ASCO Education

TRANSCRIPT [MUSIC PLAYING] Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan-Kettering Cancer Center, and editorial board member for ASCO University. Today, we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines podcast series. My name is Shana McKernan, and today, I'm interviewing Dr. Antonio Wolff from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, an author on HER2 Testing in Breast Cancer, American Society of Clinical Oncology College of American Pathologists Clinical Practice Guideline Focus Update. Thank you for being here, Dr. Wolff. Thank you for the opportunity. It is really a privilege to be here today on behalf of all of my colleagues in the ASCO/CAP HER2 testing panel, which truly represents not just a multi-disciplinary, but a multi-society effort over many years. First, can you give us a general overview of what this guideline covers? The recommendations by the ASCO/CAP HER2 testing expert panel were first released in 2007 and updated in 2013. And this is now a 2018 focus update. The aim was to improve the analytic validity of HER2 testing and the utility of HER2 as a predictive biomarker for potential responsiveness to therapies targeting the HER2 protein. In fact, in late 2017 at the San Antonio Breast Cancer Symposium, we finally had data from the NRG trial B-47, which confirmed the lack of benefit from adjuvant trastuzumab for patients whose tumors lack gene amplification and were IHC 1+ or 2+. As a result, HER2 gene amplification assessed by In Situ Hybridization-- ISH, or I-S-H, or protein overexpression assessed by immunohistochemistry, IHC, remained the primary predictors of responsiveness to HER2-targeted therapy in breast cancer. We have seen over the years a great communication among health care providers, especially pathologists and oncologists, but also much-needed infrastructure support by administrative teams regarding specimen handling in lab facilities. And they have resulted in meaningful improvements in the analytic performance and accuracy of HER2 testing. We also have had greater clinical experience with the efficacy and safety of HER2-targeted therapies that resulted in a meaningful reduction in the high frequency of false-positive HER2 test results that were observed in the mid 2000s. And this led to the 2013 guideline update panel to provide further guidance regarding less-common clinical scenarios to allow greater discrimination between positive and negative results. Since 2013, since the 2013 update, several labs and clinical investigators have reported on the practical implications of the guideline update and the observed frequency of equivocal cases. And these results have allowed the panel recently to evaluate the observed frequency of less-common HER2 testing patterns, the apparent prognostic and predictive value when retrospectively analyzed within clinical trial data sets, and the critical need to understand the underlying distribution of HER2 immunohistochemistry test results in cases that were submitted for additional tests, specifically In Situ Hybridization by a reference lab. This all led to the ASCO/CAP HER2 testing panel to prepare and now issue this 2018 HER2 testing focus update that includes five key recommendations. What are the key recommendations of this guideline? The HER2 testing guideline panel identified five clinical questions that formed the core of the 2018 focus update. Clinical question one is, what is the most appropriate definition of IHC 2+ or IHC equivocal. And clinical question two asks whether HER2 testing must be repeated on a surgical specimen if initially negative tests on a core biopsy. And these two questions were addressed in a previous correspondence by the panel that was published in the JCO in 2015. And they referred specifically to Figure 1, the algorithm for immunohistochemistry testing, and Table 2, the histopathologic features suggestive of possible test discordance. Clinical questions three, four, and five address less-common patterns observed when performing dual-probe In Situ Hybridization testing, and are now graphically summarized in four different figures, Figures 3 to 6, that focus on the algorithm for dual-probe In Situ Hybridization testing. And these three questions help clarify the 2013 recommendations that led some labs to adopt the use of multiple alternative chromosome 17 probe testing as the sole strategy to resolve equivocal HER2 test results by In Situ Hybridization, despite limited evidence on analytical and clinical validity of such strategy. The three additional questions of the 2018 focus updates are clinical question three, should invasive cancers with HER2/CEP17 ratio of 2.0 or higher, but an average HER2 copy number of less than 4 signals per cell, be considered ISH-positive. Clinical question four, should the invasive cancers with an average HER2 copy number of 6.0 or greater signals per cell, but a HER2/CEP17 ratio of less than 2.0 be considered ISH-positive? And finally, clinical question five, what is the appropriate diagnostic workup for invasive cancers with an average HER2 copy number 4.0 or higher, but less than 6.0 signals per cell, and a HER2/CEP17 ratio less than 2.0, and initially found to have an equivocal HER2 ISH test result. The recommendations regarding dual-probe ISH testing also led to a change in figure 2 that describes the algorithm for single-probe ISH testing, and includes a new footnote with a recommendation that concomitant immunohistochemistry review should become part of the interpretation of single-probe In Situ Hybridization results. The 2018 HER2 testing focus update also includes a new Table 3 that describes the patterns of HER2 ISH testing using dual probe assays showing a clear impact of the underlying distribution of HER2 immunohistochemistry test results on the frequency of these less common patterns of In Situ Hybridization. As we expect, in total, groups 2, 3, and 4 will represent no more than 5% of all cases tested by In Situ Hybridization. And the majority, 95% of cases, tested for HER2 by dual-probe In Situ Hybridization will consist of group 1, which are clearly HER2-positive , and group 5, HER2-negative. And ultimately, the available clinical outcome data from related trials, although of limited statistical power, have allowed the panel to more carefully define this expected prognostic and predictive behavior of cases tested by dual-probe In Situ Hybridization that will fall in groups 2, 3, or 4. What are the major changes from the 2013 version of this guideline? Most important, after consideration of the available evidence and expert opinions, the ASCO/CAP HER2 testing panel revised the diagnostic approach to groups 2, 3, and 4 to include more rigorous interpretation criteria for dual-probe In Situ Hybridization testing, and to require concomitant immunohistochemistry review to arrive at the most accurate HER2 status designation, positive or negative, based on the combined interpretation of the ISH and the IHC assays. The panel therefore recommends that such concomitant review be performed in the same institution to ensure parallel interpretation and quality of the two assays. As a result, most group 2 specimens will not be confirmed as HER2-positive, as very few will be immunohistochemistry 3+, and most group 4 specimens will be confirmed HER2-negative without the need for additional testing, use alternative probes, which happen a lot since 2013. At the same time, group 3 specimens will be a mixed group of results with a small number of cases shown to be amplified, and a larger number shown not to be amplified. And so for these dual-probe ISH group 3 cases, the panel allows specimens that are IHC 2+ to be considered HER2-positive. And the rationale is described in greater detail in the manuscript. And finally, how will these guideline recommendations affect patients? While the main focus was to clarify the less common test results observed with the two-probe ISH assays, the recommendations do impact users of single-probe ISH assays. As such, the panel now recommends that concomitant immunohistochemistry review should become part of the interpretation of single-probe In Situ Hybridization results to allow a more accurate HER2 designation. And this is nicely described in Figure 2. And the panel also preferentially recommends the use of dual-probe instead of single-probe ISH assays, while it recognizes that several single-probe ISH assays have regulatory approval in many parts of the world. At the end, and to conclude, these actions, we hope, will reduce the already small number of cases that have HER2 test results that are unresolved, will reduce the frequency of alternative group testing, and will remind us all of the importance of integrating the information provided by both types of assay platforms, IHC and ISH, in difficult cases, as we expect these results to be concordant in the vast majority of cases, when expertly performed. Thank you for your insights on this guideline, and thank you for your time today, Dr. Wolff. Thank you so much. And thank you to all of our listeners for tuning in to the ASCO guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. [MUSIC PLAYING] 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.

TRANSCRIPT Welcome to the Self-Evaluation episode of the ASCO University weekly podcast. My name is Apar Kishor Ganti, and I'm the Associate Director for Clinical Research and the co-leader of the Thoracic Oncology Service at the University of Nebraska Medical Center, Fred and Pamela Buffett Cancer Center. Today, we feature a self-evaluation question on locally advanced non-small cell lung cancer. I will begin by reading the question stem. A 58-year-old man with a 50-pack year history of smoking presents to your clinic with worsening cough and shortness of breath. His comorbidities include irritable bowel syndrome and coronary artery disease. A CT scan of the chest, abdomen, and pelvis reveal a two-centimeter right lower lobe mass with no evidence of lymphadenopathy in the chest. A positron emission tomography scan confirms a hypermetabolic right lower lobe mass and mildly avid mediastinal nodes. An MRI of the brain was performed and was negative. A biopsy of the right lower lobe mass was positive for squamous cell carcinoma of the lung. The patient was taken for a mediastinal lymph node evaluation by a thoracic surgeon. Additional biopsies of multiple lymph nodes were taken. Pulmonary function tests revealed that a right lower lobectomy would be feasible if warranted. Which of the following would lead you to recommend definitive chemoradiation rather than surgery as the most appropriate treatment for this patient? The answer choices are, A, metastatic squamous cell carcinoma identified in a left hilar lymph node, B, metastatic squamous cell carcinoma identified in a right hilar lymph node, C, the absence of squamous cell carcinoma in a left paratracheal lymph node, and D, the absence of squamous cell carcinoma in a right hilar lymph node? [MUSIC PLAYING] The correct answer to this question is A, metastatic squamous cell carcinoma identified in a left hilar lymph node. In the eighth edition of the AJCC TNM classification system, this tumor would be classified as T1B. The presence of cancer in a contralateral hilar lymph node represents N3 disease and thus, stage 3B. Surgery is not recommended in this setting, and definitive chemoradiation is considered standard of care. What about the other choices? Involvement of an ipsilateral hilar node would only represent N1 and stage 2B disease, for which a right lower lobectomy and mediastinal lymph node dissection are appropriate. The absence of involvement of the left paratracheal node would confirm the absence of N3 disease, while the absence of involvement of the right hilar node would confirm the absence of N1 disease. In both these scenarios, the patient would be considered resectable if other lymph node stations are not involved. Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on lung cancers, including important release for self-evaluation, visit the comprehensive E-Learning Center at university.asco.org. Thank you. [MUSIC PLAYING] 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.

TRANSCRIPT [MUSIC PLAYING] Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University. Today we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Davendra Sohal from Cleveland Clinic, lead author on Metastatic Pancreatic Cancer American Society of Clinical Oncology Clinical Practice Guideline update. Thank you for being here today, Dr. Sohal. Thanks for having me. It's a pleasure. So this update is focused on revising the recommendations on second line treatment for metastatic pancreatic cancer. Can you tell us about the studies that informed this update? Certainly. The first study is a paper published in Science on PD-1 inhibition and solid tumors. This study included 86 patients with mismatch repair deficient tumors, also known as microsatellite instability high tumors. In this study, 53% of the patients had an objective response with a disease control rate of 71% across multiple histologies. The study also included eight patients with pancreatic cancer, two of whom had complete responses with a disease control rate of 75%. This is the study that informed our recommendation for checkpoint inhibitor therapy in the second line setting. The second study is the PANCREOX trial published in JCO, which randomized patients to 5-fluorouracil or FOLFOX. With 108 patients, the primary outcome of overall survival was 9.9 months in the control 5-fluorouracil arm, and surprisingly, only 6.1 months in the FOLFOX arm. This study informed our recommendation for chemotherapy regimens in the second line setting. And what are the new and updated recommendations for second line treatment? For second line treatment of metastatic pancreatic cancer, our first recommendation now is to consider testing for mismatch repair deficiency or microsatellite instability in patients who are candidates for checkpoint inhibitors therapy. Any standard form of testing is acceptable, whether IHC or PCR or next-gen sequencing. Patients who have mismatch repair deficient or microsatellite instability high tumors should be treated with pembrolizumab given the excellent responses noted in the study we just discussed. For patients who do not meet these criteria for checkpoint inhibitor therapy, second line therapy with gemcitabine plus nab-paclitaxel can be offered to those who received FOLFIRINOX in the first line and meet other criteria for aggressive chemotherapy as detailed in the guideline. Now, for patients who receive gemcitabine plus nab-paclitaxel in the first line, fluorouracil plus nanoliposomal irinotecan is the preferred second line therapy. Where nanoliposomal irinotecan is not accessible, fluorouracil plus regular irinotecan is an acceptable alternative. As I mentioned the combination, of 5-fluorouracil plus oxaliplatin can be considered as an option in this setting, but we have noted a qualifying statement about the PANCREOX study whose results are inconsistent with the CONCORD-3 study using the same agents as the off regimen. Given these conflicting results from different studies of 5-fluorouracil plus oxaliplatin, the recommendation for its use in the second line setting has been softened. Can you also give us an overview of the recommendations from the original 2016 version that the expert panel decided were still valid? Sure. In 2016, the expert panel made recommendations which span from initial assessment through to follow up and surveillance. For every patient with metastatic pancreatic cancer, a multi-phase CT scan should be performed and baseline performance datas and comorbidities should be evaluated. Goals of care should be discussed with a multidisciplinary team, and all patients should be offered information about clinical trials. Outside of a clinical trial, standard first line treatment options include FOLFIRINOX, gemcitabine plus nab-paclitaxel, or gemcitabine alone. And the full guideline provides details on which treatment is appropriate for which patients. The panel also recommended that every patient should be offered palliative care early in their treatment. These recommendations were endorsed in the update and are reprinted in totality in the bottom line box on the second page of the article. And finally, what are some important things to note about communicating with patients with pancreatic cancer, especially in the metastatic setting? Excellent point. It is important to communicate that participation in clinical studies is strongly encouraged. These studies could include new treatments, or supportive care measures, or collection of blood and tumor samples for further research, et cetera. While chemotherapy forms the backbone of treatment, it is only one component, and that is an important point to make. The use of supportive care or palliative care is strongly encouraged for all patients with metastatic pancreatic cancer in order to maximize not just the quantity, but also the quality of life. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Sohal. Sure. Thank you very much. I'd like to thank our panel for diligent data review and dedicated discussions and the ASCO staff for all their support in producing the update. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. [MUSIC PLAYING] 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.

2018 Annual Meeting raised the curtain on a new session type: ASCO Voices. These noncompete session feature presentations no longer than 7 minutes each and bring a variety of perspectives to the stage to share stories on oncology, medicine, and the world. From big ideas to personal passions, ASCO Voices present stories that differ significantly from the remainder of session types available at Annual Meeting.  

[MUSIC PLAYING] Welcome to the self-evaluation episode of the ASCO University Weekly Podcast. My name is Teviah Sachs, and I am an Assistant Professor of Surgery at the Boston University School of Medicine and Surgical Oncologist at Boston Medical Center. Today we will feature a self-evaluation question on the treatment of gastric cancer. And we begin by reading the question stem. A 53-year-old Hispanic woman presents to her primary care physician after noticing black tarry stools for the last three weeks, and complains of mild fatigue. A stool guaiac test is performed in the office, and is found to be hemoccult positive. Her laboratory tests were notable for a white blood cell count of 6,400, a hemoglobin of 9.2, and hematocrit of 27.3%, with platelets of 653. The mean corpuscular volume was 77, blood urea nitrogen was 40, and creatinine was 1.3. A CT scan of the chest, abdomen, and pelvis was performed with IV contrast, and was notable only for nonspecific thickening of the gastric fundus. She was referred to a gastroenterologist, who performed an esophagogastroduodenoscopy, or EGD, which revealed an ulcerative mass along the greater curvature of the gastric fundus, with no evidence of active bleeding. This lesion was biopsied, and the pathology results confirmed adenocarcinoma, with signet ring cell features. A subsequent staging PET scan did not reveal any evidence of metastatic disease. What is the most appropriate next step in the management of this patient? Choice A, recommend subtotal gastrectomy. Choice B, recommend neoadjuvant therapy using epirubicin, oxaliplatin, and capecitabine, or EOX. Choice C, recommend endoscopic ultrasound. Choice D, recommend palliative radiation to control the bleeding. Or choice E, start the patient on oral iron after transfusion of two units of blood. [MUSIC PLAYING] In order to determine the appropriate treatment plan, we first need to know the local staging of the tumor based on endoscopic ultrasound, or EUS. Therefore, the answer would be choice C. Based on the findings of the endoscopic ultrasound, the next step for management can be better determined, whether it be endoscopic mucosal resection, surgical resection, or neoadjuvant chemotherapy with or without radiotherapy. Briefly the rationale for the other choices presented in this question do not represent the most appropriate therapy for the following reasons. Subtotal gastrectromy should not be entertained until staging endoscopic ultrasound is completed. If the lesion is a T1A lesion and amenable to endoscopic mucosal resection, then that would be more appropriate. Whereas if the lesion is a T4 lesion, with or without local regional adenopathy and ultrasonic evaluation, neoadjuvant therapy with EOX would be more appropriate. As for choice D, palliative radiotherapy is not indicated, as there is no active or uncontrollable bleeding, and there is no evidence of distant disease. Lastly, choice E, starting the patient on oral iron after transfusion of two units of blood is incorrect, because this patient doesn't warrant transfusion at this time, as she is asymptomatic other than mild fatigue. Thank you for listening to this week's episode of ASCO University Weekly Podcast. For more information on the treatment of gastric cancer, including opportunities for self-evaluation and board review, visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

[MUSIC PLAYING] Welcome to the ASCO Guidelines episode of the ASCO University Weekly Podcast. My name is Alexander Drilon, and I'm the Clinical Director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University. Today, we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines Podcast Series. The ASCO Guidelines Podcast Series features interviews with panelists of recently-published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin and today, I'm interviewing Dr. Supriya Mohile from University of Rochester Medical Center, lead author on "Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy-- American Society of Clinical Oncology Guideline for Geriatric Oncology." Thank you for being here today, Dr. Mohile. Thank you very much. First, what is the purpose of this guideline, and can you tell us about the research that was reviewed to inform the recommendations? Sure. So we know that our population is aging. So currently, there are an incredible number of patients who are age 65 and over with cancer. The statistics are showing that more and more older adults are developing cancer. And this was really informed by our movement in geriatric oncology that ASCO has supported over the last 10 to 15 years. When I started my fellowship, which was now close to 15 years ago, there was very little knowledge about how to treat older patients with cancer. We know that clinical trials include fewer older adults and that the older adults that are enrolled tend to be more fit than those older adults seen in community practices and being cared for by, really, community oncologists. Therefore, there is a large gap in knowledge in terms of what might be safe and effective in a phase III clinical trial that provides our evidence for cancer treatment and what might be safe and effective for an older patient-- say 75-plus-- who's being seen in community who has medical conditions such as cognitive impairment or significant comorbidities that may limit their life expectancy. So the guideline really strives to address how older patients should be evaluated and managed in oncology clinics specifically. And this guideline is geared towards older patients with cancer who are undergoing a decision or who are receiving chemotherapy because that's really where the data and the evidence for geriatric oncology practices supports at this point. There's less data for evaluating patients who are going to undergo targeted agents or immunotherapy. But we have, now, a robust level of evidence for older patients who are undergoing chemotherapy. And so this guideline could help clinicians with how to best manage and evaluate and make decisions for older patients with cancer who they're seeing in their clinic. And it can also help support other guidelines that ASCO and others put forth. For example, I sat on the ASCO Guidelines Committee, and we were looking at a guideline for bladder cancer. And some of the guidelines were related to life expectancy. So a intervention is appropriate, for example, for patients who have a 10- or more-year life expectancy. However, there's very limited information for how physicians should estimate life expectancy in our guidelines. And so this guideline includes that kind of information that could help really support other guidelines when we're talking about things like life expectancy, underlying health status, comorbidities, that might influence outcomes for older patients with cancer. In terms of what research was reviewed to inform the recommendations, well, we in the geriatric oncology field-- and many of the co-authors are geriatric oncologies-- worked with others in specific fields, such as cognition, physical health, and community oncologists and primary care doctors, to develop a very comprehensive yet practical way for oncologists to really assess older patients. As I mentioned, our field is small, and it started about 10 to 15 years ago, really focusing on this toolkit called geriatric assessment. Geriatric assessment is a compilation of, really, patient-reported outcomes that can assess health status for older patients. And we sort those pieces in the geriatric assessment into domains. And each domain is known to predict morbidity and mortality in older adults. So those domains include things like cognition, function, psychological status, comorbidities, polypharmacy, social support. And we know from the evidence in community-dwelling older adults without cancer that each of those domains are predictive of outcome. So it made sense to us, having been trained in both geriatrics and oncology, to think about this tool as a way to evaluate underlying health status in older patients with cancer. And the field started by looking at feasibility of geriatric assessment in oncology clinics. These efforts were led by Arti Hurria and the Cancer and Aging Research Group and others. And over time, there has been a lot of data showing that geriatric assessment is feasible in oncology clinics. They can be incorporated in both academic settings and community oncology clinics. In addition, there's been data to support that geriatric assessment is feasible in clinical trials. And so, as we started to grow that data in the field, then there have been large studies looking at prediction of outcomes and looking to see if geriatric assessment and the domains within geriatric assessment can help clinicians identify older patients who are at most risk from adverse outcomes from chemotherapy. And that data has grown significantly. So when that data grew, we paused as a community and really partnered with ASCO, who's been incredibly supportive, to think about a guideline to really summarize the literature-- and not only summarize the literature but to communicate it to clinicians as the audience to really communicate a way that geriatric assessment can be practically incorporated and integrated into routine clinical care for older adults with cancer. And so those are the studies we looked to. We worked with ASCO. ASCO, as you know, has a very rigorous methodology for looking at research. And in our field, the research is less RCT-based-- although randomized controlled trials are forthcoming-- but more based on large, robust, very well-done prospective observational studies. And we reviewed the literature for that in a systematic way and summarized that in the guidelines. And what are those key recommendations for this guideline? So the guideline breaks down into four important components. So the first component really focuses on the value added by geriatric assessment to routine oncology clinical care. And so that recommendation was based on data that shows geriatric assessment identifies factors that can be routinely missed in routine oncology care and are not captured by our routine oncology assessments like ECOG Performance Status or Karnofsky Performance Status assessments. So there is a very robust data that shows those domains that I spoke about earlier-- functional status, physical performance and falls, comorbid medical conditions, depression, social activity and support, nutritional status and cognition-- add value by identifying vulnerabilities or impairments that are not routinely captured in oncology assessments. And that's a very high level, or strong level, of evidence. The second component of the guideline really focuses on how to practically incorporate, or integrate, geriatric assessment into routine oncology care. And so we took a step back and looked at the literature, at what was feasible-- not for academic, robust groups that have a ton of support but really for community oncologists who are seeing many patients in their clinic, really getting their feedback on what might be practical and the quickest way, and the most high-priority tools to assess these domains. And so the tools that were identified were pulled out of the literature in that each of these tools captures an important domain that's predictive of outcomes. So we know that these tools can help identify older patients at high risk for adverse outcome. And they are practically able to be incorporated in the clinic and do not need to be done by a physician. They can be done by a technician, a staff member, a nurse. And so we thought about that in terms of selection of the tools. And so the second recommendation is that the evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. And we recommended, as a panel, the Instrumental Activities of Daily Living-- which is a short, very well-validated patient-reported outcome with a few questions to assess function; a thorough history or validated tool to assess comorbidity-- so this can happen as part of a routine history and physical exam that physicians are often already doing as part of their assessment; a single question for falls-- so have you fallen in the last six months, or have you fallen since the last visit?; the Geriatric Depression Scale as a screen for depression; the Mini-Cog or Blessed Orientation-Memory-Concentration test-- they're both very short, less than two minute type assessments of cognition-- they're administered to the patient by a staff member to screen cognitive issues; and an assessment of unintentional weight loss to evaluate nutrition. And in addition to those tools, if these are being used to evaluate an older patient who's starting chemotherapy, using a validated tool that assesses the risk of chemotherapy toxicity can be informative in helping with the discussion about risk in the informed consent process. And there are two tools that do that-- the Cancer and Aging Research Group tool, and the CRASH tool out of Moffitt, which is called the Chemotherapy Risk Assessment Scale for High-Age Patients-- CRASH tool. Both of those help predict or estimate risk of chemotherapy toxicity. There are, in addition, two additional tools that are short screening tools that can help identify patients at risk for early mortality. Those are called G8 or the Vulnerable Elders Survey-13. So this can form a sort of minimal data set to a basic geriatric assessment. There are options for each of those domains in terms of the tools to be used. So these are our recommendations, but they're not set in stone. In fact, which recommendation to use doesn't have a super high level of evidence. It's a moderate level. Because we don't know, necessarily, which one tool is better than another. We do know that these domains should be captured-- so function, cognition, depression, et cetera-- but which tool to use can be more flexible. So in the guideline, there is the main tool, sort of the recommended tool, but also options for other tools so that practices and physicians can pick what works best for them. In terms of the third recommendation, the third recommendation is focused on estimation of life expectancy. As I mentioned earlier, estimating life expectancy is often part of our guidelines when we're thinking about high-risk interventions. We want to be able to identify as best as we can, with the tools that we have available, patients who are likely to live long enough to benefit from high-risk interventions like chemotherapy, like adjuvant treatment, like high-risk surgeries-- for example, cystectomy for bladder cancer. You know, those kinds of approaches deserve a thoughtful approach to life expectancy estimation. A lot of what we do in clinical practice is Gestalt, so it's sort of the eyeball test-- well, I think my patient might live five years. I think my patient might live 10 years. And we know from the literature that the eyeball test is very subjective, and every individual physician has their different perspective on how long someone might live. And we are, as a medical community, not very good at estimating prognosis. They're all tools that could help this approach and they're all available on the web. And we recommended the Schonberg Lee Index, which is part of ePrognosis, where, as part of the assessment process, there are easy-to-capture variables that can be included. And it creates a very standardized, validated approach to life expectancy estimation that can be shared with a patient. Of note, as part of that recommendation, they do ask about cancer because cancer influences life expectancy. And our recommendation is to say no to that question. Because we're looking at life expectancy from the perspective of outside of cancer-- so in other words, other medical problems that might influence life expectancy, not the cancer, in order to inform decisions for treatment of cancer. The last recommendation really focuses on management. And here's where there are randomized controlled trials in progress. There are consensus studies that are from experts in geriatric oncology that have developed algorithms to incorporate management options for each domain impairment. So for example, one finds that a patient may be falling. That's a domain impairment we assess with the question-- that's the tool-- so have you been falling? and perhaps another type of test-- an objective physical performance test, for an example. And then, we institute, or implement, geriatric-relevant management interventions such as physical therapy, an evaluation for assistive device, a safety evaluation at home, making sure that the patient is not alone at home, looking at medications to make sure their blood pressure medicines aren't too strong and they're going to become orthostatic. So there are these algorithmic approaches to each domain. And these are outlined in several papers that have looked at these Delphi consensus approaches to these algorithms. And these algorithms are now being tested in randomized controlled trials both in the United States and in Europe. And so that's the summary for the recommendations for this guideline. So you mentioned some of those assessment tools, like the CARG tool and the CRASH tool. So how do you implement those in practice? So in the guideline, we have several examples of how a practitioner can use this toolkit to really help with clinical decision-making in a very practical way. So embedded in the guideline is an older patient being considered for adjuvant chemotherapy and the approach-- all the way from the patient is sitting in the clinical setting outside and is filling out the surveys to the plan where they come into the clinic office, someone administers the cognition tool, the nurse or the physician captures the correct information, they go online, and they plug in the information, and they print out the tools. So all of the tools will be made available on relevant ASCO websites-- so the main ASCO website, the educational ASCO websites-- and also the tools themselves, plus the guideline recommendations, and also cases. So we have one case embedded in the actual guideline, but we also, in the supplement, have several additional cases that can be reviewed to really show how to incorporate this in clinical practice. So as part of ASCO, the panel members plus the ASCO geriatric oncology task force that works out of the Health Disparities Committee are going to do our best to make the translation of these guidelines into implementation as easy as possible and have everything available. The three tools that I mentioned-- the CARG toxicity tool, the CRASH tool, and the ePrognosis tool-- are all already available online. And so those links are available in the guideline and can be used right away. The other tools will be available on the ASCO website. We will put that on so that people can download them and use them in the clinic setting. Great. And what interventions can be informed by the results of geriatric assessment? I know you mentioned physical therapy. What else can you tell us about that? So as part of those Delphi consensus process there, we developed sort of an algorithmic approach to the different interventions for each of the domains. So there is a table in the guideline that summarizes the high-priority interventions that the experts use in their clinic when they identify patients with impairments. So as I mentioned, there are things like physical therapy for people with physical performance problems or people who have functional issues, strength and balance training, assistive device evaluation, exercise programs, fall prevention. For comorbidities, thinking about communication aspects of talking to patients and caregivers about how to use multiple medications, talking to other important members of the team like the primary care doctor or pharmacist to help decrease risk from medications. For cognition, for people who have impaired cognitive status, we have very limited data about the safety of chemotherapy in this population. It's under-recognized. Even me, who have many years of working with older patients, cannot tell just by looking or talking to an older adult that they have cognitive impairment. And so screening tools are absolutely necessary. If someone has impairment on a validated cognitive screen like the Mini-Cog or Blessed that I mentioned earlier, thinking about a formal assessment of decision-making capacity and ability to consent for treatment is important. And as we start implementing practices in the clinics to really capture consent processes, even for routine chemotherapy-- off-clinical trials-- this is an important aspect to consider. Delirium risk counseling, medication review, again, are all important things to consider for somebody who has cognitive impairment. For depression, with screening for depression, there is already an ASCO guideline in place for management of patients in general who have depression. And we incorporated some of those management recommendations-- so considering cognitive behavioral therapy, if that's available, social work involvement, counseling. We do consider medications but try the other mechanisms first before medication use in an older adult because medications may have more side effects. And for nutrition, thinking about nutritional interventions, a need for extra support and availability of caregiver to provide extra support for meal preparation. So there is a table, and there's also references to other papers that have Delphi guidelines in place of how to utilize management recommendations. There is also a table that summarizes the ongoing clinical trials. And as we learn more about incorporating this as an evaluation of management plan in terms of improving outcomes for older adults with cancer, we'll be able to expand the guideline to incorporate that information, in addition. So finally, what difference does it make to patients, performing these assessments? How are they impacted by these recommendations? So we truly believe that the evidence shows that assessing older patients with a standardized validated geriatric assessment measure can improve the identification process and discussion surrounding chemotherapy risk. And that is important for this population. Because this population is less included in clinical trials and, therefore, the safety and efficacy of treatments are often uncertain for older adults who are 75-plus because just that population itself is underrepresented in clinical trials-- but also those who are older who have other medical issues. And so that discussion itself, as part of communication for informed consent, is very important. And that's outlined in the communications section of the guideline. In addition, the guideline stresses that factors that identify patients as vulnerable are captured by geriatric assessment. We have standardized tools to assess risk through toxicity tools and mortality. We have standardized tools to help assess life expectancy when one is considering an older adult for adjuvant treatment, which may be six months, a year long. If the older adult you're seeing has a life expectancy of one year based on their comorbid conditions, does it make sense to put them through a one-year program of adjuvant treatment or a big surgery? In addition, it also helps identify those older patients who are fit-- so not just identifying patients who may be at risk, but the other side of the coin is you're 80, but you're healthy. You're fit. You don't have a high risk of toxicity or higher risk than maybe those patients that were included in the clinical trial because your health status is good. And you should get treatment, right? So that conversation is also very important. And again, as I mentioned, there is an example in the guideline where we take an older adult who has some medical issues, and we take them through the process by which these tools can be used to help with the decision-making process. And also, we compare that to a patient that's 10 years older that doesn't have those same health conditions and show the comparison and the contrast between the recommendations. So the older adult, in our example, who is actually, chronologically, 10 years older is actually probably less likely to have harm from treatment than the person that was in their 70s who has other medical problems. And that just goes to show how important underlying health status is when we're making our clinical decisions for treatment. We still need to know more about direct decision-making. We know that geriatric assessment influences oncology decision-making. That data has been shown. In other words, when our oncologists get this information from geriatricians at a tumor board, or it's provided to them through a summary, they utilize that, and they change what they're going to do on average 30% to 50% of the time. Because they value that information, and that information adds value to what their plan is. But what we're still waiting for with these randomized trials is, does geriatric assessment and management approach decrease harm overall, improve survival, decrease toxicity, et cetera? There has been some data in geriatric assessment incorporated into therapeutic trials that shows that when a geriatric assessment plan is used that that might lower toxicity. But we still need more data in that area. And that was recommendation four. And so that recommendation will be more robust as the data matures from these randomized controlled trials. But just to summarize, the panel feels, and ASCO feels, based on this guideline, that there is enough data to support using the tools that we recommend to help assess and manage older adults receiving chemotherapy. Great. Thank you so much for your work on this important and very comprehensive guideline. And thank you for your time today, Dr. Mohile. Thank you very much for inviting me. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Welcome to the self-evaluation episode of the ASCO University weekly podcast. My name is Shadia Jalal, and I am a thoracic oncologist at Indiana University. Today, we feature a self-evaluation question on the treatment of limited-stage small-cell lung cancer. And we begin by the question. A 58-year-old man with a 40-pack-year history of cigarette smoking is found to have a spiculated 2.1-centimeter left upper lobe mass on CAT scan imaging that was performed for a suspected pneumonia. His physicians decided to immediately take him to the operating room for a wedge resection of that mass. A preliminary analysis of the pathology from the wedge resection during the operation revealed small-cell lung cancer. A completion left upper lobectomy and mediastinal lymph node dissection was performed. The final pathology confirmed a T1a small-cell lung cancer with negative margins and no lymph-node involvement. Subsequent work-up included an MRI of the brain with and without gadolinium contrast and a Positron Emission Tomography, or PET scan, both of which showed no evidence of distant metastatic disease. Molecular profiling of the tumor revealed concurrent P53 and retinoblastoma mutations, as is usually seen in small-cell lung cancer. The question is, which of the following is the most appropriate next step? A, the administration of four cycles of cisplatin and etoposide in an adjuvant fashion; B, definitive radiation to the chest with concurrent cisplatin and paclitaxel; C, four cycles of carboplatin and pemetrexed; D, definitive radiation to the chest with concurrent cyclophosphamide; E, four cycles of cyclophosphamide, doxorubicin, and vincristine. The correct answer is A, four cycles of cisplatin and etoposide in an adjuvant fashion. The role of surgery in patients with limited-stage small-cell lung cancer is really limited to a very small number of those patients that might present with a peripheral small tumor. As is known, small-cell lung cancer is usually more of a central tumor with lymph node involvement. In a patient like this with limited-stage small-cell lung cancer and node-negative disease, adjuvant chemotherapy with a platinum doublet-- cisplatin or carboplatin and etoposide-- is recommended after definitive surgery, including mediastinal lymph-node dissection. Small-cell lung cancer is a cancer known for early hematogenous spread, and therefore adjuvant chemotherapy is indicated. CAV, or cyclophosphamide, doxorubicin, and vincristine, or carboplatin with pemetrexed are not appropriate treatment options in limited-stage small-cell lung cancer. In fact, pemetrexed does not have activity in small-cell lung cancer. Concurrent chemotherapy and radiation could be recommended and considered in the presence of node-positive disease, which was not the case in this situation. And if concurrent chemotherapy and radiation is to be given, cisplatin with etoposide would be the appropriate regimen administered at the time of radiation. Thank you for listening to this weekly podcast recording, "Small-Cell Lung Cancer."

Victoria Lai is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center with a clinical and research focus on small cell lung cancer and other pulmonary neuroendocrine tumors.  She conducts clinical trials that aim to elucidate the underlying biology of small cell lung cancer in order to develop new biomarkers and treatments options to improve patient outcomes.   TRANSCRIPT [MUSIC PLAYING] Welcome to the recent approvals episode of the ASCO University weekly podcast. My name is Victoria Lai. I am an assistant attending physician in a thoracic oncology service at Memorial Sloan Kettering Cancer Center. Today, we will discuss the approval of nivolumab for the treatment of patients with metastatic small cell lung cancer in the third-line setting. As a background to today's discussion, we know that FDA approved therapies for small cell lung cancer are extremely limited and remain a large, unmet need. Immune checkpoint inhibitors, including nivolumab, are active therapies in several different tumor types. Nivolumab is a monoclonal antibody against PD-1 and has previously been shown to be effective in non-small cell lung cancer. More recently, the role of immune checkpoint inhibitors in the treatment of small cell lung cancer has been explored in an effort to develop more effective treatment options for these patients. On August 16 2018, nivolumab was granted an accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression after prior platinum-based chemotherapy and at least one other line of treatment regardless of PD-L1 expression of the tumor. This approval of nivolumab in the third-line setting in small cell lung cancer was based on results from the CheckMate 032 study that was initially published in The Lancet in 2016 and has since reported updated results. CheckMate 032 was a multi-center open-label trial in patients with metastatic solid tumors. The study included a subgroup of 109 patients with metastatic small cell lung cancer who experienced disease progression after platinum-based therapy and at least one other line of therapy regardless of tumor PD-L1 status. All patients received nivolumab 3 milligrams per kilogram by intravenous infusion over 60 minutes every two weeks. The primary endpoint of this study was the objective response rate. The overall response rate was 12% with a 95% confidence interval between 6.5 to 19.5% with responses seen in 13 out of 109 patients. Responses were durable for six months or longer in 77% of patients, 12 months or longer in 62% of patients, and 18 months or longer in 39% of patients. PD-L1 tumor status did not appear to be predictive of response. Of all the patients who received at least one dose of nivolumab, the most common side effects were fatigue, decreased appetite, musculoskeletal pain, dyspnea, nausea, diarrhea, constipation, and cough. Serious adverse reactions occurred in 45% of patients and included pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration. The recommended dosing schedule of nivolumab for this approved indication is 240 milligrams every two weeks over 30 minutes. The approval of nivolumab as subsequent line therapy marks a significant advancement in the treatment of patients with metastatic small cell lung cancer. Prior to this, topotecan was the only other agent approved by the FDA for treatment in this setting, which did not yield durable responses. Although the response to nivolumab was modest, the majority of patients responded to treatment were able to achieve durable responses of greater than 12 months with over 1/3 of patients achieving a durable response of greater than 18 months. Further more, responses to nivolumab were seen regardless of the patient's prior response to chemotherapy. Given that topotecan yields a response rate in the single digits as subsequent line therapy for chemo-resistant disease, nivolumab adds an especially valuable treatment option for these patients whose disease did not previously respond to chemotherapy. Nivolumab adds an especially valuable treatment option for these patients whose disease did not previously respond to chemotherapy. Responses to nivolumab were also seen in patients who had exceeded three prior lines of therapy indicating that nivolumab can still be effective in heavily pre-treated patients. With 45% of patients in this study having developed a serious adverse reaction, patients undergoing treatment with nivolumab should be monitored closely. Finally, this study did not show any correlation or responses to nivolumab with PD-L1 expression, suggesting that the role of PD-L1 as a predictive biomarker in small cell lung cancer remains unclear. Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on immunotherapy and the treatment of small cell lung cancer, please visit the comprehensive eLearning center at university.asco.org. 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.

Shadia Jalal, MD, Assistant Professor of Clinical Medicine in the Department of Medicine, Division of Hematology/Oncology at Indiana University School of Medicine discusses updated guideline for palliative care in the global setting. TRANSCRIPT Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I am the clinical director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University. Today, we feature an ASCO Guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently-published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernan, and today, I'm interviewing Dr. Nahla Gaffer, from the Radiation S Isotope Center in Sudan, an author on palliative care in the global setting, American Society of Clinical Oncology resource-stratified practice guideline. Thank you for being here today Dr. Gaffer. Good morning. Thank you, so much, Mrs. Shannon for this opportunity. First, can you give us a general overview of what this guideline covers, and what it means to be a resource-stratified practice guideline? Yes. These guidelines outline and they cover the recommended set of palliative care integration concerning personnel needed, training needed for this staff, structure, and availability of medicines at different resource levels. And by a resource-stratified guideline, we mean that it's suitable for different levels of development. Yes. For example, if you are speaking about a community level, you are speaking of primary care centers, or if we are speaking about in a different setting, like a regional hospital and also, the highest level might be the oncology center. And at every level, there should be a better structure and better training and availability of palliative care. But at all of these levels, we should have palliative care. What are the key recommendations of this guideline? Yes. The key recommendations, as I mentioned, is that we should have a coordinated system, where the patient's palliative care needs are identified and met at every level and from the moment of diagnosis. So we are speaking about, at the basic level, we should have at least a volunteer or community worker or better even, a nurse trained in palliative care. And these people have got the job to facilitate identification of patients who need palliative care at the community level. Another level is the limited level, and here, we should have at least one doctor and a nurse trained in basic palliative care, and they work with the people working in the community. And they address minor issues, prescribing basic medicines, referring patients, and they also have the ability to support the patient and the family in [INAUDIBLE]. At another enhanced level, and we are speaking here about setting like a regional hospital, there should be a team, at least of three personnel-- doctor, nurse, pharmacist. Of course, if there is a psychologist or religious chaplain, it's OK, but at least these three personnel should be trained about palliative care, so a minimum of six weeks training. And they can provide palliative care, and they can offer as outpatient service in this regional hospital. The best setting or the maximum setting is when we are speaking about a bigger hospital or an oncology center. And we are speaking that no oncology center or any facility for palliative care patients, like hospices, should exist without a well-developed palliative care team. And having personnel and all personnel working in that center should receive basic training in palliative care. The main treating doctors, for example, the oncologists, should have secondary training in palliative care, so it's a higher level of training in palliative care. And we need for palliative care physicians to supervise and develop the service. At such a setting, we should have psychologists, we should have chaplains all integrated in the service. Another recommendation is that palliative care should be given and provided at all levels ideally, at the moment of diagnosis of the patient, but especially for patients who are coming with overwhelming symptoms, whether physical, psychological, or spiritual or patients who have metastasis or patients who cannot receive active treatment for curative intent, for example, for comorbidities or age or patients with a disease with a known short life expectancy. All these patients should receive palliative care from the moment of diagnosis. Why is this guideline so important, and how will it change practice? Yes, it is very important because palliative care is important to be given to all patients at every setting. It is not expensive. It doesn't require special equipment. It can be given. It not only should be given, but it can also be given. It's not difficult to change. And this guideline is very important, because sometimes people don't hear other colleagues or junior doctors. They hear high recommendations, like from the ASCO guidelines. And finally, how will these guideline recommendations affect patients? Yes. We hope the directors of hospitals, people or personnel at administerial levels, our fellow colleagues, they embrace these recommendations more and more. As I mentioned, sometimes it needs to come from higher up, and for that, we thank the American Society of Clinical Oncology for taking this task. Once we are caring for our patients holistically, which includes social, spiritual, psychological dimensions, in addition to physical, it leads to a better quality of life, affecting not only the patient and the family in all dimensions but even leading to a better survival, and here, I mean both in time and quality. Great. Thank you for your time today, Dr. Gaffer. Thanks. Thanks a lot. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague. [MUSIC PLAYING] 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.