Role: Merck, Pfizer, Lilly, Seagen, Replimune, Personalis Research Funding (Inst.): Pfizer, Boston Biomedical, MedImmune, Onyx, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, Sanofi Recipient, Bristol-Myers Squibb, Array BioPharma, Incyte, Daiichi Sankyo, Nucana, Abbvie, Merck, Pfizer/Calithera, Genentech, Seagen Travel, Accommodations, Expenses Company: Array Dr. Aparna Parikh: Stock and Ownership Interests: C2i genomics Consulting or Advisory Role: Eli Lilly, Natera, Checkmate Pharmaceuticals, Pfizer, Roche/Genentech, Inivata, Biofidelity, Guardant Health Research Funding(Inst.): PMV Pharma, Plexxikon, Bristol-Myers Squibb, Genentech, Guardant Health, Array, Eli Lilly, Novartis Pharmaceuticals UK Ltd., PureTech, Mirati Therapeutics, Daiichi Sankyo
Drs Sumanta Pal and Brian Rini discuss front-line treatment of renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968736). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Bevacizumab Plus Interferon-alpha Versus Interferon-alpha Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 https://ascopubs.org/doi/10.1200/jco.2009.27.18_suppl.lba5019 An updated table of the front-line IO combination RCC studies that have shown an OS advantage https://twitter.com/brian_rini/status/1309609380585844736/photo/1 Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting https://aacrjournals.org/clincancerres/article/26/9/2087/83102/Targeting-PD-1-or-PD-L1-in-Metastatic-Kidney Conditional Survival and Long-term Efficacy With Nivolumab Plus Ipilimumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34180 International Metastatic Renal Cell Carcinoma Database Consortium Criteria https://www.uptodate.com/contents/image?imageKey=ONC%2F116130&topicKey=ONC%2F2984&source=see_link Molecular Correlates Differentiate Response to Atezolizumab (atezo) + Bevacizumab (bev) vs Sunitinib (sun): Results From a Phase III Study (IMmotion151) in Untreated Metastatic Renal Cell Carcinoma (mRCC) https://cslide.ctimeetingtech.com/esmo2018/attendee/confcal/presentation/list?q=LBA31 Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415096/pdf/nihms-1732721.pdf Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma https://www.nejm.org/doi/10.1056/NEJMoa2035716 The Uromigos Debate: Treatment of Favorable Risk Renal Cancer https://anchor.fm/the-uromigos/episodes/Episode-67-The-Third-Uromigos-Debate---fPD1VEGF-vs-PD1CTLA4-for-front-line-renal-cancer-emjpji Health-Related Quality-of-Life Outcomes in Patients With Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab or Everolimus Versus Sunitinib (CLEAR): A Randomised, Phase 3 Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00212-1/fulltext Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) https://clinicaltrials.gov/ct2/show/NCT04736706 Twitter poll questions: What magnitude of benefit is required to adopt triplets? OS https://mobile.twitter.com/brian_rini/status/1508450496104783877 What magnitude of absolute PFS benefit vs doublets is required to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508450910506295305 What would be the most convincing endpoint to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508451622564909057 Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436590/ OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma (OPTIC RCC) https://www.kcameetings.org/wp-content/uploads/2021/12/IKCSNA21_TIP8_Chen.pdf
Drs Schapira and Gillespie begin this series by reviewing the current research on radiation options for early-stage breast cancer and how to discuss treatment options with patients. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/963162). The topics and discussions are planned, produced, and reviewed independently of our advertiser. This podcast is intended only for US healthcare professionals. Resources Radiation Therapy for the Whole Breast: Executive Summary of an American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline https://www.practicalradonc.org/article/S1879-8500(18)30051-1/fulltext Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526720/ Hypofractionated Breast Radiotherapy for 1 Week Versus 3 Weeks (FAST-Forward): 5-Year Efficacy and Late Normal Tissue Effects Results From a Multicentre, Non-inferiority, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30932-6/fulltext Partial-Breast Radiotherapy After Breast Conservation Surgery for Patients With Early Breast Cancer (UK IMPORT LOW trial): 5-Year Results From a Multicentre, Randomised, Controlled, Phase 3, Non-inferiority Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31145-5/fulltext External Beam Accelerated Partial Breast Irradiation Versus Whole Breast Irradiation After Breast Conserving Surgery in Women With Ductal Carcinoma In Situ and Node-Negative Breast Cancer (RAPID): A Randomised Controlled Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32515-2/fulltext Once Daily Versus Twice Daily External Beam Accelerated Partial Breast Irradiation: A Randomized Prospective Study https://www.redjournal.org/article/S0360-3016(20)34566-1/fulltext Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-term Results of the Randomized Phase III APBI-IMRT-Florence Trial https://ascopubs.org/doi/10.1200/JCO.20.00650 Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2422117 De-escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA) https://clinicaltrials.gov/ct2/show/NCT04852887 Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-term Follow-up of CALGB 9343 https://ascopubs.org/doi/10.1200/JCO.2012.45.2615 PRIME II Investigators. Breast-Conserving Surgery With or Without Irradiation in Women Aged 65 Years or Older With Early Breast Cancer (PRIME II): A Randomised Controlled Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71221-5/fulltext Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 https://jamanetwork.com/journals/jama/fullarticle/2653737 Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer (EORTC 10981-22023 AMAROS): A Randomised, Multicentre, Open-Label, Phase 3 Non-inferiority Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70460-7/fulltext Regional Lymph Nodes Radiation and Breast Cancer Related Lymphedema: Where We Stand https://www.redjournal.org/article/S0360-3016(21)00165-6/fulltext Event-Free Survival With Pembrolizumab in Early Triple-Negative Breast Cancer https://www.nejm.org/doi/10.1056/NEJMoa1910549
Dr. Hayes interviews Dr. Breitbart on his research addressing psychiatric, psychological and existential adjustment as well as symptom control in advanced cancer. TRANSCRIPT SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DANIEL HAYES: Welcome to JCO's Cancer Stories-- The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insights into the world of cancer care. You can find all of their shows, including this one, at podcast.asco.org. We have a special treat today in our podcast series in that I have the opportunity to interview Dr. William Breitbart. Dr. Breitbart is the Jimmie Holland Chair of Oncology at Memorial Sloan Kettering and the Professor and Vice Chair of the Department of Psychiatry at the Weill Cornell Medical College. And as far as I can see, Dr. Breitbart, you've never left New York City. But I will get the background. And you can tell us if you took a vacation or something one time outside the city. Dr. Breitbart grew up in the Lower East Side of Manhattan. He went to Brooklyn College, graduated in 1973, then medical school at the Albert Einstein College of Medicine. And then he did his residency in internal medicine at the Bronx Hospital and trained basically at Memorial Sloan Kettering. Joined the faculty there, and has been on the faculty ever since. He has a number of accomplishments, too many for me to really review it carefully. But he's been president of the International Psycho-Oncology Society and received their Sutherland Lifetime Achievement Award. He's been president of the Academy of Psychosomatic Medicine and received their Hackett Lifetime Achievement Award. And on a personal basis, my brother was also the president of the Academy of Psychosomatic Medicine. So I'm very proud of my brother and equally proud of Dr. Breitbart. He really is responsible for a number of enormous steps forward in our field, including psychotherapeutic approaches for palliative care of patients with terminal illnesses, especially cancer. He has been involved with what I saw you call, Dr. Breitbart, "hastened to death." I had learned it as assisted suicide. I'm going to ask you a question about that. I'm interested in your comments. And more recently, meaning-centered psychotherapy for the terminally ill And we'll talk more about that, too. So in addition, I have asked Dr. Breitbart if he would also give us insights into Dr. Jimmie Holland's life and her career. Sadly, she passed away before we had an opportunity to chat with her. She was one of my favorite people in the whole world. And I think everybody that knew here said the same thing. So we'll get some insights for those of you who didn't know Dr. Holland from this call as well. Before we start, Dr. Breitbart wants to declare that he's received honoraria from Novartis and has a consulting or advisory role with Novartis. Dr. Breitbart, welcome to our program today. WILLIAM BREITBART: Thank you Dr. Hayes, pleasure to be here. Can I make just one slight correction? I actually trained in both internal medicine and psychiatry at the Bronx Municipal Hospital, which is the Albert Einstein College of Medicine, in New York City Health and Hospitals Corporation's Public Hospital. So I trained in both psychiatry and internal medicine, jumping back and forth between the two, out of a state of confusion. And then I landed in Dr. Holland's fellowship at Memorial Sloan Kettering for a variety of reasons. The main reason was though that I had developed a thyroid cancer when I was a medical resident in the middle of my training. And then I went back to finish up more of my psychiatry residency training, I became the liaison to the Oncology Clinic at Jacobi Hospital, the Bronx Municipal Hospital. I did consultations for cancer patients. I ran groups for cancer patients and also ran groups for the oncologists and oncology nurses. And I was trying to educate myself on the subject of psycho-oncology or psychiatric oncology. It actually hadn't been named yet in those days. And the only literature I could find were papers written in oncology journals by Dr. Julie Holland. And so that's where I knew where I needed to go to become more expert in this area. That's the most superficial version of how I ended up at Memorial Sloan Kettering. I could tell you the more interesting version if you're interested. DANIEL HAYES: Well, actually, what you just covered was my first question. I was going to say this is about you, not about me. But my brother also did training in internal medicine and decided to go in psychiatry, and ended up in psychiatry liaison. And I think that's what makes you two, and others like you, powerful, is that if you go to France and you don't speak French, you're not going to be listened to. And if you come to a bunch of oncologists, and you don't speak internal medicine or oncology, we're not going to listen to you. And I think clearly to me, Jimmie Holland always knew what I did. And I think you have the same strength. I'd love to hear how you actually got involved with her. Yes. Please begin. WILLIAM BREITBART: I agree with you actually about that comment. It's very helpful to have had the training in both medicine and psychiatry. And, in fact, we've trained a few fellows who've done oncology fellowships and then done our-- and a psychiatry residency and then done our psycho-oncology fellowship as well. But the real story of how I ended up in this field starts in childhood, where a lot of stories start. But my parents were both Holocaust survivors from Eastern Europe, from Poland in particular. When the war broke out, my mother was 14 years old and my father was 17 years old. And my father's family were all killed. But he ended up surviving, hiding in the woods. And he became-- Polish forest-- and he became part of a partisan fighter group, lived in the Polish forest. And one day he went looking for food and broke into this farmhouse. And as it turned out, my mother and her parents were being hidden by a Catholic woman, who hid them in a hole underneath the stove in her barn. And my father broke into this farmhouse and discovered my mother and my maternal grandparents. It turned out they were related. They were second cousins. My father said, you can't stay here. It's not safe. You should come into the woods with me and 150 other people. My grandparents were too afraid to go. But they let my mother go. So at the tender age of 14 and 17, my parents were hiding in the Polish forest, where they lived for about three years, hiding from the Nazis, and then Ukrainians, and all sorts of people who were interested in killing Jews. And they finally, after the war, crossed over to Germany. They actually found my grandparents alive. And they crossed over the border to Germany, went into this displaced persons' camp outside of Munich and got married there. And then came to the Lower East Side in late 1949, early 1950. And I was born several years later. And I grew up in this home on the Lower East Side, as you pointed out. And I grew up in a home where the Holocaust also lived. I lived in this home where the Holocaust was in every room-- didn't have a room of its own. It was in all the rooms, on all the walls-- and all the pictures that had been saved of my family, that had perished, on all the religious articles that might have been saved, et cetera. So I grew up in this environment where I understood at a very early age, maybe four or five years old, that death and suffering were very real. And that we all lived in this space between life and death. My mother would ask me every morning-- when she gave me breakfast, she would ask me the question, why am I here? And the full question really was, why am I here and everyone else is dead? Basically, what evolved out of this was the transmission of this responsibility or I guess a burden-- for me, it was an inspiration-- for me to accomplish something of such significance and impact-- in the world of suffering in particular-- in the arena of people who suffer in the face of death. And it's going to be up to me to achieve something of such significance that my parents would be able to-- my mother would be able to turn around and say, well you see we had to survive because if I hadn't survived, there wouldn't be Bill Breitbart in the world. [LAUGHTER] So that was the mission. That was the burden. That was the inspiration. And I wasn't fully cognizant of it. But I was traveling this journey-- this route that took me through college, and loving science and poetry, ending up in medical school, thinking I'd be a psychiatrist, but then falling in love with medicine. Loving both psychiatry and medicine. What I realized what fascinated-- what fascinated me was how a human being can live a mortal, finite life. How do you-- as a person who develops a life-threatening illness, how do you continue to live? How do you have the strength, the courage, to keep on living? And what gives you purpose and meaning? And so I got myself to Sloan Kettering by reading the work of Dr. Jimmie Holland and Dr. Massie. And I found myself at Memorial. I put myself in a place, with a mentor-- a group of mentors-- a place where I would breathe the same air of my patients, who were breathing the air of a human being confronting death, confronting the real prospect death being closer than-- closer than it was farther away. So that's how I ended up at Memorial. That's the real story. And I went to Sloan Kettering to do a fellowship, just to become a good clinician. I wanted to be a clinician. I never had the expectation of being a clinical researcher or an academician. I never had the ambition or aspiration to be an academic, a teacher, an advocate; never thought to be a professor of anything. I never thought I'd write books, or scientific articles, or become president of organizations, et cetera. All that happened because of my exposure to Jimmie. And my interest in research ended up being a result of one conversation that I had as a fellow. Dr. Holland, who was supposed to be my supervisor-- she's deceased now-- she was my inpatient supervisor-- my outpatient, inpatient supervisor. So we made rounds one day, which was very rare. But we made rounds one day. And I was the liaison. I was very fortunate enough to be the liaison to the Neuro-Oncology Unit and to the Pain Service at Memorial, which were both within the Department of Neurology. When Dr. Holland was recruited to Memorial Sloan Kettering in 1977, it was by the chair of the Department of Neurology, Dr. Jerome Posner-- Jerry Posner-- who recruited both Jimmie to be the Chief of the Psychiatry Service and he recruited Kathy Foley to be the Chief of the Pain Service. So I basically held on to these two meteoroids. Jimmie Holland and Kathy Foley, those are the two people who helped-- helped pull me along the road. So on the Neuro-Oncology Unit, I had done a consult on patient with brain tumors, on high-dose steroids. And he had a severe psychosis. And I asked Dr. Holland, why is it that these patients on steroids develop these neuropsychiatric syndromes? They develop depressions. And they can get delirious, and psychotic, and manic. And this was the advice that my mentor gave me-- Dr. Holland gave me-- which turned me into a scientist. And her response was, well, gee, Bill-- in her Texas twang-- well, gee, Bill, I really don't know. I really don't know. I guess you'll just have to go figure that one out yourself. [LAUGHTER] And that's what I ended up doing. I then pursued figuring it out myself. And that's what I did for the next 30 years, trying to figure out clinical problems-- when the AIDS epidemic exploded. My first research study was to study looking at patients with epidural spinal cord compression, those who had high grade versus lower grade compression. One group got high-dose steroids, the other didn't. And I did a comparison study of psychiatric syndromes in both populations. I was at Memorial when the AIDS epidemic exploded. And so I started to do studies of delirium. I did the first double-blind randomized controlled trial of neuroleptics for the treatment of delirium in the AIDS population because they all got demented and delirious. I did the first studies of pain in HIV. I did the first studies of desire for hastened death in patients with advanced AIDS and in patients with advanced cancer. And then I started to do a lot more work in inflammation and depression in pancreatic cancer patients. And eventually, everything kind of culminated. As I evolved from being a psychiatric oncologist to a psychiatric oncologist and palliative care clinician, that kind of bridged the two worlds of psychopharmacology and palliative care. And I started really looking at issues of desire for hastened death and the loss of meaning. And then developed interventions for meaning, which we call meaning-centered psychotherapy, which has been a real advance I think in our field. DANIEL HAYES: You must have been Dr. Holland's first trainee at Memorial. WILLIAM BREITBART: Well, her story-- basically, she was this young country girl in Nevada, Texas. She grew up on a farm, a cotton farm apparently. She was most influenced by the country doctor who would visit when people were ill. And when he passed away, he gave her a set of medical books, which inspired her. And she told her family, I think I want to be a doctor. And they said, well, gee, that sounds unreasonable, Jimmie. But whatever you feel like doing, go ahead. She ended up going to Baylor. And I think she was one of only three women in medical school class at Baylor. She started her residency I think at Baylor as well. And then eventually, she got married. Her first husband died tragically. I believe it was a suicide, which I think got interested in psychiatry. She ended up, I think, doing her residency at-- finishing her residency at MGH, along with Tom Hackett, people like that. And somewhere along that route, that's where she met James Holland. So James and Jimmie were, as you say, a power couple. James told me that Jimmie was his secret weapon, his secret power. But Jimmie told me the exact same thing about James. I think they fed off each other in terms of creativity and ideas. So when James moved to Roswell Park, I guess, Jimmie started a special clinic. And she called it "special" because nobody would come to a psychiatry clinic. But they would come to a place that was special because it made them feel special. And I guess it was around that time that James started collaborators-- CALGB. On the drive to work one day, Jimmie said, you ask patients every kind of question, like how many bowel movement does he have? You're very invasive in your questions. But you never ask them how they feel. And so she insisted that James do something about that. And so in order I guess to not get nagged on the car ride every day, he started a quality of life committee in CALGB. And Jimmie chaired that for quite a while. Eventually, I think James went to Mount Sinai. And Jimmie came along. And she worked at Albert Einstein-- College Hospital-- at Boston College of Medicine. And she was there with actually a bunch of pioneers of psychosomatic medicine. There was a guy named Herb Weiner, and Sig Ackerman, and Jim Strain, and Myron Hofer. These are very important names in our field of psychosomatic medicine. Jerry Posner at Memorial, Department of Neurology, was looking to bring psychiatry into-- consultative service to Sloan Kettering. And Jimmie often says they couldn't get Ned Cassem from MGH. So they picked her in second tier. And in 1977, she came there, along with a resident who graduated from Einstein, Mary Jane Massem. And the two of them had an office, with a card table-- as she described-- and a stack of index cards with the patients on them. And they set about starting a consult service. So in '77, she was the chief of the psychiatry service. And then about '78 or '9, a clinical fellowship was established. The NIMH had an initiative at that point to develop consultation liaisons, psychosomatic medicine fellowships around the country. And so she benefited from that initiative, and started a fellowship. That continued through '78 or so. And there are a couple of classes of fellows before me. I came to do the fellowship 1984 to '86. And it was during my fellowship, I think, that Jimmie and a woman named Julia Rowland, a psychologist, who's at the Smith Center now-- but was around the NCI's survivorship program for a long time. DANIEL HAYES: I actually worked with Julia at Georgetown for five years. WILLIAM BREITBART: At Georgetown, exactly. So she and Julia wrote the first-- edited the first textbook of psycho-oncology. It was called the Handbook of Psychooncology. And that's the first time I think the term "psychooncology" was used. I think it might have been 19-- late 1980s. It might have been 1989 or so that book came out. And the term psychooncology was not hyphenated at that point. There was no hyphen between the two O's. Jimmie asked me to write about six chapters. I knew a lot about delirium. I wrote that chapter. I knew a lot about suicide and cancer, which was an early interest of mine. And I knew a lot about neuropsychiatric issues and AIDS. But I didn't know very much about neuroendocrine phenomena that caused neuropsychiatric syndromes or the psychiatric aspects of head and neck cancer. I said to Jimmie, I don't know anything about these subjects, Jimmie. Do you think I'm the person to write this chapter? And she said to me, well, Bill, there are no experts in the world in this field. [LAUGHTER] So after you write the chapter, you will be the expert. So that was the philosophy. And so as a mentor, I would basically say the greatest thing about her as a mentor was that she gave you the confidence that you could achieve whatever you wanted-- whatever you were driven to achieve. She had that faith in you. The idea was that the only person who really had to believe in what you were doing was you. And if it was important to you to find the answer to that question, that you would be able to do it. She had a knack for finding people who were very driven, who joined this mission. It was really a mission. It was a calling to provide the human side of cancer care, to provide whole person care, to take care of the person who had cancer while they were going through all the cancer treatments. And the combination therapies that James Holland had come up with. DANIEL HAYES: Two stories about Jim, who I had more association than with Jimmie. Although Jimmie told me the thing she tell you, which is you got to figure out what you want to do. And then you'll be great at it, because I wasn't sure. But with Jim Holland, two things. I was the very young guy in a field to be. And I was named chair one of the committees. And he was sitting in the back. And I was talking about, well, we need a statistical plan, and that sort of thing. And in the back of the room, as only he could do without a microphone, "Well, Hayes, if you need a statistician, it's probably not worth doing." And other is, I once asked him, between you and Dr. Frye, who was my boss, Dr. Frye White-- the three guys, who actually came up with the idea of combinational therapy? And I might as well have let a fuse to a bomb because he was-- "Well, I did. I was there before they did. They came in. They were in the minority." And he sent me the protocol. That was David. So to be sure I understood that he had written it before those guys got there. He was quite a character. And I have to say, your comments about Jimmie, and being married to Jim, were like oil and water. It's unbelievable to me that they actually had a very loving, long-term relationship. She had five children with him, who are all accomplished in their own right. WILLIAM BREITBART: Yes, they are. DANIEL HAYES: And they just they just managed to make it work because he could be hard to deal with. But everybody loved him because of it. WILLIAM BREITBART: Yeah. I think the secret ingredient there is dedication. They were both people of great dedication and commitment. And they were committed to two things. They were committed to the work they did. And they were committed to each other and their family. And so I think that was the secret-- the secret ingredient. DANIEL HAYES: There are a number of things in your own career that struck me as I was going through it. That one of my own interests would be your work with hastened death. And again, I actually wrote a little sort of term paper kind of thing on this. And it was called assisted suicide. And I think we're talking about the same thing. Talk more about that, and what you've been involved with, and where you think that's going. WILLIAM BREITBART: Right. Well, my interest in that all started during the AIDS crisis, the AIDS epidemic, in the mid-'80s to mid-'90s or so. And I was right in the thick of it, in Manhattan, in New York City. And Sloan Kettering had a large population of AIDS patients, because of their interest in Kaposi's sarcoma and lymphomas. And they ended up taking care of a lot of patients. And I saw a lot of patients. And I was that age-- I was often the age of the patients-- many of the patients who I was treating. It was very difficult work, but very inspiring work. You really felt like you were doing important work, obviously. And because of many of the patients were younger men, men in their 30s, who I could relate to in many ways-- like you, I'm sure there are many patients that you treat. There are some that you feel closer to, you identify a lot more with, right. And these were-- that was the case here. And at the time, I was treating patients with AIDS. And there was no treat-- there was no therapy at all. And people were dying very difficult deaths. And I had many, many patients who asked me if I could help them die, if I could assist them in the suicide, could I prescribe their medicine, could I somehow hasten their death? And so for me, it was a clinical problem. What do I do? How do I understand this? What drives this desire to hasten your death? I knew it came out of a sense of despair. I knew it came out of a distress and a sense of despair. But at the time that this was happening, clinically there was also a big debate in our society about legalization of assisted suicide. And, in fact, I think that was the Supreme Court case of Vacco versus Quill, which was also being adjudicated at that time. And states, like Oregon, were starting to have a referendum about whether to legalize these things. So I thought, does one create policies based on popular opinion, or whatever, or a public opinion? Or do you create policies by understanding of the problem and that's informed by research? So I thought I needed to understand this. If I was going to be helpful as a psychiatrist, in this kind of a setting. And it came up occasionally with cancer patients, too. But it was just so dramatic. And it confronted me for the first time, mainly during the AIDS crisis. I felt I needed to understand it more, so that I could know how to be helpful or useful. Was I going to be able to eliminate the suffering? Or was my only option to eliminate the sufferer? And so we set about doing a set of studies, both in terminally ill AIDS patients and terminally ill cancer patients. And I actually developed and validated a scale that measured desire for hastened death. It's called the Schedule of Attitudes towards Hastened Death. Up until that point, people didn't really have a way of measuring it. They just asked the patient, yes or no, do you have-- or they might qualify it on a 0 to 4 scale or something. And so what was really interesting-- and one of my early fellows, my first fellow, the first surgeon attending from oncology, Chasnoff, who went back to Canada-- Winnipeg. And he starts to do a study. He did studies around the same time. But he didn't have a validated measure. But we ended up finding very similar things. As it turned out, about 40%-- 45% of folks who had high desire for hastened death, had a depression. About 17% of patients that had cancer-- we'll stick to the cancer data. About 17% of cancer patients have a high desire for phase. These are patients with advanced cancer, in a palliative care unit, or a hospice, whatever. And about 45% of those patients have a depression that was undiagnosed, untreated. The other factors that seem to contribute to desire for hastened death were things like lack of social support, uncontrolled pain, and severe physical debilitation. So I said, well, we can treat pain. We can increase social support. I gave a presentation one day at-- Kathy Foley had worked with George Soros and the Open Society Institute, to develop something called Project on Death in America. And I gave a talk to the board of the Project on Death in America. I was in the class of the first faculty scholars of Project on Death in America. It included a lot of people who are at the forefront of palliative care these days. But I gave a talk on this, on patient death. And one of the ethicists in the room, a famous ethicist, asked me, well, what happens to desire for hastened death if you treat the depression? And before answering that question, I said to myself, make a mental note. That's your next ROI grant, Bill. And so what I did after that, is I wrote several grants and did two studies looking at what treating depression in patients with high desire for hastened death. And I did both in AIDS and cancer patients, terminal cancer patients, two different studies. As it turns out, if you treat-- if someone who has high desire for hastened death and they have a depression, and you treat the depression, 90% of those patients, when their depression remits, the desire for hastened death remits. But there was still this segment of population of advanced cancer patients, were not depressed, did not have uncontrolled pain, or lack of social support. There were about a 40%-- 35%, 40% of the group, I didn't have the element, the factor that contributed to this desire for hastened death. So I figured there's something there that I haven't found. So we went back and did further studies. And we looked at other variables, like anxiety, hopelessness, loss of meaning. And what we discovered was that hope of hopelessness and loss of meaning were independent and synergistic factors that contributed to the desire for hastened death, and made up an additional 30% of the so-called variance. So between depression and hopelessness, independent of depression, and loss of meaning independent of depression, you could account for about 85%, 90% of the reasons why patients wanted to desire for hastened death. Based on my research and the research of others, there's still about a 10% group who are probably not in great despair. But the issue for them is, I live my life in a pretty authentic way. I've been able to control how I live my life. I should be able to. And I want to control the circumstances of my death. And they're not impaired by depression or anything like that. But when we had the findings of hopelessness and loss of meaning, I said to myself, OK, now I've got to find an intervention for loss of meaning and hopelessness. And I was looking for a drug. I went through every page of the PDR. And there was no drug for loss of meaning or loss of hope. So I had to turn to psychotherapy. Our CL psychiatrist-- you know, psychosomatic medicine psychiatrists, we like to give drugs. If there's a drug solution, we've got it. I'm your guy. So I had to force myself to turn towards psychotherapy rather later in my career, after doing all of these stimulant trials for fatigue and things like that, and other pharmacological trials for pain-- neuropathic pain, et cetera, delirium trials. There I was, starting to figure out what kind of psychotherapy can I develop to help enhance sense of meaning and hope? And that's when I turned to, ironically, a Holocaust survivor named Victor Frankl-- and turned to the work of Victor Frank, who wrote the book, Man's Search for Meaning. His big idea was that meaning is a primary motivating force for human behavior, similar to the idea of libido, and instinctual drive, and things like that. He thought meeting was another important drive. "Better" instinctual, he called it. And he thought that there were predictable sources of meaning that one could tap into. And so we basically developed-- just sat down in a room with a couple of my fellows. And we hacked out a seven-- or at the beginning, it was group intervention. So it was an eight-session intervention. And then we developed an individual format, seven sessions. And we basically developed this brief, structured psychotherapy that involved teaching patients the importance of meaning, both didactically and experientially; teaching them the various sources of meaning; and relating it to their cancer experience and living with cancer. And the whole purpose was to be able to get through cancer, and even facing death, by sustaining a sense of meaning for as long as you possibly could. And that's what we called meaning-centered psychotherapy. I ended up doing four randomized-- NIH-funded, randomized controlled trials of both individual and a group format. And now we have a-- we're in the seventh year of an R25 training grant. We're training a national and international cohort of clinicians to provide meaningful psychotherapy in the manuals and textbooks that are published. DANIEL HAYES: I'd like to segue this-- WILLIAM BREITBART: [INAUDIBLE], I designated it as a evidence-based intervention for palliative care. DANIEL HAYES: Well, I'd like to segue, that as you were talking, most of people listening to this are probably medical oncologists. And my impression is, we don't get a lot of this training that you're talking about. And the people you're training, they're probably a psychiatrist, not a medical oncologist. How have you translated that over to our world? WILLIAM BREITBART: Now, so actually the people we're training-- a few psychiatrists, not too many. We train psychiatrists, social workers, nurses, nurse practitioners, oncology nurse practitioners, oncology nurses, oncologists, chaplains, palliative care docs. We're expanding the training. And it's quite simple. And it's actually-- but we're working with a group to develop this into a digital app. It might be able to be prescribed by oncologists so that you don't even need a therapist. DANIEL HAYES: Are you in the weeds with the medical oncologists at Memorial, at Sloan. I mean, do you make rounds with them and help train them? WILLIAM BREITBART: Yeah. Jimmie started out with one psychiatrist. By the time the Psychiatry Service became a department in 1996, I think there were 12 psychiatrists and psychologists. And as of last count, I think we have 43 faculty, 25 psychiatrists and the rest psychologists, and around 200 staff, including research staff, and research faculty, and psychiatry services. So I took over as chief when Jimmie became the first chair in the Behavioral Sciences Service. And we had a cancer disparities in the Immigrant Health Service. So it's grown quite a bit. And all of us, we work in a sort of a disease management embedded model. So I originally was the psychiatrist for the Neuropsychology and Pain Service, and moved to the hepato-pancreato-biliary disease management team. But all of my psychiatrists and psychologists are embedded in the Breast Center, and in the GI group, hepato-pancreato-biliary groups, and hepato-neck, and thoracic, and all that. So we're all interacting there. DANIEL HAYES: How do you translate that outside of Memorial in New York? I mean, most oncologists don't have access to those kinds of resources. And you've got to have thought about that. WILLIAM BREITBART: About 1996, the National Cancer Center Network, the NCCN, got established and started developing guidelines. And so they asked Jimmie to head up of their guidelines for distress. And I was part of that group, and still am. And what came out of that was screening for distress, using a distress screening tool. DANIEL HAYES: The distress thermometer-- the distress thermometer. WILLIAM BREITBART: The distress thermometer, that's exactly right. And that came out of the pain work. The pain guys had the 0 to 10 scale. We didn't want to rip them off too badly. So we didn't want to do the 0 to 10 visual analog scale. So we had to come up with a different metaphor. So we called it "pain throughout." So the Distress Screening Commission on Cancer, I think, accredits cancer centers through either the Academy of Surgery-- Surgical Oncology or something like that. They mandated that for a cancer center to get accredited, you have to have a distress screening program. And if you have a distress screening program, then you have to have people who respond to these algorithms that get developed for people who they identify with high distress. So as a result of that one move, that one move of establishing distress stress as the sixth vital sign, which was Jimmie's idea, and developing distress screening, you now have-- every designated NCI-designated cancer center has to have a psychology program of some sort. Now, a lot of them aren't as big as ours. Some of them basically involve a half-time psychiatrist, a chaplain, a psych nurse practitioner, and a couple of social workers. But every cancer center has psycho-oncology present in it now as a result of that. DANIEL HAYES: I was having dinner one time with Jim and Jimmie. And she said, you two know the blood pressure, the temperature, the weight, pulse. But you have no idea, she said, how they feel. So it wasn't the last time she asked Jim on that question. And I went, what do you mean? She goes, you need a distress thermometer. She'd already published it. Of course, I didn't know that-- and pulled it out of her purse. And so she had to show the distress thermometer. WILLIAM BREITBART: That's correct. That's correct. That's correct. One of the big problems is when Jimmie started-- and you can attest to this-- that in the beginnings of oncology, it wasn't always the case that patients were told exactly what they had. Cancer was very stigmatized. The only thing that's more stigmatized than an illness like cancer is mental health, right. God forbid, you should have a problem with depression, or coping, or panic, or something. DANIEL HAYES: It's a sign of weakness. WILLIAM BREITBART: A weakness, moral weakness. Actually, we've come a long way in terms of truth telling and being transparent. And my patients now know exactly all the genetic mutations of about the tumor and stuff like that. They know everything. And they even know how their tumor is-- mutations are evolving and changing over time. But cancer was-- the idea of needing psychosocial counseling-- psychiatric help, psychological help, it was very stigmatized. So even the word "distress" was chosen out of a concern to not stigmatize patients. DANIEL HAYES: I will tell you that when-- I was at the Dana Farber. And there was a push for the Dana Farber to develop its own hospice program. And Dr. Frye, who was physician-in-chief, absolutely drew a line, and said no way because that means we've given up on those patients. We're not going to have a hospice program at Dana Farber because we don't want patients to think they're coming here to die. And I remember thinking that some of them do. And it would be very helpful if we had a way to help them figure it out. And I have to say, in preparing for this podcast, I've read several your papers. And thought, God, I wish you'd been at the Dana Farber when I was there. Or I wish I'd been at Memorial to get to work with you. But you can see I'm kind of tying things up here. Because I could listen to you for hours,but But we only have 20 or 30 minutes. And this has been terrific. WILLIAM BREITBART: I appreciate the opportunity. DANIEL HAYES: I'm sure our listeners will say, maybe-- I wonder how we can get him to come speak to our program. But I already wrote down here, we're going to invite you to Michigan. WILLIAM BREITBART: Well, in this era of Zoom-- in this era of Zoom, I'm a very cheap date because all you have to do is just connect me by Zoom. You don't have to pay for the air fare or anything. I go everywhere. DANIEL HAYES: I want to thank you for lots of reasons. One is for filling our listeners in-- many of them are young-- about who Dr. Holland was and what she did. Because we all owe her an enormous debt of gratitude for the contributions she made-- and you personally, as well. So thank you for taking your time to speak with us. And we really appreciate it. And I hope our paths cross again in the near future. Thanks a lot. WILLIAM BREITBART: Absolutely. Thank you so much. It was my pleasure. Appreciate it. [MUSIC PLAYING] DANIEL HAYES: Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
Dr. Hayes interviews Dr. Sarah Donaldson and her pioneering work in pediatric radiation oncology. TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DANIEL HAYES: Welcome to JCO'S Cancer Stories: The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of these shows, including this one, at podcast.asco.org. Today my guest on this podcast is Dr. Sarah Donaldson. Dr. Donaldson has really been instrumental in much of the development of both, in my opinion, modern radiation oncology and especially related to pediatric radiation oncology. Dr. Donaldson was raised in Portland, Oregon. She received an initial undergraduate and nursing degree at the University of Oregon in Eugene and ultimately in Portland. After a few years working as a nurse with Dr. William Fletcher, who I hope we'll get a chance to talk about later, she elected to go to medical school and spend her first two years at Dartmouth and then finished with an MD from Harvard. She was planning to do a surgery residency at the Brigham Women's in Boston but then elected to do an internal medicine internship at the University of Washington and ultimately then a residency in radiation oncology at Stanford. After a residency and a few side trips along the way, she joined the faculty at Stanford and has remained there since. Dr. Donaldson has authored nearly 300 peer-reviewed papers, probably more than that by now. That was when I last looked at her CV a couple of weeks ago, and it seems like she brings them out every week. She has served as president of the American Board of Radiology, the Radiology Society of North America, and the American Society of Therapeutic Radiation Oncology, ASCO's sister organization, of course-- ASTRO. And she also served on the board of ASCO, the board of directors, from 1994 to 1997 and, in my opinion, perhaps as importantly, on the board of directors of the ASCO Foundation for over a decade. She has way too many honors for me to lay out here, but a few that caught my eye. Named after a distinguished scientist in the past, the Marie Curie award for the American Association of Women Radiologists, the Janeway Award from the American Radiation Society, and the Henry Kaplan Award for Teaching from Stanford. And she was the inaugural recipient of the Women Who Conquer Cancer Award from our own Foundation, the Conquer Cancer Foundation. Dr. Donaldson, welcome to our program. SARAH DONALDSON: Thanks so much, Dan. It's a privilege to be talking with you today. DANIEL HAYES: I hope I got all that right. It's pretty tough to cram the distinguished career you've had into about a minute. [LAUGHS] Anyway, I'm going to start out. So I've interviewed a lot of the luminaries and the people who really started our fields or even the subfield within our field, and you yourself had quite a journey. I know you started out as a nurse. Can you just give us some background about going to nursing school and then who and what influenced your decision to become a physician? SARAH DONALDSON: Yes, I did. I can, Dan, and it's an interesting story. Because when I grew up, girls that wanted to go on to college-- and it wasn't all girls didn't go to college, but I did. The three areas that one could do in that era were become a teacher or maybe a librarian or a nurse. And so I elected to become a nurse, and I went to nursing school. And I loved nursing school. I had a terrific time in nursing school, and along the line, I met the house officers and such and ultimately got to know a surgical oncologist. That was before surgical oncology was a field, but a young man from the Boston City Hospital training program, which was a very good surgical training program at the time, who was recruited to the University of Oregon to start a cancer program. His name was Bill Fletcher-- William S. Fletcher. And when I graduated from nursing school, Bill Fletcher was looking for a right arm assistant. He was looking for somebody to help him develop a cancer program. And he offered me a job, and the job was to work with him in the operating room, either scrubbing or circulating, to run his tumor board-- and that meant just scheduling it and taking notes and such-- and working with him in his tumor clinic. And in the tumor clinic, he was at that time beginning clinical trials, and Oregon was part of something that was called the Western Cancer Chemotherapy Group, which ultimately merged with SWOG. But at that time, his helper-- me-- filled out the forms, and we sent them to patients that were entered onto the study and got consents and measured lesions and that sort of thing. And I worked hand in hand with him. In addition to working with him in those clinical parameters, he gave me a little laboratory project, and so I worked with him in the lab and learned a little bit about small animal oncologic research, et cetera. And after a couple of years working with him, he suggested that I would be a better employee if I took some additional courses, and he suggested that maybe I should take physics because at that time he was doing isolation perfusion. I was running his pump oxygenator. He asked me what I would do if there was a pump failure. I didn't know. And he said, well, I think it would be good if you took physics. Well, the prerequisite to physics was organic. I hadn't had organic, and he was also working with radioisotopes in the lab. And he said, you could really be more helpful to me if you could work in the lab. That meant I had to take organic, and the prerequisite to organic was inorganic. To make a long story short, I took these series of classes in night school while I was working for Dr. Fletcher in the daytime. And then one night, I was working on my hamster project, and he said, I think you should go to medical school. I said, I can't go to medical school. And the long and the short of it was Dr. Fletcher thought I should go to medical school, and he made that possible for me. It's a very, very interesting story, but what it means is that I was mentored by somebody who was a visionary, and he could see a lot more than I could see. And he got me excited about medical school and everything that I knew about medical school is what he had taught me, so I of course wanted to be a cancer surgeon. And then after I went to medical school and I went to the same medical school he did, I just followed his advice. Every time I needed some guidance along the way, I asked Dr. Fletcher what I should do, and he told me what I should do, and I applied. And that's what I did. And so when I came time to choosing a specialty, I decided I would train in surgery, and I applied at the Brigham and was accepted into their surgical program. It was run by Francis Moore at the time. And that was a big deal because they hadn't had women in their surgical field, and I was very excited about all of that but feeling totally inadequate because I didn't think I knew enough medicine. And so I went to Dr. Moore and said, I think I'd be a better house officer if I knew some medicine. He says, OK, well, go take a medical internship, and we'll hold you a spot. So I went to the University of Washington and took general medicine, which was a very vibrant program, a really exciting program, and I just came alive in my internship. I loved everything about it. And then I decided I wanted to be an internist. So at this point, I was offered a position in Washington, and I had already accepted Dr. Moore in Boston. And I didn't know what to do, and I asked Dr. Fletcher what I should do. And he said, Sarah, the world of-- he called it radiotherapy at the time, but what we would call radiation oncology-- needs more surgically oriented physicians. I think you should go down and talk to my friends at Stanford. So I came down to Stanford. I met Henry Kaplan and Malcolm Bagshaw and the leaderships in the department, and including Saul Rosenberg, who was one of the people who interviewed me, and I left that day visiting at Stanford making a commitment that I would come to Stanford as a radiation oncologist. So I wanted to do everything, and I met some very inspiring people along the way, perhaps like you have in your own career. And it's for that reason that I am now excited about mentoring because it's a little bit of payback because somebody opened the door for me and made it possible for me to have a most gratifying professional career, and I would like to do that for as many people as I could. DANIEL HAYES: I love that story. And there were two things about it that came out. One is I normally don't like people who namedrop, but when you can namedrop the names you just dropped-- Bill Fletcher, who I consider really one of the early surgical oncologists, Henry Kaplan, Saul Rosenberg, Franny Moore. I was in Boston of 15 years, and he was a legend. He was not the chair anymore by any means. In fact, he passed away. But it was legendary. You should be doing these interviews instead of me. [LAUGHS] You've been there. SARAH DONALDSON: Well, it's all about where you are at the time you are and meeting the right people. I think so much of my gratifying career is just because I happened to be at the right place at the right time and met the right people. DANIEL HAYES: Well, the other thing I want to say is I always believed I don't trust people I interview who say they know exactly what they want to do. And the reason I say it that way is I have a young woman who's been a technician in my lab that just got into med school, and she sat with me and said, now, when I go there, should I tell them I know exactly what I want to do? Because she's interested in the oncology. Or should I go through my rotations and see what I like? And I said, I forbid you from going there knowing what you want to do. Go to your rotation. See what you like. You're going to run into somebody who just inspires you beyond words who-- I don't know-- maybe selling shoes. But whatever it is, become like her, and you'll be extraordinarily successful. So if there are young people listening to this, I think that your story, Dr. Donaldson, is a classic for that, the way you kicked around. And actually, you didn't tell us, but I'm going to have you tell us about your trip to Paris and that experience too and how that influenced you. SARAH DONALDSON: Oh, that was another wonderful opportunity. When I finished my training, it was 1972, and that's when America was in the Vietnam War. All of my classmates were being recruited to a mandatory draft and were having to go to Vietnam, and I felt like I too should be just like all of my best friends and I too should join the military and go to Vietnam. But that wasn't possible. Women couldn't do that. So I looked for things that I could do where I could do something useful, and I thought about joining the ship Hope and all sorts of fanciful things, but basically I was lost, and I didn't know what I wanted to do. And at that time, there wasn't a carve-out of pediatric oncology as a specialty. It hadn't been defined, but there were people that were doing pediatrics. And as a resident, I had had a little rotation at the M.D. Anderson, and when I was in medical school, I had spent a fair amount of time at the Boston Children's, so I kind of knew a little bit about those institutions. But the thing was at Stanford, I knew that I wanted to be at Stanford. But Stanford didn't have a cancer program either. And so again, I went to Henry Kaplan and Malcolm Bagshaw-- at that point, Kaplan was head of the department, and Malcolm was his associate director. But they changed positions about a year after that. So I trained under both of them, really, but I went to Dr. Kaplan and said, I'm interested in pediatrics. And I said that because we didn't have a program at Stanford and that was like a carve out that nobody had addressed yet. And he said, oh, well, if you want to study pediatric cancer, you have to go to the Institute Gustavo Roussy and train under Odile Schweisguth. And I said, no, I don't speak French. I can't do that. I'd like to go to London because I like the theater. And he said, no, no, no, no, no, that's not the way it is. If you want to be a pediatric doctor, you have to go learn pediatrics and learn to think like a pediatrician, and that means you have to go and train under Odile Schweisguth. She was at the Grand Dame of pediatric oncology. She took care of all the children in Western Europe. And so I went to Institute Gustavo Roussy to be a fellow in pediatric oncology, although I did spend some time on the radiotherapy unit as well. But that's where I learned pediatric cancer because I learned from Odile. And in French, there's a formal and an informal, and I never understood the formal because when you talk to kids, you talk in the familiar form. So I was just talking to and not [SPEAKING FRENCH]. I would just say, [SPEAKING FRENCH] and such. [INAUDIBLE] French. And that's how I learned French. More importantly, I learned the biology of cancer from Odile. It was largely observational. And I learned a lot of late effects of children who were cancer survivors. So when I came back to Stanford, at that time Mal Bagshaw was chair, and he said, well, why don't you work on starting a cancer program? We'd like to have a cancer program. So I worked with the pediatric cancer doctor at Stanford. His name was Dan Wilber, and he had just come from the M.D. Anderson. And the two of us started a cancer program at Stanford. And so I've been kind of doing that ever since, of doing pediatric cancer. So I would say my skill set came along just because the right people told me where to go at the right time. DANIEL HAYES: Were the pediatricians welcoming, or did they resent the fact that you'd never been a pediatrician? SARAH DONALDSON: Malcolm Bagshaw gave me the clue to that by saying the only way the pediatricians will accept you is by having them accept you is one of their own. So you have to learn to think like a pediatrician, and then they will accept you onto their team as one of theirs because pediatric doctors are very possessive about their patients, and pediatric cancer doctors are possessive about their patients. So it worked for me. But it worked because I had had this special training under Odile Schweisguth, who was a general pediatrician, and so I was accepted because I was at that point thinking like Odile thought because that's what she taught me how to do. So I always felt like I was accepted by the pediatric cancer doctors who then became the pediatric oncologists because that field didn't really open up for a couple of years later. DANIEL HAYES: For our listeners, Dr. Donaldson and I have not met before, and I certainly have never worked with her. But she's talking, she's glossed over that when you work with the French, you really have to speak French. When you work with the pediatricians, you really have to speak pediatrician. And you've managed to do both of those. I don't know anybody who's been that successful. I should take a sabbatical and come work with you. [LAUGHS] SARAH DONALDSON: Well, I'll tell you, Dan, there was one wonderful thing that happened because shortly after I was working at Stanford doing pediatrics, our dean wanted to recruit some more people and buff up our pediatric cancer unit. And he recruited Michael Link, who had just come out of his training at the Dana Farber. And so Michael and I started working together his first day as an assistant professor at Stanford, and pediatric oncology is a team sport. Pediatric radiation oncology is a team sport. And I had a wonderful teammate, Michael Link, with whom I worked very well, and we became very fast friends. And we did pediatric lymphoma and sarcoma, bone sarcoma, and soft tissue sarcoma, and all sorts of stuff. And I had a wonderful, wonderful colleague working with Michael Link. So one of the keys to my most gratifying part of my career at Stanford has been working with Michael Link and his associates. DANIEL HAYES: As an aside, by the way, Michael and I overlapped just a little bit at Harvard, but then he proceeded me as president of ASCO by two years, and we got to be pretty close friends during that period of time. And I echo your fondness for him. He's just an amazing human being, as far as I was concerned. And he's one of the-- he may be-- I'm trying to think, has there other pediatricians that have been president of ASCO? I'm not-- SARAH DONALDSON: No, he was the first. Yeah, he's the only one to date. DANIEL HAYES: Yeah. And he left a big stamp on the society in terms of-- we always had some pediatrics involved-- you, especially-- during the years, but as president, he was able to leave a big footprint of what we do. So he was terrific. I'd also like you to talk a little bit about the early days of the co-operative groups. You threw out that you were in the Western Group that became part of SWOG, and what were the hurdles and obstacles to getting all these folks to work together? And what do you see the pros and cons of the cooperative groups in the country? SARAH DONALDSON: I know the cooperative groups mainly through the lens of the pediatric cooperative groups. I mean, I can tell you about the adult ones, but I really know the pediatric ones. And at the beginning, there was one, and then there were two. And we worked competitively, and then ultimately the pediatric doctors learned early on that the children they took care of had rare tumors, and no one physician had a whole lot of experience with any cancer. For example, this tells the story well. When Hal Maurer was chairman of Pediatrics at Virginia, he had a child with rhabdomyosarcoma. And he called his friend Ruth Hein, who was at Michigan, and said, Ruth, I've got this child with rhabdomyosarcoma. Have you ever treated a child like this? And Ruth said, oh, I had one patient, but I think you should call Teresa because Teresa, I think, had a patient. And so Teresa Vietti was at Washington University, and so Hal Maurer and Teresa Vietti and Ruth Hein and a few other really, really pioneers started to throw their lot together and decided that the way they could answer a question about these rare tumors is by deciding what was the question of the day and working collaboratively. And then Hal Maurer became the first chair of what was then called the Innergroup Rhabdomyosarcoma Study, which has now been merged into the other pediatric groups. But that same process that worked for rhabdomyosarcoma was then employed for Wilms tumor, and then subsequently down the line, brain tumors and all the other solid tumors. And of course, St. Jude was doing this with their leukemia studies and Dan Finkel, and then Joe Simone did it with leukemia. They got everybody to join in on their team, decide together around the table by consensus what is the question that we want to have an answer for, and then just treat all the patients in a consecutive fashion, analyze those, and then take that step and go on and build to the next step. That's how the pediatricians have done it because their cancers are so rare that one person doesn't have very much experience. They have to throw their lot together and work collaboratively. So they don't work competitively. They work collaboratively. DANIEL HAYES: This is very similar to the stories I of course heard from Drs. Frei and Holland that they came ultimately to CALGB to be after a couple of mis-starts. But it's one of the things I worry about COVID. It's not the same Zooming with somebody or talking on the phone as it is sitting around dinner and just saying, maybe we could do this and make it work. So I'm hoping young people are listening to this and saying, OK, maybe we can start something new that a bunch of us work together and get things done. That's a really great story. You were early on and ended up taking both diagnostic and therapeutic radiology boards, correct? When they were combined? SARAH DONALDSON: No, no I didn't. Radiology was combined at that time, but Stanford was one of the few institutions that had a carve-out for radiation oncology without diagnostic training, and I wasn't in the first class. I was in the fourth or fifth class, so my formal training was only in what was called radiation therapy, now called radiation oncology. So it was one department, and I worked collaboratively with a diagnostic radiologist because I knew nothing about image interpretation-- nothing at all. So I'd see an X-ray. I didn't know how to interpret it, and I'd have to go and ask for some help. But they were like our best friends. But the diagnostic people could take the picture, but the therapists had access to the patients. So that made all the difference in the world because we really had access to the material, the clinical material or the blood or the bone marrow or the biopsy specimens or whatever it was, and allowed us to do studies. But to clarify, no, I was not. I do not have formal training in diagnostic radiology, although I have worked with them so closely now that I feel like they're all my brothers because you cannot do radiation oncology without collaborating closely with the imagers. DANIEL HAYES: And my first interview was with Sam Helman. This has been three or four years ago. And he was still lamenting the split because he thought it was to learn both-- and for the reasons you just said. If you don't know where it is to shoot your bean, you can't shoot your bean. That's not exactly what he said but something like that. On our side, they team hematology and oncology. Like you, I never got trained in hematology. I only trained in solid tumor oncology, which has not hurt me in any way. In fact, in many respects, I focus my efforts on things I seem to know about and let somebody else worry about blood clotting. Of all the things you're well known for-- and again, it was hard for me to get it all into a minute or two, but probably teaching and mentoring. And in this conversation, I see why. Tell me how you think that's evolved in your field, especially in radiation oncology, teaching and mentoring, and the importance of the things you've done-- and perhaps some of the people you have trained yourself and you're proud of. SARAH DONALDSON: Well, when I think of all the things that I love about my professional career, I love taking care of patients. And I've had very joyous experiences of watching pediatric cancer patients grow up and watching them in their process and treating them when they're toddlers and then getting invitations to graduations and wedding invitations and baby announcements and following through that. That's very, very gratifying. But the single most important and most gratifying part of what I do is the volumetric feedback and gratification from training residents because one patient is one patient, but one trainee then goes into academic medicine and that person has 30 or 300 or 3,000 trainees. And you see your impact is just explosive. And Stanford has had a training program in radiation oncology from the very, very beginning. It was one of the first programs that did train in radiation oncology, so a lot of talented people have come through Stanford. They need to have what Bill Fletcher did for me, which was open doors and help them with networking and giving them an opportunity and giving them some guidance and being their new best friend. When your trainees trust you like that, then you can really, really have a relationship, and you can really help them. And so I am very, very, very proud of our trainees that are now all over the place as cancer center directors or directors of departments or divisions that are doing what they're doing. You just meet the best of the best. That is the most gratifying part of-- maybe it's because that's what I'm doing now, but it's the most gratifying part of medicine that I've experienced. DANIEL HAYES: This is the third time I've said this on this call-- I hope there are young people listening, and I hope they're looking for a mentor and they can find someone as generous and trusting and helpful as you have been. SARAH DONALDSON: Dan, let me just say one little thing. DANIEL HAYES: Yeah. SARAH DONALDSON: It was extremely helpful to me-- and wonderful recognition for ASCO-- to provide the opportunity that I received the Women Who Conquer Cancer Mentoring Award. Because when I won that award, I was the inaugural-- but when I won that, all of a sudden people thought that I knew something about mentoring. I'm not certain I did know anything about mentoring, but I was asked to talk about it and asked to give advice, et cetera. And it gave me a carve out that was quite novel at the time, and now, of course, it's a mandated requirement in every training program, et cetera, but it wasn't then. And for me, it was just to return what Bill Fletcher did for me. The only way I can say is that it's a pay out, and it's so gratifying. It just makes you happy to get out of bed every morning and interact with the people you do interact with. DANIEL HAYES: He was pretty young when he began to mentor you. And I think having seen and been mentored and mentored other people, I always worry about a young person trying to mentor because you've got your own career to worry about, and it's hard not to be selfish when you're building a career in academics. He must have been a remarkable-- is he still active? Is he still around? He must have been a remarkable guy. SARAH DONALDSON: He was a remarkable guy, and no, he passed away. But that was true. And that is true because junior faculty are busy making their own professional career, and they don't have time. They're busy on their own path, and it's a hard path to go on. So most junior faculty don't really have very much time to do formal mentoring. But in Bill Fletcher's case, we worked hand in hand as sort of partners. And so I think, in some ways, I was helpful to him because I could do literature searches for him. I could write the first draft of his paper. I could write the first draft of his grant. I filled out the forms. I did a lot of things that were labor saving for him, but for me, what was he doing for me? He was teaching me to suture. He was teaching me how to resect normal [INAUDIBLE]. He was teaching me lymph node drainage from cancers. He was teaching me about drug metabolism, methotrexate, and phenylalanine mustard. And 5-FU was an experimental agent. So was vincristine-- those kinds of things. So I learned a lot from him just in the ordinary practice of taking care of the patients. DANIEL HAYES: By the way, two stories I read about you-- one is how you met Henry Kaplan, and the second is the first paper you wrote with him. Can you give us those two? And then I think we've got to sign off. SARAH DONALDSON: Well, let me tell you about the first paper I wrote with him because the other one is too funny. Everybody will laugh at me. The first paper I wrote with Henry Kaplan, I worked really, really hard on it. It had to do with bacterial infections in patients with Hodgkin's disease because we were doing splenectomies on everybody, and they were getting pneumococcal bacteremias and meningitis. And I was running the ward at that time. I was taking care of a lot of patients that were sick. So I was writing up this experience. And I wrote what I thought was the perfect paper because, see, Kaplan had a high bar, and you didn't want to disappoint him. So I wrote the paper that I thought was perfection. I had gone through a lot of drafts. And I gave it to him, and he returned it to me the next day. He read it that night. But I only looked at the first page because the first page looked like a blood bath. Everything he wrote, he wrote with a red pen. And there was red writing all over the first page. I couldn't see any white paper. It was all red comments. DANIEL HAYES: [LAUGHS] SARAH DONALDSON: And I went through-- I don't know-- 24 different drafts of that paper finally being published. And so one of the things I try to do with residents now is to teach them, you have to have a hypothesis. You have to make certain you have a database. You have to have a long term follow up. You have to understand statistics, and you have to write a paper knowing what you're doing. You don't just start writing. You do a section and a section and you build it with evidence. So I enjoy doing editing, and I think I can help some trainees focus their thinking in terms of writing a grant proposal or a manuscript that's worthwhile publishing. My introduction to Henry Kaplan-- there are many, many funny stories about them, but to end them all, I will have to say that he was very, very, very good to me. He provided a lot of opportunities and was a huge role model. He taught by scarification. We were all scared to death of him, but he was absolutely a wonderful, wonderful huggable person, if you felt like you could hug him. We didn't do that very often. We might have hugged Saul Rosenberg, but we didn't hug Henry Kaplan. But they were both helpful to me, especially in understanding lymphomas. DANIEL HAYES: For those of you listening who don't know who Henry Kaplan was, I think it's fair to say he was one of the first people to prove you could cure Hodgkin's disease with radiation. Do you agree? Is that a fair statement? SARAH DONALDSON: Yes, that's where his name came. But of course, what Kaplan did was he recruited Saul Rosenberg, and the two of those worked hand in hand, and they brought to Stanford what we call the Lymphoma Staging Conference, which was a combined modality conference where we talked together over each patient. And together, they wrote clinical trials that were institution-based clinical trials. So what Kaplan did was he did a lot of technical work with the linear accelerator, but that was just a tool. My way of thinking is his most important contribution was the importance of combined modality therapy and understanding what your colleagues can contribute and what you can contribute in doing it as a team. DANIEL HAYES: And I will encourage anyone who's listening to this to go back to the website and listen to my interview with Dr. Rosenberg who laid that out in spades. And the first few patients he treated, he had a chair outside his exam room. He would examine the patient, take them out, put them in the chair, start the IV himself, go mix the chemotherapy, hang it up, and then see the next patient in the room while the first patient was getting chemotherapy. It's a little different now. [LAUGHS] Anyway, thank you so much. By the way, I have a copy of Dr. Kaplan's book on Hodgkin's disease, which was the Bible when we were training. You can't see it because it's on my bookshelf behind my camera, but I still open it up quite a while, even for a breast cancer guy. It was a classic. I also want to say, it's very clear to me you're a nurse at heart. You've been a fabulous physician and researcher and mentor, but your love for people shines through, so congratulations. I think that's terrific. SARAH DONALDSON: Thank you so much. DANIEL HAYES: Thanks for taking your time to speak with me today. I'm sure people are going to be thrilled to listen to this, and thanks for all you've done to feel. It's just really remarkable-- and what you've done for ASCO and the Foundation, which is a big, big, payback. Thanks for everything. SARAH DONALDSON: Thank you. DANIEL HAYES: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology Podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories: The Art of Oncology Podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
Alan Skarbnik (@ASkarbnik), MD, director of the lymphoma and CLL program, Novant Health (Charlotte, NC), and Aaron Goodman (@AaronGoodman33), MD, hematologist, University of California San Diego, join the show for a long-awaited debate: treating double-hit lymphoma with R-CHOP vs dose-adjusted (DA)-EPOCH-R. The conversation gets testy when the trio describe double-hit lymphoma in terms of histology and phenotype, the limitations of retrospective analyses when it comes to establishing a standard of care for this type of lymphoma, an intense breakdown of the CALGB 50303 study as it relates to the treatment argument and toxicity profiles, and so much more.
Dr. John Sweetenham, associate director for Clinical Affairs at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center and Editor-in-Chief of ASCO Daily News, discusses key abstracts on hematologic malignancies featured at the 2021 ASCO Annual Meeting. Transcript ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll. My guest today is Dr. John Sweetenham, the associate director for clinical affairs at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center. Dr. Sweetenham is also the editor-in-chief of the ASCO Daily News, and joins me to discuss key abstracts on hematologic malignancies featured at the 2021 ASCO annual meeting. Dr. Sweetenham reports no conflicts of interest relating to our discussion today, and full disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Sweetenham, it's lovely to have you back on the podcast. Dr. John Sweetenham: Thanks, Geraldine. It's a pleasure to be able to speak with you again. ASCO Daily News: Dr. Sweetenham, there are some really promising developments in therapies for adult patients with acute lymphoblastic leukemia. Can you tell us about these studies? Dr. John Sweetenham: Yes. There are two abstracts in particular at this year's meeting, which I think are of particular interest for adult patients with acute lymphoblastic leukemia. This is typically a difficult disease to treat in adults. And two abstracts in particular caught my eye. The first of these is Abstract 7001. And this describes a phase II study of a combination of a tyrosine kinase inhibitor, ponatinib, and a bispecific T cell engaging antibody, blinatumomab, which is directed against CD19 for patients with a particularly refractory type of ALL, and that's patients with Philadelphia chromosome positive ALL. This is a single arm phase II study for patients with both newly-diagnosed and relapsed or refractory Philadelphia-positive ALL. And in the protocol as described, the patients received up to five cycles of blinatumomab as a continuous infusion of the standard approved dose. And combined with this was ponatinib initially at a dose of 30 milligrams daily during cycle 1, and then subsequently reduced to half that dose until a complete molecular remission was achieved. Thereafter, the patient was continued on ponatinib for at least 5 years. And the treatment was also supplemented by intrathecal prophylaxis. Only 28 patients are on this small study. But nevertheless, I think the results are very intriguing. 95% of the patients responded to this treatment. And in the previously untreated patients, the response rate was 100%, compared with 88% in the relapsed and refractory group. And among the responding patients, 86% achieved a complete molecular remission. Remarkably, none of the patients in the newly diagnosed cohort required stem cell transplantation. And overall, with a median follow-up now of 14 months--so still relatively early, admittedly--the estimated 1 year overall survival rate is 94%, with an event-free survival rate of 81% for the entire study population. In the previously untreated cohort, no patients have relapsed or died. The 1-year overall and event-free survival rate in this particular subgroup is 100%. So what, to me, is really intriguing and exciting about this is a chemotherapy-free regimen for the upfront treatment of a particularly difficult-to-treat subtype of adult ALL. So these are truly encouraging and really quite remarkable results. Of course, they need to be qualified because it's very early days, small numbers, relatively limited follow-up, but intriguing nevertheless. The second study, which I think is really confirmatory of some earlier results, is described in Abstract 7002. And this describes the phase II results of the so-called ZUMA-3 study evaluating a CAR T-cell products directed against CD19 in adult patients with relapsed and refractory B-cell acute lymphoblastic leukemia. The phase I efficacy results were previously reported a couple of years ago at ASH. And this study represents the follow-up phase II study. Eligible patients for this study all had relapsed and refractory B-cell ALL treated with CAR T-cells that the dose that was described from the original phase I study, with a primary endpoint of complete remission rates. And key secondary endpoints in the study included duration of remission, relapse-free survival, overall survival, and the presence or absence of measurable residual disease by flow cytometry. As of September 2020 when this study was originally reported, 55 of the 71 enrolled patients that received their CAR T cell products and the complete response rate combining CR and CRI rate was 71%. And 31% of the responders had ongoing responses. Looking at the median duration of response, relapse-free survival, and overall survival, these were respectively 12.8, 11.6, and 18.2 months. But for those patients who responded, the relapse-free and overall survival were respectively 14.3 months and not yet reached. So, again, relatively early results, but nevertheless very interesting, showing after a median follow-up of 16.4 months, there was clear and quite compelling clinical benefits in heavily pretreated adults with relapsed and refractory B-cell ALL, with a median overall survival not yet being reached. So, given, again, that this is a particularly difficult group of patients to treat, it's another example of a very promising result from CAR T cell therapy in a difficult clinical situation. ASCO Daily News: Absolutely, some very interesting advances there in ALL. Well, patients who have received a stem cell transplant have felt especially vulnerable during the COVID-19 pandemic. A couple of abstracts assess the outcomes of allogeneic stem cell transplant recipients amid the pandemic. What are your thoughts on these studies? Dr. John Sweetenham: Yes, thanks. So, two abstracts of particular interest, Abstract 7033 is a study which addresses the outcomes for all patients undergoing hematopoietic stem cell transplants and cellular therapy, both autologous and allogeneic, as well as a few patients with CAR T cell therapy during the COVID-19 pandemic, really just looking overall at outcomes compared with essentially, historical controls. It was a single center prospective study, which included in all, approximately 40 patients undergoing either hematopoietic stem cell therapy or other cellular therapies who were diagnosed with COVID-19 between April of 2020 and January of 2021. As I mentioned, 40 patients were included, 25 of whom underwent allogeneic transplants, 13 autologous transplants, and 2 underwent CAR T cell therapy. And these were done for a variety of hematologic malignancies. And in the allogeneic patients, a variety of STEM cell sources were chosen. And the patients had a number of treatments for their COVID-19, directed specifically at the COVID-19, which included remdesivir, convalescent plasma, dexamethasone, and some monoclonal antibodies. The bottom line from the study, and perhaps this is really not too surprising, is that the patients undergoing hematopoietic stem cell transplantation with COVID-19 had an increased risk of mortality. And that particularly related to undergoing allogeneic versus other types of cellular therapy and the presence of concurrent immune suppression. So this study demonstrated something which I think is intuitive, but for which there hasn't been a lot of literature yet, essentially saying that patients who undergo transplant in the presence of active COVID-19 have relatively poor outcomes compared with those who are non-COVID-19 positive. The other abstract which drew my attention was Abstract 7032, a very different abstract in many ways, in that it looked at the association of COVID-19 with distress and the quality of life for patients undergoing hematopoietic stem cell transplantation. And this was a cross-sectional analysis of data from 205 patients with hematologic malignancies undergoing stem cell transplantation and enrolled in a multi-site randomized supportive care trial that they compared baseline pre-transplant distress which included depression, anxiety, and post-traumatic stress disorder symptoms, and quality of life between participants enrolled pre-COVID-19 and during the COVID-19 pandemic. Prior to the COVID-19 pandemic, 124 participants enrolled, and then 81 enrolled during the COVID-19 pandemic. Interestingly enough, in multivariate regression models, enrollment during COVID-19 was not associated with pre-transplant depression, anxiety, PTSD symptoms, or quality of life. So the conclusion is interesting in that this study reports that contrary to the generally held notion that the COVID-19 pandemic has worsened distress in patients with cancer, there was no difference in distress or quality of life in these patients with hematologic malignancies prior to or during the COVID-19 pandemic. ASCO Daily News: Yes, that's an interesting conclusion as you say, and a little unexpected. Well, let's focus on chronic lymphocytic leukemia. Are there any new therapies on the horizon for patients with CLL? Dr. John Sweetenham: So, two abstracts this year's ASCO [Annual Meeting] describe what I think is significant advances with newer therapies, which I think are now really finding their place in the therapeutic algorithm for CLL. Abstract 7500 reports the results of a large randomized comparison on a head-to-head basis between ibrutinib, the first in class Bruton tyrosine kinase inhibitor, and a more selective tyrosine kinase inhibitor, acalabrutinib. This was a randomized, head-to-head non-inferiority study which compared acalabrutinib with ibrutinib in patients with previously treated CLL of all risk groups. And overall, 533 patients were randomly assigned between these two therapies. And at the median follow-up of around 41 months. Now, acalabrutinib was found to be non-inferior to ibrutinib, with a median progression-free survival of 38.4 months in both arms of the study. But importantly, acalabrutinib was found to be superior to ibrutinib in terms of toxicities, which included the incidence of atrial fibrillation. Among the other secondary endpoints of the study were incidences of grade 3 infection, which were comparable between the two arms, as was the rates of Richter's transformation. Not surprisingly, because the routine tyrosine kinase inhibitors are such effective drugs in CLL, the median overall survival was not reached in either arm of the study. Acalabrutinib demonstrated a lower incidence of hypertension, arthralgia, and diarrhea compared with ibrutinib, but a somewhat higher incidence of headache, 34% versus 20%, and cough at 28% versus 21%. And of note, adverse events led to treatment discontinuation in just over 14% of patients on acalabrutinib versus 21% of those treated with ibrutinib. So in summary, acalabrutinib demonstrated a non-inferior progression-free survival with less cardiotoxicity and fewer discontinuations due to adverse events when compared with ibrutinib. So I think that this does pave the way for some of the later generation tyrosine kinase inhibitors, which certainly appear to maintain the efficacy of ibrutinib, but appear to have somewhat lower toxicity. This study was conducted in the relapse refractory setting. And clearly, the next question is going to be whether in the frontline setting, we would expect to see similar findings with acalabrutinib. The other study of note, I think, from the CLL abstracts this time is Abstract 7501. And this is a summary of the so-called CAPTIVATE study. This is a multi-center phase II study of first line ibrutinib combined with venetoclax, a BCO2 inhibitor, for patients with CLL. The study is important because it uses a fixed duration regimen. And to give that some context, many of the newer treatments, oral treatments for CLL with ibrutinib being the initial drug of this type, have been given continuously into either disease progression or until the patient becomes intolerant of the treatment because of side effects. And so there has been an ongoing series of investigations looking at whether it's possible to give these treatments in a fixed duration way rather than indefinitely because of the risks of long-term toxicity and so on. So in this study, patients less than age 70 with previously untreated CLL received three cycles of ibrutinib, and then 12 cycles of the combination of ibrutinib plus venetoclax, and then study was completed at the end of those 12 cycles. The primary endpoint of this study was the complete response rates with secondary endpoints of overall response rate, duration of response, minimal residual disease rate, and then progression-free and overall survival. To date, 159 patients have been enrolled on this study, with a median time on study of around 27.9 months. With a fixed duration combination, the complete response rate was reported at 55%, and the overall population was consistent across all of the high-risk groups, including those with adverse cytogenetic findings. Of the 88 patients who achieved a complete response, 78, representing 89%, had a duration of greater than 1 year. And the overall response rate for the entire group was 96%. And as I mentioned, there was no difference in those patients who had a 19p deletion, so another example of a novel first line regimen given at fixed duration which is chemotherapy-free and is providing really quite remarkable and intriguing results in the upfront setting for patients with CLL. ASCO Daily News: Great. Thanks for highlighting those two interesting studies on CLL. So focusing on Hodgkin lymphoma, can you tell us about advances using PET-directed therapy? And how do you see this evolving in the future? Dr. John Sweetenham: Yeah, absolutely. So, Abstract 7507 describes what I think is a very important study further investigating the use of functional imaging in therapy of that adaptation in patients with Hodgkin lymphoma. So typically, in the early-stage setting for patients with non-bulky early-stage Hodgkin lymphoma, there is now a wealth of evidence that interim PET scanning after a couple of cycles of ABVD chemotherapy, or other induction therapy, is a strong predictor of eventual outcome and can enable you to tailor the use of radiotherapy and potentially omit radiation therapy in patients who are PET negative early in the course of their chemotherapy. In patients with bulk early-stage Hodgkin lymphoma, that's been a little more controversial as to whether PET scanning on an interim basis early in the course of treatment is really reliable. So this is really quite an important Alliance study, CALGB 50801, which has tested the PET adapted approach in patients with bulk Hodgkin lymphoma. So eligible patients had stage IA through IIB classical Hodgkin lymphoma with disease bulk, which was defined as greater than 10 centimeters or more than 1/3 of the maximum intrathoracic diameter on a conventional chest X-ray. And the patients received two cycles of ABVD chemotherapy followed by a centrally viewed PET scan. If the PET scan was negative, defined as Deauville 1 through 3, patients who were PET negative received four additional cycles of chemotherapy but no radiation therapy. If the PET after two cycles was positive, the patients received intensified chemotherapy with escalated BEACOPP plus 30 Gray of involved site radiation therapy, with a primary endpoint in this study of progression-free survival. 101 patients have been enrolled on the study, of whom 94% were evaluable. 78% of these patients were PET negative after two cycles of ABVD. And in this group, the progression-free survival is 93.1. Of the remaining patients who were PET positive after two cycles of ABVD and went on to receive more intensified chemotherapy plus radiation therapy, the progression-free survival was also impressive at 89.7%. The overall survival in the study is also excellent. But the take-home message here is that excellent progression-free survival outcomes can be observed in patients with early-stage bulk Hodgkin lymphoma if they are PET negative after two cycles of ABVD, go on to complete six full cycles, but did not receive radiation therapy. And this is really a further important advance and omits the long-term risks of radiation therapy for a very significant proportion of these patients with bulk disease. Similarly, for those who are PET positive after two cycles and their treatment has escalated to more intensive chemotherapy retaining radiation, their long-term progression-free and overall survival is excellent. So, I think this is one more piece of evidence for the usefulness of functional imaging as a biomarker for response in patients with Hodgkin lymphoma which can lead to de-escalation of therapy in those patients with a good prognosis, and escalation of therapy for those who are likely to need more intensive therapy to achieve an equivalent outcome. ASCO Daily News: Excellent. Well, that's great news. Well, my last question is about mantle cell lymphoma. There's an interesting study that has real-world data for outcomes in MCL in community-based practices across the United States. What can you tell us about this study, Abstract 7504? Dr. John Sweetenham: Yes, thanks. So, as you mentioned, this is a study which is retrospective in nature and included patients with adult mantle cell lymphoma [who were] treated over a 10-year period from 2011 through the end of 2020. Just over 3,400 patients were included in this analysis, of whom 85% had been treated in a community oncology setting, and 85% were patients undergoing front line therapy. From a demographic point of view, the disease characteristics were very consistent with published data. Chemoimmunotherapy was the most common first line treatment, usually with either bendamustine and rituximab or R-CHOP. And the cytarabine-based regimens comprised a minority with only 14% of patients receiving these. 667 patients received rituximab maintenance in this study, and 243 received a frontline stem cell transplant in first remission, most of these transplants being autologous. The median follow-up for survival on this study was 45.3 months. The 36-month overall survival for the entire group was 67%. This large real-world cohort of patients primarily treated in community-based practices demonstrates outcomes which are somewhat inferior to those which we've seen reported from prospective trials. This suggests the need to focus on developing treatments that can be delivered effectively in the community setting. And perhaps the best example of this is that the use of stem cell transplantation in a community setting was uncommon even in those patients who are less than age 65. And what this gives us a clue to is the fact that maybe real-world considerations, including access to trials, access to treatments as a whole, suggests that these considerations may influence the eligibility for stem cell transplantation and some of the other more intensive approaches to treatment. ASCO Daily News: Absolutely. Well, thank you so much, Dr. Sweetenham, for highlighting these interesting advances in therapy for hematologic malignancies. It's always a great pleasure to speak with you. Dr. John Sweetenham: Thanks, a pleasure to speak with you too, Geraldine. And thanks for giving me the opportunity to talk about some of these exciting data. ASCO Daily News: Of course. And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate and review us wherever you get your podcasts. Disclosures: Dr. John Sweetenham: None disclosed 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.
During the 2nd European Myeloma Network Meeting, the Multiple Myeloma Hub spoke to Professor Graham Jackson, Newcastle University, Newcastle upon Tyne, UK, and Professor Philippe Moreau, CHU de Nantes, Nantes, FR. We asked, If maintenance after induction reduces therapy options at relapse, is it still worth it?Currently, the only approved maintenance therapy for multiple myeloma is lenalidomide. When answering whether this treatment is worth it, Jackson provides meta-analysis results of the CALGB 100104, IFM 2009, and Myeloma XI studies demonstrating improved progression-free survival by around 20−30 months compared with placebo. Jackson and Moreau then discuss alternative treatments in patients who are refractory to lenalidomide, focusing on optimizing carfilzomib + dexamethasone, daratumumab, bortezomib + dexamethasone, and pomalidomide + dexamethasone-based regimens. Hosted on Acast. See acast.com/privacy for more information.
Dr. Hayes interviews Dr. Muss on geriatric oncology. TRANSCRIPT PRESENTER: 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. DAN: Welcome to JCO's Cancer Stories, The Art of Oncology brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Today, my guest on this podcast is Dr. Hyman Muss. Dr. Muss has been instrumental in several facets of the history of oncology, the generation and conduct of cooperative groups, the establishment of medical oncology as our board of the subspecialty, and perhaps he's most well known as one of the founders of the field of geriatric oncology. Throughout his career, he's devoted much of his efforts to research in breast cancer mentoring many young investigators, and, frankly, I'm very proud to consider myself one of those. Dr. Muss's personal journey is fascinating. He was raised in Brooklyn, which even though he spent the last 50 years in other locations, including Boston, North Carolina, and Vermont, our listeners will appreciate from his dialect within the first 10 words from his mouth that he is, indeed, from Brooklyn. He received his undergraduate degree at Lafayette College in Eastern Pennsylvania, where he was elected to Phi Beta Kappa. He got his medical degree at the State University of New York downstate in Brooklyn, where he was elected to the AOA. He did his internship and his residency at the then Peter Bent Brigham Hospital, now the Brigham and Women's Hospital in Boston. That shows how old you are, Dr. Muss. HYMAN MUSS: [LAUGHS] DAN: Then he took a tour to Vietnam for a military tour of duty. He won a bronze star during that experience. He returned stateside, and he obtained his medical oncology fellowship at the then Sidney Farber Cancer Institute, which is now, of course, designated the Dana-Farber Cancer Institute. Following his fellowship in 1974, Hy joined the faculty at Bowman Gray School of Medicine at Wake Forrest, and there he served many roles over the next 22 years before he then moved to the University of Vermont to head the division of hematology oncology. After 10 cold years in Vermont, he got tired of the snow, and he returned to North Carolina and this time at the University of North Carolina, where he is now the Mary Jones-Hudson distinguished professor of geriatric oncology and the director of the geriatric oncology program in the University of North Carolina Lineberger Cancer Center. Dr. Muss has authored over 500 peer reviewed papers, and like most of the guests on this program, he's just simply won too many awards for me to list them all. However, in addition to his bronze star from the US military, I know he is particularly proud of being an eagle scout. And if you ever meet Hy and he's got his tie on, you have to ask him about his tie tack because it is an eagle scout tie tack, one of the few people I know who has one of those. Dr. Muss has served ASCO faithfully in many roles. He served on the board of directors from 2004 to 2007, and perhaps importantly, he was the recipient of the Allen S. Lichter Visionary Leader Award in 2020, which was well deserved. I knew of very few people with the vision that Hy Muss has shown for our field. Dr. Muss, welcome to our program. HYMAN MUSS: Thank you so much. My mother would have loved that introduction. DAN: [LAUGHS] Let's start with your origin story. I know you weren't bit by a radioactive spider in Brooklyn and became Spider-man, but seriously, I've heard you speak about your father, who was a dentist, and your uncle, a family practitioner, who, I think, shared an office or something. And this sounds a little bit different than the typical medical establishment that we work in these days. How did that influence you? HYMAN MUSS: Oh my god. How different it is. I grew up in Brooklyn. And I went to PS-167, and we lived in a little brownstone. And my father was the neighborhood dentist, and my uncle was the neighborhood GP, a term not used anymore. And I grew up with them, and I didn't always know I wanted to be a doctor. But I used to do house calls, especially with my uncle. And patients loved him. An interesting digression is he went to Howard University. He got a minority scholarship. He was picked out of Brooklyn. He had a lot of African-American patients too, and he would take me in his Buick. And I'd go, and I'd get candy and ice cream and love what he did. And I loved the patient interaction that he had. And I think that was instrumental eventually in college of me after working in a chemistry lab for a semester doing research on cyclic ketones to say I don't think I can do this for a living and consider medical school, which I think was probably one of my best choices. So I had a great upbringing and saw medicine. If my parents saw a credit card or an Epic EMR, they wouldn't know what it was. They'd think it was science fiction. DAN: And I'm sure you were HIPAA compliant when you were making the rounds with your uncle, right? HYMAN MUSS: Oh, yeah. So when he got very sick and he couldn't really do his practice anymore, my father said go to your uncle's office and take his records down to the basement. And I went in, and my uncle's records were 3 by 5 index cards with the name of the patient, Mary Jones, diabetes, and her phone number. That was it. That was it. And I could move them down in a cardboard box. And today when we see one patient and start one Epic note, we got 85,000 documents in there, so it was great. DAN: How did you get to Lafayette College? HYMAN MUSS: My father had a patient, and I inherited from both my parents loquaciousness. And my dad would talk with all his patients, and bring them up occasionally, have a scotch with them. And he had a patient-- I was probably a junior or a senior in high school. I was really-- didn't know what I wanted to do. I wasn't the greatest student academically in high school. Although, I went to Brooklyn Tech, a terrific high school. Rich Schilsky went to Stuyvesant, and the patient told my dad that he knew of a small college in Pennsylvania, a boys college, that was really good academically about 100 miles from home. Told me about it. I went and saw it, and liked it, and went there, and it really changed my life going to Lafayette. I got one on-- I went from 6,000 boys in my high school, no women, to a small college with maybe 1,200 boys, but I got to know my professors. It was a lot of one to one. It was terrific, and it still is. DAN: It's amazing how many people I've interviewed where what they do is serendipity. This sort of thing. Didn't know what I wanted to do, and I was-- you may have heard Dr. Freireich when I interviewed him. Told me that when he grew up in Chicago, his mother was a single parent, and so he started stealing hubcaps to pay for his tuition. [LAUGHS] The founder of our field was a juvenile delinquent. HYMAN MUSS: Oh, god. Yeah, no, I wasn't that bad. But Lafayette really changed my life, and I had people who actually knew me, knew my name, knew what I was interested in. I had some-- I was a chemistry major, not a really premed. And I had some wonderful professors, and I think they were disappointed when I didn't go for PhD graduate school in chemistry. DAN: Again, it's just amazing, and I remember this every time I run into a med student, where I think I don't have time to do this. And just one little comment or pat on the back and suddenly they're off in a different way, so I think all of us keep that mind. I've interviewed several of the pioneers, who many of them were so-called yellow berets at the NIH in the 1960s to avoid going to Vietnam and, frankly, changed the picture of medicine in America I think, especially oncology. But so far, only you and one other interviewee, Larry Baker, who I know you know and good friends, actually joined the military and was sent overseas. He did it sort of unwillingly. It looks, to me, like you did it more willingly. It's not that he was unwilling, but it wasn't in his career plans. That must have really been a very frightening but enlightening experience. Are you willing to give us any back stories on this and talk about it? HYMAN MUSS: Of course. So I was in medical school. Vietnam was going, and the draft was hot. And we were all worried that if we got drafted out of medical school or out of residency, we'd have to repeat a whole year. So there was something called the Barry plan. And what it was is you joined the military, you could join any service, and they would let you finish medical school and actually credit me for time in the military during medical school. And then they promised in residency not to draft me in the middle of the year. So I joined the Barry plan, and so I knew I had to go into the military. And so when my time came because I had good training, I was at the Brigham then, the military said, well, if you want to do three years instead of two years, we'll send you to this place or that to do research. And I didn't want to spend another year, so I know the minute I told them that I was heading to Vietnam. I did go to the NIH to look at a cardiology training. And I got there, and I was the only guy sitting in that interview area who hadn't written 10 papers. So I knew I was going to Vietnam after that day too. And I didn't about the NCI. I didn't know about cancer. Some of my close friends and your friends went to the NCI. Had I known, it would have been a terrific thing, and I would have applied. I would have worked with the greats there at the time. But I didn't know, so I went to Vietnam. And I was with an artillery battalion. I wasn't anything elegant. I never saw any units with MASH with women or anything. I was married three months. It was extremely hard on my wife, Loretta, who you know well, but I learned a lot about myself then. I was 27 years old. I didn't have 25 smart people behind me to ask questions to, residents, and terrific faculty, and colleagues, and I got to know myself. I was terrified when I went, terrified, but I got to know the system. And you learn how well-run the military is. Unlike some of our clinics, they really know how to do it. I got a very valuable experience there, and I set up a drug amnesty program, which is why I won the bronze star. It wasn't anything like I was in front of a machine gun. We had a major drug problem in Vietnam. Young people, nothing to do, time on their hands, frequently poor kids who got drafted and went in. It was the poor kids. World history, so I set up a program to try to help a lot of them not really get deep into bad drugs. And I think we had some success. Hard to measure. DAN: So when you say you were an artillery unit, were you like the doctor for the artillery unit? HYMAN MUSS: I was it. DAN: Were you patching up injuries and stuff, or taking care of sore throats, or what? HYMAN MUSS: I did. I did a lot of sore throats. I did a lot of venereal disease. I did back pain. I set one or two fractures. The first fracture I set, I had a big book in another part of our little aid station called the Palma. It was like a-- we didn't have YouTube. I needed YouTube videos. I put this cast on this guy. It probably weighed 300 pounds, and he said, doc, have you done this before? And I said, oh, yeah, I've done this a lot. So I did that, and I took care of a heart attack or two on the base in the base hospital. Although, I was in a unit that had little field units out with artillery, and I used to go a few times a week in a helicopter and check on the medics and troops. So it was an extremely valuable experience. DAN: That's incredible. Well, let's go on. You already sort of alluded to this, but I've asked almost everybody. What made you go into oncology, especially in the 1960s when there wasn't oncology? You came back to the Brigham. What got you interested in doing cancer? HYMAN MUSS: When I was an intern and resident at the Brigham, our chief of hematology was a guy named William Moloney, and I know you know him. DAN: I sure do. HYMAN MUSS: And he was an incredible guy. He was a professor at Harvard, but if you think my Brooklyn accent is heavy, you should have heard his Boston-Irish accent. It was off the wall. And he was the most terrific guy. He kind of served as my dad for part of the time because my dad had passed. He would round every day, and we'd see all the hem patients. And we had all the AMLs, so I'm talking about, oh, 68 to 70. I never saw a remission. Never. And they all passed away, but he loved the patient care. And I got interested, and so when I was in Vietnam and when I got out of the Vietnam and was back, I thought, what do I want to do? And I said, I really like that hematology. DAN: I'll just say that Dr. Moloney was almost exclusively hematology. HYMAN MUSS: He was almost all exclusive. He used to grow little AML cells in little chambers in mice and treat them with drugs, and so I decided to do hematology. And I came back, and I think in my first weeks there he said, Hy, you're not going to believe this, but you can actually put these people into complete remission and take their leukemic bone marrow and make it look normal. And I'm saying, oh, yeah, right, because I had used all these regimens like VAMP, methotrexate, all the things that never worked. And we had two new drugs, ara-C and daunomycin. And so I used to go up and treat these patients' IV pushes, ara-C and daunomycin, big doses, and I started seeing remissions. And I said, this is amazing. And then during that year, we had our first child, and I started to run out of money. DAN: So this is when you're still a resident? HYMAN MUSS: This is when I'm now a fellow. That year, we were very short of cash. I had a new baby, and I went to Dr. Moloney and talked with him. And he said, I'll try to help you, and he talked with a guy named Dr. Francis Moore, who was chief of surgery, one of the icons of surgery. And Dr. Moore talked with some of his donors in the Brooklyn area, and I became the first Sidney Farber Cancer Research fellow. I knew nothing about cancer, solid tumors. So as the requirement was, I had to go over to the Jimmy fund, the Sydney Farber Cancer Center and see cancer patients. And all my hardcore hem friends said, oh, you're not going to like it, but it's worth doing for the stipend I got. The first day I was there I knew medical oncology was for me. I loved-- it was open. We were treating everyone with CAF-- CMFVP, the old regimen, every single cancer. There was so much to be learned. There was so much opportunity for clinical trials. And then in the middle of that year, Tom Frei came, and he was so inspiring. And I knew that I was going to do an onc career. There were no hem-oncs then. There were hardly any oncology fellowships, so I got to love that. I did two years, not three. DAN: So let me interrupt you for just a moment just for our speakers-- our listeners. So Tom Frei was one of the three who were the first to put combination therapy together. HYMAN MUSS: Right. DAN: Jay Freireich, Jim Holland-- actually, it was Jim Holland's idea frankly. I figured that one out, and Tom Frei. So, again, in terms of pioneers, you were right there with the first pioneer. HYMAN MUSS: And I did little combinations of things I'm not going to tell you about. They're embarrassing. They didn't work, but I learned so much. And actually, Ezra Greenspan was in that early group in breast cancer treating patients with hormonal agents and chemotherapy. But I learned from them, and I just love the clinical environment. And those days, there was nothing. I've witnessed other miracles like Larry Einhorn developing platinum and curing testis patients. I'm old enough, every male I saw with testis cancer and mets died. Everyone. Drugs like that were virtually miraculous, and we're doing so many great things today. So I was at a really great crossroads. DAN: Who else was at your level at the time, especially before Dr. Frei? You must have been pretty much alone. HYMAN MUSS: There was a fellow named Jacob [INAUDIBLE] you may remember, who was there and was really interested in chemotherapy timed by your biologic clock, and a few other people, people like Craig Henderson and others who came in after. I preceded them, so I was virtually one of the few oncology trainees at that time. DAN: And who mixed up your chemotherapy? HYMAN MUSS: I did. DAN: And who started the IVs? HYMAN MUSS: I did. DAN: And who-- HYMAN MUSS: You don't want to know. I was very careful with daunomycin, and so Dr. Moloney had a little office in the Brigham. And it had a little bathroom, and a very popular regimen-- and we had a lot of lymphoma patients-- was COP, cyclophosphamide, vincristine, and prednisone, COP. So I would go into that little bathroom. It's very hard to dissolve this stuff. I put it all in a little sink. I'd have to tell the patients I'm going to be in here a minute. Don't come in. And I would put it all in syringes. I'd put them in a little chair, like kids sit in in school. Put your arm on the side. I'd start the IV and give it to them. When I got to the Farber in the second year, now they were training because they had so many kids. They had nurses that could do some of that, but I think I recall giving it there. But in the Brigham, I gave the chemo. DAN: Did you do any pediatric work with Dr. Nathan? HYMAN MUSS: I did a few months in peds with Dave Nathan, another amazing, amazing guy, and that's where I met people like Larry boxer. DAN: Larry was a colleague of mine here at Michigan. HYMAN MUSS: I know. DAN: Passed away about two years ago. Just a wonderful guy. He also, by the way, was my attending physician when I was a med student at Indiana on pediatrics-- HYMAN MUSS: Oh my gosh. DAN: --just by coincidence. HYMAN MUSS: His wife, Grace, was one of my colleagues. DAN: Let's move on a little bit. From there, I know you went to Wake Forrest. And I have to say, how does a kid from Brooklyn, who has been at Harvard in the middle of, really, no oncology probably outside of the coast, end up in North Carolina? HYMAN MUSS: At the Brigham, I knew I wanted to do a career in-- I wanted to try academics, but I didn't want to go in the lab. And I was actually offered a job by Gene Brown Wald and others at that time to work to stay in the Harvard system and do work on methotrexate in the lab. High dose methotrexate was hot then, and I couldn't see myself in a lab. I worked with Frank Bunn, one of the world's great hematologist at the Brigham, who is-- really became a great friend and knew me. And he said, Hy, I know you don't-- laboratory work isn't for you, so he knew someone at Wake Forrest doing work on sickle cell anemia. They were infusing urea to try to prevent sickling. And he called this fellow, and they said they were looking for oncologists, clinicians. And I went down there and another open place. I met my future boss at that time, a guy named Charlie Spurr, who is also one of the pioneers in oncology. Gave nitrogen mustard after the war. Just a terrific guy and probably my most-- among my most impressive mentors, and they offered me the job. And I told Loretta about it. I was thinking of Rochester and some other places, but I decided on this job. And one of the reasons was the other places I went it had snowed, and I was delayed and couldn't get out. True story. You talk about serendipity. And I came out here. There was some azaleas blooming, and I said, I'm going. And it was a difficult adjustment for a kid from Brooklyn to go down here. My mother, who was alive at that time, never heard of North Carolina. She was one of these women born in a candy store in Greenwich Village over a candy store by a midwife, and she said, they're going to kill you down there. And I said, I think it'll be fine, and Loretta got out of the car when we drove down here and cried. But it turned out that Wake Forrest and my mentorship and ability to work in their cancer center was incredible in my career, so I was able at Wake Forrest to really set up lots of research studies in breast cancer, prostate cancer, brain tumors. It was an open field there. They didn't have, really, many people like me, and it just was absolutely terrific. DAN: Let me segue that. There's a lot more I want to talk to you about, but I got to know you because of our experience in CLGB and the cooperative groups. And it was clear to me right away you were a major player, but I also-- and you still are as far as I can see at CLGB Alliance. But you're one of the few people I know who then went off and started his own group, the Piedmont Group. What was the background? What made you think you could compete with the big boys, and how did you get those folks to play? And how did you also straddle two different groups at once? HYMAN MUSS: Well, we had a very-- Dr. Spurr was an amazing man, and he realized that most oncology was going to be practiced in the community. Even at that time when I started my career, I would drive out to these small towns occasionally once a week, once a month, and actually give some of the chemo still or train nurses in practices. There were no medical oncologists around there. I took the second set of boards, so I think I'm talking about 1975 or something. And so he knew that, and we cultivated some very strong community relationships. And we didn't have CCOPs and NCORP there. Although, Dr. Spurr and his colleagues were instrumental in getting CCOPs and things going in this country, so community people didn't have a lot they could do. It wasn't a formal mechanism. And so we formed a little small group called the Piedmont Oncology Association. It was kind of fluffy. We didn't have 5,000 bylaws or anything. It was just a conglomerate group, and ironically, I published a New England Journal study out of that group reviewing all the things, and how long to give chemo, things that people like yourself have really expanded on and made much better. But we work with them, and then there was an announcement to form regional cooperative groups from the NCI. And I was involved in CLGB but not heavily at that time. We didn't have all the traveling and things that we had, and now we've replaced it with Zoom meetings and things. And so I knew a lot of these people. I'd seen a lot of their patients. So we applied, and we got funding for the POA. And we did OK for a few years, and it actually is still in existence as an educational group. But we couldn't compete with the large cooperative groups. We did well with accrual, but the brainpower to develop and keep up all the diseases-- disease sites were emerging. I was writing prostate cancer stuff. I couldn't keep up with the expertise nor could my colleagues. So it was a good experiment, and a lot of them ended-- my colleagues ended up in CCOP and now NCORP and have made major contributions. And I suspect we got people used to trials and protocols, but it was a short lived experiment. DAN: Well, short lived but changed practice. And by the way, some of your colleagues still talk about it and what a great experience it was, so you're the-- all right the next thing I want to talk to you about is your real love, which is geriatric oncology. And you got involved in geriatric oncology before the word existed as far as I can see. Two things, one is you weren't geriatric at the time. Although you are now, as am I. And, two, is-- just talk about the people you got involved. I know Dr. Hazzard had a big influence on you, but also Ludovico Balducci and Harvey Cohen. And tell us about how that all got started. HYMAN MUSS: Yeah, so when I was in my career at Wake Forrest, Bill Hazzard, who's one of the grand old men of geriatrics, wrote one of the first textbooks, and is still hanging around as professor emeritus, came to all the faculty and said, I'd like you to work with one of our residents in a project related to your specialty and geriatrics. So he came to me specifically and said you would like to do this. He's my chair. He's got to promote me someday, so I said, oh, of course. So what we did is Dr. Spurr was ahead of his time, and actually, we had codified all people in local protocols, our POA, into a database system with the punch cards from IBM, those little cards. I can remember that great movie about those African-American women where there's one woman who's the only one who knows how to use those cards. DAN: In NASA, yeah. HYMAN MUSS: I could go and actually ask our statisticians to run things, so what we did was we compared. We had metastatic breast cancer. We had no upper limits of age on protocols, which was very common then. We were patronizing to older people, and we compared women above 70 with 50 to 70 and less for metastatic breast cancer. And when I looked at the data, I had about 60, 70 patients, and I work with a wonderful woman who's now a medical oncologist named Kathy Christman. She was the resident, and we put this together in a paper. And we submitted it to JAMA, and I thought, oh, they're going to-- this will be gone. And they accepted it actually without any revision. Then I had to get my friends to read it because if you read the-- if you hear the way I talk and see the way I write, we need a lot of editing here. So in any event, it got there, and I really enjoyed the project. And I started learning about other people. Then what happens-- and you know this, Dan, your biomarker and all your expertise-- your friends start calling you. Hey, Dan, should we be doing this or that? And so they'd start to call me about older women with breast cancer and say, you think she could tolerate chemo? And so I got more and more interested. And then in the CALGB at that time, there were some other people interested, Peggy Kemeny, et cetera. DAN: Harvey Cohen, I think. HYMAN MUSS: Harvey Cohen. And we formed the-- and Rich Schilsky. DAN: And Stuart Lichtman was also a big player, as I recall. HYMAN MUSS: Stu Lichtman, yeah. I'm going to mention-- so we thought we'd form something on cancer in the elderly, and Rich Schilsky backed this up. And we made a working group, and one thing led to another. And then we became a committee. We were very successful. We wrote clinical trial protocols not just in breast cancer. We had terrific people like Stu Lichtman. Harvey and I chaired that committee for 22 years. We didn't even know it was that long, and we saw such evolution in our field. At that time, there was expertise evolving nationally with people like Ludovico Balducci. And I should add that early in my career at ASCO, BJ Kennedy, who's really considered one of the fathers of oncology, used to get up at meetings and when he heard a presentation and there were no older people, he said, where are all the older people there? And if you know BJ, he was not a man who was afraid to get up and speak his mind. And so he was really-- pushed this too, and Ludovico, and our cooperative group. And we slowly built up a wonderful committee. It really evolved, and then we pulled in people like the late Arti Hurria, one of the world's most incredible people, who really taught us how to get geriatric assessment into clinical trials and do it in the community. And it just evolved, and it's never-- DAN: You just stole my question, which is that you just told us about the first generation, and the second generation has taken this and run with it. This is why you're being interviewed. You were a pioneer. Arti was a settler. HYMAN MUSS: Oh, yeah. DAN: In terms off-- and we miss her so much. For our listeners, I think many of you know, she was tragically-- lost her life. She tragically lost her life in a car accident a few years ago, and she was on the board of directors. I remember standing with her during cocktail hour before one of the board of directors meetings, and I said, you know, Arti, you're going to be president of ASCO someday. And, well-- and she kind of looked at me like, are you kidding? And I said, no, I'm not kidding at all. You're on your way. It's such a tragedy. Actually, the final thing I want to do is I was going to ask about BJ Kennedy and his role in geriatrics, which you covered, but that allows me to segue into BJ's role in our field becoming a field. And you sort of stepped into his shoes, in my opinion, with the American Board of Internal Medicine, but BJ, I think, was responsible for our becoming a boarded subspecialty. Can you talk more about that? HYMAN MUSS: Oncology, we were relatively new, and to become an ABIM subspecialty, you have to show a need, that there's a need and enough patients and that you're doing something uniquely different and beneficial. And for a long time, the hematologists were a little-- think what do those oncologists do? They have one drug. They have 5FU. DAN: 5FU for colon cancer. HYMAN MUSS: Yeah. And maybe nitrogen mustard or something. But so they felt there's certainly a need. There's no question cancer was a need, but they really can't do much for their patients. And it was people like BJ, Jim Holland, and other visionary guys that really worked with ABIM and pushed to make it a specialty. And I think we began in 1973. I think hematology was 30, 50 years before because there was so much more knowledge in that field. And so it took people like BJ and Jim Holland, strong, outspoken people, to convince the board and not back off. Well, come back when you guys really have something to do for patients. No, we're doing things for patients now. This was well before pall care and all the other things we do non-treatment related that are so wonderful for patients. And they pushed it, so this was crucial in BJ building this, and being on the front line, and doing this, and building the whole field. And then what can I say? I think we're all in the greatest field in medicine, most exciting, best biology, can do tremendous things for many sick patients. But they were the people that really got us going or it would have taken 10, 20 years more. DAN: Yeah, it's a remarkable story. And actually to cap it off, I think you probably saw two days ago, the ACS, Siegel et al, put out their annual cancer statistics. And the last year, which was to 2018 to '19, was the greatest reduction in age specific mortality in the history of the statistical thing. And overall, since the '80s, there's been about a one third reduction in the odds of dying of cancer in this country. And it all started back with you and the generation ahead of you. I mean, there are very few specialties that can look at that kind of success, and look backwards, and talk to the people who were there. The cardiologists can't talk to Harvey and-- HYMAN MUSS: Yeah, I owe so much to my friends supporting us through the years, like you, like Larry Norton, one of my also great mentors and friends, Rick Schilsky, for just supporting the field, and the studies, and things or it never would have happened as well, and so many wonderful people involved. And so many nice things that ASCO has done, like education, and developing YIAs, and things. As you say, it's got to be the new generation. It's going to be the [INAUDIBLE], and William Dales, and all these absolutely terrific people that are going to have to push this field, Heidi Klepin. And I just was in the right place at the right time in all of this and had tremendous friendships and mentoring. DAN: Well, and I can't remember who said it, but those who don't remember history are destined to make the mistakes of others. So one reason I'm doing this is so all those people know what it took to get us there and the history behind it. So I want to finish this by thanking you for all you've done for me as a mentor, and all you've done for our field in terms of pioneering geriatrics, and the Board of Internal Medicine, which you've been on now for, what, 15 years I think. HYMAN MUSS: Yeah. Well, I'm off now, but I-- DAN: Oh, you're off now. OK. And mostly for our patients. So many of our patients are alive and doing well because of what you've done, so thank you very much. Appreciate your time today, and looking forward to being on the river with you someday soon. HYMAN MUSS: Oh, yeah. DAN: For our listeners, we both like to fly fish, so-- HYMAN MUSS: Thank you so much, Dan. I appreciate you allowing me to do this. I'm very grateful to ASCO. Thank you. DAN: Until next time, thank you for listening to this JCO's Cancer Story, The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.
Retiring ASCO Chief Medical Officer Dr. Richard L Schilsky gives a far-reaching interview with ASCO in Action podcast host ASCO CEO Dr. Clifford A. Hudis, who examines Dr. Schilsky’s trailblazing medical career, his leadership in ASCO and indelible mark on its research enterprise, and what he sees for the future of oncology. ASCO’s first-ever Chief Medical Officer even offers some friendly advice for Dr Julie Gralow, who starts as ASCO’s next CMO on February 15, 2021. In a touching tribute, Dr. Hudis also shares what Dr. Schilsky’s friendship and mentorship has meant to him personally, and suggests that Rich will still be supporting ASCO on critical priorities moving forward. Don’t miss this exchange with one of oncology’s greats! Transcript DISCLAIMER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. CLIFFORD HUDIS: Welcome to this ASCO in Action podcast brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. The ASCO in Action podcast is a series where we explore the policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Dr. Clifford Hudis. And I'm the CEO of ASCO and the host of the ASCO in Action podcast series. For today's podcast, I am especially pleased to have as my guest my friend, colleague, and mentor Dr. Richard Schilsky, ASCO's chief medical officer. Now, I am sure that many of our listeners have already heard that Dr. Schilsky will be leaving ASCO in February of 2021, retiring. However, I want to reassure everybody that even in retirement, he will continue to make contributions and provide leadership to all of us. And his illustrious and path-blazing career in oncology spanning more than four decades is not quite over thankfully. Rich is ASCO's first chief medical officer. And as such, he has made a truly indelible mark on all of us. He started with a proverbial blank piece of paper. The position had no precedent. It had no budget. It had no staff. But now after just eight years in the role, he has helped make the CMO a critically important position at the society. And I have to say that success is more than anything due to Rich's vision and his leadership. And that's some of what we'll be talking about today. So Rich, thank you very much for joining me today for what I hope is going to be a great casual but informative conversation about your amazing career, your unique role at ASCO, and maybe most importantly in the end what you see for the future of oncology not just in the United States, but around the world. Thanks for coming on, Rich. RICHARD SCHILSKY: Thanks, Cliff. It's great to be here today. CLIFFORD HUDIS: So with that, let's just dive right in and start at the very beginning. Rich, tell everybody why you decided to become an oncologist and maybe share a little bit about what those early days looked like for you and, in that context, what it was like to have cancer at the beginning of your career. RICHARD SCHILSKY: Well, I knew from an early age that I wanted to be a doctor. And in fact, I had written a little essay when I was in sixth grade as a homework assignment called My Ambition. And my mother had tucked that away in a scrapbook. And I found it a number of years ago. And on rereading it, it was quite amazing to me to see what I was thinking about even then. Because I said not only did I want to be a doctor, but I didn't think that was enough, that I wanted to be a medical researcher because I wanted to discover new information that would help people heal from whatever their diseases might be. And so it was never really any doubt in my mind that I would be a physician. I went to medical school at the University of Chicago. But I was living in New York City at the time having grown up in Manhattan. And the only year we had off in medical school, the only time we had off in medical school, was the summer between the end of the first year and the beginning of the second year. So during that time, I went back to Manhattan. And I was able to get a fellowship from the American College of Radiology that allowed me to essentially hang out in the radiation therapy department at New York University Medical Center, which was within walking distance of where I grew up. And so I would go over there every day. And I was taken under the wing of a young radiation oncologist. And of course, I wasn't really qualified to do anything at that point except to follow him around, talk and listen to the patients. But that turned out to be a really formative experience for me because we saw the whole gamut of cancer. We saw head and neck cancers. We saw lung cancer. We saw patients with breast cancer and prostate cancer. And in those years-- this is the early 1970s-- many of these patients have fairly locally far advanced disease and were quite debilitated by it. But listening to their stories, hearing about their hopes and their struggles, really demonstrated to me the human side of cancer. So I went back to school and thought about this in the context of my own personal experience, which dated back to when I was in college when my mother's mother, my maternal grandmother, was diagnosed with breast cancer. This was 1968. And as you well know, there were very few therapies available for breast cancer in the late 1960s, mostly hormone therapies. And my grandmother had the treatment that was considered standard of care at that time, which was extended radical mastectomy followed by chest wall radiation. And some years after that first mastectomy, she had a breast cancer that developed in the opposite breast and had a second extended radical mastectomy and chest wall radiation. And these were very traumatic and disfiguring procedures for her to go through. Anyway, long story short is after another few years, she developed bone metastases and then brain metastases. And there was really very little that could be done for her other than hormone therapies. And having observed her go through that illness and realizing how limited our treatment options were and then having the experience after my first year in medical school pretty well cemented for me that I wanted to be an oncologist. I thought actually about being a radiation oncologist. But then I did my internal medicine rotation in medical school, fell in love with internal medicine. And that sort of put me on the path to be a medical oncologist. The clinical challenge of caring for cancer patients, the emotional attachment to those patients, and, of course, even then, the unfolding biology of cancer was so intellectually captivating that I actually applied for oncology fellowship when I was a senior medical student. So even before going off to do my medical residency, I had already been accepted as a clinical associate at the National Cancer Institute to start two years hence. And that's how I became an oncologist. CLIFFORD HUDIS: So it's so interesting. Because, of course, the story I'm sure for many people interested not just in oncology, but even medical education, there are little things that don't happen nowadays that happened with you like that last little vignette about the early acceptance into an advanced training program before your fellowship among other things. Can you remind us about the timeline? Because I think one of the things that many of our listeners often can lose sight of is just how new oncology really is as a specialty. ASCO itself founded in 1964. And the first medical oncology boards were mid-'70s, right? So you were in med school just before that second landmark, right? RICHARD SCHILSKY: That's right. I graduated from medical school in 1975. I started my oncology fellowship in 1977. And I got board-certified in medical oncology and joined ASCO in 1980. And so that was the time frame at that point. CLIFFORD HUDIS: So the internal medicine was actually, if I heard you right, just two years, not the now traditional four. RICHARD SCHILSKY: Yeah. I was a short tracker. I did only two years of internal medicine training rather than three. I did my training at Parkland Hospital and University of Texas Southwestern in Dallas with at that time a legendary chair of medicine, Don Seldin, who I had to get permission from him to leave the program prior to completing the third year of residency because I had already been accepted into fellowship at NCI. And he, Seldin, who was a brilliant chairman and a brilliant nephrologist, was not at all interested in cancer. And it took a bit of-- I was going to say arm twisting, but it really took bleeding on my part to get him to agree to allow me to leave the residency program to go to the NCI. But he eventually agreed. And in those years, the first-year clinical fellowship at the NCI was like being an intern all over again. There were about 15 of us. We were on call overnight in the clinical center once every two weeks. We cared for all of our inpatients as well as had a cadre of outpatients. We did all of our own procedures. We had no intensive care unit. So patients who were sick enough to require ventilator support, we cared on the floor in the inpatient service on our own with guidance from senior oncologists. It was a bit different from the way it is now. But, of course, it was fantastic on-the-job training because we just learned a ton and had to learn it very quickly. CLIFFORD HUDIS: So that's actually a great segue to the advances because there was a lot to learn then. But, wow, there's a lot more to learn, I think, now. And I have real sympathy for trainees and younger oncologists for the breadth of what they need to learn. Again, just testing your memory, but platinum came along pretty much in the mid-'70s as well, right? That was a pivotal expansion of the armamentarium for us. So what do you see-- when you summarize progress in cancer research and care over these decades, what do you think are the most pivotal or revolutionary milestones that you identify over the span of your career? RICHARD SCHILSKY: Yeah. It's really interesting to think about it historically. There were the early years of discovery in oncology from the 1950s to the 1970s when we really had the introduction of the first chemotherapy drugs and the miraculous observation that people with advanced cancer could actually obtain a remission and, in some cases, a complete remission with chemotherapy and combination chemotherapy in particular. And so that was the formative years of oncology as a medical specialty and really proof of concept that cancer could be controlled with drugs. When we got into the 1980s, the 1980s in many respects were the doldrums of progress in clinical oncology. There really was not a lot of innovation in the clinic. But what was happening and what was invisible to many of us, of course, was that was the decade of discovery of the fundamental biology of cancer. That's when oncogenes were discovered, when tumor suppressor genes were discovered, when it became clear that cancer was really a genetic disease. And that is what transformed the field and put us on the path to targeted therapy and precision medicine as we think of it today. So I think that clearly understanding the biology of cancer as we do now and all that it took to lead us to that point, which was a combination of understanding biology, developing appropriate technology that would, for example, enable the sequencing of the human genome and then the cancer genome. And the other formative technology in my opinion that really changed the way we care for cancer patients was the introduction of CT scanning. When I was still a fellow at the NCI, we did not have a CT scanner. If we needed to get detailed imaging of a patient, we did tomography. And if you remember what tomograms looked like, they were really blurry images that you could get some depth perception about what was going on in the patient's chest or abdomen. But they really weren't very precise. When CT scanning came along, it really revolutionized our ability to evaluate patients, assess the extent of disease, stage them in a much more precise way, which then allowed for better patient selection for curative surgery, better radiation therapy planning. So we don't often point to imaging advances as some of the transformative things that paved the way in oncology, but I think imaging is really overlooked to some extent. So I think the technology advances, the biological advances, are the things that really allowed the field to move forward very quickly. And by the time we got into the mid-1990s, we were beginning to see the introduction of the targeted therapies that have now become commonplace today. And then it was around 2000, I think, that we saw the introduction of Gleevec. And I'm reminded always about an editorial written by Dan Longo in The New England Journal a few years ago. And Dan and I were fellows together. We worked side by side on the wards at the clinical center and became very good friends. And Dan in his role as a deputy editor of The New England Journal wrote an editorial a few years ago that was titled "Gleevec Changed Everything." And Gleevec did change everything. It changed our entire perception of what were the drivers of cancer and how we might be able to control cancer very effectively and potentially put it into long-term remission. Now, of course, we know now that the whole Gleevec story is more of an exception than a rule in targeted therapy. And, of course, we know that tumors become resistant to targeted therapies. But we couldn't have known any of this back in the early years of oncology because we had no real insight into what caused cancer to grow or progress. And the notion of drug resistance, while we realized that it occurred, we had no idea what the mechanisms were. So it's such a different landscape now than what it used to be. It's quite remarkable. CLIFFORD HUDIS: So as you tell the story, there's, of course, a lot of focus on technology, whether it's biology and understanding the key features of malignancy or imaging or more. But what I also note in your story and I want to come back to is the people. And I can't help but reflect on where we are in this moment of the COVID-19 pandemic. Yes, we've moved to telemedicine. Everything can be accomplished via technology. And, yet, the human touch is so important. When we think about being in the room with people, when we think about face to face from the context of career development and your own career, you touched on Dr. Seldin, I think, already from the perspective of internal medicine training. But are there are other mentors or important shapers of your career that you think we should know about? RICHARD SCHILSKY: Well, probably, the most influential person early in my career in medical school was John Altman. John, you may know, was the inaugural director of the University of Chicago's NCI-designated Cancer Center, which was one of the very first NCI-designated cancer centers in 1973 after the National Cancer Act of 1971 created the cancer centers program. And John, who was a leading oncologist studying Hodgkin and non-Hodgkin's lymphoma, was a faculty member there. He was the director of our cancer center as I said. He took me under his wing even when I was in medical school and served as a real role model and mentor to me. When I was in my internal medicine training as I mentioned earlier, Don Seldin, the chair of medicine, was never particularly interested in oncology. So, to some extent, I didn't have-- I had great internal medicine training. But I did not have good mentorship in oncology. When I got to the NCI, then my whole world really opened up. And the two pivotal people there in my career were Bob Young, who was chief of the medicine branch and was my clinical mentor and remains a mentor and friend to this day, and then, of course, Bruce Chabner, who was the chief of the clinical pharmacology branch. And in my second year of fellowship when we all went into the laboratory, I went into Bruce's lab. And that's where I really got interested in the mechanism of action of anti-cancer drugs and ultimately in drug development and early phase clinical trials. And both Bob and Bruce remain very close to me even today. CLIFFORD HUDIS: So I'm concerned about time on our call today on our discussion. Because we could obviously fill lots of hours on all of these remarkable experiences and amazing people you worked with. But I'm going to ask that we fast forward a little bit. You and I share, I think, passion and love for ASCO. So I think that it's reasonable for us to focus a little bit on that for the time we have left here. You didn't start out obviously as chief medical officer at ASCO. But you were a really active ASCO volunteer and leader. Maybe tell us a little bit about some of the ASCO volunteer roles that you engaged in and what that meant to you at the time and how that led to this role. RICHARD SCHILSKY: Well, I'll be brief. I joined ASCO in 1980 at the first moment that I was eligible to join ASCO. I had attended my first ASCO meeting the year before, 1979, when I was still in my fellowship training. And it was clear to me even then when the whole annual meeting was about 2,500 people in two ballrooms in a hotel in New Orleans that that was a community of scholars and physicians that I wanted to be a part of. And so, over the years, I did what people do even today. I volunteered to participate in whatever ASCO activity I could get involved with. Over the years-- I think I counted it up not too long ago-- I think I served or chaired 10 different ASCO committees, more often serving as a member, but in a number of those committees also serving as the chair over many years. And as I became more deeply involved in ASCO and saw other opportunities to engage, I had the opportunity to run for election to the board and was-- after a couple of tries was elected to serve on the board and then eventually elected to serve as ASCO president in 2008-2009. But the attraction of ASCO in many ways was a community of diverse but, in many ways, like-minded people, people who had similar passion and drive and focus. But I think what you get at ASCO in many ways is the wonderful diversity of our field. If you work in a single institution for much of your career as I did and as you did, you get to know that institution pretty well. You get to know its perspectives and its biases and its strengths and its weaknesses. But there's a whole world of oncology out there. And you can get exposed to that at ASCO because you meet and work with colleagues from every clinical setting, every research setting, people who have remarkable skills and interests and passions. And it's just a wonderful environment to help develop your career. So I consider myself to be extremely fortunate to have had the journey in ASCO that I've had culminating, of course, with ultimately my coming on the staff as ASCO's first chief medical officer. CLIFFORD HUDIS: We often joke about that blank sheet of paper. But in retrospect, it's very obvious that you had built up that collection of LEGO blocks, and then you assembled them all into the ASCO Research Enterprise, a name you gave it. And it really, in retrospect, builds, I think, very cleanly upon all of your prior experience, but also the vision that you developed based on that experience for how research should be conducted. Can you maybe share with everybody the scope and vision for the ASCO Research Enterprise, what the intent was, and where you see it going, and what it includes today? RICHARD SCHILSKY: Sure. I won't claim that I came to ASCO with the whole thing fully developed in my mind. As you said, when I came, I literally did have a blank slate. Allen Lichter, who hired me, said, come on board and help me make ASCO better. And so I, in a sense, reverted to what I knew best how to do, which was clinical research. And having in my career been a cancer center director, a hem-onc division chief, a cooperative group chair, I had a lot of experience to draw on. And it was obvious to me that ASCO was fundamentally an organization that took in information from various sources, evaluated it, vetted it, collated it, and then disseminated it through our various channels, most notably our meetings and our journals. But ASCO itself did not contribute to the research enterprise. And that seemed to me to be a lost opportunity. We knew that ASCO had lots of data assets that could be of interest to our members and to the broader cancer community. But they were scattered all around the organization and not particularly well annotated or organized. So we began to collate those. And they are now available to ASCO members on the ASCO data library. I recognized that we did not have an organized unit in ASCO to support or facilitate or conduct research. So, in 2017, we formed the Center for Research and Analytics and brought together staff who were already working at ASCO but scattered in different departments but all people who had an interest in clinical research or research policy and brought them into this new unit, which has really become the focal point for research work at ASCO. We recognized that ASCO members for many years were interested in surveying their colleagues, surveying other ASCO members, to help advance research questions. But ASCO actually had a policy that prohibited that. So that never really made good sense to me. It seemed like a lost opportunity. And we were able to create a program and have the ASCO board approve it whereby any ASCO member could opt in to participate in what we now call the Research Survey Pool. And in doing so, they are essentially agreeing to participate in research surveys conducted by their colleagues. So that program is now up and running. There are, I think, eight surveys that have been completed or are currently in the field. And this is now a service that ASCO provides through CENTRA to its members to enable them to survey their colleagues for research purposes. Most importantly, I think we saw an opportunity back in 2014 or 2015 to begin to learn from what our colleagues were doing in clinical practice as they began to deploy precision medicine. And there was a lot of genomic profiling that was going on at that time. It was revealing actionable alterations in roughly 30% or so of the tumors that were profiled. But there was a lot of difficulty in doctors and patients obtaining the drugs that were thought to be appropriate to treat the cancer at that particular time because most of those drugs would have to be prescribed off label. And there was not a sufficient evidence base to get them reimbursed. And, moreover, even if they could be reimbursed, there was no organized way to collect the patient outcomes and learn from their experiences. So that led to us developing ASCO's first prospective clinical trial, TAPUR, which really solves both of those problems. Through the participation of the eight pharmaceutical companies that are engaged with us in the study, we are providing-- at one point, it was up to 19 different treatments free of charge to patients. These are all marketed drugs but used outside of their FDA-approved indications. And we were collecting data on the patients, the genomic profile of cancer, the treatment they received, and their outcomes in a highly organized way. And so now this is a study that we launched in 2016. We're now almost to 2021. We have more than 3,000 patients who have been registered on the study, meaning consented to participate, more than 2,000 who have been treated on the study. And we are churning out results as quickly as we can about which drugs are used or not useful in the off-label setting for patients whose tumors have a specific genomic profile. So we built all this infrastructure. And having this in place has also then allowed us to respond rapidly to unmet needs. So when the COVID-19 pandemic overwhelmed all of us, and when our members were looking for information about what was the impact of COVID-19 on their patients, one of the things we were able to do because we had CENTRA, because we had a skilled staff and an infrastructure, was to very quickly stand up the ASCO COVID-19 registry, which we launched in April of this year. And there are now about 1,000 patients who've enrolled in the registry from around 60 practices that are participating. And we will follow these patients now longitudinally and learn from their experiences what has been the impact of the COVID-19 illness on them and their outcomes, how has it disrupted their cancer care, and ultimately how that impacts their overall cancer treatment outcomes. So as I now contemplate leaving ASCO after eight years having started with a blank slate, I'm very proud of the fact that I think I'm leaving us with a remarkable infrastructure. We now have a clinical trials network of 124 sites around the country participating in TAPUR that we never had before. We have through the work of CancerLinQ a real-world evidence data generator that is beginning to churn out valuable insights. We have a capacity to survey ASCO members for research purposes. We have an ability to stand up prospective observational registries to gather information longitudinally about patients and their outcomes. We have a core facility in CENTRA with highly skilled data analysts and statisticians that can support these various research activities. So ASCO is now primed, I think, to really contribute in a very meaningful way to the gaps in knowledge that will forever exist in oncology just because of the complexity of all the diseases we call cancer. And that's what I mean by the ASCO Research Enterprise. It is in fact remarkable and, I think, powerful enterprise if we continue to use it effectively. CLIFFORD HUDIS: Well, that's an interesting segue to my next thought, which is really about what comes next. I'll talk about you. But let's start with ASCO first. Your successor, Dr. Julie Gralow, obviously has been announced publicly. She's an accomplished clinician and researcher. She has a known recognized passion for patients, patient advocacy, clinical research through her leadership at SWOG but also health care equity and global oncology. So from your perspective, having created all of these assets and resources, what advice would you give Dr. Gralow publicly on how to make the position hers, what to take us to next? And I do want to acknowledge for everybody listening that the hints I've been making up until now are that Rich has agreed that he will continue to contribute as a leader to TAPUR for the short term, at least, at least the next year helping Julie get fully oriented to this program and others. So what will your advice be to Julie? RICHARD SCHILSKY: That's a great question. She's a great selection. And congratulations on hiring her. I think there are two key issues, I think, maybe three. One is to have a broad scope and cast a wide net. Oncology care and cancer research and cancer biology are incredibly complicated and nuanced and broad in scope. And although Julie is an accomplished breast cancer clinician and researcher, in this role at ASCO, you have to be very broad. You have to understand all of cancer care, all of cancer research, all of policy and advocacy not as an expert in necessarily in any one aspect of ASCO's work, but you have to understand the impact of all of those things on cancer care providers and on cancer patients. And it's important to always be looking to the future. The future is going to be here before you know it. And we as a professional society have to prepare our members for that future. So that leads me to the second point, which is listen to the members. The members are the people on the front lines who are delivering care to patients every day. And, fundamentally, ASCO's job is to be sure that our members have all the tools and knowledge and resources that they need to deliver the highest quality care to patients every day. So listening to what they need, what their struggles are, what their burdens are, is extremely important. And then the third thing I would recommend to her is that she get to know the staff and colleagues that she'll be working with. ASCO has a remarkably accomplished, skilled, motivated, passionate staff, many of whom have been with the organization for years, if not decades, who understand what ASCO can and cannot do and who understand what our members need. And she will be well advised to spend a good portion of her first few months on the job just listening and learning from her colleagues. CLIFFORD HUDIS: That's always good advice for anybody making a big career move. But, of course, the wisdom you bring to it is palpable and much appreciated. And I'm sure Julie will be taking your advice. And, by the way, so will I continue to do that even after you make your move. So speaking of your retirement, can you share with us a little bit about what it's actually going to look like for you? Is it about family? Or are you still going to have some professional engagement? Again, I suggest that there might be some already, but maybe you could expand on it. RICHARD SCHILSKY: Yeah. I'm still fully focused on my work at ASCO. And, of course, as you know, when I wake up on February 15, I will no longer be ASCO's chief medical officer. And it's going to be a bit of a rude awakening. Fortunately, I will be able to continue my engagement with ASCO through the TAPUR study as you mentioned. I will, of course, forever be at ASCO member and a donor to Conquer Cancer and be willing to serve the society in any way. I have a number of activities that I've been involved with even throughout my time at ASCO. Not-for-profit boards, for example-- I'm on the board of directors of Friends of Cancer Research. I'm on the board of directors for the Reagan-Udall Foundation for FDA. I plan to continue with those activities as long as they'll have me. I've been serving the last few years on the board also of the EORTC, the large European cooperative clinical research group. And I expect to continue in that role. Beyond that, I will see what opportunities come my way. I think one of the things about retirement if you will that I'm looking forward to is the opportunity to pick and choose what to work on based on what interests me without having the burdens of having a full-time job. On the personal front, of course, we're all looking forward to crawling out from the pandemic. I've basically been locked in my home outside Chicago since March. And I'm looking forward to getting back out to a little bit of a social life. As you know, I have two grown daughters and now three grandchildren, two of whom are in Atlanta, one of whom is near by us in the Chicago area. So looking forward to spending time with them as well. So it will be a change for me to be sure after working as hard as-- I feel like I've worked for really now 45 years since I graduated from medical school. But I also feel like I'm not quite done yet and that I still have ways in which I can contribute. I just feel like at this point, maybe it's time for me to choose how I want to make those contributions and spend a little bit more time doing some other things. CLIFFORD HUDIS: Well, both you and my predecessor, Allen Lichter, are modeling something, have modeled something, that I think is not often discussed but can be very important. For people and for institutions, change is not a bad thing. And setting the expectation that you will pour your heart and soul into something but not necessarily do it alone or forever and not prevent others from taking that role at some point, that's a really-- I think it's a selfless kind of sacrifice in a way. Because, of course, you could stay and do what you're doing for longer. But as you and I have discussed, there is a value for all of us collectively in having fresh eyes and new people take organizations in a new direction. That's how I ended up here frankly. And I think that's the kind of opportunity you're creating right now, something that should be celebrated in my opinion. RICHARD SCHILSKY: Well, thanks. And I couldn't agree more. When I look back at the arc of my career and having all the different kinds of leadership roles that I've had, I basically have made a job change every 8 to 10 years. I was the director of our cancer center for nearly 10 years. I was associate dean for clinical research at the University of Chicago for eight years, another position that I created from a blank slate at that institution. The exception was serving 15 years as a CALGB group chair. But that was a position I really loved and enjoyed and felt like at the end of the first 10 I hadn't quite accomplished everything I wanted to accomplish. But the point is that I think it is both necessary for organizations to have regular leadership change. And it's also refreshing for us as individuals. There gets to a point where you feel like you can do your job in your sleep. And I actually think that's a good time to make a change. Because if that's the way you feel, you're not being sufficiently challenged. And you're probably not being sufficiently creative. And so it's a good time to move on and refresh your own activities and give your organization a chance to bring in someone to hopefully build on whatever you've created and bring it to the next level. CLIFFORD HUDIS: Well, I agree with all that, although I think your comment there about doing the job in your sleep would not apply because I'm pretty confident that the environment and opportunities have continued to evolve in a way that has made it interesting from beginning to end. But you don't have to rebut me on that. I just want to thank you very, very much, Rich. As we set up this podcast, I expected that we would have a really fun and enlightening conversation. And, of course, you did not disappoint. We could talk for much, much longer if we only had the time. On a personal note to you and for the benefit of our listeners, I want to share that Rich has been for me a remarkable friend and mentor and colleague. I first met Rich at the very beginning of my career when my mentor, Larry Norton, pushed me out from Memorial into the larger world. And he did that first and primarily through ASCO and the Cancer and Leukemia Group. Those are really the two places where I was exposed to the world. And through the CALGB, Rich really began to offer me and others, many others, opportunities that shaped careers plural, mine and others. So when I got to ASCO as CEO, Rich was there. And I knew I could always depend on you to be clearheaded, intellectually precise, constructive, visionary. And the thing about you, Rich, is that you never would say yes to anything unless you knew for sure you could do it and indeed, I think, how you could do it. I always share this story which your staff at CENTRA pointed out to me. And I have to admit that I hadn't picked it up myself. But in all the years of now working down the hall from Rich, probably hundreds and hundreds of hours of meetings, he never has taken a note in front of me. And, yet, everything we talk about, every action item we conclude to pursue, they all get done. So I don't know, Rich. You have a remarkable way of organizing your thoughts and your plans, keeping it together, and getting things done. And I'm going to miss that tremendously in the years ahead. So, Rich, I want to say congratulations. Congratulations on reaching this really important milestone in your life. Thank you on behalf of ASCO and the broader oncology community and the patients we care for and their families for making the world a better place. And just as a small thing, thank you for joining me today for this ASCO in Action podcast. RICHARD SCHILSKY: Thank you, Cliff. It's been great. CLIFFORD HUDIS: And, for all of you, if you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. And, while you're there, be sure to subscribe so you never miss an episode. The ASCO in Action podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. Until next time, thank you for listening to this ASCO in Action podcast.
Dr Hayes interviews Dr Ganz on pioneering quality of life studies. PRESENTER 1: 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. PRESENTER 2: Welcome to JCO's Cancer Stories: The Art of Oncology, 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 role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. DANIEL HAYES: Today, my guest on the podcast is Dr. Patricia A., Patti Ganz. Dr. Ganz has been a pioneer in establishing an entire field in our discipline, the discipline of survivorship. And really, this has been based on studies of quality of life and toxicities of therapy in patients with established active cancers that Dr. Ganz was involved with for really, the last four decades. Dr. Ganz was born and raised in Los Angeles. She received her undergraduate degree at Radcliffe, graduating in 1969. And correct if I'm wrong, Patti, I understand you were in the last class before the merger with Harvard. But I see you got your degree from Radcliffe and Harvard. So she received her medical degree and completed her residency and incidentally was chief resident and then medical oncology fellowship, all at UCLA. She then joined the faculty at UCLA and spent much of the early part of her career at the UCLA associated VA hospital. In 1992, she moved back to the mothership where she is now professor of medicine in the David Geffen School of Medicine, a professor of health policy and management in the Fielding School of Public Health, a distinguished professor of medicine and health policy and management, and the associate director for population science research in the Johnson Scott Comprehensive Cancer Center, again, all at UCLA. Dr. Ganz has authored over 400 peer reviewed papers, way too many chapters and reviews for me to recount here. And since 2017, she served as editor-in-chief of the Journal of the National Cancer Institute, one of the leading journals in oncology. She has an enormous list of honors that, again, is too long for me to go through today, except for a few I'd like to highlight. She's received two of ASCO's highest honors, the American Cancer Society award in 2008, and the Joseph B. Simone award for excellence in quality and safety in the care of patients with cancer in 2016. She was also the recipient of the Ellen L. Stovall award for the advancement of cancer survivorship care. She was a founding member of the National Coalition of Cancer Survivorship, and she was inducted into the Institute of Medicine, now designated the National Academy of Medicine, in 2007. And she's really played a major role in the efforts of the Academy to improve quality of care in medicine and particularly in oncology. Dr. Ganz, welcome to our program. PATRICIA GANZ: Thanks, Dan. It's great to be with you. DANIEL HAYES: So just to start out, there are so many things I'd like to talk to you about. One of those, in my opinion, you've been the epitome of role models for women in academics. And a lot of this series has mostly been men, because it was mostly men who started a lot of what we do way back 40, 50, 60 years ago. I know you grew up in LA. What shaped your decision to go into medicine in the first place, and then to stay in academics? PATRICIA GANZ: I went through college at Harvard and Radcliffe in a very turbulent time, in the late 1960s. Social issues were very important to us then, political issues just as they are now. And I was a biology major. And I was thinking about what I would be doing in the future. And for me, I really felt that I had to do something connected with people. And that was part of my decision. But of course, I had a major influence from my father, who was a physician. He actually went to the University of Michigan. And he always encouraged me to think about medicine, although he said ophthalmology, radiology, those are good careers for women. So you know, I had this lurking in the background. I didn't want to necessarily do exactly what my parents said to me. My mother was someone who also had been working in a family business for many years. So I had them behind me saying it was possible to have a career and to move forward in medicine. And of course, summers, doing various kinds of research that was involved with a potential career in medicine. So it wasn't a big surprise. Now why did I come back to LA? I guess that's a good question. Nowadays, when people actually are applying to medical school, I think they apply to 20, 30, 40. In those days, I think I only applied to six, if you can believe it. And three of them were UCs, and three or four of them I guess where on the east coast, or Northwestern with another one. It was a tough time. It was just on the feminist movement, also social change in terms of more African-Americans being admitted to medical school. And it was a tough time for those who were underrepresented, such as women. And in fact, at Harvard Medical School, I think family took 10 women. UCSF maybe took seven or eight women, where I'd gotten accepted there. And when I finally went back to school at UCLA, there were only three women in my class. So again, quite a striking difference than the way things are now. But I did come back to LA because UCLA was pass/fail. Having heard about the competition and medical school people being pretty cutthroat, I said, mm, probably good to go to a place where that wasn't the big issue. In addition, I actually met my future husband in a lab, working in a lab before my senior year in college. And I guess that might have been a motivation as well. DANIEL HAYES: And have you seen major change in attitudes regarding sex/gender in academics now? Do you feel that we've really made advances, or is it all just covering of a system that still exists? PATRICIA GANZ: I could speak for an hour on that, so I'm not going to do that. But I have to say that being a minority in the class was not unusual. Because at Harvard and Radcliffe, there were 300 women in my class at Radcliffe, and 1,200 men. And obviously, in the science classes I took, the women were in the minorities as well. But for women at that time, getting into medical school, they were actually a lot smarter and a lot better than the men because we were highly selected. However, my class, the three women-- one was me coming from an elite Ivy League school. One was a blonde valley girl who was coming from a California State University and another was a Korean immigrant. So we were all quite diverse-- yeah, even then. But by the time I graduated, we had a few women who transferred in. And actually, my husband who was a physicist at that time, went to medical school at UCLA five years later, and his class had about 25% women. So things were rapidly changing then. DANIEL HAYES: So I understand you really started doing hospice care when you were at the VA initially. And how has that colored what you ended up doing in terms of your career? I mean, in the 1980s, there wasn't a lot of hospice care. It must have made you think about and led to what you're doing now, what you've done. PATRICIA GANZ: That's an excellent question, Dan. And it was actually the late-- 1978, where I joined the faculty. And the chief of medicine said, you know, we have this kind of intermediate care unit. We'd like you to start a hospice for our oncology service, et cetera, et cetera. And there was actually a national hospice randomized trial that was going on at one of the other VAs here in Los Angeles. And having come out of my oncology training and thinking about it, I really thought well, you know, lot of those things that we're offering people at the end of life, like pain control and psychosocial support and things like that, we should really be doing that earlier for people. Because why should it just be reserved for those last few weeks? And so as I develop my unit at the VA, I actually called it a palliative care unit, a palliative care ward. Because at the VA I worked at, we had patients who actually often were in the hospital for five or six weeks getting their radiation, traveling by bus to the radiation facility. So they would be in for five days a week and then go home on the weekends. And these-- again, this was 1978, what were we seeing? We were seeing lung cancer. We had men with widespread prostate cancer who needed palliative radiation to the bones. We had a lot of colon cancers. So I was taking care of those patients. And while they weren't in imminent need of end-of-life care, they had trajectories which clearly were not good if they had advanced cancer. And it seemed reasonable-- I had a wonderful team, a physiatris, a psychologist, a social worker, even the pharmacist made rounds with us. It was just wonderful. And I essentially took all of the things that the palliative care end-of-life focus that hospice used and brought it up to the earlier part for some of these patients who, in fact, could be cured. I can think of someone who had localized small cell carcinoma who I took care of for many, many years. He was in getting chest radiation and whole brain. And you know, he lived a long time but he got all the tender, loving care that our nurses and our team were able to provide early in his course. DANIEL HAYES: You know, it segues really into my next question, which is in my own training, in the early 1980s at the Dana-Farber, especially led by Dr. Fry, Tom Fry, who's one of the fathers of medical oncology. We were really trained to learn how to treat and hopefully cure cancer. And there was very little regard to the toxicities. Dr. Fry used to tell us, cure the cancer first, we'll figure out the toxicities later. And at least the shackles begin to fall from my eyes as I began to see what you and others started to say. Well, you know, these people are going to survive. We need to worry about that. And personally, I think you almost-- not quite, but almost single-handedly taken our field beyond just treating the cancer, but worrying about the quality of life of survivorship. When you were starting that, either at the Bay area or when you went back to the main campus, what were the hurdles? Were there people who told you, you were wasting your time? Most have been told this is a fool's errand. You'll never get promoted by doing this kind of research. And you have done OK, I think. PATRICIA GANZ: Yeah. You know, I actually wanted to even go back to my training, you know? Because in the late '70s, there was actually-- in my heme/onc division, it was mostly liquid hematologists who were the leaders. And there were one or two solid tumor oncologists. And because I was interested in medical oncology primarily, I was the mentee of this person in his clinic. And essentially, what happened-- this was in the early days of adjuvant TMF chemotherapy. And you know, I was giving women chemotherapy for 12 months. And they didn't want to take it. They wanted to stop because of the toxicities of treatment. And he typically had me see those patients who needed that kind of support and symptom management and things like that, which were rather primitive, obviously, at that time. Because he was very technocrat in terms of knowing the literature and making those kind of decisions about therapy, but not managing all of this. So because of this collaborative relationship in his clinic for a couple of years, that's essentially where I began to see these issues because patients felt comfortable talking to me about it. Early on actually, at the VA, I was very fortunate, first of all, just to say I was a biology major in college. I never took a psychology class, ever. I took maybe a sociology class, which was on China at the time, but really wasn't trained in behavioral science. And I was very fortunate because there was a psychiatrist who was very interested in understanding the impact of cancer and its treatment on patients. And again, mind you, the five year survival was less than 50% at that time. And certainly, for the patients we saw with lung, colon, prostate that was metastatic, very much shorter. And he got a grant from the VA to do an intervention trial in the veterans and their spouses. But in order to be able to understand what patients were experiencing, Ian, the psychologist he hired as a project director, said, well, we've really got to interview patients and talk to them and find out what they're dealing with. And the psychological or psychosocial literature at that time was rife with issues related to coping. And coping is a concept that is not easy to explain to people. And certainly, it isn't necessarily universal in terms of many cultures. So it was difficult, then, to kind of operationalize this. And again, because I work with this great team, they began to interview our patients in clinic, and really, in detail, understood the day-to-day things that people were dealing with in terms of their cancer and the side effects from the treatment and their social relationships. And then we, all of a sudden, began to think of ourselves as a multidisciplinary team. And in fact, the person, Joe Collin, who was the associate director for population science at the Cancer Center at that time at UCLA, kind of said, gee, you make the ideal multidisciplinary team, you know-- a psychiatrist, a psychologist, and some medical oncologists. And it was from that time forward, that we began working together and I got my first grant. And really, they taught me so much about measurement, reliability, and validity. And in fact, we published our first paper together in JCO the second volume, which was on the Karnofsky performance status we visited, where they compared their ratings of the Karnofsky with my ratings of the Karnofsky for the clinic patients. And because they did a systematic interview about what patients were experiencing, noted that the function of patients was much worse than what I as even a sympathetic clinician would rate them. So that was really so important for me and working with them. And again, I think that's been the hallmark of my career to have had so many psychologists and psychiatrists, behavioral scientists, who embraced working with me, partly because I gave them access to patients if they wanted to study them, but I was also interested in really understanding, in a very rigorous way, how we could measure some of these things. DANIEL HAYES: Yeah, that raises another issue. In my career as a clinical investigator and translational investigator, pretty much inherited the tools to do what I want to do, how to do a clinical trial. It's always struck me that you, and I guess, Charles McKinsey and others had to make up your own tools, basically, to get it out of the realm of touchy-feely, if you will, and into the realm of true quantitative science so you could describe what you've done and how you've done it. How did you go about building those tools? PATRICIA GANZ: So again, a lot of these strategies or approaches to measurement were available in the social science literature. And they were just beginning to be translated into medicine. And again, this goes back to when I was training at UCLA. The Rand Health Insurance Experiment was going on in the '70s. My attendings in clinic were all involved in that. And John Ware, who was a great psychologist/methodologist, developed huge measures to look at patient outcomes in that big insurance experiment trial, which then got adapted into many other instruments that are widely used, such as the SF-36, and more recently, the Promise measures, which are publicly available. So I kind of was-- again, I had these kind of parallel streams of exposure. Health services research was very prominent at UCLA. These were my clinic attendings. And there was a very robust community of health services and health outcomes researchers. So I saw myself as kind of being an oncologist who could use those methods and apply them to the cancer problem. And there certainly weren't too many people out there. In addition, I had good fortune to begin to work in the cooperative groups, Ware and SWOG, with someone like Carol Moinpour, who led the efforts there in terms of patient-reported outcomes for many years, and then actually had a sabbatical in Switzerland, working with some of the IBCSG people and really having a time to just self-educate myself about this methodology. So I'm really self-educated, but have had wonderful collaborators who have kind of held my feet to the fire and said, you know, that's not rigorous enough, on occasion, certainly. DANIEL HAYES: So you were doing team science before the word came up, before the term. PATRICIA GANZ: Yeah, exactly. Certainly, when you have certain gaps in your knowledge, you need those collaborators. DANIEL HAYES: You know, this brings up-- I alluded to her just a moment ago. But when I think of cancer survivorship and quality of life, I think of you. But I think a lot of the late Jimmie Holland, who sadly passed away before I was able to interview her for this series. Can you just-- I think maybe some of our listeners don't know of her, haven't heard of her. We've got a lot of people young people listening to this. Can you just give a little background about Dr. Holland and the things she did? PATRICIA GANZ: Sure. Dr. Holland was a psychiatrist who really invented the field of psycho-oncology. And really, because she was working almost always in a cancer hospital, cancer setting-- I believe first at Roswell Park with her husband, James Holland-- she began to notice the neglect, if you will, of the impact of the cancer on the whole person and on the psychological aspects of cancer. And because of her being within a cancer hospital setting and then later moving to New York and obviously leading this effort at Memorial Sloan Kettering-- and really being very involved with CALGB and now the Alliance-- was able to introduce very early into the cooperative groups, the need for not just looking at the disease and its treatment, but to look at the after effects or show what were going on in the patient and how they were dealing with the illness. And she actually developed one of the first collaborative groups in psycho-oncology, which had people like Gary Morrow, who's at Rochester and who's had one of the big ENCORE research bases and has really continued to carry on a lot of psycho-oncology research across the country. Following what was really an early innovative approach, she developed a whole training program at Memorial. She trained many outstanding psychologists, psychiatrists working in this field and textbooks. I had the good fortune to work with Julia Rowland for a number of years. Julia was a direct descendant, if you will, Dr. Holland, having been at Memorial working with her and leading some of their early survivorship work. But she just trained probably more than a generation of people to take this seriously. As I kind of mentioned in an email to you, just as I would go to the ASCO meeting to listen to what Dr. Fisher or Dr. Bonadonna had to say, because I was interested in breast cancer and it was very exciting to hear the new reports of adjuvant therapy, I would also go to hear her and to Barry Castle, who was another leader in the field at the University of Pennsylvania, who basically were bringing rigor and clinical expertise to characterizing the patient experience, and publishing papers often in high profile journals like the New England Journal. So they were really role models for people who wanted to go into this field, although they weren't oncologists. And I think that's where I had kind of a double opportunity. Number one, I was perceived as a card-carrying oncologist. I was treating patients. I was in a cooperative groups. I was involved in trials, but I was also saying what about this secondary objective to our trial to look at the experience of the patients? So having entree to the patients, being perceived as one of the oncology community was, again, a really good thing to do. Although I must say that there were dozens and dozens of conferences where I was the last speaker on the program because quality of life was down there at the bottom-- not so much anymore. DANIEL HAYES: Your stories are great. I have one brief anecdote again, for the younger listeners. Jim and Jimmie Holland where as different as night and day. And Jim Holland, who was one of the three guys with Dr. Fry and Dr. Freireich-- who decided to put two drugs together and suddenly, we were able to cure some cancers-- was blustery. You might even call him a blowhard. I loved him, but I will never forget as a very junior person in CALGB, and I was appointed to be chair of a committee. And I was running my first committee meeting-- and needless to say, I was nervous anyway. And all of a sudden in the back of the room, Jim Holland, without a microphone, screams out something about, Hayes, if this is the way you think it's sounding, when I'm reading to you now, duh, duh-- so I went ahead and got through the reading. And later, Jimmie walked up to me and said, you know, he really loves you. His bark is much worse than his bite. PATRICIA GANZ: No, and you know, I think the early days of oncology were so much like that. Because again, we would have these wonderful people come to the microphone and ask a question. In the case of Dr. James Holland, he didn't need a microphone. But the point is, that we actually saw these people in real life, posing questions, challenging sometimes what was presented in a meeting, but also being very collaborative. And I think it was wonderful. And I think it's good that we have-- you know, our meetings today, obviously, are quite different because of the pandemic. But in our large meetings, we have scheduled discussions which is good, but it doesn't have the same spontaneity that we obviously were fortunate to experience in an earlier time. DANIEL HAYES: Yeah, I agree. You know, I think probably, of the many, many contributions and things you're known for, I believe your role in the Institute of Medicine then, now the National Academy of Medicine, regarding survivorship may be your greatest impact on what we do. How do you think that's translating now, to use the word translational science, which it really is? And when I was present, I was struck. There are probably 15 million cancer survivors in the United States right now. Have we really changed how they do based on your report, or is that falling on deaf ears? What do you think's going on with that? PATRICIA GANZ: Well, you know, there's several things that have happened. So the report that was in 2006 was led-- actually, Ellen Stovall was actually one of the co-leads of that committee. And you know, that was very seminal in that it was-- it's called the lost in transition report. And it really called out-- at that time, there were 10 million survivors, and that this whole large body of the population didn't really know, didn't have much direction about what to do after treatment and were kind of lost, because the oncology care system didn't really give them any guidance. And if somebody went to their primary care doctor, they would say, uh-oh. I don't know what that's about. You go talk to your oncologist. And then the oncologist would say, oh, that's a weird symptom, but it's not-- you know, you don't have any evidence of disease. That would be the typical thing. But it was usually an ongoing long-term effect of the treatment or possibly a late effect that was emerging, you know, such as a cardiac problem or a neurological problem that might be a secondary to previous treatment. And so the patients really weren't getting good care. And they kind of said we need there to be a group of people-- whether it's an oncologist or someone else-- who will take an interest and really tell us what do we need to be on the lookout for. And that was kind of a way to say, we need an end-of-treatment discharge summary. And it became actually very apparent. I was on the ASCO board actually during that time with the NICCQ report. I don't know if you remember that, but it was a report that ASCO did looking at the quality of care for breast and colorectal cancer patients. And what they found was you could find the op report from the surgeon. You could find the radiation therapist's summary note. But the chemotherapy flow sheets-- and this is, again, before electronic records-- were the only way you could even find out if somebody a series of treatments. And that went on, sometimes, over several years. So there was kind of no summary after the medical oncologists finished their treatment. So they try and figure out, even if you were the treating physician many years later and you needed to retreat someone, it was hard to know what was happening. So in some ways, the treatment summary and care plan had two roles. One was to say, well, what did they actually get? And the patient should know what they got in case many years later, you find out there's the late effects. But also, what do we need to look out for? And so really, again, building on what the childhood cancer survivor people had been doing for many, many years in terms of long term and late effects, this became an issue. Now Ellen Stovall, who was really focused on quality of care for cancer patients, and again, unfortunately, passed away a few years ago from complications of her Hodgkin's disease, really wanted there to be treatment planning and not just the treatment summary and care plan at the end of treatment. So I was actually fortunate in 2013 to lead another-- to lead, at this time, a report on quality of care and quality of care for cancer patients. Because Joe Simone had done one in the late '90s, and this was kind of a catch-up report. But it was also focused on the large and growing number of cancer patients, and many of them older. And with the baby boomers going into an age where cancer is very common, you know, how was our health care system going to approach this? And so we were, in that report, in many ways, echoing what had come about in the earlier survivor report, but saying you need to do this right from the very beginning. And it is very important for survivors. If we're going to be worried about fertility preservation, we need to do it right upfront. If we're going to be worried about potential complications in terms of cardiac toxicity occurring later, we need to be thinking about it in terms of planning the treatment for patients so that maybe they don't need to get chest radiation if they're a lymphoma patient. But chemotherapy and the very targeted therapies and the sensitive PET scans might help us avoid using unnecessary radiation to those individuals. So it has to be upfront thinking about what's going to have happen afterwards. And as part of the 2013 IOM report, we basically had many different recommendations which were kind of, I would say-- I kind of want to say pie in the sky, but futuristic. And one of them was that the insurers-- primarily Medicare, but other insurers-- should insist on patients having a treatment plan at the time of diagnosis, that their needs should be met, that they should have an understanding of the financial impact of the treatment decisions they're making, and that this should be part of a quality of care assessment strategy. And again, the thought was OK, maybe three, four, or five years from now, that will come about. But lo and behold, a year later, CMS picked this up and we had the development of the oncology care model, which in essence, took from our report the 10 or 13 point items that need to be part of initial coordinated care, which also included our survivorship care plan and treatment summary at the end of treatments. So I think to me, actually, that's one of the most significant accomplishments because now I see there's going to be a second version of the oncology care model, that many practices across the country have adopted these things. And as they've been part of the oncology care model, they're delivering this care to everyone, whether patients are insured by CMS or a private insurer. So I think this is an example of how long it takes to implement anything. Again, part of what I see our role, or my role as a health services researcher, is implementation science. If we know what works and what's important, it may take 15 years before it happens, but you need something like CMS to have a bundled payment plan. Or in the case of the treatment summaries and care plans, we have the American College of Surgeons who have championed that. And without these external regulatory policymaking organizations and payers, we don't get a lot of change. A long-winded answer, but to me, that's where the rubber hits the road. DANIEL HAYES: Well, I agree completely. I think that'll be your legacy, among many things. I mean, isn't it also part of the QOPI designation for QOPI accreditation in ASCO, isn't the survivorship plan? PATRICIA GANZ: Yes, the treatment summaries and care plans. I don't know-- I haven't seen any data. Recently, when I was more involved with the ASCO quality care committee, I saw some of those results. I don't know how compliant or adherent people are. But actually, part of the complaints that people have had has been, oh, it's hard to do this treatment summary. But if you actually start out with your initial treatment plan-- and we're actually doing this now on our Epic system at UCLA. There's something called the oncology history. And if you actually begin documenting from the beginning of treatment, you can actually move toward a treatment summary that's easily generated from the electronic record. But it's hard when you have to go back and do it retrospective. DANIEL HAYES: I was going to say, for all the young people who, at the end of a very long day, find themselves also having to do this long-term care plan for their patients, you could blame Patti Ganz for the work she started 30 years ago. PATRICIA GANZ: Yeah, OK. DANIEL HAYES: Actually, in the few remaining moments we've got, I want to bring up your new role as editor-in-chief of JNCI, the Journal of National Cancer Institute. I believe that you and Dr. Disis are the first women who have been editors-in-chief for major oncology journals. In fact, I don't believe it, I know it. You've been in the role now about three years. JNCI has always sort of had a niche that the other journals don't cover very well, in my opinion, and that they do. In taking it over, what are you keeping and what's your vision for the way you'll mold it in new ways and take it in new ways? PATRICIA GANZ: So I've been very fortunate, I was-- you know, I actually had a lot of experience at JCO as an associate editor for many years. And then I was also on the editorial board, and then deputy editor or associate editor and deputy editor of JNCI for quite a while as well. And Carmen Allegra took it over when Barry Kramer stepped down seven, eight years ago. And I knew Carmen from NSABP and RG. We had worked together closely. And I was kind of amazed when he took it over with all the obligations that he had as head of a heme/onc division and other roles, both leading gastrointestinal cancers at the NCI and NSABP Foundation. So he was doing a lot, and I thought, oh my gosh, you know? This is a difficult job to do as well. He basically moved the Journal a bit more towards a clinical perspective. And again, the history really is that JNCI was one of the first cancer journals. And maybe there was cancer research, but it was one of the first journals. And it essentially covered everything from soup to nuts, a lot of basic science. If you go back and see some of the highest cited papers, many different fundamental assays and so forth were published in JNCI. But if you look at the space in oncology, now there are 240-250 cancer journals so that we have many more outlets where some of the more basic science and translational science-- certainly, AACR has many wonderful journals-- so that we actually moved away, I think with Carmen's tenure, from the more basic work. And we really are taking almost no basic work. Things have to be clinical, in a sense that there has to be a translational component, cell line studies. And in vitro and animal models are not something that we're covering anymore. And again, that's a transition that I think occurred in prior years. I'm certainly continuing that. But I think because of my interest in breast cancer, obviously, and outcomes research in psychosocial work, we get more of those papers than perhaps when Carmen was the JNCI editor. But it's stiff competition, you know. We've had a strong epidemiological bent. We still get a lot of epidemiological and genetics papers. And I guess when I think about what I'm doing, it's really cancer prevention and control. That's what I've been doing for over 25 years, both in my academic research leadership position at UCLA, in my own research, and it's very broad. It's really applying all of the disciplines, if you will, of public health to the cancer problem, which means epidemiology, biostatistics, behavioral science, health outcomes research, you know, all of these things-- environmental science. All of these things are very important in both the etiology of cancer, the prevention of cancer, as well as the management of cancer. And so it's this cancer prevention and control swath that I think is our niche, if you will. So it's not as narrow as some journals. We're not just doing clinical trials, although we have them. But we're trying to have the broad scope of cancer prevention and control. That's pretty much how I see it. DANIEL HAYES: OK, thank you so much. Our time has come to an end. I can't tell you how much I appreciate your taking time to talk with us today. But more importantly, taking time to change the field of oncology in the way you have over the last 40 years. I think a lot of the things that our doctors are doing in clinic every day are a direct result of one person, and that's you. And there aren't many people who can say that. So thanks for all you do. Thanks for all your contributions, and I very much appreciate your sharing your history with us today. PATRICIA GANZ: Thanks so much, Dan. It was really a pleasure to speak with you and share what I've learned over time. Thanks so much. PRESENTER 2: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories: The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.
Dr. Hayes interviews Dr. Mayer on his training at NCI and running DFCI’s fellowship. 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. Welcome to JCO's Cancer Stories-- The Art of Oncology, 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 role of cancer care. You can find all of these shows, including this one, at podcast.asco.org. Today, my guest on this podcast is Dr. Robert J. Mayer. Dr. Mayer is the Stephen B. Kay Family Professor of Medicine at Harvard Medical School where he is also the Faculty Associate Dean of Admissions, in addition, the faculty Vice President for Academic Affairs for Medical Oncology at the Dana-Farber Cancer Institute. Dr. Mayer was raised in Jamaica, New York. And, Bob, I always thought you were raised in Brooklyn, but I looked it up on the map. And it looks like Jamaica is about two blocks in the middle of Brooklyn. So we'll say you're from Jamaica. Actually, I was a little bit to the east of there in Nassau County. That counted a lot then, Queens versus Nassau, but anyway. So it gets even more esoteric. Bob received his undergraduate degree in 1965 from Williams College, which is way out west in Massachusetts, and then went to Harvard where he got his MD in 1969. He did his residency in internal medicine at Mount Sinai in New York City and then was a clinical associate in the medicine branch of the National Cancer Institute from 1971 to 1974. He served a fellowship in medical oncology at what was then the Sidney Farber Cancer Institute. And then he joined the faculty in 1975. He has spent much of his career at leading clinical research in leukemia and GI malignancies. He was the chair of the CALGB, now called the Alliance TI Cancer Committee for years. But, perhaps more importantly, he was director of the fellowship program at, originally, the Sidney Farber and then the Dana-Farber Cancer Institute for 36 years. And then he was also head of the fellowship program at the Dana-Farber/Partners cancer program from 1995 until 2011. And, frankly, he was my fellowship director from 1982 to 1985. So I owe a great part of my career to Dr. Mayer. He's co-authored over 400 peer-reviewed papers and another 130 chapters and reviews. He serves as associate editor for both the Journal of Clinical Oncology and The New England Journal of Medicine. And, as have many guests on this program, he served as president of ASCO, in his case, in 1997, 1998. And he received the ASCO Distinguished Achievement Award in 2019 for his ongoing leadership in our society. Dr. Mayer, welcome to our program. Pleasure to be with you, Dan. So I have a lot of questions. And, again, I usually do this, you know, two guys in a cab. How did you do that in the first place? What got you interested in oncology coming out of Williams and at Harvard? And, at that time, there wasn't much in oncology. What made you want to take care of cancer patients? Well, I was a third-year medical student at Harvard sort of sleepwalking through the curriculum, undecided what my life was going to be, planning to go back to New York, and I came across an attending physician on a pediatrics rotation, a hematologist by the name of David Nathan. And we hit it off. And I became really interested in blood cells and how looking at smears and bone marrow morphology could tell you a lot about the status and health and nutrition of individual patients. Nathan took a shine to me. And, when I was a fourth-year student and was going to face probably a military service, and there were military actions going on in Southeast Asia, he called me to his home one night and shoved a whole pile of paper in front of me, said fill this out. I want it back tomorrow. And this was an application to be a clinical associate at the National Cancer Institute where he had spent several years I guess a decade before. So I did what I was told. And, when I was a intern, I guess my first day as an intern, I got an overhead page from the-- in the hospital, call from Bethesda informing me that I had been accepted. I had had 10 or 11 interviews. One of them turned out to be a person who would be important in my life as a friend and a mentor, George Canellos, who was first time I met him. And, in 1971, I found myself at the NIH. That's quite a story. And Dr. Nathan, of course, went on to start the Jimmy Fund, probably had already started the Jimmy Fund Clinic at the time, and became the CEO, I think, of Children's Hospital in Boston. He became the CEO of Dana-Farber actually. I do want to just recollect with you my first day or two in Bethesda because some of the people who found themselves there took it more seriously than others. And I was assigned to the medicine branch. And the medicine branch had a chief who was a breast cancer-oriented investigator by the name of Paul Carbone who went on from there to an illustrious career as the founding head of the Cancer Center at the University of Wisconsin and the leader of the Eastern Cooperative Oncology Group. And Paul, at that point, the first day I met him, told us that, if we messed around, moonlighted, didn't show up, we'd be on a Coast Guard Cutter as fast as he could do the paperwork because, technically, we had a position in the Public Health Service. Under Carbone, there were two branches. One was leukemia, and that was headed by Ed Henderson. He was a lanky guy from California, a wonderful man, went on to a career with Cancer and Leukemia Group B and with the Roswell Park in Buffalo for many years. And he was my branch chief. And the other branch was solid tumors. They weren't solid tumors like we think of them today. They were lymphomas. And that was headed by Vince DeVita and had Bob Young, George Canellos, Bruce Chabner, and Phil Schein, all illustrious founders of so much that has become oncology. So that was the setting. And the last thing I'll mention was about this. I came there as a trained internist, but I was assigned to pediatric leukemia. And I learned very quickly that what separated the wheat from the chaff, in terms of families, parents thinking that you were a good doctor, was your ability to maintain the 25 gauge scalp vein as venous access in these children because there were no port-a-caths, no Hickman lines, and, obviously, access was something that was critically important. You know, I think everybody who is listening to this needs to understand that what you just described started out really with just Gordon Zubrod who then brought in Frei, Holland-- or Holland first and then Freireich. And then they brought in the next group, which I believe you would agree is Canellos, DeVita, Bob Young, and others. And then you were sort of in the third wave. And you could just see it began to expand the whole field of oncology really just from a few people going out. Do you agree with that? I do. I do. When I came to the NIH in 1971, there was no defined, certified subspecialty of medical oncology. The first time the medical oncology board examination was given was in 1973. It was given every other year. I was in the group that took it the second time in 1975, but this really wasn't a subspecialty. In 1973 also was the time that the first comprehensive multi-authored textbook on medical oncology was published by Jim Holland and Tom Frei, Cancer Medicine. And I remember devouring that as I prepared for the board examination, but there was no book like that. There was no reference, no UpToDate, no computer to surf the web and find information. And so this was all brand new. It was quite exciting to be there as part of the action. You sort of jumped ahead on what I wanted to ask you, but I'm interested in the establishment of medical oncology as a subspecialty. Can you maybe talk about Dr. BJ Kennedy and his role in that? I think he was pretty instrumental. Was he not? BJ was at the University of Minnesota. He was an extraordinarily decent man. And, somehow, the internal medicine establishment viewed him as a peer and a colleague, which I would have to say was not what they considered many of the pioneers, if you will, in medical oncology. I can remember, in my second or third year at the NIH, traveling around the country to look at fellowship programs. And I was always being met by senior established hematologists who arched their eyebrows and said now where's the pathophysiology. Where is the science here? They really thought that the animal models, the mouse models, the Southern Research Institute that Gordon Zubrod had been such a pioneer in fostering was pseudoscience. I can also remember, when I found myself back in Boston, the establishment of Harvard Medical School didn't initially take oncology very seriously, but there were patients. And there was optimism. And all of us in that generation really believed that we could make a difference, and we could learn a lot and do good for patients and for medicine. And I think we have. So, in my opinion, now, appropriately, our fellows have a very strict curriculum of what they're supposed to learn and how and when and why laid out, again, in a pretty rigorous formal manner. You told me before, at the NCI, it was just sort of learn it. It's up to you. Can you talk about that training? And then, when you went to the Sidney Farber, you then turned that into a training program. The medicine branch was fantastic training, but it was learning from taking care of patients and from your colleagues. The quality of my peers was extraordinary, but there was no formal curriculum. The faculty there each were doing research, the members of the faculty. And, for a month, they would come out of their cave, if you will, their laboratory, and they were very smart and were doing fascinating things, but they didn't have long-term patients. Or there was no real process. And the NCI was sort of like a Veterans Administration hospital in the sense that it opened around 7:30 or 8:00 in the morning, closed at 5:00 or 6:00 in the afternoon. One of us would be on call at night with a couple of nurses, but it was rather primitive in its support mechanisms. We were assigned a group of patients. And then, on rotation, those patient numbers would increase. And we were expected to do everything conceivable for that patient. And, at that time, the oncology care offered in Bethesda at the NIH or the NCI was free. It was paid for by the government. And much similar care was not available in other places. So I would have patients flying in from Omaha and New York or Norfolk or Tampa, Florida. And they would be housed in a motel that was on the edge of the NIH reservation, but, if one wants to talk about continuity of care, you knew everything about every one of those patients because you were the only person who knew them. So what were the circumstances then that you ended up in Boston? Well, that's an interesting story because it gets back to David Nathan. I was working after my clinical year in a basic laboratory as I could find. It was run by Robert Gallo, Bob Gallo, who was one of the co-discoverers years later of the HIV virus. But, one day, I got a phone call from Dr. Nathan's secretary saying that he was going to be in Washington a week from Tuesday or whatever. And he wanted to meet with me in the garden of the Mayflower Hotel. OK, fine. So I trotted over to the Mayflower Hotel, and there was Dr. Nathan. And he said, you know, Dr. Farber is getting old, but there's a new building. And there's going to be a cancer center. And he's just recruited Tom Frei to come from MD Anderson. And it's time for you to come back to Boston. Didn't say would you like to come back, would you think about coming. No, he, just applied to the NIH, shoved the papers. Here, it's time for you to come back to Boston. So, a few Saturdays after, I flew up to Boston. And, in that interim, Dr. Farber passed away. He had a heart attack, an MI. And there was Tom Frei who I met for the first time, made rounds with him. We hit it off. And he told me that he would like me to spend one year as a fellow and then join the faculty and become an assistant professor. Well, I didn't need a plane to fly back to Washington. I thought this was tremendous because I was looking at hematology scholarships around the country. And there was no career path. And this seemed to be a career path in a field that I was really interested in. And he talked to me really about coming back to do leukemia because that's what I had been doing at the NIH. And, a year later, I found myself, July 1, 1974, being part of the second fellowship class at what's now Dana-Farber. There were six of us. There were six the year before. We were piecing it together step by step. There, again, was nothing chiseled in marble. There was no tradition. This was try to make it work and learn from what works. And, what doesn't work, we'll change. You must have had a lot of insecurity coming into a program that really had just started. There had to be chaos involved in that. Well, there was a little chaos, but, to be honest, I was really engaged in it because it was exciting. I thought that oncology, as I still do, is this marvelous specialty or subspecialty that unites science and humanism. And, because other people weren't interested or maybe weren't capable of providing what we thought was the right level of care, to be able to sort of write the playbook was a terrific opportunity. We sort of-- and it extended into the year that you were a fellow as well-- followed the medicine branch mantra in the sense that we assigned fellows patients. And they took care of those patients and were expected to do everything that was necessary for them. There weren't rotations at that time that you would spend a month on the breast cancer service and then a month doing lymphoma. You would see new patients or follow-up patients. We didn't really have enough patients or enough faculty at that point to be smart enough to think about that being a better way or an alternative way to structure a trainee's time. I remember, at the end of my first year, when I finished that year as what I think Tom Frei called a special fellow, I was the attending on the next day, which was July 1. And I remember that a fellow, a first-year fellow who was just starting, Bob Comis who became also the chairman of the Eastern Cooperative Oncology Group years later, a marvelous lung cancer investigator, was the trainee. And, on that day, we went ahead and did a bone marrow on a patient with small cell lung cancer and being a fellowship director just started because there was no one doing it. And Frei said please move ahead. I have to say, when I started in 1982, I just assumed this was the way everybody in the country was training fellows in oncology. It really didn't occur to me that that was only a few years old and the way you had set it up. A few years ago, the Dana-Farber had a banquet to celebrate the 48-year career of a guy named Robert J. Mayer. And I was asked to speak. And I got up. There were over 300 people in the audience, all of whom had been trained there. And, as I looked around, I sort of put my prepared words aside and said look at the people sitting next to you. They are either former or to be presidents of ASCO, ACR. They're cancer center directors, department chairs, division chiefs, and a bunch of really terrifically trained oncologists all due to one guy, and you're the one. So you started with Bob Comis-- I've never heard you tell that story-- to really training some of the greatest oncologists in the world in my opinion, myself excluded in that regard, but, nonetheless, you must be quite proud of that. Well, yes, but I want to flip it around the other way because, for me, this became a career highlight, the opportunity to shape the patterns, to make the people who trained here leaders, and to have them-- right now, the director of the NCI is a Dana-Farber alumnus. To have people who are of that quality-- and you certainly represent that, as an ASCO president and one of the hallmark leaders of the breast cancer community-- this is what a place like Dana-Farber and Harvard Medical School, hopefully, not too much arrogance, is supposed to be doing. And to have that opportunity, to be able to fill a vacancy that nobody even appreciated was a vacancy, and then to develop it over enough time that one could really see what worked and see what didn't work is an opportunity that most people don't have. And I'm so grateful for it. Now, Bob, I want to just, in the last few minutes here, you've obviously been a major player in ASCO. Can you kind of reflect over the last 25 years since you were ASCO president, the changes you've seen, and what you think of your legacy? I know you don't like to brag too much, but I think there's a reason you got the Distinguished Service Award. And can you just reminisce a bit about what's happened and then where you think we're going as a field? Well, ASCO has been my professional organization. The first meeting I went to was in a hotel ballroom in Houston, the Rice Hotel, which doesn't exist anymore. And it was a joint meeting of ACR and ASCO in 1974. There were 250 people. And everybody was congratulating each other at the large number of attendees. I had the opportunity, in large part because of Tom Frei and George Canellos and other people, to become involved in picking abstracts for leukemia presentations, being part of the training committee, and then chairing the training committee. I actually had the opportunity to be one of the four people who started the awards program, which now has the Young Investigator Award and Career Development Award and things of that sort. These are just opportunities because they weren't there before. And, if you're willing, and you put in the time, I guess people come back to you and give you the chance to do these things. I became then involved in the JCO, the Journal of Clinical Oncology. I became involved in the debate about physician-assisted suicide and palliative care that led to some very educational debates and probably spawned the field, to some degree, of palliative care. I had the opportunity to be at the forefront of starting the Leadership Development Program that was really Allen Lichter's idea, but I was able to devote the time to make that happen. And, most recently, I've been on the Conquer Cancer Foundation now for almost two decades. And watching that grow has been a joy. ASCO, when I came, was a very small trade organization, if you will, didn't quite know the questions to ask, had a hired office, a management office, that was based in Chicago, came to Alexandria in about 1994 or somewhere in that range with its own office and its own staff, and now is the world organization for oncology. And I think that that growth, that expansion, that international, multidisciplinary pattern, if you will, is a reflection of the growth of oncology in medicine. I have to say, if you take a look at the popularity poll of what the best and the brightest young physicians choose in their careers, when I was in training and, Dan, when you were in training, most went into cardiology. Maybe some went into GI. Now there are more people going into oncology than any other medical subspecialty. Maybe that'll change after COVID, but that's the way it's been. And our hospitals now are filled with cancer patients, and those hospitals are very dependent on the care that we provide cancer patients. I guess the other thing I would say is, looking from a guy with some hair left, although gray, but looking at it from afar, all of those high-dose chemotherapy programs, the notion of dose, of cell poisons, alkylating agents, the solid tumor autologous marrow programs that were so fashionable in the 1980s, have been, in large part, replaced by such elegant, targeted therapy, now immunotherapy, circulating DNA. Who would have thunk any of that when I was taking care of those children with leukemia 45 years ago? So I think this is such an exciting field. I'm so-- continue to be so pleased and proud of the quality of the trainees. Last night, we had a virtual graduation session for the people completing their fellowship here. And I hate to say it. They're as good as ever. And, if we thought and, Dan, if you thought your colleagues that you all and we all were the best, they're all phenomenal. And it's really a reflection on how the pioneers in this field had a vision, how the need for science to understand cancer was so important, and how medicine has changed and how oncology now is a respected and acknowledged discipline of scholarly work. Well, you had two things that I'm fond of commenting on. One of those is I frequently say publicly I wish I was 30 years younger for a lot of reasons, but because of the scientific excitement that's going into oncology and, also, so that I could run the way I used to, but I can't. That's one. The second is I don't think I would choose me to be a fellow. I'm really intimidated when I do interviews with our residents and say, you know, I wasn't nearly in that kind of category of the people we're interviewing now, which is great. I think our field is in good hands, going to move forward, and things are going. Bob, we've talked about a lot of your contributions to training and education, but you've also had a major influence on the way patients with leukemia are treated. Can you talk more about where the 7 and 3 regimen came from? The 7 and 3 or 3 and 7 regimen-- 3 days of an anthracycline, 7 days of continuous infusional cytosine arabinoside, was developed in the early 1970s. And it was developed by Jim Holland, more than anyone else, when he was at Roswell Park. And it emerged from a series of randomized, phase III trials conducted by what was then called the Acute Leukemia Group B, what became CALGB and then the Alliance. In the early 1980s, the late Clara Bloomfield, who I considered a giant in the world of leukemia, invited me to write a review of the treatment of acute myeloid leukemia for seminars in oncology that she was editing. And, in preparing that, I started reading a series of manuscripts published in the early 1970s, which meticulously, step by step, examined the value of two versus three days of anthracycline subq versus IV push versus infusional cytosine arabinoside, 3 days, 5 days, 7 days, 10 days of infusional cytosine arabinoside. And this was all really work of Jim Holland. He was a magnificent scholar, a humanist, and a tremendous booster too and giant in the start of this field. Thank you. I agree. Bob, we've run out of time, but I want to just thank you for taking time today to speak to me and our listeners, but also thank you for what I consider the many contributions you've made, both scientifically-- we didn't really even get into that, your work on leukemia and GI-- but I think, more importantly, establishing a training program that's been the model for, probably worldwide, how to train people in oncology and the contributions you've made to ASCO. So, for all that, I and everybody else are very appreciative. Thanks a lot. My pleasure. It's a pleasure to be here with you. Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.
Dr. Hayes interviews Dr. Bloomfield on her role as one of the first physician-scientists to investigate treatment for acute myeloid leukemia (AML). TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Welcome to JCO's Cancer Stories-- The art of Oncology 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 role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. [MUSIC PLAYING] Welcome to today's version of the ASCO Cancer Stories podcast. Today, my guest on the podcast is Dr. Clara Bloomfield. Dr. Bloomfield was instrumental in the early studies investigating the biology of leukemias and lymphomas, and also the interaction between various molecular markers and treatment. She founded the Correlative Science Committee of The Cancer and Leukemia Group B, which is now designated the Alliance in the 1980s. And I believe that was probably the first such committee in the cooperative groups, and she chaired it for at least 25 years. Her work resulted in numerous groundbreaking insights that led to changes in practice. Personally, and having worked with her for several of those years in CALGB, I really consider her one of the first investigators to perform what we now blithely called, quote, "translational," end of quote, science in cancer. Dr. Bloomfield was born in New York City, but her father, who was an expert in labor and industrial relations, moved the family to Washington, DC during World War II. And after the war, he then took a position at the University of Illinois, leading Dr. Bloomfield to have a nearly lifelong association with the Midwest. She attended undergraduate school at the University of Wisconsin, but then graduated from San Diego State College during a brief foray to the West Coast. She returned to the Midwest to attend medical school at the University of Chicago, and then completed her internal medicine residency and her medical oncology fellowship at the University of Minnesota, where she stayed on faculty until 1989. She then became chair of the Department of Medicine at Roswell Park Cancer Institute in Buffalo for the next eight years, and then moved to the Ohio State University, where she accepted the position as director of the comprehensive and now designated the James Cancer Center. She's remained at OSU and is currently a distinguished university professor and the William G. Pace II professor of cancer research and a senior advisor at the OSU James Cancer Center. Dr. Bloomfield has authored hundreds of peer-reviewed papers. She is an elected member of the National Academy of Medicine and the National Academy of Sciences. She's, frankly, won just too many awards that I can name here. But importantly, she served on the ASCO board of directors, and in 2009, she gave the David A. Karnofsky Memorial Lecture, the highest honor our society can bestow. Clara, welcome to our program. Thank you. You know, I have a lot of questions for you, many of which I thought about that I should have asked you 30 years ago or so when we first started working together in CALGB. But I think the biggest one is, how did you get interested in leukemia in the first place? Were any particular personal insights that resulted in the basis of your career? Or was it just happenstance? I think it happened because in grade school, I had a number of classmates who developed leukemia. And they were sent to the National Cancer Institute because people in those days didn't treat leukemia. And they returned with steroid-bloated faces and soon died. And I thought, well, wouldn't it be cool to develop medicine that could save kids from dying? I'd already decided to become a doctor, so seeing the real-life effects of cancer helped shape my early desire to become an oncologist. So that must have been about the same time, a little bit after, that Drs. Frei, and Freireich, and Holland started combination therapy for leukemia. They must have had a big impact on your career then. I don't remember. [? No, ?] I'm kidding. Actually, the other question-- I know that you spent some time at Stanford and ran into Henry Kaplan. And there was a cute anecdote, I think, about how you presented with his backing at one of the conferences. Can you tell us a little bit about Dr. Kaplan and your work with him? Sure. During my junior and senior years in medical school, I did a sub-internship at the University of California at San Francisco. And I saw a patient with Hodgkin's disease who was not being treated with curative intent. And I said to the attending, you're not giving this patient modern therapy. And the attending replied, well, if you're so smart, we'll have you do grand rounds on how to treat Hodgkin's disease. Remember, I was a medical student. So I called Professor Henry Kaplan at Stanford for advice. And he was great, and he said, well, they never want me to come. I'd be happy to come and help you give grand rounds. So to the surprise of my attending and awe as a medical student, I conducted grand rounds at the University of California at San Francisco with Professor Kaplan. That must have been a big surprise. Yes, I think it was. Actually, one of my interviews has been with Saul Rosenberg, and he also had some great stories about Dr. Kaplan when they first started giving chemotherapy at Stanford. And Kaplan was apparently quite supportive of doing this. So-- Yes, he was. --I never got to meet him. Yeah. Another question, again, about the time you entered the field, I referred to what I consider the big three, Frei, Freireich, and Holland, but their therapy was really pretty empiric for leukemia. It was just hoping that giving more drugs would be better than one drug. But you really got us into genetics. What made you do that? I mean, what made you think that we could treat people, really, with precision medicine better than we did in those days? Well, my second research project I had as a fellow, which was presented at ACR in May of 1972 and published in April of 1973, involved daunorubicin-prednisone therapy for AML. And in that, the question was raised in patients without Auer rods, the question were these of CML in blast crisis was raised, so chromosome studies were done. And this got me started studying cytogenetics in leukemia, and subsequently molecular genetics. And also, you asked if I had a role model, and the answer is no. I did not have a role model. I know that very early on in your career, you published a very controversial paper suggesting that the Philadelphia chromosome could be found in acute lymphocytic leukemia, which at the time, I think, was probably heresy, since it had been associated with CML. I understand that you interacted with Avery Sandberg, the [? tube ?] giant. I remember hearing about Avery Sandberg when I was a freshman in college in genetics, and he supported you. What was the background behind that? At the 1975 ASH meeting, I presented an abstract, I gave a talk on the Philadelphia chromosome-- on Philadelphia chromosome positive acute leukemia. And after that talk, many prominent cytogeneticists raised questions about the validity of my findings. However, Avery Sandberg, while surprised by the findings, said, she may be right. Sometimes these youngsters get things that we've missed. And did you walk out beating your chest? That must have been quite a moment. I was happy that he-- I was happy that he supported me. Well, I want to go on to some of your other work, but I'm going to tell you that in our fellows clinical conference here a couple of weeks ago, which I attend every week, one of the fellows started talking about FLT3 leukemia. But his comment was leukemia is described as the most genomically defined cancer. And I didn't bring it up at that meeting, but I thought, you owe Clara Bloomfield for that statement. You should be really proud of your work. I almost picked up the phone to call you to tell you that our fellows don't know that you did the work. They should, and that's why we're doing these podcasts. So the only thing-- I know you challenged dogma was the treatment of older patients with leukemia. And as you and I both get older, I think it becomes more near and dear to our heart. Can you give some insight into that? I mean, my impression, when I was a fellow, was we just kind of said, oh, you're over 60, it's not worth treating you. But I think you really challenged that and changed that dogma. So ASH [INAUDIBLE] the third paper I published and project that I started on when I started as a fellow, because I was asked to do this by one of my attendings, was to look at treating older patients with acute leukemia. In the early 1970s, which we're talking about, it was considered that standard intensive treatment of patients with acute leukemia over the age of 40 or 50 years of age was malpractice or at least wrong. So when I was asked to look at this, we had a few patients over the age of 60 with AML treated with what was then standard intensive chemotherapy. So I compared the outcome of patients aged 21 to 40, 41 to 60, and 61 to 86 years. And what I found was that patients aged 41 to 60 and greater than 60 responded equally well. As a result, we said that patients over 60 should be treated. This meant that what we did was told major researchers in leukemia that they were wrong. This caused quite a stir, as you might imagine. And interestingly, within the next five to 10 years, they all came back to me and said they had been wrong. In that regard, I watched you in CALGB. I was on the solid tumor side, obviously, but you were really a pioneer in organizing and conducting translational research and correlative research in leukemia in the cooperative groups. When you started, I don't think there was any of that, was there? Were there a lot of obstacles to doing that? I think everybody just takes it for granted now, especially with so-called precision medicine. But what did you have to do to get that started at CALGB? From 1982 on, I was chair of the Correlative Science Committee in Cancer and Leukemia Group B. In 1984, I actually started to have NIH grant to support correlative science in the CALGB cooperative group. In 1984, we already had a trial in Cancer and Leukemia Group B to do cytogenetics in acute leukemia. I mean, a lot of this work was based on my work in cytogenetics. And while there may have been clinicians who were opposed, I had the support of important people like Professor Janet Rowley and the cytogeneticists at the CALGB institutions. And there really were not significant obstacles that I can remember. Of course, if there were people who tried to block me, I probably didn't care and worked around them. I'm sure that's true. I am too. This is part of what-- when you're one of the few women, as I was when I started in the field, I mean, I suppose I was always getting blocked about things, I just don't think much about it. I didn't then and I don't now. That segues into my final question, actually. And these days, more than half of our medical students are women. More than half of our residents are women at the University of Michigan. More than half of our fellows in hem-onc are women. Increasingly, the faculty is there. But when you started, you were really a pioneer, I think, in introducing women into clinical and laboratory research in oncology and academic medical leadership. And I just want to list the things, because I don't think you will, that I think you've done. First, I understand you were the first woman chief resident at the University of Minnesota, the first woman full professor in medicine at the University of Minnesota, one of the first women chairs of medicine in the United States when you were at Roswell Park, the third woman to be director of an NCI-designated Cancer Center. And frankly, as I was preparing this, I was on an airplane and I was watching A Matter of Sex about Ruth Bader Ginsburg, and I thought, this is a really familiar story. Do you have any war stories that you thought were particularly telling when you began? And especially, for example, I know you have a story about what the dean told you when you were considering becoming an academic professor. Do you have anything to inspire the people listening to this podcast? I'm sure there were some probably pretty aggressive war stories that I don't remember. And as I said, I don't tend to think about what happened in the past since I'm trying to keep up with the present. But I guess there are a couple of stories. Unbelievably, when I was a medical student, I always sat in the front row in class because that was the only way I could see the slides. And the dean, medical school dean, called me into his office and said it was not ladylike to sit in the front row. And I told him-- it's unbelievable really-- I told him that when he became a lady, he could tell me how to act like one, and walked out on him. But the more important story, I suppose-- that I can remember-- is that when I was appointed an associate professor, which occurred three years after I became an assistant professor, so the head of medicine called me in and said, congratulations, Clara. This is a great accomplishment. He went on to say, however, that since your husband is on the faculty and gets a good salary, we are not going to increase your salary. So when I came home, I told my husband, where upon he called the dean, who called the University president, who said, you be sure she gets the same salary or higher than the highest one you've ever given a new associate professor in medicine. Thus, my pay issue was immediately resolved. It's hard to believe that's a true story, except I saw similar things myself as I was going up, and they were getting corrected, at least. Well, anyway, we're running out of time. And I just want to thank you for all the things you've done, the contributions you've made to the field. Your legacy is incredible, in my opinion. And I think people will long remember what Clara Bloomfield has done in terms of changing how we treat leukemia, changing the treatment of leukemia into groups of patients who traditionally weren't treated, like older folks, and probably the pioneering work you did in bringing women into science and medicine, especially in oncology. So thanks for taking time to speak with me today. And I think people are going to be really thrilled to listen to your story as they drive to work and say, wow, I didn't realize that that's what it was like back in the old days. So thanks so much. And I think, especially, our young and translational scientists, particularly women, and also, most importantly, our patients deserve to give you credit for all of the things you've done and [? thanks ?] you've done. Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
Matt Kalaycio, MD, of the Cleveland Clinic joins Blood & Cancer host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to preview the potentially practice changing research that will be reported at the 2019 annual meeting of the American Society of Hematology. Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, addresses the isolation that comes from dealing with a serious chronic illness, especially around the holidays. * * * Help us make this podcast better! Please take our short listener survey: https://www.surveymonkey.com/r/podcastsurveyOct2019 * * * FDA approves atezolizumab combo as first line for advanced NSCLC Atezolizumab is a monoclonal antibody and is already approved for adults with metastatic NSCLC with disease progression. By Laura Nicolaides The Food and Drug administration as approved atezolizumab in combination with paclitaxel and carboplatin chemotherapy for first-line treatment of adults with metastatic, nonsquamous non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations. * * * ASH abstracts discussed in the podcast: Abstract 1: Post-transplantation cyclophosphamide after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON-96 trial in recipients of matched related and unrelated donors. Abstract 261: Superior survival with post-remission pediatric-inspired chemotherapy compared to myeloablative allogeneic hematopoietic cell transplantation in adolescents and young adults with Ph-negative acute lymphoblastic leukemia in first complete remission: Comparison of CALGB 10403 to patients reported to the CIBMTR. Abstract 322: Nonmyeloablative allogeneic transplantation confers an overall survival benefit with similar nonrelapse mortality when compared with autologous stem transplantation for patients with relapsed follicular lymphoma. Abstract 6: Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-cell therapies, and is active in treatment through multiple lines. Abstract LBA-5: Validation of BCL11A as therapeutic target in sickle cell disease: Results from the adult cohort of a pilot/feasibility gene therapy trial inducing sustained expression of fetal hemoglobin using posttranscriptional gene silencing. Abstract LBA-6: Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: Primary analysis results from the randomized, open-label, phase 3 study Candor. Abstract 1588: A randomized trial of EPOCH-based chemotherapy with vorinostat for highly aggressive HIV-associated lymphomas: Updated results evaluating the impact of diagnosis-to-treatment interval and pre-protocol systemic therapy on outcomes. Abstract 940: Elucidating the role of IL6 in stress erythropoiesis and in the development of anemia under inflammatory conditions. Abstract 57: Patient harm from repetitive blood draws and blood waste in the ICU: A retrospective cohort study. Abstract 59: Impact of iron supplementation on patient outcomes in women undergoing gynecologic procedures: Systematic review and meta-analysis of randomized trials. Abstract 126: Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed/refractory follicular lymphoma: Primary analysis of the full efficacy population in a phase Ib/II trial. Abstract 168: Risk of hemorrhage in patient with polycythemia vera exposed to aspirin in combination with anticoagulants: Results of a prospective, multicenter, observational cohort study (REVEAL). Abstract 326: Safety and effectiveness of apixaban, LMWH, and warfarin among venous thromboembolism patients with active cancer: A retrospective analysis using four U.S. claims databases. Abstract 327: Safety and effectiveness of apixaban, LMWH and warfarin among venous thromboembolism patients with active cancer: A subgroup analysis of VTE risk scale. Abstract 566: Phase II study of oral rigosertib combined with azacytidine as first line therapy in patients with higher-risk myelodysplastic syndromes. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd Ilana Yurkiewicz on Twitter: @ilanayurkiewicz
In this episode, we'll listen to Dr. Srikala Sridhar, Dr. Scott North and Dr. Alicia Morgans discuss the important trials presented at ASCO 2019. 01:01 - ENZAMET Study 12:49 - TITAN Study 19:00 - KEYNOTE-426 Study 28:25 - CALGB 90601 (Alliance) 38:29 - HCRN:GU14-182
Dr. Felipe Moraes, autor do MOC, fala sobre os destaques em câncer de rim e câncer bexiga desta ASCO e destaca estudos, como, KEYNOTE-426 e CALGB 90601 (Alliance).
This JCO Podcast provides observations and commentary on the JCO article “Dose-Adjusted EPOCH-R Compared to R-CHOP as Frontline Therapy for Diffuse Large B Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial CALGB 50303 (Alliance)” by Bartlett et al. My name is Patrick Stiff, and I am Division Director of Hematology-Oncology at Loyola University Stritch School of Medicine in Maywood, Illinois. My oncologic specialty is hematologic malignancies and stem cell transplantation. CHOP has remained the chemotherapy backbone of choice for the treatment of diffuse aggressive non-Hodgkin lymphoma since the 4 arm randomized SWOG study was performed 25 years ago1. Since then, only the addition of rituximab has improved patients' outcome2. Investigators have tried to improve outcomes by employing other strategies like increasing drug intensity, shortening the interval between cycles, adding newer agents, changing the method of administration, and adding transplantation, but none clearly demonstrated a survival advantage. Among these strategies is an infusional one designed to increase apoptosis and inhibit BCL6 and p-glycoprotein in resistant cells. While SWOG tested infusional CHOP in 2001 and found no difference in outcomes, compared to bolus CHOP3, the NCI group has explored a modified CHOP infusional regimen known as EPOCH consisting of etoposide, vincristine, and doxorubicin given simultaneously as a continuous 4 day infusion with a bolus dose of cyclophosphamide at the end of the 4 days along with daily oral prednisone Combined with aggressive dose escalations based on nadir myelosuppression, they tested this regimen with rituximab, EPOCH-R, reporting an impressive 5 year PFS of 79% in an unselected study of 72 patients from 3 centers4. Based on this, 18 CALGB institutions treated 69 patients with dose adjusted EPOCH-R, demonstrating a similar 62 month TTP of 81%, with an impressive 100% TTP for the germinal center B cell subgroup as defined by the Hans algorithm, all seemingly superior to R-CHOP5. Equally impressive was a Phase II study in mediastinal B cell NHL with a 5-yr EFS of 93% administered without consolidative radiotherapy, added frequently to R-CHOP6. Therefore, a head-to-head comparison was the natural next step. The trial that accompanies this podcast was designed to compare the PFS and OS at 3 years between patients treated with 6 cycles of dose adjusted EPOCH-R to the standard R-CHOP. The trial opened in 2005 and enrolled 524 patients with either DLBCL, primary mediastinal BCL or intravascular large cell NHL over an 8+ year period to its close in 2013. Seventy-four % had stage III/IV disease and 12% high IPI disease. Eighty-eight percent of the R-CHOP and 82% of the dose adjusted EPOCH-R cycles were administered with 75% of the dose adjusted EPOCH-R patients receiving initial dose escalations per protocol. At a median follow-up of 5.2 years the 5 year PFS and OS were 66 and 85% for the R-CHOP treated patients no different from the 68 and 77.5% for the dose adjusted EPOCH-R patients. Prognostic factors for PFS were age > 60, IPI, and double expressers (15.6% of the 270 with complete data) for MYC, BCL-2 and BCl-6. There were a number of post hoc subgroup analyses performed. Of these, the PFS for the combined High and High intermediate IPI group was higher for the dose adjusted EPOCH-R group (p = 0.041) but no difference in OS was noted. In none of the other subgroups was a benefit seen for dose adjusted EPOCH-R including CNS relapses, mediastinal B cell NHL, double expressors or those with MYC positivity although percentages of these subgroups were small. There were however significantly increased grade III-IV myelotoxic and non-myelotoxic complications for the infusional regimen. Should we take these results as the final word on the lack of a benefit of dose adjusted EPOCH-R in the treatment of DLBCL? In other words is this a case of "déjà vu all over again"?. This trial recruited slowly, 524 patients over more than 8 years, with < 5% of US eligible patient enrolled. The reasons seem obvious. Encouraging enrollment on a trial comparing a familiar outpatient regimen administered over hours, versus a 4+ day in-patient regimen was at best difficult. Recall also that this trial took place during the Great Recession, with patients/families fearful of losing their jobs dealing with an in-pt regimen. Slow accrual in and of itself should not have been impacted outcome. But these were not a unselected group as the authors concluded. First by design, all who had an ECOG PS of > 2 (20% of the phase II study5) were excluded. Second there was the requirement for submission of fresh/frozen material including a second biopsy if needed thereby likely eliminating mostly patients with rapidly progressing disease. Together possibly with some investigator bias, given the promising Phase II data, there was a decrease in High IPI enrollment of only 12% versus the 20% in the Phase II study, which extended to other high risk patients including double expressors, C-Myc positive, and mediastinal B cell disease. Combined these led to the 3 year PFS for R-CHOP of 72%, 17% better than the planned outcome. However, considering the trial exclusions, and ultimately a PFS similar to that of other recent R-CHOP experiences7,8 one could argue that the 3-yr 55% PFS endpoint for this trial was far too conservative. While the R-CHOP PFS was 17% better than planned, the dose adjusted EPOCH-R 5-yr PFS was 7% worse than the Phase II results, which is difficult to explain considering the earlier studies, in which the more favorable patients did better5. A lower administered dose intensity compared to prior studies4,5 was not apparent with the incidence of grade III/IV febrile neutropenia and neurotoxicity similar to the Phase II trial. However 82% vs 91% of those in the Phase II study completed all dose adjusted EPOCH-R cycles with the decrease mostly due to on treatment deaths and AEs, suggesting that when used in a more 'real world setting' this regimen is more toxic than initially seen. Might those who completed therapy also have had dose reductions or delays that could also have impacted PFS? Finally, this report does not include PFS based on cell of origin(COO), which for patients with germinal center B cell of origin in the Phase II study was 100%. Perhaps the germinal B cell percentage was lower than in the Phase II studies as well. So what can be concluded about these negative results? The authors conclude that there was a "potential patient selection bias", at least partially explainable by trial design, and that this "may preclude generalizibility….to specific subgroups". I would conclude that given the outcome and toxicity data, for the low and low intermediate IPI patient, R-CHOP remains the treatment of choice. The post hoc PFS improvement for the high risk subgroup might argue for dose adjusted EPOCH-R, but the lack of an OS advantage in this subgroup needs to be acknowledged. However, other compelling phase II studies in high risk subsets, e.g double hit, underrepresented in this trial, still makes the efficacy of dose adjusted EPOCH-R in certain circumstances an open question. This concludes this JCO Podcast. Thank you for listening.
The Landmarks in #OncoPharm continues down its breast cancer-centric track with the landmark CALGB 9344 trial that established the role of paclitaxel in the adjuvant setting --> https://ascopubs.org/doi/pdf/10.1200/JCO.2003.02.063
A roundtable discussion featuring perspectives from Drs Tanios Bekaii-Saab and Alan P Venook on emerging research and cases from their practices. Introduction — Indications for and Practical Implementation of Biomarker Analysis for Patients with Metastatic Colorectal Cancer (mCRC) Biomarker assessment for patients with mCRC (0:00) Perspectives on genomic testing platforms used to perform biomarker analysis for mCRC (3:16) Role of rebiopsy and repeat biomarker assessment for patients with progressive mCRC (7:11) Biology of mCRC and Role of Tumor Sidedness in First- and Later-Line Decision-Making Implications of RAS testing for selection of therapy (10:22) Tumor sidedness and therapeutic decision-making (13:55) Similarities and differences in the design and primary endpoints of the Phase III CALGB-80405 and FIRE-3 trials evaluating first-line chemotherapy in combination with cetuximab and/or bevacizumab for KRAS wild-type mCRC (18:12) Prognostic and predictive relevance of primary tumor sidedness in patients with RAS wild-type mCRC on the CALGB-80405 and FIRE-3 trials (22:11) Efficacy of EGFR inhibitor- versus bevacizumab-based treatments for left- versus right-sided RAS wild-type mCRC (23:28) Choosing between EGFR inhibitor- and bevacizumab-based treatments as first- and second-line therapy for patients with symptomatic left-sided RAS wild-type mCRC (31:39) Case (Dr Venook): A woman in her thirties with left-sided RAS wild-type mCRC receives first-line FOLFOXIRI (40:14) Therapeutic options for younger patients with left-sided RAS wild-type mCRC and disease progression on first-line FOLFOXIRI (43:58) Case (Dr Bekaii-Saab): A man in his sixties with left-sided RAS wild-type mCRC and disease progression after 2 years of first-line “stop-and-go” FOLFIRI/bevacizumab receives FOLFIRI/panitumumab (45:56) Activity of cetuximab versus panitumumab and practical considerations for use (49:37) Clinical experience with and management of EGFR inhibitor-associated dermatologic toxicities (51:45) Second opinion: Second-line therapy options for patients with left-sided RAS wild-type mCRC and disease progression on first-line FOLFIRI/bevacizumab (55:48) Faculty perspectives on therapeutic algorithms for first- through later-line therapy for left- versus right-sided RAS wild-type mCRC (1:00:43) Current and Future Treatment Options for Patients with BRAF Mutations Efficacy of EGFR inhibition in patients with mCRC and atypical (non-V600E) BRAF mutations (1:08:18) Clinical presentation of and prognosis for patients with mCRC and a BRAF V600E tumor mutation (1:12:22) Activity and tolerability of EGFR/MEK/BRAF-inhibitor combinations in patients with mCRC and a BRAF V600E tumor mutation (1:13:59) Importance of BRAF testing in mCRC; strategies for first-line therapy and beyond (1:16:13) Improved tolerability with triplet EGFR/MEK/BRAF-inhibitor combinations in comparison to anti-EGFR monotherapy or doublet combinations (1:19:54) Case (Dr Venook): A woman in her forties with mCRC, a BRAF V600E tumor mutation and rapid disease progression on first-line FOLFOXIRI/bevacizumab attains long-term disease stabilization with encorafenib/binimetinib/panitumumab (1:22:13) Case (Dr Bekaii-Saab): A man in his fifties with mCRC and a BRAF V600E tumor mutation receives second-line encorafenib/binimetinib/cetuximab on a clinical trial (1:23:27) Optimal Management of Microsatellite Instability (MSI)-High or DNA Mismatch Repair-Deficient mCRC Assessment of MSI status and tumor mutation burden as predictors of response to immune checkpoint blockade (1:26:47) Sequencing of anti-PD-1/PD-L1 checkpoint inhibitors for MSI-high mCRC (1:33:19) Neoadjuvant ipilimumab with nivolumab for early-stage colon cancer (1:36:39) Activity and tolerability of immune checkpoint inhibitors alone and in combination in patients with MSI-high mCRC (1:37:34) Case (Dr Bekaii-Saab): A woman in her fifties with MSI-high, right-sided mCRC and a RAS mutation receives second-line pembrolizumab (1:42:11) Case (Dr Venook): A woman in her forties with Stage III CRC initially treated with adjuvant FOLFOX experiences disease progression and receives an assessment of MSI-high disease (1:46:37) Perspective on pseudoprogression in patients undergoing immune checkpoint inhibitor therapy (1:48:50) HER2 Positivity and Other Potential Biomarkers Biology and epidemiology of mCRC with HER2 amplification/mutation (1:51:16) Activity of and duration of response to dual HER2-targeted therapy in patients with mCRC and HER2 amplification/mutation (1:54:09) Therapeutic options for patients with mCRC and HER2 amplification/mutation (1:55:45) Case (Dr Venook): A man in his fifties with left-sided, RAS wild-type mCRC and HER2 amplification/mutation receives fourth-line trastuzumab/pertuzumab (2:00:13) Case (Dr Bekaii-Saab): A woman in her sixties with left-sided, RAS wild-type mCRC and HER2 amplification/mutation receives third-line trastuzumab/tucatinib on a clinical trial (2:01:57) Activity of tucatinib in patients with mCRC and HER2 amplification/mutation (2:04:40) Optimizing the risk-benefit ratios of systemic therapy options for patients with mCRC (2:07:36) Modulation of the gut microbiome to enhance response to anti-PD-1 immunotherapy; effects of antibiotics on response to immune checkpoint inhibitors (2:11:12) Select publications
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. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist, and I'm a researcher at the University of Michigan Rogel Cancer Center. And I'm also the past president of the American Society of Clinical Oncology. Over the last and now the next several podcasts, I've been really privileged to be your host for a series of interviews with the people I feel are the founders of our field. Over the last 40 years, I personally have been fortunate to have been trained and mentored and I've also been inspired by many of these pioneers. And it's my hope that through these conversations. We'll all be equally inspired by gaining an appreciation of the courage and the vision and the scientific understanding and the anecdotes that let these men and women to establish the field of clinical cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, I think we can also imagine and work together towards a better future for our patients and their families during and after cancer treatment. Today, I'm really pleased to have my guests on this podcast Dr. Norman Wolmark, who was his mentor and longtime colleague, Dr. Bernard or Bernie Fisher, was responsible for the unbelievable success of one of the most influential cancer cooperative groups in the world, the National Surgical Adjuvant Breast and Bowel Project, or the NSABP, which of course, in recent years has now been merged with two other corporate groups to become the NRG. Doctor Wolmark as a professor of surgery at Drexel served as the executive medical officer from 1979 to 1994 during Dr. Fischer's leadership of the NSABP. And then he became the chairman and PI of the group until 2004 when he assumed the same role with the merger into the NRG. The NSABP is generally credited with what is now called de-acceleration of therapy, in particular of local therapy of breast cancer by applying the scientific method to compare a modified radical mastectomy to radical mastectomies and subsequent breast conserving treatment a modified radical mastectomy, as well as testing the concept of sentinel node mapping, which we now use routinely. NSABP was also one of the pioneer groups to test the value of adjuvant systemic therapy. They started with adjuvant chemotherapy, comparing L-phenylalanine mustard, or L-PAM to nothing in the 1970s, and later, tamoxifen versus nil. Other successes of the NSABP include one of the first trials or adjuvant trastuzumab. And further, NSABP was the first to report the prognostic value of the genomic test to guide the use of adjuvant chemotherapy in ER-positive breast cancer. Incidentally, it also conducted the largest and the most definitive set of studies of chemo prevention, first with tamoxifen versus nil, and then later, comparing raloxifene to tamoxifen. Not just breast cancer-- in gastrointestinal malignancies, the NSABP made seminal observations regarding radiation for rectal cancer and adjuvant chemotherapy in colorectal cancers. Dr. Wolmark himself has published over 300 peer reviewed papers, numerous other commentaries and reviews, and frankly, I started to list your honors, Dr. Wolmark, but I ran out of space. You've just had too many to count here. I think it is safe to say that the reduction of both mortality and toxicities related to breast and GI cancers over the last four decades, coupled with improvement on how we treat people, is in large part due to the brilliance and the courage and the hard work of doctors Wolmark and Fisher. Most importantly, I think they showed so many of us the importance of challenging dogma, for example, how study and thinking in breast cancer and applying the scientific method to clinical research and practice. [GASPING] I have to take a deep breath, Norm. Welcome to our program, and thank you for joining us. Well, thank you, Dan. I think after that glowing and complimentary introduction, which was far too generous, probably the most strategically sound decision that I could make is to thank you and to terminate this discussion, because I don't think that I can possibly improve on it. But I don't suppose that that's the purpose of this endeavor here. Yeah, no. People aren't tuning in to hear me. They're tuning in to hear you. And this is hero worship on my part. I want to start out with your background. I know you grew up in Montreal. You graduated from undergraduate, medical school, and later, you did your surgical training at McGill. What were the circumstances that your family was in Canada? And what got you interested in medicine and, specifically, surgery? Well, that's an interesting question. I did not grow up longing to become a physician. As a matter of fact, my interests at McGill, certainly during undergraduate school, included biochemistry. And I was in the honors biochemistry program and was going to pursue a career in nucleic acid research. And at the last moment, I had a change of heart and decided to go into medicine at McGill. And McGill was not an embracing environment for surgeons. I think surgery, certainly in our era, was regarded as a sub-medical species. And it wasn't until my internship and early residency that I embraced the possibility of developing and evolving a career in surgery. Was that attitude out of also having been at McGill-- long before you were there, I know, but most places were dominated by the surgeons. And then medicine came along after that-- Mayo Clinic, for example. Do you know? Was this an outgrowth of Osler's influence? Well, I don't know that it was an outgrowth of Osler's influence, but it was certainly difficult for us to escape Sir William Osler. I think at the graduation after our second year, we were provided with a leather bound copy of Aequanimitas, which of course, nobody read, because medical students are not interested in the history of medicine. It was only years later that I read most of Osler's non-scientific works. That's interesting. So then you went to Pittsburgh to do your surgical residency and then two years at the NCI and a year at Memorial. But then, you returned to Pittsburgh. Why Pittsburgh in those days? Well, what drew me to Pittsburgh in 1973 was my interest in clinical trials. And in 1973, there was a lot of excitement going on in clinical trials and breast cancer directed by Bernie Fisher and the NSABP. So that was something that attracted me, that one could apply the scientific method to evolve therapy. And this was something that I desperately wanted to participate in as a result of my background in basic research and biochemistry. So tell us about the heady days in the early '70s and even further back, if you'll recount sort of Dr. Fisher's history as well, of starting the NSABP. What was his vision? What was his plan? Why did he do that? How did you get involved? The whole evolution of cooperative groups and in particular, the NSABP, was an outgrowth of the initiative of the National Institutes of Health and more specifically, I think, to Bernie Fisher's mentor, IS Ravdin, at Penn. And that led to the creation by the NIH of the Cancer Chemotherapy National Service Center. And this was started by three surgeons and Michael Shimkin at the NIH, who was a medical oncologist, or what was then called a chemotherapist. And from that grew a number of disease-oriented initiatives called the surgical adjuvant chemotherapy projects for specific diseases, breast being one of them. And this was 1957. And by 1958, the NSABP had randomized its first patient. And certainly, Bernie Fisher was amongst the founders of the NSABP and then, of course, became chairman of the group in 1967 and moved it to Pittsburgh in 1970. What did it take to get a bunch of surgeons to believe that more than just surgery was important? The group started in a modest fashion. There were 23 institutions. And I think it's certainly an enormous credit at Bernie Fisher for demonstrating that a cooperative group could indeed be cooperative, with multiple heterogeneous surgeons joining under the rubric of the NSABP to evolve the state of the art breast cancer and challenge existing dogma. One of my first meetings, Dr. Fisher and Dr. Irvin of New York City were in a debate that I thought was going to get into a fistfight, with Dr. Fisher trying to explain the systemic therapy of cancer and that it was more than just surgery, and Dr. Irvin believing if you did super-radical mastectomies, you could cure more. You must have been in the middle of some of those discussions as well. I was, and remember them, and remember the acrimony, the hostility that existed at that time. As a matter of fact, there were societies that were created to counter the influence of the NSABP. The retreat from radical mastectomy was highly contentious. And of course, the debate of the two mutually exclusive hypotheses was certainly extant in Halsted's era. But Bernie Fisher determined instead of debating the issue to test the two mutually exclusive hypotheses using the scientific method, namely the randomized prospective clinical trial, which convinced surgeons that variations on the theme of operative nuance were not going to increase survivorship, that breast cancer was a disease with systemic components at its initiation, and the retreat from a radical mastectomy and the ascent of systemic therapy are inextricably intertwined. And they are so largely because of the efforts of Bernie Fisher and the NSABP. This is an interview with you, except that you know Bernie Fisher better than any of us-- who, incidentally, turned 100 years old in August of this year. What were the driving forces for him to think this way? Do you know? Was there a sudden aha that systemic therapy ought to be as important as the surgery? I know he did some preclinical studies to suggest this. Can you give us more background of what he was thinking and how he got there? Well, when I first joined him in 1973, it was a unique environment. There was a continuum between the laboratory and the clinic. And hypotheses were generated in the lab from murine models and applied to clinical research, which we now call translational research. And certainly, I think he was influenced in many ways by the preclinical work that he did in murine models on metastases and multiple other observations to challenge the sanctity of the radical mastectomy, which was based on the belief that breast cancer was a local, regional disease and spread in a logical, predictable, stepwise manner, again, along fascial planes. This, of course, to scientists, was something that did not stand up to a solid review of the data. Through the years, I've picked up many pithy comments from Dr. Fisher. One of them is that-- what was it? In God we trust. And for everything else, we like data, which I always thought was a great statement, something to that effect. The other was, you may be logical, but breast cancer is not. That really has stuck with me through the years, which is, it doesn't follow a logical string of linear progression. But rather, it becomes systemic, or it doesn't, which I think changed the field. Well, Bernie always challenged existing dogma that was based on empiricism. I think Bernie taught us to challenge the individual who ascends to the professorial pulpit armed with a retrospective case series. And based on personal charisma or the institution that that individual represented, such an individual was able to influence the way a disease was treated for decades and then close to 3/4 of a century. Challenging that dogma, insisting that therapy be evolved based on data rather than retrospective case series, I think, is a lasting contribution. He blazed the trail for the rest of us. Since you were there for a lot of this, how about some of the other luminaries of the time? Dr. Crile had a lot to do with the early thoughts that maybe you didn't need to do mastectomy. Can you enlighten us on some of the other folks that were some of the early pioneers in the field? There were certainly proponents of lesser operative procedures starting with [INAUDIBLE] and in the UK, Vera Peters, in Canada, Barney Crile, or George Crile, Jr. at the Cleveland Clinic. But again, these were based on anecdotalism. There were very few randomized prospective trials challenging the sanctity of the radical mastectomy. There were some-- Sir Hedley Atkins, the Guy's Hospital trial comparing breast-preserving versus mastectomy, a trial that had few patients and was reported, I think, in 1971 was a case in point. And then Umberto Veronesi with the quadrantectomy study, which was reported in 1981, preceded B-06. But certainly, B-06 had an enormous impact in 1985. And I think to Bernie's credit, he was able to convince his colleagues, even his detractors and his coevals of the value of breast preservation. But more importantly, I think he was able to convince surgeons of the biologic behavior of breast cancer with its systemic components. Yeah, I agree. I remember that paper. Actually, I remember most your papers. B-04 for was the predecessor. And of course, if there is a Rosetta Stone for the NSABP, it was comparing radical mastectomy to total mastectomy, which was a heroic trial to have initiated in 1971. If there is a bellwether turning point, it was B-04. This was the trial that truly compared the two mutually exclusive hypotheses to enormous, enormous resistance by the surgical community. And the paradox was that the 23 institutions that participated in the NSABP were run by surgeons. I came into the field in 1982. I have seen maybe three radical mastectomies in my life based on the fact that B-04 was beginning to change that whole field. And the three or four patients I saw had horrendous qualities of life because of that radical mastectomy. So I think our listeners, the younger ones, need to understand how courageous this was. Let me ask another question. I don't think you were part of it then, but as Dr. Fisher began to, then, think about adjuvant chemotherapy, why L-PAM? Most of the people listening to this probably have never heard of L-PAM, let alone used it. Why was that chosen as the chemotherapy to use in the first trial? Well, that's an interesting question. CMF was being developed at the NCI-- Paul Carbone, Vince DeVita, George Canellos. And L-PAM was an oral agent. And we speculated, sotto voce, of course, Bernie and I, that the reason the NSABP got L-PAM was that it was oral and could be given by surgeons, whereas the CMF, which was more difficult to administer, went to Gianni Bonadonna, who reported on the CMF data in the adjuvant setting a year after the L-PAM data were reported in 1975. Ironically-- correct me if I'm wrong-- but I think the relative benefits of both were almost identical. And the reason L-PAM fell out of favor was the secondary leukemias. Is that your perception? Well, L-PAM fell out of favor, certainly. We did L-PAM, then L-PAM 5-FU, then L-PAM 5-FU plus doxorubicin in a stepwise, sequential manner. I think CMF was embraced. Had there been a direct comparison earlier on, perhaps L-PAM would have had a role. But I think it faded away. And it faded away for us largely because when we compared CMF to four cycles of AC, which could be given in a much shorter time, there was no difference. So AC became the standard, certainly for us. Moving on a bit, as I've already-- another of Dr. Fisher's statements that I've lived on is that the hallmark of a good clinical trial is that it raises more questions than it answers. I love that because it means you have to keep thinking. Can you give us examples how you and Dr. Fisher started designing the next trial as the first one was starting to finish, and how that led, one way to the other? I've always been struck by the fact that the NSABP has been more linear in its trial design than most of the other cooperative groups. Well, it was a continuum. The next trial was based on the results from the previous trial or the anticipated results from the previous trial. A case in point, B-04, total mastectomy, where lymph nodes are not fulgurated, left behind completely untreated, compared to radical mastectomy, where they were removed. 40%, it turned out, of the total mastectomy group had histologically positive nodes. And yet, the outcomes were the same, which supported the use of systemic therapy, that patients were failing not because inattention to operative detail, but because they had systemic metastases. Well, you can ask, how did you transpose this data or know about this data to start your next trial? Well, in that era, the results were available to us in real time. We had a magnetic board, for example, for B-04, where every patient that was entered into the study, of course, anonymized, was on that board, and we could see the treatment failures in real time. So we had a pretty good understanding of what the results were when B-06, for example, was started, and certainly when the L-PAM trial was initiated. To us, in that era, alpha-spending meant buying a suit at Bergdorf Goodman. It's only later that these restrictions, appropriately so, were initiated. So we were able to be very nimble in transposing the data from one trial to formulate the hypothesis for the next trial. And that led to, I think, a very elegant, sequential, logical, stepwise series of trials, which I think in this era, could not be conducted. Did you ever get concerned that you were jumping ahead to the next trial with insufficient follow-up with the last one, and you'd get ahead of yourself in terms of unexpected toxicity showing up or, for example, in the deacceleration of therapy, that in fact, you were wrong, and then you had a bunch of patients that you had given less than enough therapy? I can't think of the fact that you have. But was that a concern as you were designing these? Every clinical trial is a concern. And yes, there was a concern. But we believed that we were basing these trials on objective data, data that were generated through clinical trials and the scientific method. So let me ask another question, because I was never in the NSABP, but I was always struck by the fact that your statisticians sat at the table and thought as much about the biology as they did the p-values. Do you want to talk about some of the statisticians you've had the chance to work with? Absolutely. I think that's an accurate description. Carol Redmond was the first statistician with whom I came in contact and was an integral part of clinical trial development, discussing not only sample size, p-values, interim analyses, but also the biology of the disease and what the biologic end points were going to be, and what the ancillary end points ought to be, and calculate appropriate sample sizes to answer these questions. We were very fortunate to have outstanding biostatisticians who were giants. Sam Weiand, who followed Carol Redmond, who was at the University of Pittsburgh, went to the Mayo Clinic, and returned to us around 1994, '95, and John Bryant, who was absolutely instrumental in the joint analysis for the Herceptin trials, B-31 and N9831, who was a driving force, and was certainly a driving force behind the development of the Oncotype DX genomic profiling. These weren't simply numbers people. They were colleagues. They were part of the assault on the hill. I have to jump in for two reasons. One is I never worked directly with John Bryant, but I can't say how many times I called him and said, what do you think of this? because I knew he would understand the biology as well as the statistics. I miss him dearly. He sadly passed away about a decade ago. As do I. The other is, as you know, we lost Jim Holland this year. My first presentation at CALGB, Dr. Holland was sitting in the back of the room and yelled from the back of the room, because he never used a microphone, not unlike my colleague on the line right now, by the way. Dr. Holland yelled from the back of the room, Hayes, if you need a statistician, it's not worth doing. And I said, well with all due respect, Dr. Holland, and there's a lot of respect here, I have to disagree with you. Did Dr. Fisher get along with the statisticians the way you have? Did he feel that this was a two-way street? Or were there times he said, my way or the highway? There's always robust dialogue and discussion. I think that both Bernie and I embraced our statisticians as colleagues. I have to be very careful. This was not unwelcome embracing. But they were always an integral part of developing and analyzing the protocol. And they were colleagues. And certainly, Bernie had that approach and philosophy as well. So let me, perhaps, describe in 1973, when I first arrived, what struck me as extraordinary. There was passion, excitement, drama. We weren't sure where we were going. But we knew we were getting there fast. And we embraced the journey, the quest. And that was an extraordinary time where we knew that the standard of care was going to be changed. We couldn't predict the outcomes, but we knew that what we were doing at the time would have a lasting impact on the field. Actually, that was my question, which was, did you realize what you were doing in the late '60s and early '70s was as exciting as it was? Sometimes, I think we're in the middle of something, and we don't realize how it's going to turn out. And you've just answered my question, which was it must have been years-- It was challenging the basic sanctity of the dogma, the tyranny that existed at the time. And that, in itself, was a courageous and extraordinary thing to do. And I have to say because of that work, and others, but we've seen a remarkable reduction in mortality due to breast cancer over the last 30 years, probably by more than a third, not quite half. And it's because of these kinds of challenges of dogma and courage to move forward. So I think we all owe you and Dr. Fisher and those who were involved in the early days, then also in the other groups, just an enormous debt of gratitude. My final question to you, Norm, and everybody asks this where did you get your style of presentation? I've argued, although I know you're Jewish, you could have been a Baptist minister. Where did this come from? I have no idea. Everybody loves it. Well, that's certainly very gracious of you, Dan. I've certainly, in the era of protocol B-04 and B-06, I have been summarily booed by an audience in unison. So that may not be a uniform perception. Well, I hope that our listeners who are driving to work or having their morning cup of coffee and listening to this have enjoyed it. I certainly have. Thank you for being so gracious and taking the time to do this. Thank you for all your contributions to the field and for mentoring so many, including myself, frankly. And I consider you a great mentor and a great friend. So I appreciate it deeply. Thank you, Dan. It's been my privilege.
We begin this episode with a discussion of two recent clinical trials in lymphoma: CALGB 50303 and REMoDL-B, respectively published in the Journal of Clinical Oncology and The Lancet Oncology. We include a primer on the history of lymphoma and the development of R-CHOP. We follow that with an in-depth interview with Dr. Ameet Sarpatwari of the Harvard Medical School on Risk Evaluation and Mitigation Strategies (REMS), the Orphan Drug Act, and, broadly, the purpose of the US FDA. CALGB 50303: doi.org/10.1200/JCO.18.01994 REMoDL-B: doi.org/10.1016/S1470-2045(18)30935-5 Dr. Sarpatwari's online course: https://www.edx.org/course/the-fda-and-prescription-drugs-current-controversies-in-context Back us on Patreon! www.patreon.com/plenarysession
The paper examines the cost-effectiveness of schedules of bone-modifying agents in patients with breast cancer and skeletal metastases and supports the 3-month administration of the generic zoledronic acid in terms of cost and efficacy. Read the accompanying article on JCO.org.
Listen as Dr. Philip McCarthy provides an update on the CALGB-100104 (Alliance) randomized trial.
Prof Sagar Lonial (Emory University, Atlanta, USA) and Dr Paul Richardson (Dana-Farber Cancer Institute, Boston, USA) discuss the highlights in multiple myeloma treatment arising from day one of ASCO 2016. They discuss the results and implications of data coming from upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy. This is a randomised phase III study of the European myeloma network with results showing that PFS is significantly prolonged in pts randomised to HDM (OS not yet mature). One of the key highlights from day one looked at a meta-analysis of three studies (IFM 2005-02, CALGB 100104 [Alliance], GIMEMA RV-209) that had previously demonstrated PFS in patients with multiple myeloma, but were not originally powered for OS. This meta-analysis now demonstrates that lenalidomide maintenance after high-dose melphalan and ASCT significantly prolonged OS versus placebo/no maintenance. Some early phase trials were also discussed including a phase I/II trial of ixazomib, an oral proteasome inhibitor, cyclophosphamide, and dexamethasone for newly diagnosed multiple myeloma (NDMM). A phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma and a phase I/II study of carfilzomib, pomalidomide, and dexamethasone (KPd) in patients with relapsed/refractory multiple myeloma (RRMM).
Dr McCarthy talks to ecancertv at EHA 2016 about a meta-analysis into the efficacy of lenalidomide (LEN) maintenance to treat multiple myeloma (MM) following high-dose melphalan and autologous stem cell transplant (HDM ASCT). LEN has proven efficacious in reducing disease progression, but these studies were not powered for overall survival (OS). In analysing data from 1,200 patients, gathered over three previous trials (IFM 2005-02, CALGB 100104 [Alliance], GIMEMA RV-209) that match the criteria (had patient-level data, had a control arm, and achieved database lock for primary efficacy analysis of patients with newly diagnosed MM receiving LEN post ASCT), Dr McCarthy reports that LEN maintenance significantly prolongs OS compared to control. He encourages LEN maintenance as the standard of care HDM ASCT, and introduces further studies into LEN as a single agent or as part of a therapeutic combination.
Dr Sikov talks to ecancertv at SABCS 2015 about survival outcomes from the CALGB 40603 study involving women with stage II-III triple-negative breast cancer (TNBC) who were treated with carboplatin, bevacizumab, or both in addition to standard neo-adjuvant chemotherapy. The aim of the study was to assess the effects of adding carboplatin or bevacizumab on complete response (pCR) rates. Standard neo-adjuvant chemotherapy used in the trial was weekly paclitaxel then dose-dense doxorubicin plus cyclophosphamide. The effect on pCR have been reported (J Clin Oncol 2015;33:13–21) and showed improved pCR with the addition of both the chemotherapy and the anti-angiogenic agent. At SABCS 2015, the effects on the secondary endpoints of event-free (EFS) and overall survival (OS) were presented, with 3-year rates of 74.1% and 83.2%, respectively, although the study was not powered to assess the different treatment effects on either of these endpoints. What it shows is that patients with TNBC who achieved pCR with study treatment had significantly better EFS and OS than patients who did not.
Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the use of single agent vs. doublet chemotherapy in elderly patients.
Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the use of single agent vs. doublet chemotherapy in elderly patients.
Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the use of single agent vs. doublet chemotherapy in elderly patients.
Prof Peeters talks to ecancertv at ASCO 2014 about the results of the results from a large federally funded phase III study demonstrate that four common first-line treatment regimens – bevacizumab plus chemotherapy and cetuximab plus chemotherapy – are equally effective for patients with metastatic colorectal cancer and no KRAS mutations.
The results of CALGB 50202 reported by Rubenstein and colleagues demonstrate the feasibility, safety and efficacy of the MT-R induction and EA consolidation regimens in newly diagnosed PCNSL patients.
Dr. David Gerber, University of Texas-Southwestern, discusses the key results and potential implications of the CALGB 30504 trial of maintenance sunitinib for extensive stage SCLC.
Dr. David Gerber, University of Texas-Southwestern, discusses the key results and potential implications of the CALGB 30504 trial of maintenance sunitinib for extensive stage SCLC.
Dr. David Gerber, University of Texas-Southwestern, discusses the key results and potential implications of the CALGB 30504 trial of maintenance sunitinib for extensive stage SCLC.
Dr. David Gerber, University of Texas-Southwestern, discusses the key results and potential implications of the CALGB 30504 trial of maintenance sunitinib for extensive stage SCLC.
Dr. David Gerber, University of Texas-Southwestern, discusses the key results and potential implications of the CALGB 30504 trial of maintenance sunitinib for extensive stage SCLC.
Dr. David Gerber, University of Texas-Southwestern, discusses the key results and potential implications of the CALGB 30504 trial of maintenance sunitinib for extensive stage SCLC.
Drs. Mary Pinder, Nate Pennell, and Jack West discuss whether the finding of improving progression-free survival with maintenance sorafenib for SCLC should change the standard of care for treatment of extensive stage disease.
Drs. Mary Pinder, Nate Pennell, and Jack West discuss whether the finding of improving progression-free survival with maintenance sorafenib for SCLC should change the standard of care for treatment of extensive stage disease.
Drs. Mary Pinder, Nate Pennell, and Jack West discuss whether the finding of improving progression-free survival with maintenance sorafenib for SCLC should change the standard of care for treatment of extensive stage disease.