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22/01/2021

Conversations with the Pioneers of Oncology: Dr Hyman Muss

Dr. Hayes interviews Dr. Muss on geriatric oncology. Dr. Daniel F. Hayes is the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center. Dr. Hayes' research interests are in the field of experimental therapeutics and cancer biomarkers, especially in breast cancer. He has served as chair of the SWOG Breast Cancer Translational Medicine Committee, and he was an inaugural member and chaired the American Society of Clinical Oncology (ASCO) Tumor Marker Guidelines Committee. Dr. Hayes served on the ASCO Board of Directors, and served a 3 year term as President of ASCO from 2016-2018. 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 h

22/01/2021

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36 min
23/05/2018

37. Cardiotoxicity After Breast Cancer Radiotherapy: Which Part of the Heart Matters Most?

This podcast includes commentary upon a large case control series that examined the incidence of cardiac injury in association with radiation dose to distinct segments of the left ventricle and coronary arteries. Read the associated article by Taylor et al on JCO.org.

23/05/2018

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12 min
05/08/2020

Metastatic Pancreatic Cancer Guideline Update

An interview with Dr. Davendra Sohal from the University of Cincinnati, and Dr. Daniel Laheru from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins on "Metastatic Pancreatic Cancer: ASCO Guideline Update." This update covers new information on targeted therapies for metastatic pancreatic cancer. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines Transcript The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Davendra Sohal from the University of Cincinnati, and Dr. Daniel Laheru from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, co-chairs on Metastatic Pancreatic Cancer, ASCO Guideline update. Thank you for being here, Dr. Sohal and Dr. Laheru. Hi, Brittany. Thank you for inviting us. Happy to be here. Thanks. First, I'd like to note that ASCO takes great care in development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. But Doctor Sohal, do you have any relevant disclosures that are directly related to this guideline topic? No, I do not have anything directly in conflict. Thank you. And Dr. Laheru, do you have any relevant disclosures that are related to this guideline topic? Thank you, Brittany. I do not either. Great. Than delving into the guideline content, Dr. Laheru, can you tell us what prompted an update to this guideline? Yeah, sure. So what has been seen in almost every cancer is that with careful understanding of the molecular alterations of individual cancers, that targeted therapies have been developed for almost every cancer. And so for pancreas cancer, we have not had an opportunity in the past to use targeted therapies. Because for pancreas cancer, many of the genetic alterations that are found in other cancers are not seen in pancreas cancer. And so the guidelines were updated based on new evidence of the use of certain targeted therapies for pancreas cancer. Then Dr. Sohal, what are the key updates that were made to the recommendations in this guideline iteration? So the key updates relate to the so-called targeted therapies, the genomic-driven therapies that have now come up with evidence that pertains to pancreatic cancer as well. The overarching update is that every patient with metastatic pancreatic cancer who is a candidate for treatment should have tumor or somatic, the so-called somatic genomic profiling, as well as germline genomic testing, because these can lead to treatment recommendations. And those treatment recommendations include PD-1 checkpoint inhibitor therapies for microsat light instability high tumors, track the TRK fusion inhibitors, such as larotrectinib and entrectinib for track fusions in tumors. And PARP inhibitors, such as olaparib for germline BRCA1 or BRCA2 mutations to be used as maintenance therapy after stable disease on platinum-based therapy. Then Dr. Laheru, can you speak to the importance of this guideline and how it will drive changes to clinical practice? Yes. So as Dr. Sohal said, these specific genetic alterations, the mismatch repair deficiency, the use of PARP inhibitors for BRCA1, BRCA2 germline mutations or somatic mutations that are pathologically significant, and for the NTRK fusion transcripts, even though these mutations for pancreas cancer are quite unusual, less than 5%, for example, for NTRK fusion transcripts, 5% to 10% for BRCA1, BRCA2 germline mutations, and probably 1% or 2% for a mismatch repair deficient pancreas cancer, the committee felt that we should inform the larger cancer community that even though these mutations are uncommon, if they are found, they could be very important for individual treatment for pancreas cancer. And so this is why we really felt that it was time to provide an update, because of the recent information with the olaparib maintenance and with the NTRK inhibitors for the NTRK fusion transcripts. Great. And then finally, Dr. Sohal, how do you envision that this guideline update will affect patients? I think it expands our armamentarium for pancreas cancer patient management. It affords opportunities for better treatments, targeted therapies, which have hopefully higher efficacy and lower toxicity than standard chemotherapy, even though, as Dr. Laheru said, the proportion of patients being eligible for these therapies may be only around 5%. Still, in a disease where there are not many options, every 1 in 20 patients can get these therapies based on tumor genomic profiling and/or germline testing. And the other slightly different but associated topic is that if germline testing finds something in the patient, a bad gene, then obviously, that patient's blood relatives can be tested for that germline finding, and there may be implications for further testing and surveillance of family members. Well, thank you both for your work on this metastatic pancreatic cancer guideline update. And thanks for taking the time to speak with me today, Dr. Sohal and Dr. Laheru. It's our pleasure, Brittany. Thank you very much. Certainly. Thank you so much. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available on iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

05/08/2020

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7 min
24/07/2019

ASCO Guidelines: Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer Guideline

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

24/07/2019

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13 min
02/05/2018

Recently Approved Drugs: Blinatumomab for B-cell precursor ALL

Alex Ganetsky, PharmD, BCOP, oncology clinical pharmacy specialist at the Hospital of the University of Pennsylvania in Philadelphia discusses the approval to blinatumomab (Blincyto, Amgen Inc.) for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.

02/05/2018

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5 min
17/02/2022

Somatic Genomic Testing in Patients with Metastatic or Advanced Cancer Provisional Clinical Opinion

An interview with Dr. Funda Meric-Bernstam and Dr. Amber Johnson from the University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr. Mark Robson and Dr. Debyani Chakravarty from Memorial Sloan Kettering Cancer Center in New York, New York, authors on "Somatic Genomic Testing in Patients with Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion." They discuss the key statements of the provisional clinical opinion, including the topics: multigene panel-based genomic sequencing with disease-specific approved markers, assessment of mismatch repair deficiency and/or microsatellite instability-high status and tumor mutational burden, testing for gene fusions and exon skipping variants, decision making for panel tests with no approved disease-specific markers, and elements to consider while reviewing genomic testing results. Read the full PCO at www.asco.org/assays-and-predictive-markers-guidelines.

17/02/2022

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22 min
27/06/2018

Recently Approved Drugs: Durvalumab for patients with stage III Non-Small Cell Lung Cancers (NSCLC)

Rami Manochakian, M.D., a thoracic clinical oncologist at the Mayo Clinic in Florida, presents information on the recently approved drug in oncology, durvalumab for patients with stage III Non-Small Cell Lung Cancers (NSCLC) after the completion of radiation therapy.

27/06/2018

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11 min
13/11/2019

Cancer Topics - ASCO Guidelines: Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx Guideline

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

13/11/2019

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13 min
03/01/2013

Estimating the Risk for Contralateral Breast Cancer as a Guide for Surgical Treatment

This podcast discusses approaches to risk assessment of contralateral breast cancer and factors which predict the risk.

03/01/2013

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7 min
08/02/2019

How Should We Interpret Indeterminate Pulmonary Nodules at Diagnosis in Children With Rhabdomyosarcoma?

This JCO podcast provides observations and commentaries on the JCO article entitled "Indeterminate Pulmonary Nodules at diagnosis in Rhabdomyosarcoma: Are they clinically significant?" A report from the European Pediatric Soft Tissue Sarcoma Study Group by Bas Vaarwerk, MD et al. My name is Alberto Pappo and I am the head of the division of solid tumors at St Jude Children's Research Hospital in Memphis, TN. My oncology specialty is pediatric oncology. In this report, Bas Vaarwerk, and investigators from the European Pediatric Soft Tissue Sarcoma Study Group evaluated the significance of indeterminate pulmonary nodules at diagnosis in children with rhabdomyosarcoma defined as the presence of less than 5 pulmonary nodules measuring less than 5mm or 1 pulmonary nodule that measured between 5 and 9 millimeters. This analysis included 316 patients who were enrolled on the EpSSG RMS 2005 study for non-metastatic rhabdomyosarcoma from September 2005 through December 2013 and for whom chest computed tomography scans were obtained at diagnosis and were available for review. Treatment in the EpSSG RMS 2005 study was stratified according to risk group, pathology, post-surgical stage, site, nodal involvement, size and age. All patients received multi agent chemotherapy with ifosfamide (except for low risk patients), vincristine and actinomycin D (IVA chemotherapy). High risk patients were randomized to IVA or IVA with doxorubicin and after 9 courses if in complete remission, were eligible for a second randomization between end of therapy and additional maintenance therapy with 6 courses of vinorelbine and cyclophosphamide Local control was determined by risk group, tumor site, age and response to therapy and radiotherapy was given at week 13 in doses ranging from 36 to 51.4Gy. All chest computed tomography scans were reviewed by the local radiologist at the treating center. Data was obtained and recorded using case report forms. All computed tomography scans were performed with minimum slice thickness of 3 to 5 mm. The median age at diagnosis for the 316 eligible patients was 5.4 years and the median follow up time for the cohort was 75 months. There were 249 (78%) patients who did not have a pulmonary nodule and 67 (21%) who had at least one indeterminate pulmonary nodule. Patient and treatment characteristics were similar between the 2 groups; 80% of the patients presented with Group III unresectable disease, 54% had high risk disease, and 71% had favorable histology tumors such as embryonal histology tumors. Twenty four percent of patients received maintenance chemotherapy and 77% were treated with local radiotherapy A total of 100 nodules were identified in the 67 patients. Nodules ranged in size from 1 to 8 mm. 69% of the patients presented with one pulmonary nodule, 92% of the patients had nodules that measured less than 5 mm 85% of the nodules were unilateral. The 5-year event-free survival for patients with indeterminate pulmonary nodules was 77% and for those without nodules 73.2%. These differences were not statistically significant with a p value of 0.68. The 5-year overall survival rates were 82% for patients with indeterminate pulmonary nodules and 80.8% for those without nodules. The differences between these 2 groups were not statistically significant with a p value of 0.76. There were no significant differences in outcomes based on the number or size of the nodules. Similarly, there were no differences in clinical outcome based on histology, fusion status, age and type of chemotherapy received. Lung metastases developed in 3% of patients with indeterminate pulmonary nodules and in 1.6% of patients without nodules a value that was not statistically significant. The authors conclude that the presence of indeterminate pulmonary nodules in newly diagnosed children with rhabdomyosarcoma as defined in this report does not adversely affect the outcome of these patients and these children can be adequately treated with non-metastatic risk-based clinical protocols. This report highlights the challenges of assigning risk and therapy based on the presence of a limited number of small pulmonary nodules in children with newly diagnosed rhabdomyosarcoma when they are detected using newer imaging modalities such as thin cut computed tomography of the chest. The authors have successfully demonstrated in this retrospective study that newly diagnosed patients with rhabdomyosarcoma who present with indeterminate oligometastatic disease to the lung which in this study was defined as the presence of 4 or fewer pulmonary nodules measuring less than 5 mm or one nodule that measures 5 to 9 mm, have similar outcomes to patients who present without pulmonary nodules. More importantly, these patients can be treated with less intense trials that may include the use whole lung irradiation which is known to significantly increase the risk of breast cancer in childhood cancer survivors. The authors have implemented a standardized definition for indeterminate oligometastatic lung disease which is highly reproducible and easily implemented. Their results are thought provoking and deserve further validation in a well- designed prospective clinical trial. Because of the lack of pathologic correlation with imaging findings in this report, it is not possible to determine which patients truly had oligometastatic disease to the lung. It is conceivable that some of the 67 patients with indeterminate nodules did not have actual metastatic rhabdomyosarcoma in the lung, or alternatively these results may also indicate that current risk-based therapies for localized disease are effective at eradicating small oligometastatic disease. It is important to point out however, that in this report, about one fourth of the patient population was assessed using reconstruction widths of ≤ 1.25 mm, which might have identified a larger number of small nodules of uncertain significance. In addition, 69% of the patients with indeterminate nodules had only one nodule, 92% had nodules that measured less than 5 mm and 85% had unilateral disease. All of these factors have been associated with a significantly lower likelihood of identifying biopsy proven metastatic disease in pediatric patients with sarcomas. These findings raise questions as to whether thin cuts In summary, this report opens new areas for clinical research that could lead to a uniform strategy for defining metastatic pulmonary disease in pediatric rhabdomyosarcoma and a more precise method for risk-stratifying disease in this patient population. This concludes this JCO Podcast. Thank you for listening.

08/02/2019

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8 min

ASCO Podcasts by the American Society of Clinical Oncology, cover a range of educational and scientific content, offering enriching insight into the world of cancer care. Hear innovative interviews with the authors, researchers, and clinicians who are defining today’s standard of care and tomorrow’s breakthroughs. You can find all ASCO podcasts and limited series at ascopubs.org/podcasts