ASCO Guidelines

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

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

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

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

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

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

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

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

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

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