ASCO Guidelines

An interview with Dr. Fabrice André from Institute Gustave Roussy in Paris, France, and Dr. Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, NY, authors on "Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update." This updated guideline provides precise guidelines on previously endorsed genomic assays and recommendations on the use of new biomarkers to guide endocrine therapy and chemotherapy in patients with ER-positive HER2-negative tumors, and for those with HER2-positive or triple-negative breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines. TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Fabrice André from Institut Gustave Roussy in Paris, France, and Dr. Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, NY, authors on "Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update." Thank you for being here Dr. André and Dr. Jhaveri. Dr. Fabrice André and Dr. Komal Jhaveri: Thank you. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of guidelines and ensuring that the ASCO conflict of interest policies follow each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. André, do you have any relevant disclosures that are directly related to this guideline. Dr. Fabrice André: No. Brittany Harvey: Thank you. And Dr. Jhaveri, do you have any relevant disclosures that are related to this guideline topic? Dr. Komal Jhaveri: No. Brittany Harvey: Great, then let's talk about the content of this guideline update. So, Dr. Jhaveri, what prompted the update to the biomarkers for adjuvant endocrine therapy and chemotherapy in early-stage breast cancer, and what is the scope of this guideline update? Dr. Komal Jhaveri: So, since the biomarker guideline published in 2016, there were several new publications that came out between January 2016 and October 2021 that provided perspectives on the use of some of the genomic assays broadly, or specifically in women based on menopausal status, age or number of lymph nodes. Additionally, new biomarkers such as programmed cell death receptor ligand 1 or PD-L1, stromal TILs, circulating tumor DNA, or circulating tumor cells, or new applications, like extended endocrine therapy have also been developed. So, this updated guideline provides precise guidelines on previously endorsed genomic assays and also provides recommendations on the use of new biomarkers to guide endocrine therapy and chemotherapy in ER-positive HER2-negative, HER2-positive, and triple negative breast cancer. Brittany Harvey: Great. Thank you for setting the stage for this guideline. So, then Dr. André, I'd like to review the key recommendations of the guideline for our listeners. So, starting with, which biomarkers should be used to guide decisions on adjuvant endocrine and chemotherapy for patients with newly diagnosed ER-positive HER2-negative breast cancer? Dr. Fabrice André: Thank you. So, when we are focusing on a newly diagnosed patient with ER-positivity HER-2 negative in the context of the question about deciding on chemotherapy. First, the 21 gene recurrence score should be used in patients with node-negative and in patients with 1-3 node positive who are postmenopausal. In premenopausal, this test will be used only in patients with node-negative. The second test that is recommended is the MammaPrint 70-gene signature. And here the recommendation is to use this test if the patient is older than 50 and is node-negative or 1-3 node-positive. If the patient is 50 years or younger, the clinician should not use this test. Then also a recommendation is that the clinician could use the 12 gene risk score EndoPredict if the patient is postmenopausal and has breast cancer node negative or 1-3 positive-node. And finally, for the genomic test for the patient, the doctor could use PAM50. If the patient is postmenopausal and has breast cancer that is node-negative. Something new in this recommendation is the recommendation that the clinician could use Ki67. If the patient is postmenopausal and has stage I-II breast cancer with very specific recommendations on the cut off for positivity. Brittany Harvey: Great. Thank you for reviewing those recommendations, Dr. André, and highlighting the new Ki67. So, then, in your introduction, Dr. Jhaveri, you discuss the application of assays for extended endocrine therapy. So, which biomarkers should be used to guide decisions regarding extended endocrine therapy for patients with ER-positive HER2-negative breast cancer? Dr. Komal Jhaveri: Thank you. So, a quick word about extended endocrine therapy. I think extended adjuvant endocrine therapy, which is beyond five years of primary endocrine therapy, has certainly demonstrated improved outcomes, however, with modest absolute benefit and added toxicity and tolerability issues. Furthermore, while extended endocrine therapy is endorsed by clinical practice guidelines, clear guidance on individualized approaches to optimize patient selection for prolonged endocrine regimens, also remains limited. And this really underscores the need for prognostic and predictive information from genomic assays that can help guide this important clinical question we face. One such example that has now borne out has been the breast cancer index and really collected evidence from now five studies supports the prognostic and predictive utility of this assay, such that if a patient has node-negative or one to three positive nodes, and has been treated with five years of primary endocrine therapy, to guide decisions about extended endocrine therapy, the clinician may offer Breast Cancer Index with either tamoxifen or aromatase inhibitors or tamoxifen, followed by an aromatase inhibitor. Brittany Harvey: Great, thank you, Dr. Jhaveri. So, then, Dr. André, which biomarkers should be used to guide decisions on adjuvant therapy for early-stage HER2-positive breast cancer or triple-negative breast cancer? Dr. Fabrice André: Well, first, we have to be sure that we are good at defining HER2-positive breast cancer and triple-negative breast cancer. So, it's always good to remind colleagues to have quality control assessment in place for HER2, estrogen receptor, and progesterone receptor stainings. So far, when it's about predicting the benefit of adjuvant chemo or trastuzumab, there is no genomic test that is recommended in patients with HER2-positive or triple-negative breast cancer. Brittany Harvey: Great, thank you. So, then, Dr. Jhaveri, what recommendations did the expert panel make regarding emerging biomarkers? Dr. Komal Jhaveri: When we're talking about emerging biomarkers, we're referring to stromal TILs, we're referring to PD-L1, circulating tumor cells, and circulating tumor DNA. And while there is a lot of emerging data, currently, clinicians should not be utilizing these new biomarkers to guide decisions about adjuvant endocrine therapy or chemotherapy, as we do not have sufficient evidence to support their use. Brittany Harvey: Great and that's important for clinicians to know. So, then finally, Dr. André, in your view, how will these updated guideline recommendations impact both clinicians and patients? Dr. Fabrice André: So, we know Komal mentioned this at the beginning that now there is a very large amount of new publications, new data coming every day in the field of cancer. So, the only way for clinicians to deliver the best treatments for patients is to have the right guidelines with the right methodology, and ASCO is really putting in place a very rigorous methodology to deliver guidelines. And this is the best way to be sure that all patients will have access to the best decision by the doctor. So guidelines are also here to decrease the disparities in terms of the expert decision, and any patient in the world can have access to the best decision, thanks to guidelines delivered by ASCO and all the colleagues of the panel that worked very hard to deliver these guidelines. Brittany Harvey: Excellent! Well, thank you both so much, and the entire expert panel for your work to update these guidelines, and for taking the time to speak with me today, Dr. André and Dr. Jhaveri. Dr. Komal Jhaveri: Thank you. Dr. Fabrice André: Thank you, Brittany. Brittany Harvey: Thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines in interactive resources in the free ASCO guidelines app available in iTunes or Google Play Store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO the mention of any product or service organization activity or therapy should not be construed as an ASCO endorsement.

Dr. Lisa Carey, a medical oncologist from the University of North Carolina Lineberger Comprehensive Cancer Center, sheds light on the recent updates regarding pembrolizumab for early-stage triple-negative breast cancer. She discusses the significance of the Keynote 522 trial and its implications for patient care. Additionally, she explains that PD-L1 testing is not necessary in these cases and shares insights on the broader practical applications of the guidelines. Dr. Carey also addresses outstanding questions regarding chemotherapy strategies and surgical considerations.

An interview with Dr. Linus Chuang from Danbury Hospital and Norwalk Hospital, Nuvance Health in Connecticut and New York, co-chair on "Management and Care of Patients with Invasive Cervical Cancer: ASCO Resource-Stratified Guideline Rapid Recommendation Update." Dr. Chuang discusses the updated recommendation on the use of pembrolizumab in patients with persistent, recurrent, or metastatic cervical carcinoma, based on the results from the KEYNOTE-826 study. For more information, visit, www.asco.org/resource-stratified-guidelines. Transcript BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Linus Chuang from Danbury Hospital in Norwalk Hospital, Nuvance Health, in Connecticut and New York, Co-Chair on "Management and Care of Patients with Invasive Cervical Cancer-- ASCO Resource-Stratified Guideline Rapid Recommendation Update." Thank you for being here, Dr. Chuang. LINUS CHUANG: Thank you for having me. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline is available online with a publication in the Journal of Clinical Oncology Global Oncology. Dr. Chuang, do you have any relevant disclosures that are directly related to this guideline topic? LINUS CHUANG: No, Brittany. BRITTANY HARVEY: Thank you. Then talking about the content of this publication, so what prompted this rapid update to the "Management and Care of Patients with Invasive Cervical Cancer-- ASCO Resource-Stratified Clinical Practice Guideline," last published in 2016? LINUS CHUANG: ASCO Rapid Recommendations Updates highlight revisions to ASCO guideline recommendations on "Management and Care of Women with Invasive Cervical Cancer, the ASCO Resource-Stratified Clinical Practice Guideline" that was published in September of 2016. We revised the guidelines to reflect new and practice-changing data on the use of pembrolizumab combination therapy in patients with metastatic, recurrent, or persistent cervical cancer in enhanced and maximal settings. BRITTANY HARVEY: Great. Then based off this new data for the pembrolizumab combination therapy, what are the updated recommendations from the guideline panel? LINUS CHUANG: Based on this recently published report about the KEYNOTE-826 study, the checkpoint inhibitor pembrolizumab alongside standard chemotherapy with or without bevacizumab as first-line therapy significantly improved the overall and progression-free survival in patients with persistent, recurrent, or metastatic PD-L1 expressing cervical cancer. BRITTANY HARVEY: Great. Thank you for providing that recommendation. So what should clinicians know as they implement these recommendations, and for which settings do these recommendations apply? LINUS CHUANG: This trial included 617 patients, pembrolizumab 200 milligrams delivered intravenously every three weeks in combination with standard chemotherapy and with or without bevacizumab for up to 35 cycles. It's worth emphasizing based on the following study results the median progression-free survival was 2.2 months longer in the pembrolizumab group that have a PD-L1 combined positive score of 1 or more. And the progression-free survival at 12 months was also longer by 20% in the pembrolizumab group when compared to the placebo group. The overall survival rate at 12 and 24 months were higher in the pembrolizumab group-- 75% and 53% respectively-- compared with the placebo cohort-- 63% and 41% respectively. According to the study, the most common adverse reactions, which occur in more than one in five patients in the pembrolizumab group, are anemia, neutropenia, alopecia, and peripheral neuropathy. Based on this data our rapid communication recommended this regimen be used in the enhanced and maximal settings where the pembrolizumab is available. BRITTANY HARVEY: Great. Thank you for reviewing that data in the context of this recommendation. So how will these guideline recommendations impact patients? LINUS CHUANG: So pembrolizumab with the standard chemotherapy with or without bevacizumab demonstrated improvement in the progression-free and overall survival much longer than those without the pembrolizumab group. And this has emerged as a front-line therapy for the group of patients that have persistent, recurrent, or metastatic cervical cancer with PD-L1 expression cervical cancer. BRITTANY HARVEY: OK, thank you. And then finally, what emerging evidence is the panel anticipating regarding treatment of invasive cervical cancer? LINUS CHUANG: This is an exciting time. Exploration of other PD-1 and PD-L1 inhibitors, monotherapy, or as part of combination therapy for cervical cancer will expand the management of patients with recurrent or metastatic cervical cancer that progressed after platinum-based chemotherapy. It is also important to explore the ability of pembrolizumab with chemoradiation with or without concurrent and maintenance pembrolizumab to improve outcomes for patients with high-risk locally advanced cervical cancer. BRITTANY HARVEY: Great. That's very exciting to see that evidence coming to fruition. So I want to thank you so much for your work to rapidly update this guideline and for your time tonight, Dr. Chuang. LINUS CHUANG: Thank you for having me today. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/resource stratified guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. SPEAKER 3: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

An interview with Dr. Andrea Eisen from Sunnybrook Odette Cancer Centre and Ontario Health in Toronto, Ontario, co-chair on "Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update." This guideline updates recommendations for which patients with primary breast cancer should be treated with bone-modifying agents, and which bisphosphonates are optimal. Read the full guideline at www.asco.org/breast-cancer-guidelines. TRANSCRIPT [MUSIC PLAYING] BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Andrea Eisen from Sunnybrook Odette Cancer Center and Ontario Health in Toronto, Ontario, lead author on "Use of Adjuvant Bisphosphonates and other Bone-Modifying Agents in Breast Cancer," American Society of Clinical Oncology and Ontario Health Cancer Care Ontario Guideline Update. Thank you for being here, Dr. Eisen. ANDREA EISEN: Thanks very much for the opportunity. BRITTANY HARVEY: And I'd like to note that ASCO takes great care of the development of its guidelines and ensuring that the ASCO conflict-of-interest policy is followed for each guideline. The full conflict-of-interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Eisen, do you have any relevant disclosures that are directly related to this guideline topic? ANDREA EISEN: I have no disclosures. BRITTANY HARVEY: Thank you. Then let's talk about the content of this guideline. So what prompted an update to this guideline published in 2017, and what is the scope of this update? ANDREA EISEN: So ASCO has a guideline update process which triggers updates and reviews when new data are available. And for this particular guideline, an update was prompted by publication of three randomized trials. And during the update process, a fourth trial was published that was relevant for the guidance document. BRITTANY HARVEY: Great. That's great background. So then next, I'd like to review the key recommendations of this guideline for each clinical question, starting with, which patients with primary breast cancer should be treated with bone-modifying agents? ANDREA EISEN: The first recommendation for this guideline is that adjuvant bisphosphonate therapy should be discussed with all postmenopausal breast cancer patients, regardless of their hormone receptor status, or HER2 status, who are candidates to receive adjuvant systemic therapy. BRITTANY HARVEY: Great. And then what is recommended for which bisphosphonates should be used for breast cancer adjuvant therapy, and what doses, duration of administration, time to initial treatment, and routes are optimal? ANDREA EISEN: For this question, there were a number of different regimens available for review and inclusion in the guideline, because the studies used several different treatment protocols. However, the guideline recommends that adjuvant bisphosphonates should be started early, and ideally within three months of the definitive surgery or within two months of completion of adjuvant chemotherapy. The options for treatment include oral clodronate, oral ibandronate, or several different dosing regimens of zoledronic acid. BRITTANY HARVEY: Great. So then you've just mentioned three different bisphosphonates. So what is the role of the bone-modifying agent denosumab as an adjuvant therapy for primary breast cancer? ANDREA EISEN: This was a difficult, and perhaps the most contentious area that the committee considered, because there are two very important clinical trials that were reviewed. The first, the ABCSG trial, and the second was the more recently published D-CARE study. The guideline committee does not recommend the use of adjuvant denosumab for the prevention of breast cancer recurrence in early stage breast cancer patients. BRITTANY HARVEY: That's helpful for clinicians to know, both which are recommended and which aren't recommended at this time. So then finally, Dr. Eisen, in your view, what is the importance of this guideline update, and how does it impact both clinicians and patients with cancer? ANDREA EISEN: There are at least two issues that make this guideline particularly timely and important. First, there's new clinical trial guidance available, in particular with respect to scheduling and dosing of bisphosphonates and route of administration. These data also highlight the benefits of bisphosphonates. The second is that the new evidence confirms our previous recommendation that denosumab is not recommended as adjuvant treatment in early stage breast cancer patients. During the development of this update, it became apparent that the uptake of adjuvant bisphosphonate usage in breast cancer patients is probably suboptimal. And there is a number of reasons for this across different jurisdictions. Some reasons include variable access to different formulations of the bisphosphonates. For example, oral clodronate, which is well studied, is not available in the United States. The second issue that was highlighted was variable access for patients with respect to insurance coverage. And we also identified that even in jurisdictions where funding is fully provided for adjuvant bisphosphonates, uptake might be suboptimal. So we hope that publishing this guideline and reviewing the evidence and highlighting the potential benefits in terms of reduction in recurrence and improvement in survival will result in more utilization of the bisphosphonates. We recognize that there are potential toxicities associated with the treatment and that the benefits versus risks have to be weighed carefully. The guideline committee recommended the utilization of an online risk assessment tool to help in those discussions with patients and to determine which patients have sufficient risk to justify using bisphosphonates. BRITTANY HARVEY: Great. Those access issues are important to highlight. And I appreciate all of the work that you've done on this guideline update and also for taking the time to speak with me today, Dr. Eisen. ANDREA EISEN: Thanks very much. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.ASCO.org/breast cancer guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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

An interview with Dr. Mark Kris from Memorial Sloan Kettering Cancer Center in New York, NY, author on "Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA Completely Resected NSCLC: ASCO Guideline Rapid Recommendation Update." Dr. Kris discusses the results and impact of two recently published RCTs, and the updated recommendations on the use of osimertinib and atezolizumab. For more information, visit, www.asco.org/thoracic-cancer-guidelines. TRANSCRIPT [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Mark Kris, from Memorial Sloan Kettering Cancer Center in New York, New York, author on Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage One to 3A Completely Resected Non-small Cell Lung Cancer ASCO guideline rapid recommendation update. Thank you for being here, Dr. Kris. MARK KRIS: You're very welcome. And on behalf of the Adjuvant Guideline Committee, thank you for giving this opportunity today to speak to you. I have had financial report from AstraZeneca, Pfizer, Sanofi Genzyme, and also editorial support from Hoffman-La Roche. Every year, 35,000 Americans received the diagnosis for early stage lung cancers. And that is, lung cancers that could be helped by surgery. It's a large number of patients. Many of them can be cured by operations, but not all. When people fail to be cured by surgery, the problem is not an unsuccessful surgery, but rather the spread of cancer to other parts of the body, very often cancer that's not suspected by any test that we have in 2022. What physicians do is to give medicines before or after surgery to try to increase the chance of cure with a successful surgery. And the guideline we're talking about today deals with the recommendations of the American Society of Clinical Oncology Adjuvant Lung Cancer Guideline Committee for new treatments to increase the chance of cure in patients that have successful lung cancer surgeries. BRITTANY HARVEY: Great. Thank you, Dr. Kris, for both that background and for providing your disclosures for this guideline. You just mentioned what this guideline's purpose is, but this is specifically a rapid update. So what prompted this rapid update to the adjuvant systemic therapy and adjuvant radiation therapy for stage one to 3A completely resected non-small cell lung cancers, which was last updated in 2017? MARK KRIS: In the last year, there have been extremely important developments in the lung cancer field. There have been two medicines that have been proven to delay or prevent the recurrence of lung cancer after a successful surgery. One of them is a targeted therapy, the other an immunotherapeutic. And both of these medicines have had the clinical trials that discovered them presented at major meetings, including the ASCO meeting. They also have had major publications in medical journals. And both of these medicines are now FDA approved. This is a new therapy, great addition to our therapy, and it includes drugs that are available to every doctor in the United States for patients in this situation. So there was the need to get this information out early and to get the word out to doctors everywhere to consider these medicines for the appropriate patients. BRITTANY HARVEY: Understood. Then based off this new data for these new therapies that you just mentioned, what are the updated recommendations from the guideline panel? MARK KRIS: The current recommendations, and I'll break it up into two settings. One of them is for stage 1B, B as in boy. And these are larger tumors, but only tumors in the lung. And the second set of recommendations are for lung cancers that also have evidence of spread to the adjacent lymph nodes or lymph glands. Now up until these new recommendations, for the people with the 1B cancer, and that is the larger tumor only in the lung, the recommendation was there was no routine recommendation. That each case got discussed individually and a decision was made whether or not to recommend a chemotherapy program based on the drug cisplatin. It's not right for every patient and requires a fair amount of discussion and evaluation to decide who it's right for. What the guideline adds now, though, is for genetic testing of the tumor tissue removed at surgery to search for the presence of a certain mutation, the EGFR mutation, in the tumor tissue. And if that mutation is found, the recommendation is to give the drug osimertinib, a pill, for three years following a successful surgery and following chemotherapy. What they found in that trial was that people who received this pill had a clear and dramatic improvement in the return of the cancer. The cancer was greatly delayed or, hopefully as time goes on, we'll learn did not return at all. This is an important change, because up until then, there was no specific recommendation for patients in this 1B group. Now if you have the EGFR mutation in the tumor, we are recommending that every patient could receive osimertinib. The other big change here is because there is the need to know if a mutation is present, part and parcel of that is the routine testing of tumor tissue. To make this happen, your surgeon and medical oncologist need to obtain tumor testing on every person to see if these EGFR mutations are present. And if indeed they are, to recommend osimertinib. The second development was the identification of a drug called atezolizumab. And this is a drug that energizes the immune system. They call it a checkpoint inhibitor, an anti-PD-1 PD-L1 drug, a lot of different names. What they found in this second trial is that patients whose tumor tissue had some identified presence of this particular protein, the PD-L1 protein, again, a routine test, if you had this protein present and you received the atezolizumab, you, again, had improvement in the delay of cancer and as time goes on, hopefully that the cancer won't return at all. Again in that trial, the use of the atezolizumab followed cisplatin-based chemotherapy, our old recommendation. So these two papers led to these really important changes in our recommendations to all patients with this illness. Patients with EGFR mutations get osimertinib. Patients that don't have an EGFR mutation but instead have expression of pd-l1 and have a lung cancer that's in a lymph gland as well as the lung, they routinely now have the checkpoint inhibitor, atezolizumab recommended. BRITTANY HARVEY: Thank you for that summary of these new recommendations. So then what should clinicians know as they implement these recommendations for osimertinib and atezolizumab? MARK KRIS: One change in treatment that these new medicines have brought about is the need to do genetic testing, generally a comprehensive panel of genetic testing, some call it NGS testing, multiplex testing, on the tumor tissue removed at surgery. You need to know if this EGFR mutation is present. And if so, you're a candidate to receive the osimertinib stages 1B, stage two, and stage 3A. Conversely, if that EGFR mutation is present, the benefit from atezolizumab is much less. And for those patients, to know if atezolizumab could be useful, you need to do a separate test, a so-called immunohistochemistry test. That can be done in any pathology department in the US. And this test looks for the presence of this pd-l1 protein. And if the protein is there, it means that the drug atezolizumab can be useful. And that mutation is found really in the majority of patients that don't have the EGFR mutation. BRITTANY HARVEY: Great. And then in your view, how will these guideline recommendations impact patients? MARK KRIS: Well, we are very interested in delivering to our patients what they want. And that is, after surgery to live lives free of cancer and to live lives as they choose and a life not dictated by the cancer. The way to do that is to prevent the recurrence of the cancer, extend the time that they are free of cancer so they can live their normal life. And both of these medicines have been able to do that. What we can do now is offer patients the chance for a more normal life, or extension of their normal life without cancer by adding on these new medicines after cisplatin-based chemotherapy and after their surgery. BRITTANY HARVEY: Definitely. This is an important intervention for patients. So then finally, Dr. Kris, what are the outstanding questions regarding adjuvant therapy for patients with stage one to 3A completely resected non-small cell lung cancer? MARK KRIS: I think the biggest question that remains is what do we do for those patients that don't have the EGFR and don't have this pd-l1 standing? At present, our recommendation is that we would recommend cisplatin-based chemotherapy. And there would be some consideration for radiation as well if there's a spread to mediastinal lymph glands, and I would urge a consultation with the radiation oncologist when the mediastinal lymph glands were involved with the cancer to see if that can be helpful. But we don't have this extra treatment today to recommend to these patients like we do for the ones with EGFR and pd-l1. The second thing we'd like to do would be able to better tell who needs these extra treatments and who needs more intensive extra treatments. Some people are cured by surgery alone. And it would be fantastic to know who those people were so as to focus our efforts on those people that need additional therapy and spare the people that don't need additional therapy the lifestyle disruption that comes on with treatment. And there are a bunch of emerging technologies, and I want folks to know that docs across the country, researchers, are working hard to find ways to say, who needs the treatments. And three things are being tested now. One of them is a more detailed examination of the tumor tissues. This is particularly important in patients that got their chemotherapy before surgery, and our pathology colleagues are working to see how effective treatments are given the drugs before surgery. And there's more and more a push to give drugs not after surgery, but before surgery, because then we can tell in the tumor specimen that's removed at the time of surgery if they worked or not. The second thing is to examine these tissues, not just with the eye of the pathologist under the microscope, but to use digital images and to use artificial intelligence to look at the tumors that are present, and perhaps also tumor that's present after initial therapy, and take the appearance of that cancer and correlated with the long term outcome. So to be able to tell using machine learning, artificial intelligence, advanced computing systems, whether or not the cancer is likely to recur. And there's been some preliminary work in this presented at the ASCO meeting last year that this promise appears to be inching toward reality. It's not simply pi in the sky. The last thing that's being developed is the ability to look for traces of cancerous DNA in the bloodstream. What you would do is check for cancerous DNA before surgery and check again after surgery. And if we find that cancerous DNA persists in the bloodstream, that would be a trigger to give therapy or give more intensive therapy. And a number of clinical trials have already reported on this that it is feasible and possible, and the early results are that it likely will be another way to tell who will benefit from therapy, who needs it most, and hopefully who doesn't need it, if we can. So a lot of questions to be answered, a huge amount of research. I'm quite confident that it's going to lead to more effective therapies. It's going to lead to more targeted therapies and it's going to lead to sparing patients from getting treatments when their cancer is already taken care of. BRITTANY HARVEY: Absolutely. We look forward to that promising research to improve outcomes for patients. So I really want to thank you for all your work on this guideline rapid recommendation update and for taking the time to speak with me today, Dr. Kris. MARK KRIS: And if I could just say a final word, I'm doing this today on behalf of the Guideline Committee led by Laurie Gaspar from University of Colorado in Denver and Katherine Pisters from M.D. Anderson. They and the other panel members very quickly did this. This whole process happened in just a few months. It was very quickly brought together and posted on the ASCO website. I believe it was posted on January 10th and will shortly appear in the Journal of Clinical Oncology to get the word out. I think to me it's a testimony to ASCO's willingness to quickly get out cancer advances to our patients and the process that ASCO has put in place, I think, worked really well here, going from an idea to get this information out to getting it out to practitioners all over the country in just a few months. BRITTANY HARVEY: Absolutely. We thank the co-chairs and the entire panel for their work on this guideline. And also, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/thoracic cancer guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

An interview with Dr. Nancy Baxter from the University of Melbourne in Melbourne, Australia, and Dr. Jeffrey Meyerhardt from Dana-Farber Cancer Institute in Boston, MA, co-chairs on "Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update." This guideline updates recommendations for adjuvant therapy for patients with resected stage II colon cancer. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines. TRANSCRIPT [MUSIC PLAYING] ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Nancy Baxter from the University of Melbourne in Melbourne, Australia, and Dr. Jeffrey Meyerhardt from the Dana-Farber Cancer Institute in Boston, Massachusetts, co-chairs on adjuvant therapy for stage II colon cancer ASCO guideline update. Thank you for being here, Dr. Baxter and Dr. Meyerhardt. NANCY BAXTER: Thank you for having us. JEFFREY MEYERHARDT: Thanks. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines in ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Baxter, do you have any relevant disclosures that are directly related to this guideline topic? NANCY BAXTER: I don't, Brittany. BRITTANY HARVEY: Thank you. And Dr. Meyerhardt, do you have any relevant disclosures that are directly related to this guideline topic? JEFFREY MEYERHARDT: I don't, either. Thank you. BRITTANY HARVEY: Thank you, both. And getting into the content of this guideline, what prompted this guideline update, and what is the scope of this guideline? NANCY BAXTER: Well, it's been since 2004 that we've had a guideline that gives us advice about stage II colon cancer and the use of adjuvant therapy in this group of patients. And it's one where clinicians often have a lot of challenges in helping patients make decisions about what's best for them in terms of long-term survival from colon cancer. There have been changes in guidelines for stage III colon cancer. And so we thought it was timely to reevaluate our best practice recommendations for stage II colon cancer patients. JEFFREY MEYERHARDT: Yeah, I agree, Dr. Baxter. I think that this is one of the most challenging conversations that oncologists have with patients. Should they get chemotherapy? What type of chemotherapy? And as you know, there are a variety of higher risk features, of which we're able to sort of tease out a little better relatively, in terms of thinking about someone's stage II disease and trying to bring all that data together and provide some framework in the conversation for clinicians to have with patients. BRITTANY HARVEY: Great, thank you both for that background information. So then this guideline covers four clinical questions. And I'd like to review the recommendations for each question. So Dr. Baxter, starting with question 1, what does the guideline recommend for patients with resected stage II colon cancer regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy versus surgery alone? NANCY BAXTER: So overall, what we did was we looked at the risk that individual patients with stage II colon cancer have. So for patients that are at low risk of recurrence-- and so those are patients with stage IIA or T3 tumors that have at least 12 sample lymph nodes in the surgical specimen and don't have any high-risk features, and I'll go over those with the later recommendations-- these patients do not need adjuvant chemotherapy. It should not be routinely offered to them because the harms may outweigh the benefits. And so the evidence of that, although the quality of the evidence was relatively low, there is quite a bit of evidence that, really, the benefits do not outweigh the risks in this particular group. That is different for patients that are at higher risk, though, within the stage II group. And so those are the patients with stage IIB or stage IIC colon cancer. So those are T4 lesions that either penetrate through the visceral peritoneum or invade surrounding organs. And in those patients, adjuvant chemotherapy may have more benefit. And so a discussion of the potential benefits and risks of harms associated with chemotherapy should be had with patients. And those are patients that should be offered adjuvant chemotherapy for their disease. Now, there's a group of patients with high-risk features-- so not the stage IIB or stage IIC-- but there's a group of patients within stage IIA. So these are patients that are T3 patients where there are high-risk features. And chemotherapy may be offered to these patients, based on their risk features. So I'll go over a little bit about what the high-risk features are that might make patients included in this group. So that is sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphatic invasion, poor or undifferentiated tumor grade, intestinal obstruction, tumor perforation, and grade BD3 tumor budding. That's more than, or equal to, 10 buds in the tumor. And so that's because these patients are at higher risk of recurrence, and the chemotherapy may be more beneficial in these patients because they have a higher baseline risk of recurrence. There were a few risk factors that it was really challenging to make any decision on. And that was specifically circulating DNA. We know that that's an area of great interest, but there really was not enough evidence of the predictive value of ctDNA when you're looking at adjuvant chemotherapy in this group to make a recommendation. We'd expect future versions of this guideline to have some recommendations about that. We do know that there is controversy around the timing of chemotherapy. So we didn't include reports on this for the guideline because we didn't have enough related to stage II colon cancer and the role of adjuvant therapy. But the trials have generally started patients on chemotherapy within six to seven weeks of surgery. And finally, all of this needs to be a part of shared decision-making. So particularly for patients at higher risk-- so stage 2A at higher risk-- it's important that this is discussed-- the risks and benefits of chemotherapy, and the possible benefits with respect to the risk of recurrence for these patients-- is discussed as part of the shared decision-making process to come to an ultimate decision about the use of chemotherapy. BRITTANY HARVEY: Understood. Thanks for detailing those recommendations stratified by risk and identifying what those high-risk features are. So then, additionally, Dr. Meyerhardt, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for patients with tumors that exhibit mismatch repair deficiency or microsatellite instability or patients with proficient mismatch repair, or microsatellite-stable, tumors? JEFFREY MEYERHARDT: Yeah, so this was a specific question that we also looked at. What we know is about 15% of stage II colon cancers have evidence of mismatch repair or microsatellite insufficiency. And data that was realized now several decades ago on several different papers-- one larger one published in The New England Journal by Dan Sargent-- showed that patients who have stage II disease who receive a fluoropyrimidine only seem to not benefit if they have microsat instability. And there was actually some evidence that they may actually have harm, or have a worse outcome. So it is not a routine recommendation to use a fluoropyrimidine-only treatment regimen in patients who have MSI-high or deficiency of mismatch repair in stage II disease. However, there are some qualifying statements that we reviewed and were important to think about in patients. So what we know is, again, some of those patients will have some high-risk features and particularly T4 tumors or some other high-risk features, except for poor differentiation, that the use of oxaliplatin may actually be a consideration in those patients. And that's basically from indirect evidence of a disease-free survival benefit with the addition of oxaliplatin in the population of patients with stage II disease that were included in the MOSAIC trial, one of the original trials that looked at the addition of oxaliplatin to a fluoropyrimidine as adjuvant therapy for colon cancer. We specifically carved out poor differentiate is not considered a high-risk prognostic feature in those patients. And so poorly differentiated tumors alone should not be a part of the decision in offering adjuvant therapy with a fluoropyrimidine or fluoropyrimidine-oxaliplatin for MSI-high or deficient mismatch repair protein tumors. And the other patients who have either proficient mismatch repair proteins or microsatellite instability are actually including the other parts of the guideline, so what Dr. Baxter just talked about and some of the other questions that we tackled that you'll be going to next. BRITTANY HARVEY: Great. Thank you for covering those recommendations for that particular patient population. So then, Dr. Baxter, if adjuvant therapy is recommended, is there a benefit to adding oxaliplatin to fluoropyrimidine-based chemotherapy? NANCY BAXTER: Well, this is obviously a question that oncologists will face when they're deciding to give adjuvant chemotherapy to high-risk stage II colon cancers or people with T4 stage IIB or C colon cancers. And you know, here's where it's challenging to make recommendations. Because we don't have a lot of evidence for this specific group. And this is why clinicians have such a challenge making recommendations for these patients. Because actually, there's insufficient evidence to routinely recommend the addition of oxaliplatin, meaning that we have to base our decisions on the best evidence that we have. And the best evidence we have, as we've talked about, is the MOSAIC trial. And so in the MOSAIC trial, a time to recurrence was longer with oxaliplatin-based adjuvant chemotherapy. And so it may be for some patients that the addition of oxaliplatin makes sense in terms of improving their overall outcome. And again, it needs to be a shared decision-making approach with the discussion of the potential benefits and risks of harms of the addition of oxaliplatin to fluoropyrimidine-based chemotherapy, so again, discussions between the oncologist and the patient. But that is with the exception of patients who are MSI-high. So those patients need oxaliplatin. If they're going to get chemotherapy, they shouldn't have 5FU-based chemotherapy alone, as we've just discussed. BRITTANY HARVEY: Great. And definitely, that shared decision-making is key. And I appreciate you reviewing the evidence behind these recommendations, as well. So then, the last clinical question addressed in this guideline, Dr. Meyerhardt, if adjuvant oxaliplatin-containing chemotherapy is considered, are outcomes affected by reducing the treatment duration from six months to three months? JEFFREY MEYERHARDT: Sure. So this was the last clinical question that the committee considered. And it is based on the IDEA collaboration. So the IDEA collaboration was the International Duration Evaluation of Adjuvant Chemotherapy. It was six trials that were done internationally-- one in the United States, one in Japan, and four in Europe-- that included patients both with stage II and stage III colon cancer. They receive three versus six months of therapy. Each of the trials had different chemotherapy choices in the sense that the United States trial, FOLFOX was the only choice that could be offered to patients, where in all the other trials, it was a physician and patient choice regarding the use of FOLFOX or capecitabine and oxaliplatin. And that, as people who know the data, is relevant to some of the discussion. And so the goal of the collaboration was to look at if we can give patients three months of therapy and not compromise outcome. And the main reason for that is we know that the peripheral neuropathy that's cumulative with oxaliplatin increases with more months of treatment. So patients who only receive three months of oxaliplatin have less likelihood of more significant cumulative neuropathy and will have less impact on function by receiving less oxaliplatin overall. Four of the trials included patients with stage II disease. And those trials, again, pooled their data and looked at the duration question in terms of for stage II patients. Those patients had high-risk disease, some high-risk feature, as discussed earlier. And what was shown is that for the patients, overall, there was not clear evidence of noninferiority with three versus six months. But when you looked at the patients who received capecitabine and oxaliplatin, the absolute five-year disease-free survival was 81.7% versus 82% for three versus six months of CAPOX, so essentially the same, with a hazard ratio of 1.02, and the confidence interval spanned across 1. And so those really didn't look like there was any compromise in outcome for patients to receive CAPOX for three months versus six months. For those patients who received FOLFOX, three months of chemotherapy led to a five-year disease-free survival of 79.2% versus 86.5% if you received six months of FOLFOX with a hazard ratio 1.41. So again, those data would suggest that if one was to choose FOLFOX, giving six months of therapy for high-risk stage II patients may be preferable to not potentially compromise some benefit in terms of disease-free survival. So again, the overall conclusion was it's a discussion with a patient regarding choice of therapy, whether receiving capecitabine, oxaliplatin or FOLFOX and then, based on that, consideration of the duration where we were most comfortable saying that three months of capecitabine, oxaliplatin is sufficient for high-risk patients when appropriate discussion between the clinician and the patient. BRITTANY HARVEY: Great. Thank you for explaining the nuance of that trial and your recommendation. So finally, to wrap us up, in your view, how does this guideline impact both clinicians and patients? JEFFREY MEYERHARDT: Yeah, so again, the last time ASCO had addressed guidelines for stage II patients was over 15 years ago. And there are more data. It was really early in the days of understanding the incorporation of oxaliplatin. There was no data versus the three versus six months. And there were less analyses trying to look at some of those particular high-risk features. So these are all important considerations in those discussions with stage II patients. And the importance of the guidelines are really to provide that framework on the various things you think about when you have a stage II patient and how to have those shared decision-making discussions with the patient. Again, it's not, probably, appropriate for all patients to receive adjuvant therapy, particularly lower risk. And even for higher risk patients, it is weighing the plus or minuses of the potential toxicities with what we know potentially are benefits. NANCY BAXTER: Yeah, I think that's very true. And I think, as anyone who treats colon cancer, or stage II colon cancer patients, is aware, this is not a homogeneous population. So in terms of the outcomes, there are people that do extremely well with surgery alone and people who, unfortunately, recur even after chemotherapy and surgery. And the future needs to focus on being able to differentiate those patients most likely to benefit from chemotherapy from those that are not likely to benefit. What we found in reviewing the evidence is we've moved forward from 2004, but we still have a long way to go. So I really hope when the next guideline is written that we're much closer to being able to identify those patients who would most benefit from chemotherapy in this group. Because we know there are patients who benefit from chemotherapy in this group. It's just we're still not perfect at identifying those people. So again, these conversations with patients are so important to talk about the limits of our knowledge, which I think is another important thing of this guideline is establishing what the limits of our knowledge are. But I think there are patients that you can confidently not give chemotherapy to. And that's very reassuring, both to clinician and to patients. And then this guideline kind of outlines the limits of our knowledge. And that's also important for clinicians and patients to understand. BRITTANY HARVEY: Definitely. I appreciate you both highlighting the importance of shared decision-making throughout this conversation that we've had. So I want to thank you so much for your work on this important guideline update and for taking the time to speak with me today, Dr. Baxter and Dr. Meyerhardt. NANCY BAXTER: Thank you very much. JEFFREY MEYERHARDT: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/gastrointestinal cancer guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

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

An interview with Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, VA, and Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, FL, co-chairs on "Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline." This guideline comprehensively addresses the treatment of brain metastases from non-hematologic solid tumors, including surgery, systemic therapy, radiation therapy, and timing of therapy. Read the full guideline at www.asco.org/neurooncology-guidelines. TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, Florida, and Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, Virginia, Co-chairs on Treatment for Brain Metastases, American Society of Clinical Oncology, Society for Neuro-Oncology, and American Society for Radiation Oncology Guideline. Thank you for being here, Dr. Vogelbaum and Dr. Schiff. MICHAEL VOGELBAUM: My pleasure. BRITTANY HARVEY: Before we begin, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in The Journal of Clinical Oncology Dr. Vogelbaum, do you have any relevant disclosures that are directly related to this guideline topic? MICHAEL VOGELBAUM: I have no disclosures relevant to this guideline. BRITTANY HARVEY: Thank you. Then, Dr. Schiff, do you have any relevant disclosures that are directly related to this guideline topic. DAVID SCHIFF: Hi, Brittany. No, I do not. BRITTANY HARVEY: Great. Then first, Dr. Schiff, can you give us an overview of the scope and the purpose of this guideline? DAVID SCHIFF: Sure. Our overall purpose was to provide guidance on the appropriate treatment of adult patients with parenchymal brain metastases from solid tumors, encompassing surgery, radiation, and systemic therapy, as well. Previous guidelines in this area were for the most part produced by neurosurgeons and radiation oncologists for their respective professional organizations, although they did incorporate multidisciplinary input. But over the last decade, treatment options for certain types of brain metastases have undergone a substantial change. The expanding armamentarium for medical oncologists in treating both extra-CNS disease as well as brain metastases highlighted the need for a new set of guidelines to evaluate the role of systemic approaches, such as targeted agents and immunotherapy, for the primary treatment of brain metastases in the context of more established treatments like surgical resection, radiosurgery, and fractionated radiotherapy. Additionally, recent studies have clarified the role of radiation techniques like whole brain radiation with hippocampal avoidance and radiosurgery to surgical resection cavities. By assembling a multidisciplinary group of experts from surgical neuro-oncologists, medical oncologists, neuro-oncologists, and radiation oncologists, we sought to provide as comprehensive and up to date a set of therapeutic guidelines as possible. In order to accomplish this, the panel performed a systematic review of randomized as well as nonrandomized evidence from 2008 through April, 2020. We focused on the roles of surgery, systemic therapy, and radiation therapy, as well as the timing and interactions among these modalities. And we included all randomized clinical trials, as well as large single arm phase II studies and institutional case series, and we also reviewed case control and cohort studies. BRITTANY HARVEY: OK, great. That's helpful background. And then you mentioned a couple focus areas, as well, of the systematic review. And so I'd like to review the key recommendations that were based off that evidence. So, starting with surgery, Dr. Vogelbaum, what are the key recommendations for surgery in adult patients with brain metastases? MICHAEL VOGELBAUM: So, the role of surgery, I think, was well established via randomized trials to some degree, and then via some of the larger single arm studies. Patients with suspected brain metastases without a primary cancer diagnosis were felt to benefit from surgery to obtain a diagnosis and undergo removal of the tumor. But more to the point, patients with larger tumors with mass effect-related symptoms are the ones most likely to benefit from surgery. What we also noted was that patients who have multiple brain metastases with extensive and uncontrolled systemic disease are unlikely to benefit from surgery unless the remaining disease is controlled via other measures, typically medical measures. We also contemplated the type of resection performed, the technique being used. There was some developing literature looking at the techniques of either an en bloc resection or a piecemeal resection. And when we critically evaluated the literature, we felt that no recommendation could be made regarding the method of resection, as there was not sufficient evidence to support one approach over another. Another technique that is being used more recently is the use of laser interstitial thermal therapy, which is a minimally invasive technique to treat tumors in general. But again, there was insufficient evidence to really be able to make a recommendation for or against the use of LITT, as it's called. BRITTANY HARVEY: OK, thank you for reviewing both those techniques and those recommendations and highlighting where there wasn't enough evidence to actually make a recommendation. So, then, following that, Dr. Schiff, what does the guideline recommend for patients with brain metastases regarding systemic therapy, including chemotherapy, immunotherapy, and targeted agents? DAVID SCHIFF: Brittany, there is a role for systemic therapy as the initial or primary modality in some cases, but I think it's really important to emphasize this only pertains to patients whose brain metastases are asymptomatic and those with particular histologies or molecular profiles. So, there are really-- there are three primary sites for which targeted or immunotherapy can be considered. The first is non-small cell lung cancer, for which osimertinib, or if you're in China, where there's access to another drug called icotinib, specifically for EGFR-mutated disease, alectinib, brigatinib, and ceritinib are appropriate approaches in ALK-rearranged asymptomatic brain metastases. And finally, pembrolizumab in combination with pemetrexed and a platinum agent in immunotherapy naive patients whose tumors express PD-L1. The second primary tumor is melanoma. And for melanoma patients who have asymptomatic BRAF V600E mutant brain metastases, dabrafenib with trametinib is an appropriate option to consider. For all melanoma patients with asymptomatic brain metastases, ipilimumab with nivolumab is also an option. And finally, for breast cancer, the combination of tucatinib, trastuzumab, and capecitabine for HER2 positive asymptomatic brain metastases in patients who have progressed on previous anti-HER2 antibody therapy. When patients treated with systemic therapy progress intracranially, local therapies such as surgery, radiation, and radiosurgery should not be deferred. BRITTANY HARVEY: OK, those are helpful notes for clinicians, and particularly around the primary tumor sites. So, then, Dr. Vogelbaum, what are the key recommendations for radiation therapy in patients with brain metastases? MICHAEL VOGELBAUM: So, Brittany, the panel started by noting which patients would not benefit from radiation therapy, in particular, those with asymptomatic brain metastases and a poor performance status, with a Karnofsky Performance Score, or KPS, of less than or equal to 50, or performance status of less than 70 and no systemic therapy options. In those cases, radiation therapy is unlikely to be of real benefit. But then when speaking to the different modalities of radiation to be used, a lot of the review focused on the two most commonly used modalities, which is Stereotactic Radiosurgery, or SRS, versus Whole Brain Radiotherapy, or WBRT. And the first recommendation was that SRS alone as opposed to either whole brain radiotherapy alone or a combination of the two should be offered to patients with one to four unresected brain metastases, except for the situation of small cell carcinoma, which has a different approach that's used often with prophylactic cranial irradiation. So, that's a separate group. But for others, SRS is the modality that should be offered. And then for patients who underwent surgical resection of their brain metastases, we know that there needs to be some form of radiation treatment to the surgical cavity. And the recommendation was that SRS alone should be offered to those patients if the surgical cavity can be safely treated, and considering the extent of remaining intracranial disease. Obviously, for patients who have a lot of disease but otherwise have a treatable systemic disease, then whole brain radiotherapy may make more sense. But for the ones that are more limited after surgery, it should be SRS. And then when the panel considered a situation where you have patients with more than four unresected metastases and the options included radiosurgery, whole brain radiotherapy, or radiosurgery plus whole brain radiotherapy-- and in general, these are reasonable options. But it was felt that SRS may be preferred for patients with better prognosis or where systemic therapy that is known to be active in the central nervous system is available. Additional recommendations revolved around both protective, radioprotective, and radiosensitizing agents. So, in terms of trying to protect memory, there are two approaches that are used. One is to give memantine during whole brain radiotherapy, or to do whole brain radiotherapy using a hippocampal avoidance technique. And it was felt that either one of those or both should be offered to patients who will receive whole brain radiotherapy and have no tumors in the hippocampus, and they're expected to live more than four months. And then finally, that radiation sensitizing agents should not be offered to patients, because they've not been shown to be effective. BRITTANY HARVEY: Understood. And it's helpful to know both what those recommendations are for specific approaches, and as you said, critical to know who will and who will not benefit from radiation therapy. So, then we've just reviewed the key surgery, systemic therapy, and radiation therapy recommendations. Dr. Schiff, did the panel recommend anything regarding the timing of surgery, radiation therapy, and systemic therapy? MICHAEL VOGELBAUM: The panel had just a couple of points in this regard. Although there are some recent data suggesting a decreased incidence of leptomeningeal metastases in patients who undergo radiosurgery before craniotomy, as compared to the reverse sequence, the panel concluded no recommendation on this point regarding the specific sequence of therapy could be made. And to reiterate, for those circumstances in which systemic therapy may be of use for brain metastases, that therapy should proceed, local therapy like surgery or radiation, only if the brain metastases are asymptomatic. BRITTANY HARVEY: Great. Thank you both for reviewing these recommendations. In your view, Dr. Vogelbaum, what is the importance of this guideline, and how will it impact clinicians? MICHAEL VOGELBAUM: I think one of the important points that David raised that at the beginning was that this really is the most comprehensive look at the evidence revolving around the treatment of patients with brain metastases and leptomeningeal disease. And in particular, this may be new information for an audience that has not been involved in that treatment for many decades, the medical oncology community. So, I think some of the impact on clinicians may be that the guidelines will help them understand the durability of surgery and radiosurgery, and those had been the only treatments available for a long time. And so now we have these new medical therapies that are showing activity in the brain, but one needs to balance that against what is known about the effective treatments in the past. Some of the new targeted immunotherapies may not provide as consistent or durable of a benefit as has been shown previously with surgery and radiotherapy. Hopefully, understanding this challenge with respect to consistency and durability will serve to support the development of phase 0 or window of opportunity clinical trials to better understand the determinants the biological determinants of response or resistance to systemic therapies we want to improve on that, for sure, and those clinical trials are going to be essential for us to be able to do that. And then ultimately, also, identify opportunities to synergistically combine radiation and medical therapies and better understand the timing of these combinations. This is a great area for clinical trial development in the future. BRITTANY HARVEY: Definitely. We'll look forward to future research in those areas. So then, finally, Dr. Schiff, to wrap us up, how will these guideline recommendations affect patients? DAVID SCHIFF: Yeah. Over the last 30 years, the management of brain metastases have involved hugely, from an area where almost everyone got whole brain radiation therapy and many patients died from their brain disease. The use of local therapies like surgical resection and radiosurgery has greatly improved local control of brain metastases. And with options like radiosurgery alone for a limited number of brain metastases, systemic therapies as the initial approach, and hippocampal avoidant whole brain radiation therapy with memantine, patients are experiencing improved long term cognitive function and quality of life, as well. So, I think the careful delineation of the role of each of these modalities that these guidelines provide will really help maximize benefit and minimize the risk for this very large number of cancer patients. BRITTANY HARVEY: Definitely, improve quality of life is always a goal. So, I want to thank you both for your work on these guidelines and thank you for taking the time to speak with me today, Dr. Vogelbaum and Dr. Schiff. DAVID SCHIFF: My pleasure. MICHAEL VOGELBAUM: Thank you, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe, so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, MD, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, NY, co-chairs on "Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline". This guideline addresses evidence-based therapies for patients with newly diagnosed and recurrent gliomas. Read the full guideline at www.asco.org/neurooncology-guidelines. TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. SPEAKER 2: Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, Maryland, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, New York, co-chairs on therapy for diffuse astrocytic and oligodendroglial tumors in adults American Society of Clinical Oncology and Society for Neuro-Oncology guideline. Thank you for being here, Dr. Blakeley and Dr. Mohile. SPEAKER 3: Thank you. SPEAKER 4: Thank you. SPEAKER 2: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with a publication of the guideline in the Journal of Clinical Oncology. Dr. Blakeley, do you have any relevant disclosures that are directly related to this guideline topic? SPEAKER 3: No, I do not. SPEAKER 2: Thank you. And Dr. Mohile, do you have any relevant disclosures that are related to this guideline topic? SPEAKER 4: No, I don't have any relevant disclosures. SPEAKER 2: Great. Thank you. Then let's get into the content of this guideline. So Dr. Mohile, can you start by giving us a general overview of the scope and purpose of this guideline? SPEAKER 4: Yeah, so over the past 10 years, there have been several positive clinical trials in various glioma subtypes, and several of them have demonstrated a benefit for chemotherapy. The primary purpose of this guideline is to help practicing clinicians understand how these trials might impact treatment for patients with gliomas. During this period, there's also been two updates to the World Health Organization classification of gliomas, and the terminology of gliomas has changed. So what we call tumors today is different from what we might have called them 10 years ago. And so a second purpose of our guideline is essentially to provide a key or a translator so a clinician can look at a pathology report today in 2021 with a current terminology and know what to do with that patient and what treatment best fits for that patient today based on what they would have been called in a trial several years ago. SPEAKER 2: Great. That makes a lot of sense. So then Dr. Blakeley, looking at this guideline, it addresses four clinical questions, which are after maximal safe surgical resection, what are the evidence-based therapies for adults with newly diagnosed glioma including optimal regimens, settings, and timing of therapy? Then also, what are the appropriate therapies for adults with recurrent glioma, including optimal regimens, settings, and timing of therapy, followed by what should the effect of MGMT promoter methylation status be on choice of therapy and if there are subpopulations that should affect the choice of therapy. I'd like to review the key recommendations for those clinical questions. In reading through the guideline, the expert panel provided recommendations based on the IDH mutation status and the diagnostic categories in the WHO 2016 and 2021 classification systems for tumors of the central nervous system. So it seems appropriate to review the recommendations in this manner as well. Starting with IDH mutant astrocytic and oligodendroglial tumors, what is recommended for patients with oligodendroglioma, IDH mutant, 1p19q deleted CNS WHO grade 2 or 3? SPEAKER 3: Absolutely, and I'll just summarize for our listeners to help simplify that as you said, essentially, all of the guidelines are divided along molecular markers. And the first cohort are 1p19q co-deleted gliomas. Something that is a 1p19q deleted gliomas also an oligodendroglioma. Those are interchangeable. If you are 1p19q co-deleted, you have oligodendroglioma and vise versa. In general, 1p19q co-deleted tumors also are IDH mutant. So you can consider that one bundle. And oligodendroglioma is something that is 1p19q co-deleted and IDH mutant. And for that whole classification, whether it's WHO grade 2 or WHO grade 3, the recommendation is for radiation followed by the combination of procarbazine, CCNU, and vincristine, based on two prospective studies that showed similar results at different time points. There are a couple of modifications to that guideline. There is a statement that if people feel that the combination of Procarbazine, CCNU, and Vincristine, also called PCV, is too toxic, they can consider temozolomide as an alternative for this subclass of tumors 1p19q co-deleted IDH mutant. And also, importantly, the 1p19q co-deleted grade 2 gliomas are some of the best performing tumors in terms of prognosis of all glial tumors and maybe all CNS tumors. And so there is a statement in the recommendations that say-- it says it is reasonable to defer therapy under appropriate circumstances. And the text goes into what those appropriate circumstances might be, including how much of a resection could be achieved, what the functional status of the person is, how old they are, et cetera. But big picture-- 1p19q co-deleted tumor equals an oligodendroglioma, and those are almost all IDH mutant. And the bottom line recommendation is radiation followed by PCV with the parentheses saying temozolomide might be a reasonable alternative to PCV, and if you have a particularly benign presentation with a grade 2 tumor, you can consider deferring that therapy start for a time. The next big bundle is astrocytic tumors that are not 1p19q co-deleted. So in the guidelines, those are termed as 1p19q non-co-deleted. And those tumors do come in two flavors-- IDH mutant or IDH wild type. And I'm going to focus on the IDH mutant because they track closer to the oligodendroglioma, but they are kind of a bridge between the very good prognosis associated with oligodendrogliomas and the more aggressive prognosis associated with malignant gliomas. And for this cohort, the 1p19q non-co-deleted IDH mutant cohort, the recommendation is for radiation therapy with adjuvant chemotherapy, and there is data that supports that adjuvant chemotherapy being either PCV or temozolomide. We don't prioritize between those two regimens. And why I'm highlighting the word adjuvant is in some centers, there is a tendency to use temozolomide concurrent with radiation therapy. And the recommendation for these 1p19q non-co-deleted IDH mutant WHO grade 2 tumors is not to use it concurrent but to use it in the adjuvant setting. And then I will round out with talking about IDH wild type. So now we're, again, 1p19q non-co-deleted but IDH wild type. Those tumors may act closer to the glioblastoma. And in that setting, we would say-- the recommendations say to treat with radiation and consider concurrent temozolomide as you would with glioblastoma or only adjuvant temozolomide as you would with the lower grade astrocytoma. SPEAKER 2: Great. Thank you for going through that and providing such clarity to those recommendations. Then following that, Dr. Mohile, moving on to glioblastoma and other IDH wild type diffuse glioma, what are the key recommendations for people with newly diagnosed glioblastoma IDH wild type CNS WHO grade 4? SPEAKER 4: So in the current classification, IDH wild type CNS World Health Organization grade 4 is what we've known of classically as glioblastoma. And for patients with glioblastoma who are fit and can tolerate therapy, we recommend treatment with radiation, concurrent temozolomide, and a six month course of adjuvant temozolomide. We also recommend that they can receive alternating electric field therapy along with the adjuvant temozolomide. Now the recommendations become a little bit more complicated for patients who might not be as fit-- so patients who might be older, have poor performance status, have other measures of frailty. And the way we wrote this is we said that if a patient who is undergoing a six week course of radiation, if that course of radiation, if the benefits did not outweigh the harm, then you could consider alternate regimens. And these include shorter courses or hypofractionated courses of radiation with or without chemotherapy and also includes courses that are chemotherapy alone. So in people who have tumors that have MGMT promoter methylation, we can consider the option of temozolomide alone. So this would be specifically for patients who either are older, more frail, who we feel are going to have difficulty going through a radiation course. There is some data to support this temozolomide alone approach. SPEAKER 2: Thank you. I appreciate you going through those recommendations very clearly as well. You clearly put a lot of effort into these recommendations. So then, Dr. Blakeley, what is recommended for patients with astrocytomas IDH wild type CNS WHO grade 2 or 3? SPEAKER 3: Yes, thank you. So as Dr. Mohile was just saying, for glioblastoma, you can really think about the recommendations for WHO grade 4 very similarly for IDH wild type independent of grade. And that is a new shift in the management of gliomas in adults. Previously, the histologic grading had a lot of weight on whether or not we would offer radiation and chemotherapy. But with the new prognostic and predictive value known associated with the IDH1 mutation or lack of mutation being IDH wild type, the recommendation is if somebody is IDH wild type CNS WHO grade 2 astrocytoma or grade 2 or grade 3, they would be offered treatment similar to a glioblastoma, which would be concurrent radiation and temozolomide followed by adjuvant temozolomide as long as performance status and all other factors support doing so. SPEAKER 2: Understood. I appreciate you providing that information as well. So were there additional areas where the expert panel found evidence either insufficient or was unable to make a recommendation? SPEAKER 4: Yeah, so there's two tumor types where we didn't have enough data to make a specific therapeutic recommendation. The first, unfortunately, is in recurrent glioblastoma. And there were no randomized controlled trials that demonstrated a benefit of one therapy over another. And so our recommendation is that when available, patients should be referred for a clinical trial. The other area is in a tumor type called diffuse midline glioma. This is a tumor characterized by the h3k27 mutation more commonly seen in children. But we do see this in adults. And here as well, there were no randomized trials that could clearly give us guidance on what the best therapy was even in the newly diagnosed setting. And our recommendation here also was, if available, to be considering a clinical trial. SPEAKER 2: Understood. It's important to recognize where there are areas where we're lacking evidence as well. So then, Dr. Blakeley, in your view, why is this guideline important and how will it change practice? SPEAKER 3: Thank you. Well, as Dr. Mohile said at the start, it is quite challenging to review the literature for gliomas in adults because we've had different nomenclature applied across clinical trials and diagnostic studies over the last 10 to 15 years. And this document and these guidelines really seek to be the clearinghouse to help clinicians match up what they see on the pathology report for their patient to the data that is published on phase III studies that has influenced our current standards of care. So I think the most important way it will change practice is bringing clarity to the data that already exists but has not been accessible to providers trying to help patients make the best decisions for them. It also importantly highlighted how much more work is needed. We desperately need new clinical trials for patients with glioblastoma and patients with astrocytoma IDH wild type 1p19q non-co-deleted WHO grade 2 and 3 and the other areas that Dr. Mohile highlighted. But we're hopeful that this will help provide clarity on both what we do know to help us identify patients who have the best chance of truly meaningful benefit from chemotherapy and where we need to invest more resources. SPEAKER 2: Absolutely. It seems like this will be a helpful resource for how to treat now and a guide as to what areas of research should be investigated in the future. So in addition to that, Dr. Mohile, finally, how do you view that these guideline recommendations will impact patients? SPEAKER 4: Yeah, my hope is that this will help standardize our approach to patients with gliomas. In the United States, patients with gliomas get care in all kinds of different settings. And when they're seeing an oncologist, particularly in the community, this might be a very small percentage of the types of cancers that they might be seeing, and it's hard to keep up with all of these trials and hard to keep up with the changes in classification. So our hope is that this guideline helps that oncologist in providing them the clarity, as Dr. Blakeley said, on how to approach treatment here so that all of our patients are getting the best standard of care based on the best available evidence and that they're being considered in those areas where there is not good evidence or referral for clinical trials so that in 10 years, when we put together the next guideline, that we're able to make some progress on some of these questions. SPEAKER 2: Great. Well, thank you both for all of your work that you did to review the literature and produce these evidence-based recommendations and, as you said, provide a real clear and helpful resource to both clinicians and to improve the quality of care for patients. And thank you for taking the time to speak with me today, Dr. Mohile and Dr. Blakeley. Finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]