ASCO Guidelines

An interview with Dr. Muriel Brackstone from London Health Sciences Centre and Dr. Tari King from Dana Farber and Brigham and Women's Cancer Center, authors on "Management of the Axilla in Early-Stage Breast Cancer: OH (CCO) and ASCO Guideline." This guideline addresses management & timing of surgical and radiotherapeutic treatment of the axilla in early breast cancer. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey. TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] 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 podcast.asco.org. My name is Brittany Harvey, and today I am interviewing Dr. Muriel Brackstone from London Health Sciences Center in London, Ontario and Dr. Tari King from Dana-Farber and Brigham and Women's Cancer Center in Boston, Massachusetts, authors on "Management of the Axilla in Early-Stage Breast Cancer" Ontario Health (Cancer Care Ontario) and American Society of Clinical Oncology Guideline." Thank you for being here Dr. Brackstone and Dr. King. DR. MURIEL BRACKSTONE: Thank you. DR. TARI KING: Thank you for having us. BRITTANY HARVEY: First, I'd like to note that we take great care in the development of our guidelines in both the ASCO and Ontario Health Cancer Care Ontario program and evidence-based care. Conflict of interest policies were followed for this 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. Brackstone, do you have any relevant disclosures that are directly related to this guideline topic? DR. MURIEL BRACKSTONE: No, I don't have any conflicts to disclose. BRITTANY HARVEY: Thank you. And Dr. King, do you have any relevant disclosures that are directly related to this guideline topic? DR. TARI KING: No, I do not have any relevant disclosures. BRITTANY HARVEY: Great, thank you. Then let's get into some of the content of this guideline. So first, Dr. Brackstone, can you give us a general overview of what this guideline covers? DR. MURIEL BRACKSTONE: Sure. This guideline reviews how best to diagnose and treat any lymph node spread in breast cancer patients with early-stage disease. It also reviews the role of radiation and surgery in treating the axilla to reduce the risk of regional cancer recurrence in these patients. BRITTANY HARVEY: Great, thank you. Then I'd like to review some of the key recommendations that this guideline covers. So this guideline addresses five specific objectives. So I'd like it if we could go through each of those. So for each of these objectives, could you give an overview of those high level recommendations? First, Dr. King, the first objective is about which patients with early-stage breast cancer require auxiliary staging. DR. TARI KING: Yes, thank you. So I think the two main takeaway points from this objective-- the first is that sentinel lymph node biopsy really is the standard of care for axillary staging for all breast cancer patients when it is felt that information about the lymph node status is necessary. So this really is in the majority of patients that we see and care for with early-stage breast cancer. We want to know the status of the axillary lymph nodes. That's important in our subsequent treatment recommendations. And there's really no role for axillary lymph node dissection as a staging procedure any longer. Sentinel lymph node biopsy is the staging procedure of choice. Now, there are some patient populations, however, where we may decide that we don't need the information from the axillary lymph nodes to make subsequent treatment recommendations. And one particular group which is called out in this guideline is for those women who are over the age of 70 with early-stage, again, clinically node-negative hormone receptor-positive, HER2-negative breast cancer, where the information from the sentinel lymph node biopsy is not going to alter subsequent systemic therapy recommendations. And this is really based on several lines of work demonstrating that omitting sentinel node in these older women, again, with hormone receptor-positive, HER2-negative breast cancer, does not negatively impact their long term outcomes. And so this is an opportunity for us to tailor our approach to a particular patient population without having a negative impact. BRITTANY HARVEY: Great, thank you, and thank you for reviewing for which patients this is specifically targeted to. So then for the second objective, Dr. Brackstone, is further auxiliary treatment indicated for women with early-stage breast cancer who did not receive neoadjuvant chemotherapy and are sentinel lymph node-negative at diagnosis? DR. MURIEL BRACKSTONE: No. We use this guideline to confirm that in patients who have early-stage disease and go to surgery first, so they're not having neoadjuvant chemotherapy. And in those patients, if their sentinel lymph node excision for staging is negative, that no further axillary surgery is required. Now, with regards to axillary radiation, it may be considered in the subset of patients whose breast cancer risk is high for recurrence-- so the triple negative subtype, patients who are under 50 years of age, or those with medial tumors. BRITTANY HARVEY: OK. And then Dr. King, for the third objective, which axillary strategy is indicated for women with early-stage breast cancer who did not receive neoadjuvant chemotherapy and are pathologically sentinel lymph node-positive at diagnosis after a clinically known negative presentation? DR. TARI KING: Thank you. Yes, so this recommendation really addresses a very large population of our breast cancer patients. Those that present with clinical T1 and T2 but node-negative early-stage breast cancer, we take them to the operating room. We perform a sentinel biopsy, and about 20% to 30% of them will actually end up having positive lymph nodes. And traditionally, we thought that we needed to do axillary lymph node dissection in the setting of positive nodes. But we now have multiple clinical trials that have addressed this question. And we now know that it is safe to avoid lymph node dissection in women found to have one or two positive sentinel nodes. We've had trials that have compared lymph node dissection to axillary radiotherapy or lymph node dissection to observation alone. And with either of those strategies, we've seen excellent local control in the women who have not undergone lymph node dissection. And so it really provides us, again, an opportunity to dial back or tailor our therapies to the patient's individual disease burden. Now, certainly, patients that have more than one or two positive nodes, and the guideline specifically states how to manage patients with three or more positive nodes. And those patients do need additional axillary treatment, either in the form of lymph node dissection or lymph node dissection plus axillary radiotherapy and in some scenarios. Also, the guideline is very clear to define that there are some differences in the level of recommendation for women undergoing breast-conserving surgery and found to have one or two positive nodes as opposed to women undergoing mastectomy and found to have positive nodes. So certainly, we have the larger body of data in the breast-conserving therapy group, but the guideline is very clear to also highlight the data that is available for the mastectomy group. And again, the overall recommendation is that not everybody with positive nodes needs additional lymph node dissection. And that we have alternatives which we know minimize the morbidity of our treatments. BRITTANY HARVEY: Great. Thank you for addressing the evidence base behind both of those recommendations as well. So following that, Dr. Brackstone, for the fourth objective, what axillary treatment is indicated? And what is the best timing of axillary treatment for women with early-stage breast cancer? And when is neoadjuvant chemotherapy used? DR. MURIEL BRACKSTONE: Right. So this guideline was really used to formalize a recommendation against repeating the sentinel lymph node biopsy procedure twice in patients, before and after chemotherapy. We really found that the risk of false negativity in a repeat procedure was too high. So for patients who are having neoadjuvant chemotherapy-- so patients with higher risk cancers-- the axillary ultrasound is useful to guide a biopsy of any suspicious lymph nodes to document if they're positive. If the clinical exam and the ultrasound are both negative, then the sentinel lymph node excision should be done at the time of surgery after chemotherapy. If they do have a positive lymph node that's confirmed by biopsy before their chemotherapy, and those lymph nodes respond really well to chemotherapy and are no longer palpable, then their staging can occur by sentinel lymph node procedure at the time of surgery. And that avoids what we have standardly done up to now, which is the axillary dissection and the risk of lymphedema that comes with that. If the sentinel lymph nodes are negative when you're doing your surgery after neoadjuvant chemotherapy, then we are recommending that no axillary lymph node dissection is required. If any of the lymph nodes are positive after neoadjuvant chemotherapy through the sampling technique, then a completion axillary lymph node dissection is still recommended, at least for now, until the results of some ongoing clinical trials looking at avoiding axillary node dissection are completed, which will be in the next several years. In both of those scenarios, however, locoregional radiation is still recommended. BRITTANY HARVEY: Great, thank you for providing some clarity around those specific scenarios. So then finally, Dr. King, regarding the fifth and last objective, what are the best methods for identifying sentinel nodes? DR. TARI KING: Thank you. Yes, so this objective encompasses several different clinical scenarios as well. The first being, when you are performing a sentinel lymph node biopsy procedure, do you need to use single tracer or do you need to use dual tracers to help you identify the lymph nodes? We know that in the up upfront surgery setting that you can absolutely identify the nodes with a very low false-negative rate with a single tracer. And this guideline highlights that single tracer is appropriate in patients who are undergoing upfront surgery. The guideline suggests that the physicians start with radiocolloid, and if there is a good signal, then blue dye can be omitted. In contrast, though, in patients that are receiving neoadjuvant chemotherapy, the data there supports really that the use of dual tracer is important and improves the identification rate, as well as decreases the false-negative rate of the procedure. This recommendation also includes guidance on when ultrasound should be used. As you just heard from Dr. Brackstone that they do recommend ultrasound prior to neoadjuvant chemotherapy. But in patients undergoing upfront surgery, again, with early-stage disease, clinically node-negative disease, the guidelines states that preoperative axillary ultrasound staging is not recommended. But in anybody who has suspicious or potentially abnormal nodes, then preoperative axillary ultrasound is recommended to confirm nodal status. And then finally, it is important to note that nodal staging cannot be solely performed with axillary ultrasound. So sentinel lymph node biopsy is still, again, indicated even if the ultrasound is negative. There are many clinical trials going on around the world right now to address that question. But right now, the evidence still certainly supports that we cannot rely on a negative axillary ultrasound, and sentinel lymph node biopsy should be performed. BRITTANY HARVEY: Great. Well, thank you both for reviewing those key recommendations around the objectives. So then Dr. Brackstone, in your view, what is the importance of this guideline? And how will it both impact clinicians and patients? DR. MURIEL BRACKSTONE: Thank you. I would say for clinicians that the guideline was written in an effort to collate all of the clinical trial data and the variable practice patterns across institutions in an effort to standardize treatment. In order to deescalate therapies that don't improve patient outcomes. And hopefully, provide some clarity for clinicians who treat breast cancer. For patients, I would say that deescalating treatments that are entrenched as standard, but where data demonstrates no known significant disease-free survival or overall survival benefit, that these are important because patients can suffer long term side effects from treatments, such as lymphedema, that could potentially be avoided if they're not clinically indicated. BRITTANY HARVEY: Great. Thank you both so much for your work on these evidence-based recommendations. And for taking the time to give a summary to our listeners, Dr. Brackstone and Dr. King. DR. TARI KING: 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/breast-cancer-guidelines. Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at www.surveymonkey.com/r/ascoguidelinesurvey by August 1. The link is also available in the episode notes of this podcast. 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 Kim Woofter, RN from Advanced Centers for Cancer Care and John V. Cox, DO, MBA from UT Southwestern Medical Center, co-chairs on "Oncology Medical Home: ASCO and COA Standards." They review the standards for the OMH model, which is a system of care delivery that features coordinated, efficient, accessible, evidence-based care and includes a process for measurement of outcomes to facilitate continuous quality improvement. For more information, visit www.asco.org/standards. TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Kim Woofter, RN from the Advanced Centers for Cancer Care in South Bend, Indiana, and John Cox, DO, MBA, from UT Southwestern Medical Center in Dallas, Texas, co-chairs on Oncology Medical Homes, American Society of Clinical Oncology, and Community Oncology Alliance Standards. Thank you for being here, Ms. Woofter and Dr. Cox. JOHN COX: You bet. KIM WOOFTER: Thank you for having us. BRITTANY HARVEY: I'd like to note that ASCO takes great care in the development of its standards and ensuring that the ASCO conflict of interest policy is followed. The full conflict of interest information for the expert panel is available online with the publication of the standards in JCO Oncology Practice. Ms. Woofter, do you have any relevant disclosures that are directly related to these standards? KIM WOOFTER: No, I don't have anything to disclose. BRITTANY HARVEY: Thank you. And Dr. Cox, do you have any relevant disclosures that are related to these standards? JOHN COX: I do not. BRITTANY HARVEY: Great. Then let's talk a little bit about these standards. So first, can you give us a general overview of the purpose and scope of these standards for the Oncology Medical Home or OMH model? KIM WOOFTER: Sure. I'll start this one out. The purpose was to collaboratively define a care delivery system with a standardized set of expectations and goals, and it all centered around the delivery of high quality, cost-effective care. And one of the reasons this is so important to all of us right now is to be ready for value-based care. We all need to really have a care delivery system that's patient-centric and has a standardized set for all of us to follow. Dr. Cox, do you see this any differently, or what would you have to say? JOHN COX: No, I think you've said it well, Kim. I think one of the challenges we all have when we talk about Oncology Medical Home or a system of care is to be challenged to address that question in a simple answer. I would give the predicate that we have had a blossoming of the complexity of oncology care in our science, yet one of the thorny issues that faces oncology practice is how do we equitably and efficiently provide quality oncology care. And if you were to challenge many clinicians to define how they provide quality oncology care, you get diverse opinions about that. The Oncology Medical Home certification program and the system of care that Kim highlighted attempts to put forward a comprehensive set of standards that helps us define what quality oncology care looks like and to answer those questions in care delivery. BRITTANY HARVEY: Great. Then, given that scope, what are the key statements made by the expert panel in these standards? JOHN COX: I'll take a stab at that, but also offer a little bit of insight into the development of Oncology Medical Home. We actually had some 20 years of history with different medical home certification programs to draw on, including significant contributions by oncologists who have worked in different programs to help define what Oncology Medical Home is. So when we took on this project, a collaborative project between ASCO and the Community Oncology Alliance, COA, we drew upon that great history of previous certification programs. These programs focused on different aspects of care delivery, including aspects that are focused on improving patient engagement and access to practice, ensuring that evidence-based medicine is provided in a practice, looking at how quality is measured and how that feedback is given to practices and how that feedback is used to have quality improvement programs, focusing on palliative and end-of-life care, and addressing one of the unique features of medical oncology delivery, which is the delivery of chemotherapy and how we do that safely. So this was a very comprehensive set of standards. Kim, I don't know if you want to add to this. KIM WOOFTER: No, I think you stated that very well. And the piece that I really love about this project, and what we focused heavily on, is the equitable delivery of care. We all fundamentally believe that every cancer patient deserves and has the right to high quality, cost-effective care, and this was just the baseline. And I think Dr. Cox explained it very well, that one of the key elements is the quality improvement process, or the re-evaluation continually of how we deliver care, the outcomes of care, the patient satisfaction with that care. So as we developed this, we knew this was just the foundation. This is the starting point. We've brought some unity around the discussion. We've used evidence to come up with these standards and really defined what's gone on prior to this time. And what's exciting is this is just the beginning of what will evolve over the years to come. BRITTANY HARVEY: Great. It sounds like this is a really comprehensive document. So I'm reading through the standards. It looks like there's a little bit of a deeper dive on two subcomponents of the OMH model-- first, clinical pathways, and second, survivorship care plans. How do the standards address these two? JOHN COX: Oh, I'll dive in first again. And not to step on Kim at all about this, but many of the listeners to this podcast will be very familiar with ASCO guideline development. And the traditional clinical guidelines are completely infused and based on an evaluation of what the evidence base is. Care delivery is a bit more complex. Much of care delivery focuses on best practices that have been learned in practice through trial and error-- observation, if you will. So many of the standards that are in Oncology Medical Home certifications are really based on best practices. However, we knew that we would be challenged to evaluate those standards that had significant cost or significant resource dedication in a practice. If we were going to build those aspects of a certification program forward as being a best practice in a care delivery model, we would need to justify, or at least examine, what evidence base is present to show that it had value. Two of the most consequential standards that are going to require significant resource development by any practice is the measurement of evidence base through a pathway program. The other one was the significant discussion that has been around survivorship and survivorship care plans. So those two areas of the standards we took a deep dive in in this process. Kim, do you want to add to this? KIM WOOFTER: Yeah. I really appreciate Dr. Cox's description. He's spot on, as always. I think having managed to practice myself for many, many years, the struggle with the implementation of a clinical pathway program and survivorship care plans or for survivorship program have always been somewhat difficult. And what I love about the standards is we clearly define that pathways are no longer a homegrown list of what I like to do or how I like to treat. It is absolutely evidence-based. Your pathways have to truly reflect the importance of clinical research and what that has done to lead up to the intelligence of that delivery. What I think is so important, too, is ASCO still did a little bit of work and set the pathway for us on this in that it needs to be a comprehensive list. It needs to have systematic review. We have to demonstrate adherence to pathways and also document when somebody goes off a pathway. And I think that's very important as you manage a practice and as you prepare for this delivery system. It's no longer what we do in the back room. It's very well-defined and very measurable. As far as survivor care plans, I love that we have migrated a little bit on this standard. I think the nation has migrated. Over the years-- and I'll include the COC in this discussion. Originally, it was check the box, have a survivorship care plan and a visit to explain what the future would look like. And we now know that isn't the best way to handle survivorship. Patient satisfaction and outcomes are much better when we have a survivorship program. And that's what the standard calls out. It is not just a care plan or a piece of paper. It is support. It is ongoing evaluation of the patient. It's integration with the primary care and when to transition back to primary care. So what's exciting is it is now a program versus just a care plan. BRITTANY HARVEY: Thank you both for explaining the evidence-based reasoning behind those two components. So then you've both noted earlier the importance of these standards for quality oncology care. So why are these standards important, and how will their implementation impact clinicians? KIM WOOFTER: I'll jump in to why I think they're important-- and I think the whole industry, the whole ecosystem of oncology care thinks they're important-- is we need standardization. We need real, evidence-based standardization. And we need to prepare ourselves in all settings-- community oncology practice settings, academic settings-- for the value-based care that we're going to be required to deliver every day, all day. And clinicians, I believe, will embrace this. They'll embrace this because it's taken away some of the ambiguity of what care delivery should look like, and it levels the playing field, if you will. It also helps with the dialogue with patients and their employers. I think we could all argue that patients and employers are the ultimate payers. And they now have a mechanism by which they can evaluate, am I getting the highest quality, most affordable care? And these Oncology Medical Home standards will be the foundation for that discussion. And I'm excited that everyone will be involved in that discussion. So I think that's why they're very important. BRITTANY HARVEY: Great. And then, finally, how will these standards impact patients? JOHN COX: Well, I think our whole goal in delivering efficient and quality oncology care is to be very patient focused. I would underline that this entire concept of an Oncology Medical Home is built around a patient centered care. So every standard that this program identifies has the patient at the center of care. And I think anybody who reads through the standards can see that every aspect of this is focused on some issue that they can relate to patients in their practice stumbling over. We have this wonderful technology of care. But right now, I would challenge oncology practice universally that as our science has become more complex, patients are having to jump through more hoops to get that quality care. Specialization breeds fragmentation. What we want this program to do is to define what a oncology practice must do to help that patient have a coordinated care approach for all aspects of their cancer journey. And I want to come back and just put a coda, a real strong statement, is this is a care delivery system. We are trying to take as comprehensive view of the delivery of oncology practice in the certification program as we can. It's not intended to parse. It's intended to focus on the patient and to provide a comprehensive system of care. The other challenge is we know that the only way there can be efficient and easily accessible practices that can provide this kind of care is that they be adequately funded. And though this certification program does not speak to funding directly-- this is about the quality of care delivery-- we wanted to build a program that payers in industry could look at and build their reimbursement systems around. We hope that as new reimbursement models, alternative payment models come to bare, that if practices are pursuing this certification program, they will be able to meet the demands of the payer and apply this toward a comprehensive, meeting the standards of any alternative payment program. And to that end, I really want to defer maybe a little more discussion of this to Kim. Kim, we sort of present two ends of the barbell, if you will, of care delivery. I, a practitioner, Kim is on the point of the sword in dealing with her practice about the reimbursement issues and contracting. So when we talk about this, what is the impact for patients? Part of that is recognizing that patients have insurance. They have employers. They have people who are paying for this care. And that's really important to address. Kim, I'm long-winded. Maybe I'm trying to wrap too much into this answer. But I'll let you add to the issues of reimbursement and how this affects patients. KIM WOOFTER: Well, thank you, Dr. Cox. You're never too long-winded. I always love to hear you speak, and your insight is spot on. And I think, from a patient's perspective, what's exciting about this program is it engages and empowers patients right from the beginning. You'll see, very well spelled out in the standards, that one of the requirements is that you educate that patient about what an Oncology Medical Home really means, what the components are. And that empowerment of the patient allows them to be part of the voice for quality oncology. As we work with their payers, their employers, the patient themselves understand the value of what we are doing in collaboration. They understand that we provide them access, 24/7 access, you'll see, as part of the requirement. And they understand very well and can help us communicate to everybody in the ecosystem that this comprehensive package is what gives them the highest quality, allows them, like I said, the most access. It allows them safe chemo delivery. And as they communicate that, it will become the desired standard. The patient is absolutely the ultimate winner here. Everything we do as clinicians and administrators is based around the patient. Outcomes, satisfaction, end-of-life initiatives. And I believe by putting this comprehensively and well-defined into one set of standards, we have helped the patient to achieve that goal. BRITTANY HARVEY: Well, it sounds like these standards will have a real positive impact for patients and quality oncology care delivery. So I want to thank you both for your work on the development of these Oncology Medical Home standards and for taking the time to speak with me today, Dr. Cox and Ms. Woofter. KIM WOOFTER: It was our pleasure. JOHN COX: It's our pleasure. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the standards, go to www.asco.org/standards. 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. Zeba Aziz from Hameed Latif Hospital in Lahore, Pakistan, Dr. William Burke from Stony Brook University Hospital in Stony Brook, NY, and Dr. Keiichi Fujiwara from Saitama Medical University International Medical Center in Saitama, Japan, authors on "Assessment of Adult Women with Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource Stratified Guideline." This guideline provides recommendations in three resource-constrained settings on diagnosis and staging of adult women with ovarian masses and treatment of patients with epithelial ovarian (including fallopian tube and primary peritoneal) cancer. Read the full guideline at www.asco.org/resource-stratified-guideline. TRANSCRIPT ASCO: 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 podcast.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. Zeba Aziz from Hameed Latif Hospital in Lahore, Pakistan, Dr. William Burke from Stony Brook University Hospital in Stony Brook, New York, and Dr. Keiichi Fujiwara from Saitama Medical University International Medical Center in Saitama, Japan, authors on Assessment of Adult Women with Ovarian Masses in Treatment of Epithelial Ovarian Cancer: ASCO Resource Stratified Guideline. Thank you for being here, Doctors Aziz, Burke, and Fujiwara. 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 and the Journal of Clinical Oncology, Global Oncology. Dr. Burke, do you have any relevant disclosures that are directly related to this guideline topic? DR. WILLIAM BURKE: I do not. BRITTANY HARVEY: And Dr. Fujiwara, do you have any relevant disclosures that are related to this guideline topic? DR. KEIICHI FUJIWARA: Yes. I have the consultancy for the PARP inhibitors development. BRITTANY HARVEY: Thank you. And then Dr. Aziz, do you have any relevant disclosures that are related to this guideline? DR. ZEBA AZIZ: No, I don't. BRITTANY HARVEY: Thank you. OK, so first, Dr. Burke, can you give us a general overview of what this guideline covers? DR. WILLIAM BURKE: Sure, Brittany. The purpose of this guideline is to provide expert guidance in treatment of adult women 18 years and older with epithelial ovarian cancer, including fallopian tube and primary peritoneal cancer, to clinicians, public health leaders, patients, and policymakers in a resource-constrained setting. To do this, ASCO has established a process for development of resource stratified guidelines, which includes a mixed methods of evidence-based guideline development, adaptation of the clinical practice guidelines to other organizations, and formal expert consensus. This guideline summarizes the results of this process and presents resource-stratified recommendations. The recommendation of this guideline centers around the four key clinical questions pertaining to the care of women with ovarian cancer. BRITTANY HARVEY: Great. And then, as you just mentioned, this is a resource-stratified guideline. So Dr. Fujiwara, can you tell our listeners about the four-tier resource stratification used for the development of this guideline? DR. KEIICHI FUJIWARA: Oh, yes. So we have the four tiers resource stratification, which were basic, limited, enhanced, and maximum. So for the basic, it's the core resources or fundamental services that are absolutely necessary for any public health or primary health care systems to function. So the basic levels of this typically are applied in our single clinical interactions. For the limited, so this is the second tier resources or services that are intended to produce major improvements in outcomes such as, for instance, cost-effectiveness, and are attainable with a limited financial means and modest infrastructures. So the limited level of service may involve single or multiple interactions. And the third tier is enhanced. The third tier resources or services that are optional, that are important, enhance the level of resources should produce further improvements in the outcome and to increase the number of the quality of options in the individual choices. Lastly, the fourth tier is a maximal, so high-level or state of the art resources, or services that may be used or are available in some high-resource countries, and/or may be recommended for the high resource setting guidelines that do not adapt to resource constraints, but that nonetheless should be considered for a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for the broad use of the resource-limited environment. BRITTANY HARVEY: Great. Thank you for going over those. So next, I'd like to review the key recommendations of this guideline. This guideline addresses four overarching clinical questions. So first, Dr. Aziz, what are the key diagnostic and staging recommendations for patients with symptoms of epithelial ovarian cancer? DR. ZEBA AZIZ: Thanks, Brittany. Basically, as pointed out, we have three levels. The basic level usually involves one or two encounters, and at the basic level, the doctor makes a clinical assessment of a suspected ovarian mass, takes a good history and physical, and the family history is also important at the same time. At the basic level, one can do a chest X-ray and an ultrasound to confirm the suspicion, and then the doctor should ideally send the patient to a limited or an enhanced level-- wherever the patient can go. At the limited and enhanced level, again, you have to do diagnostics, which include a CT scan and an MRI if it's available and feasible. You can do the biomarker studies for CA125 and CEA level, and to make a diagnosis, you can do a CT-guided biopsy. You can also do a cell cytology and if a cell block preparation can be made through cell block. Very rarely, if need be, and if you think that you need to make a diagnosis and you can't do anything else, laparoscopy can be done. Once the diagnosis is made, you then go for staging. And the staging is usually done when you're doing a CT scan and you do an abdominal and pelvic CT scan. You do a CT scan of the chest if you think it's needed. Otherwise, a chest ray will suffice. And then you go forward and get a diagnostic workup done and send it to the surgeon for either and decide on a multidisciplinary with a neoadjuvant or surgical assessment testing. BRITTANY HARVEY: Great. Then so next, Dr. Fujiwara, what are the overarching recommendations for surgery with women with stage one to four epithelial ovarian cancer? DR. KEIICHI FUJIWARA: Yes. So the purpose of the surgery is to diagnose, stage, and/or for treatment. So we strongly recommended the ovarian cancer surgery should be performed by trained gynecological oncologists or surgeons with oncologists' surgical expertise. If it is not suitable, we strongly recommend to refer those patients to the highest-resourced level center with an oncology surgical care capacity. For the staging purpose, where the feasible patients with a presumed early stage ovarian cancer should undergo surgical staging by train surgeons. In basic setting, surgical staging is not feasible. Thus, it is not recommended. For the treatment purpose of the women with advanced ovarian cancer, which is a stage three or four, should receive optimal surgical debulking to remove all visible disease to improve overall survival by trained surgeons. BRITTANY HARVEY: Great. And then Dr. Burke, what are the key recommendations for optimal adjuvant and systemic therapy for patients with stage one to four epithelial ovarian cancer? DR. WILLIAM BURKE: Sure. Well, one of the most important things is that access to appropriate evidence-based chemotherapy agents, contraindications to chemotherapy, and potential side effects of chemotherapy should be evaluated and managed in every patient. Basic resource settings that most likely lack the capacity to provide safe administration of chemotherapy should refer patients to a higher level center for evaluation. Limited settings without skilled capacity should refer patients to settings with access to specialized care. Some other notes include that clinicians should be able to document pathology and stage to determine eligibility for adjuvant chemotherapy. If pathology confirmation is not possible due to patient or resource limitation, alternatives can be discussed. Clinicians should not administer systemic treatment, adjuvant chemotherapy, to patients with ovarian low malignant potential tumors or early stage, microinvasive borderline tumors, independent of stage. Combination chemotherapy with paclitaxel and carboplatin is the standard of care for adjuvant therapy in ovarian cancer. However, single agent carboplatin may be utilized due to resource limitation or patient characteristics. Only in enhanced settings, highly selected cases can be assessed for appropriate evidence based intraperitoneal chemotherapy following optimal debulking, where there are resources and expertise to manage the toxicities. BRITTANY HARVEY: Great. And then the last overarching clinical question-- Dr. Aziz, what is recommended for patients with recurrent epithelial ovarian cancer? DR. ZEBA AZIZ: You know, with recurrent ovarian epithelial cancer is a tough option, especially in patients residing in the low-middle income countries. Supportive care treatment should be started together with whatever we have to do. So there are three options. There's one patient who presents with a rising CA125 with no evidence of disease and asymptomatic. We can elect to follow these patients, and it's easier to follow them until they become symptomatic or they have evidence of disease. If you have small volume disease which is resectable, you send them to an enhanced level setting, ideally where surgery can be done. Then you also look at patients and divide them into platinum resistant or platinum sensitive. If they're platinum sensitive, you can give a platinum-containing regimen, but if they're platinum resistant, you can put them on a non-platinum chemotherapy-- a single agent or whatever-- but these patients are tough to manage in that part of the world. BRITTANY HARVEY: Definitely. Well, thank you all for reviewing each of those key recommendations. The full recommendations are available in the guideline, but those are some important highlights. Thank you very much. So Dr. Burke, in your view, what is the importance of this guideline, and how will it change practice? DR. WILLIAM BURKE: Sure. Well, I think the importance of this guideline is that it globally targets health care providers, including gynecologic oncologists, surgeons, nurses, and palliative care clinicians, as well as non-medical community members, including patients, caregivers, and members of advocacy groups, providing them with resource-stratified clinical guidelines, recommendations that can be implemented across many health settings. The guideline will hopefully raise awareness among frontline practitioners, and provide guidance to provide adequate services in the face of varied and sometimes limited resources we see throughout the world. BRITTANY HARVEY: Great. And Dr. Aziz, how do you envision that these guidelines can be applied in low and middle income regions? DR. ZEBA AZIZ: These are extremely important guidelines for our part of the world. Remember that there are about 70 low-middle income countries, and all these countries-- and within each country-- there's marked variability in training of physicians who encounter cancer patients. There's also difficulty by the patients in accessing a few tertiary care centers, cancer care centers which are present, and most of all, financial implications, because you have to go there, you have to stay there, you have to get your chemotherapy, and this is true for the marginalized population. You also have to remember that more than 50% of our patients are treated in a limited resource setting, and the availability of enhanced resources are very difficult for them. And these limited settings are in public sector hospitals, where the doctors-- some of the doctors are very good, but the physicians or surgeons are overworked. They have resources ranging from minimal to moderate, depending on the funds available. And because they're overworked and there are few working hours, detailed counseling of the patient is infrequent because there are a large number of patients there. And the majority of surgeries, which is the cornerstone of ovarian cancer, is done by the postgraduate fellows who are there. Sometimes the senior consultants do surgeries, but most of the time, it is done by them. First time chemotherapy is easier to deliver because it does not have any expensive medicines. There are a lot of generics for carboplatin and taxanes regimen available, so it's not a major problem. But treating the side effects, again, becomes very expensive, and the patients have to come back and forth. The relapsed disease is very difficult to treat because we don't have too many options there and it is expensive. We've also seen that patients who are treated at an enhanced level do much better. Their survival outcomes are better, the supportive care treatment is better, and the progression-free survival is also better. BRITTANY HARVEY: Great. Thank you for reviewing that information. And then finally, Dr. Fujiwara, Dr. Aziz touched on this a bit on how it impacts patients, but how else do you view that these guideline recommendations will affect patients? DR. KEIICHI FUJIWARA: Yes. As Dr. Aziz said and Dr. Burke said, this guideline is written for the patients around the world in a different medical environment. So I think that it is very useful resource of information for patients to receive the best ovarian cancer treatment that suits the actual situation of each country or regions. BRITTANY HARVEY: Great. Well, thank you all for your work on these important guidelines. It sounds like they're going to have a real impact globally, and so I really appreciate both all of your work on these guidelines, and also for taking the time to speak with me today, Dr. Aziz, Dr. Burke, and Dr. Fujiwara. DR. ZEBA AZIZ: 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/resource-stratified-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines available on iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

An interview with Dr. Jennifer Griggs from University of Michigan and Dr. Gary Lyman from Fred Hutchinson Cancer Research Center & University of Washington, co-chairs on "Appropriate Systemic Therapy Dosing for Obese Adult Patients with Cancer: ASCO Guideline Update." This guideline updates recommendations on appropriate dosing of systemic antineoplastic agents – including cytotoxic chemotherapy, checkpoint inhibitors, and targeted therapies – for obese adults with cancer. Read the full guideline at www.asco.org/supportive-care-guidelines. TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcasts.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Jennifer Griggs from the University of Michigan and Dr. Gary Lyman from Fred Hutchinson Cancer Research Center and University of Washington, co-chairs on appropriate systemic therapy dosing for obese adult patients with cancer ASCO guideline update. Thank you for being here, Dr. Griggs and Dr. Lyman. DR. GARY LYMAN: Thank you, Brittany. DR. JENNIFER GRIGGS: Thanks for having us. 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. Griggs, do you have any relevant disclosures that are directly related to this guideline topic? DR. JENNIFER GRIGGS: No, I don't. BRITTANY HARVEY: And Dr. Lyman, do you have any relevant disclosures related to this guideline? DR. GARY LYMAN: I have no relevant disclosures to this guideline. BRITTANY HARVEY: Great. Thank you, both. Then let's get into the substance of this guideline update. So Dr. Lyman, can you explain what prompted an update to this guideline on appropriate dosing for obese adult patients with cancer last published in 2012, and what is the scope of this update? DR. GARY LYMAN: Thank you, Brittany. Yes, this is an update of a previous guideline, several years old, that was prompted by evidence that there was wide variation in how chemotherapies at that time were being dosed, particularly in the overweight and obese population. Some were capping the dose, some were giving the full weight-based dosing, and all sorts of permutations in between. So that guideline was greeted, I think quite favorably, and, in fact, led to changes in clinical practice in many institutions and I believe also in the cooperative group research networks. Since that time, however, a whole array of new therapies have come along. These, we'll talk about briefly in this podcast, include the novel targeted therapies based on molecular targets, as well as the new checkpoint inhibitors, and other monoclonal antibody therapies, where the dosing issues, in general, are different for many of these agents. And specifically for patients who are overweight and obese, we thought it was important that we update this guideline, review the evidence in total appropriate to the dosing of these new agents in overweight and obese patients, and make updated recommendations that would be more relevant to that practice of oncology in 2021. BRITTANY HARVEY: Great. Thank you for explaining the previous version of the guideline and for explaining the expanded scope. So given that, I'd like to review those key recommendations made in this guideline. So Dr. Griggs, what are the recommendations regarding dosing of cytotoxic chemotherapy in obese adults with cancer? DR. JENNIFER GRIGGS: With rare exception, we recommend, and the evidence supports, using actual body weight when we calculate doses. So whether it's just per kilogram, milligrams per kilogram for example, or per meter squared, using body surface area, we recommend that the actual body weight of the patient be used with no compromise or capping, no maximizing the dose as if it were calculated using 2 meter squared for example. There's no evidence that that's necessary to avoid side effects, and, in fact, there's increasing evidence that doing so, that limiting the doses in patients, is associated with decreased benefit of the treatment. Since the original guideline came out, there's been no convincing evidence that has made us change our recommendation. So again, in brief, we recommend that actual body weight be used in calculating the target dose for cytotoxic chemotherapy. BRITTANY HARVEY: Great. Thank you. That's very clear for clinicians. So Dr. Lyman, you mentioned this in your introduction to the scope of this guideline, what are the recommendations for dosing of checkpoint inhibitors and targeted therapy in obese adults with cancer? DR. GARY LYMAN: Well, Brittany, these are the new agents that I referred to in the introduction that have appeared in broad usage in oncology and other disciplines since our 2012 guideline recommendation. Many of these are monoclonal antibodies, and they just generally have a wider therapeutic index and distribute an extracellular fluid and plasma with less correlation with body size descriptors, such as weight or body surface area. They may be, in fact, in some cases are amenable to fixed dosing schedules. So this has all led to a whole array of new agents approved by the FDA for cancer therapies that are being dosed on a wide variety of means, some based on dosing like we have done for classical chemotherapy that Dr. Griggs discussed using body surface area, in some cases body weight, and then some being dosed base on fixed dosing-- fixed size regardless of the body size that the patient represents. So it gets a little complicated, because currently the monoclonal antibodies and many of these therapies are dosed in different ways, versus fixed dosing is recommended for some of the immunotherapies, alemtuzumab, afatinib, as well as targeted therapies like pertuzumab, which are relatively recent. And then weight-based dosing, milligram per kilogram, is used for other checkpoint inhibitors, like ipilumumab, as well as other monoclonals like bevacizumab and trastuzumab among others. And then again some were still dosing based on body surface area, such as rituximab and cetuximab. So the bottom line is these agents will be dosed and the approved dosing by the FDA will generally be based on the schedule and dosing that was used in the pivotal clinical trials. And different companies in different disease areas have chosen different ways of dosing these. So for us, with this guideline, and this is true of overweight and obese patients in particular, we recommend dosing these agents based on the FDA approved dose and schedule for that agent. But be aware, as I indicated, that it will vary from agent to agent and category of agent from one to the other. Because of the convenience and perhaps some safety issues related to fixed dosing, additional data has been submitted to the FDA for some agents, nivolumab, for instance, and pembrolizumab, to suggest that a different dosing schema, fixed dose schema can be used, and that has led to a modification in those dosing recommendations. So even if you think you know, if you're not using these agents day in and day out, you really should check and make sure you're using the currently recommended dosing. And final point is, in the overweight and obese patient, any dose modification because of adverse events or scheduling changes should be applied independent of the patient's obesity or overweight status. In other words, any dose modification that you would apply a healthy weight patient is the same type of dose modification you should apply in the overweight and obese patient and not modify solely based on the patient's weight or obesity status. BRITTANY HARVEY: Definitely. Great. That was actually going to be my next question. So Dr. Griggs, do you have anything to add about for obese adult patients with cancer who experience high grade toxicity-- should clinicians modify dosing and schedules differently than they would for non obese patients? DR. JENNIFER GRIGGS: Well, as Dr. Lyman says, the same with checkpoint inhibitors and targeted therapies, we don't recommend and the evidence doesn't support making changes in a different way. That is, there's no interaction between obesity status and the recommendation through dose modification. So in a patient who has severe toxicity related to chemotherapy as well as the targeted agents and checkpoint inhibitors, we recommend that standard dose modifications be made, and moreover that if the patient does better that one consider dose escalation again, if there were for example another concurrent illness that might have contributed in part to the toxicity. So if that other factor resolves, let the dose be increased again to try to maintain that relative intensity dose over time that we consider ideal. BRITTANY HARVEY: Great. Thank you for reviewing that for the cytotoxic agents in addition to the immune checkpoint inhibitors and targeted therapies. So then, Dr. Lyman, the last clinical question of this guideline-- how should body surface area be calculated? DR. GARY LYMAN: Well, this is the issue alluding to when I mentioned that there could be safety concerns with these complex calculations. And we tried to make it simple in the guidelines. There are multiple BSA-- Body Surface Area-- calculators out there. You can search them on the web, you can go to textbooks, and there's a whole range of them. And we actually looked at this. This goes back to the original guideline, and it holds true today, that if you compare that the dose calculated by these different calculators, it's very close to one another. So our bottom line recommendation-- if you're going to use body surface area for calculating the dose of conventional cytotoxic therapy or any of these other agents where that dosing approach is recommended, any of these calculators are going to give you a safe and hopefully effective dose of the therapy. And we don't prefer or recommend one over the other. Again, there are many on the web. Many institutions have their preferred and may even have embedded the calculator within the EMR or computer order entry system. Many prefer the Mosteller, the Du Bois, the Boyd, there's a whole variety of these, but all of them will generally yield very similar calculations. We haven't mentioned, and just to point out, as most oncologist know certainly, is one drug group, a specific agent, carboplatin is dosed differently. And for carboplatin, we calculate the dose based on a target area under the curve and GFR, so that the Calvert formula calculates the dose differently for carboplatin. And that's for historical as well as pharmacologic reasons. So again, as Dr. Griggs mentioned, for classical chemotherapy, body surface area is the most common one. But any of the approved calculators or available calculators will give you essentially the same dosing recommendation. And I would follow what's recommended by your institution. BRITTANY HARVEY: OK. Well, thank you both for reviewing the key recommendations in this guideline update. So finally, Dr. Griggs, in your view, why is this guideline update important, and how will it impact both clinicians and patients with cancer? DR. JENNIFER GRIGGS: Dr. Lyman and I have viewed this as a really important guideline and guideline update. Because, as we know, the prevalence of obesity is increasing and obesity is associated with an increase in the risk of cancer-- many cancers, not all. And moreover, people who are obese tend to have worse outcomes. And so to try to level out and keep people from systematically what we consider underdosing people who are obese with chemotherapy is very likely to improve outcomes for an important group of our patients. In addition, the update, because it's been updated now since 2012, we have more evidence that what we're recommending, what the evidence has supported thus far historically and in trials, is actually safe. There's been no signals, in other words, that the original guideline needed to be altered for certain patients or drugs. And now, with this update, we're pretty confident, based on what we know from the FDA and clinical trials, that using actual body weight is not just appropriate, but it's also recommended. So it's an important issue for the population and for our patients, and it's important for clinicians to have the confidence to use actual body weight when calculating anticancer drug doses. BRITTANY HARVEY: Great. Thank you, both, for all the work you did to update this evidence-based guideline and thank you for taking the time today to speak with me on the podcast, Dr. Griggs and Dr. Lyman. DR. GARY LYMAN: Thank you, Brittany. DR. JENNIFER GRIGGS: Thanks, Brittany. We want to thank our co-authors on the guidelines, as well as the ASCO staff for their tremendous work. DR. GARY LYMAN: Yes, we couldn't do it without all of them, and it's a tremendous team effort. BRITTANY HARVEY: Definitely. We thank them all as well. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available on iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Jessica Geiger, MD, from Cleveland Clinic and Patrick Ha, MD, from the University of California, San Francisco, co-chairs on "Management of Salivary Gland Malignancy: ASCO Guideline." This guideline provides recommendations for preoperative evaluation, surgical procedures, radiotherapy techniques, the role of systemic therapy, and follow-up evaluations for patients with salivary gland malignancies. Read the full guideline at www.asco.org/head-neck-cancer-guidelines. TRANSCRIPT SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Jessica Geiger from Cleveland Clinic and Dr. Patrick Ha from the University of California San Francisco, co-chairs of management of salivary gland malignancy ASCO guideline. Thank you for being here, Dr. Geiger and Dr. Ha. DR. PATRICK HA: Thank you, Brittany. DR. JESSICA GEIGER: Thank you. 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. Geiger, do you have any relevant disclosures that are directly related to this guideline? DR. JESSICA GEIGER: No, I don't. BRITTANY HARVEY: And Dr. Ha, do you have any relevant disclosures that are related to this guideline? DR. PATRICK HA: No, I do not. BRITTANY HARVEY: Thank you both. Then let's talk about some of the content of this guideline. So first, Dr. Geiger, can you give us a general overview of the purpose and the scope of this evidence-based guideline on the management of salivary gland malignancy? DR. JESSICA GEIGER: Sure. So salivary gland cancers-- they're relatively rare, and they encompass a wide variety of both histologies, but also biologic behaviors of cancers. This is a very multidisciplinary tumor, so surgeons, radiation oncologists, pathologists, medical oncologists-- they all play an integral role in treating these patients. And the purpose of this guideline was to bring all of these disciplines together and to develop an as strong as possible, evidence-based way of approaching the diagnosis of such cancers and then approaching it from all modalities of therapy-- surgical, radiotherapy, systemic therapy-- in a very evidence-based and organized fashion. BRITTANY HARVEY: Great, then as you just mentioned, this is a multidisciplinary guideline, and it covers six different subtopics on the management of salivary gland malignancy-- preoperative evaluation, surgical management, radiotherapy, systemic therapy, follow up, and treatment options for recurrent and metastatic disease. I'd like to go through and review the key recommendations from each of those sections for our listeners. So first, Dr. Ha, what is the guideline recommend regarding preoperative evaluation for patients with salivary gland malignancy? DR. PATRICK HA: Great, so I'd first like to start off by saying that we were focusing on salivary gland malignancy. So again, these are tumors where we may not know the diagnosis, but we're suspicious of this being cancer as opposed to a benign tumor. So along those lines, there are many different imaging recommendations-- first off, that some sort of imaging would be helpful if there's a suspicion of cancer, and then drilling down a little bit more specifically if there is concern about bone involvement. And then CT scan was recommended if it was more of a concern about the soft tissue or perineural invasion or skull-based invasion, then MRI was suggested. And we did spend some time focusing on the strength of and the importance of tissue biopsies, either with fine needle aspiration biopsy or core needle biopsy as a real helpful tool to help clinicians determine what sort of procedures and care this patient might need. Additionally, with the onset of more understanding of the pathology in the markers, it was felt that using these biopsies-- these FNAs or core biopsies-- to perform either molecular or immunohistochemical studies could further help clarify what the diagnosis would be and thus lead to sort of more specific and defined treatment subsequently. BRITTANY HARVEY: And then following those evaluation and imaging and biopsy recommendations, what are the key surgical recommendations? DR. PATRICK HA: Yeah, so again this is probably known to most people-- that when it is considered resectable, the surgery is really the mainstay upfront management option for these patients. We spent some time looking at the different types of surgeries and felt that it was a bit up to the discretion of the surgeon, but it depends on the location as to what type of surgery exactly needs to be done. But the idea is obviously we would want a complete resection of it and margins where possible. And then we address the nodes and the ability for these cancers to sometimes spread regionally. And basically, if these are high risk or high grade cancers, specifically if there are things like the grade of the tumor itself-- the type-- and then whether there were other concerning features about it, than a neck dissection electively would be offered. If there were N positive disease, then the neck dissection definitely should be performed. And then there was discussion as well about the facial nerve and how to manage that, wherein the evidence mostly reported trying to preserve the facial nerve whenever possible. And then we did talk a little bit about the possibility of palliative resection, which can occur sometimes in the presence of distant metastatic disease upon presentation. And it was felt again that there is a palliative component to surgery if the metastatic disease didn't seem to be rapidly progressive or imminently lethal. So these are all the difficult decisions that we discussed regarding surgery. BRITTANY HARVEY: OK, thank you. Then Dr. Geiger, how does this guideline address radiotherapy for patients with salivary gland malignancy? DR. JESSICA GEIGER: Well, as Dr. Ha mentioned, this is primarily a surgical disease. So most of the recommendations regarding radiotherapy involve the post-operative setting. But if you look at the guideline, we have actually laid out 10 recommendations regarding radiation, and they're dependent on various factors with each cancer, so the histology of the disease, other tumor pathologic factors, such as T-stage, vascular, lymphatic invasion, margin status, perineural invasion-- all of that goes into the recommendation here. There's also considerations for what nodal basins to cover, based on where the tumor is, and even the type of radiation, and, of course, the timing of radiation. All of that is important to be considered, and all of those specific features are mentioned within the recommendations. BRITTANY HARVEY: Great. And then in addition to those radiotherapy recommendations, what's the role of systemic therapy for patients with salivary gland malignancy? DR. JESSICA GEIGER: Well, unlike the radiation section, where I said we have 10 specific recommendations, we're limited with the evidence for the use of systemic therapy in the curative setting of these diseases. So one point that I will make is, again, we're very limited based on evidence, and this is what is driving such a guideline-- is evidence, evidence, evidence. And we just don't have it. There are several large studies that are ongoing, but until those results flesh out, we were limited. And so our recommendations are based on the lack thereof, and often are considered low quality or moderate strength of recommendation at best, based on our expert panel. Basically, outside of a clinical trial, we're not recommending the addition of radiosensitizing chemotherapy with post-op radiotherapy. Again, that can be contentious, especially in the clinical realm, where there's a wide variety of biologic behavior. So some of the more aggressive diseases, we know that oncologists are advocating for the use of chemotherapy. But again, the evidence is not there yet, and so we weren't able to make that informative within this guideline. And then we also addressed tumors that are expressing different markers, like androgen receptor, HER2, and make a recommendation for the use of targeted therapy, again noting a lack of evidence for it outside of a clinical trial currently. BRITTANY HARVEY: OK, thank you for explaining the reasoning and the evidence behind those particular recommendations. So then for patients who have then completed treatment for salivary gland malignancy, Dr. Ha, what are the timelines and recommendations for follow up for these patients? DR. PATRICK HA: Well, so again, this is where the data are really not strong. And so you'll notice that pretty much all of these recommendations were informal in consensus. But similar to the NCCN guidelines for general cancer follow up was believed by the panel that early follow up more frequently and just sort of spaced out over time was important. And then there was an emphasis on some form of imaging often, whether that be CT or MRI, it's sort of up to the practitioner. And then perhaps for a couple of years after treatment, that might be important. It was also felt that, as everyone probably knows, that one of the areas where this may spread to distantly is in the lung. So getting some sort of chest imaging between years 2 and 5 would be important as well, just in case one can detect an asymptomatic yet potentially treatable metastasis. So again, a lot of informal consensus. The idea is that we feel it's important to continue to follow these patients to look for signs of recurrence, whether that's with imaging or physical exam. We thought that either would be an option. BRITTANY HARVEY: Definitely. And the last section of recommendations for this guideline is on recurrent or metastatic salivary gland malignancies. So what are those treatment options, Dr. Geiger? DR. JESSICA GEIGER: Well like before, when we're talking about systemic therapy, again, informal consensus is sort of driving the majority of these recommendations, again highlighting lack of strong evidence. That said, there are several different clinical situations that we address within these recommendations. So whether a patient presents with diffusely metastatic disease with a large tumor burden or oligometastatic disease, where maybe just one or two local or regional areas have recurred. And so in that latter case, you could discuss with the patient is it worthwhile to do some locally ablative therapy, such as SBRT, or possibly a resection versus, for more widely metastatic disease, starting systemic therapy. Now, there's also a recommendation specifically for the histology adenoid cystic carcinoma. And that is based on studies that have been done with tyrosine kinase inhibitors. And so there's some evidence for that outside of cytotoxic chemotherapy. And then we also make a mention, which is very important, again on checkpoint inhibitors, but also on some of the targeted therapies-- doing next generation sequencing, looking for molecular markers that drive the progression of these diseases, and then in subsequent targeted therapies for this. So we really try to encompass any and all particular situations that an oncologist may encounter with these diseases and offer some guidelines and recommendations regarding the appropriate management. BRITTANY HARVEY: Great. Thank you both for reviewing those key points of the recommendations. This guideline goes through a lot of content, and so it's interesting to hear more about what kind of those details are for each section. So Dr. Ha, in your view, what is the importance of this guideline, and how will it impact clinicians? DR. PATRICK HA: Well, I think that we realized we had a lot to cover in just a short amount of time. And I think that we felt that while the data may not be as strong with-- full of randomized clinical trials as perhaps other disease subgroups, we felt it was important to organize what the current state of the data are, because these are rare cancers, and there are some nuances between some of the histologies even that it may be difficult to keep up to date all the time. So organizing it into one document where it we have clearly delineated what areas we feel are common practice amongst experts and what areas actually do have some studies and perhaps some deeper level of understanding and depth of studies would be important, so that clinicians understood where it was that they have to be a little more creative and areas where they felt like hey, we feel like this is important to do. So I think that that would be useful for clinicians. And I think also it provides a framework for future studies, meaning that we hope that whenever these get updated and 5 or 10 years that there will be more studies. But it also does, I think, help for those of us who are in the field to organize where those gaps are so you can look at the guidelines and really understand OK, these are the areas that we need better understanding of how to treat patients. BRITTANY HARVEY: Definitely. It's helpful to understand both where there is evidence and where there is no evidence and where informal consensus takes rule. So then finally, Dr. Geiger, how will these guideline recommendations affect patients? DR. JESSICA GEIGER: Well, when it comes to cancer treatment, there is a lot of fear in the unknown. And I feel that patients are always asking am I doing the right things? Am I looking to make sure that I'm getting the best of care? And I think with any guideline-- this one included-- patients can rest assured that they don't have to make the trip and travel to a large academic center necessarily-- that they can feel comfortable knowing that their providers are following the data and following such guidelines that have been brought forth in one single document. Even though the patients aren't going to necessarily have this document at hand, they can have confidence within their oncology team. And then I think they'll also benefit from, as Dr. Ha was saying, as medical professionals being able to identify gaps and bring forth clinical trials. That's the only way that we're going to be able to move this field forward, particularly in such a rare disease that many histologies as salivary gland malignancies. And so while being treated in a regional oncology office or a community oncology office, maybe their provider will then recommend clinical trials that are open and have that additional opportunity for patients, if they so desire. So knowing that they're getting great standard of care based on evidence, but then also the opportunity to create new evidence for us to better treat patients in the future. BRITTANY HARVEY: Definitely. Well, I want to thank you both so much for your work on developing these evidence-based guidelines and for taking the time to speak with me today on the podcast, Dr. Geiger and Dr. Ha. DR. JESSICA GEIGER: Thanks. DR. PATRICK HA: 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/head-neck-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available on iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

An interview with Dr. David Hui from MD Anderson Cancer Center and Dr. Margaret L. Campbell from Wayne State University, co-chairs on "Management of Dyspnea in Advanced Cancer: ASCO Guideline." This guideline outlines a hierarchical approach to dyspnea management, beginning with identifying and managing potentially reversible causes, followed by the use of non-pharmacologic interventions, and then pharmacologic interventions. Read the full guideline at www.asco.org/supportive-care-guidelines TRANSCRIPT SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. David Hui from MD Anderson Cancer Center in Houston, Texas, and Dr. Margaret Campbell from Wayne State University in Detroit, Michigan, co-chairs on "Management of Dyspnea in Advanced Cancer: ASCO Guideline." Thank you for being here, Dr. Hui and Dr. Campbell. DR. DAVID HUI: Thank you. It's wonderful to be here. DR. MARGARET CAMPBELL: Yeah, it's my pleasure. 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. Hui, do you have any relevant disclosures that are directly related to this guideline topic? DR. DAVID HUI: I have no relevant disclosures. BRITTANY HARVEY: Thank you. And Dr. Campbell, do you have any relevant disclosures that are related to this guideline topic? DR. MARGARET CAMPBELL: No, I do not have any relevant disclosures. BRITTANY HARVEY: Thank you. Then let's get into some of the guideline content. So first, Dr. Hui, can you give us a general overview of the purpose of this clinical practice guideline? DR. DAVID HUI: Yeah. This clinical practice guideline is on dyspnea in patients with advanced cancer. And this symptom of shortness of breath, or dyspnea, is very common in our patients and extremely distressing. And the evidence base is rapidly evolving, so the purpose of this guideline is then to summarize the up-to-date information and provide some recommendations for clinical practice to help alleviate this very challenging symptom. BRITTANY HARVEY: Great. Then let's review some of those key recommendations of this guideline. So Dr. Campbell, what is recommended for screening and assessment of dyspnea in patients with advanced cancer? DR. MARGARET CAMPBELL: Well, as David mentioned, this is a highly prevalent symptom. But we know that in clinical practice, sometimes patients won't disclose their symptom unless they're asked. And it gives us an opportunity to be certain that we don't overlook the symptom, particularly when it's in the early stages, mild or moderate stages, where we can intervene rapidly. So in order to treat a symptom, we have to know that the symptom exists. So in the guideline, we recommend at every clinical encounter that there be an assessment for dyspnea. So every clinical encounter could be every time the patient presents in the outpatient clinic, or it could be every day if the patient is an inpatient. Every day on rounds, or every time vital signs are obtained, there would be an assessment of the patient's dyspnea. BRITTANY HARVEY: Great. Then, reading through this guideline, it takes a hierarchical approach to the management of dyspnea, addressing first potentially reversible causes, then the use of non-pharmacologic interventions, and finally pharmacologic interventions. So first, what does the guideline state regarding addressing those potentially reversible causes of dyspnea? DR. DAVID HUI: Yeah, well, this is a very important aspect that you highlighted is that we really want clinicians to remember that it's not just about treating this symptom. It's ideally identifying what are the causes of shortness of breath that we could reverse. And in many patients, there may be multiple factors contributing to the shortness of breath. Some patients may have some effusion, perifusion contributing to it. They may also have underlying emphysema. And other times they may have some complications, such as blood clots. And so it's important to kind of identify the issues that may be at stake. And some of them are very treatable, and patients may have significant improvement in their shortness of breath right away. So I think it's a combination of identifying the complications and comorbidities in those patients. And of course that along with treating the cancer if the cancer is the cause of the dyspnea as well. BRITTANY HARVEY: Great. Then so after addressing those potentially reversible causes, Dr. Campbell, what are the recommended non-pharmacologic interventions? DR. MARGARET CAMPBELL: Well, in the case of a patient whose dyspnea is not severe but is a difficult to tolerate symptom, we propose that the clinician begin with a hierarchical approach from the easiest, simplest interventions that are non-pharmacologic that may actually help improve the symptom experience. So that might be as simple as changing the patient's position. And depending on where their cancer is located, they may find that they are more comfortable sitting up straight propped with pillows, for example. In addition, circulating air around the face has a fairly strong evidence base. And that can be accomplished, weather permitting, by putting the patient's chair near an open window. Or it can be accomplished with a small handheld fan blowing on the face. For some patients whose blood oxygen levels are low, then the application of supplemental oxygen may be helpful to correct the low blood oxygen. Those are the major interventions that we would suggest, but there could be others. If the patient is still ambulatory, then perhaps a walking aid, avoiding stairs. And some of that comes back to our comprehensive assessment. If we could determine what triggers the patient's shortness of breath, then perhaps we can suggest interventions to minimize that, like pacing activity. So similarly, if the patient's in the hospital but has dyspnea, we would want to pace their clinical activity. We wouldn't want them to have their bed, bath, their breakfast, their linen change, their physical therapy all in the same short period of time. We would want to see those interventions staggered through the day. BRITTANY HARVEY: Definitely. That makes a lot of sense. So then, Dr. Hui, what pharmacologic interventions are recommended for patients with advanced cancer and dyspnea? DR. DAVID HUI: Yeah, and so building on Dr. Campbell's discussion of the non-pharmacologic interventions, sometimes patients will continue to have quite a bit of shortness of breath. Or it's a very acute or severe presentation, such as in the hospital setting, then we do recommend some pharmacologic interventions. So the front line measure for that would be systemic opioids. And I recognize that, nowadays, opioids, there's still a lot of stigma around the use of it and concerns. But it is after careful review by the committee and based on the existing evidence that we do recommend this as the main pharmacologic agent. For patients, of course, the use of opioids need to be carefully monitored, and patients should be educated very carefully on how to use them properly for shortness of breath. There are a number of other pharmacologic agents that may be considered for selected populations, other than opioids. So if patients have a higher level of anxiety, then a short-acting benzodiazepine may be considered for those individuals. And for patients with more structural causes of shortness of breath, such as airway obstruction, systemic corticosteroids may be considered. And for patients with airway obstruction, then bronchodilators may be helpful as well, although the evidence around that is still on the weaker side. And there are some patients who, despite very active intervention with many of these non-pharmacologic and pharmacologic measures, who continue to have very severe shortness of breath. And for those who are, let's say, in a palliative care unit setting and have refractory dyspnea, palliative sedation is mentioned as an option for patients as a last resort. BRITTANY HARVEY: OK, thank you both for reviewing those interventions for patients. So Dr. Campbell, in your view, why is this guideline important? And how will it change practice? DR. MARGARET CAMPBELL: Well, for a busy oncologic clinician who may not have a lot of time to search the literature because of a busy practice, what this puts in one place is an opportunity to do a quick guideline that could suggest a treatment course. For a palliative care provider, who may have more experience with non-cancer diagnoses, this guideline focuses on the patient with advanced cancer. So I think there's an opportunity for clinicians in both of those fields who would be taking care of advanced cancer patients to find a benefit. BRITTANY HARVEY: Definitely. And then finally, Dr. Hui, how will these guideline recommendations impact patients with advanced cancer? DR. DAVID HUI: Yeah, well, I'd like to echo what Dr. Campbell said. I would also say that perhaps one of the strongest recommendations of this guideline is actually for patients with dyspnea and advanced cancer to be referred to palliative care. Because dyspnea is such a multi-dimensional symptom and often just the tip of the iceberg in terms of what patients are going through. So just the very presence of it really highlights that there is likely a high supportive care burden, and it would be a good idea for a team specializing in relieving of this symptom to be there to work with the oncology team to help patients. So we hope that with this guideline, that there will be more patients who will have access to palliative care teams. And I think that will be one important impact. And there is a lot of evidence that palliative care can help our patients. And other, maybe, impacts, I think, down the road for maybe future patients would be that we highlighted that more research is really needed in this field. The guideline clearly highlighted some areas we need to work on for further research. And it is not easy to do research in dyspnea and cancer patients because these patients are so sick. And yet these are the very patients who need to have better interventions. And so with this guideline, we hope that it can stimulate further research and to support some patients in the future as well. BRITTANY HARVEY: Great. Well, it definitely sounds like these will have a positive impact for both researchers and for patients with advanced cancer. So I want to thank you both for your work on these guidelines. And thank you for taking the time to talk with me today, Dr. Campbell, and Dr. Hui. DR. DAVID HUI: It's my pleasure. DR. MARGARET CAMPBELL: Mine also. 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/supportive-care-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.

An interview with Dr. Natasha Leighl, Dr. Andrew Robinson, and Dr. Gregory Riely on "Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO and OH (CCO) Guideline Update." This guideline provides recommendations on systemic therapy for patients with stage IV NSCLC whose cancer has driver alterations, focusing on seven targets - EGFR, ALK, ROS-1, BRAF V600e, RET, MET exon 14 skipping mutations, and NTRK. Read the full guideline at asco.org. TRANSCRIPT PRESENTER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcasts.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. Natasha Leighl from Princess Margaret Cancer Center in Toronto, Ontario, Dr. Andrew Robinson from Queen's University in Kingston, Ontario, and Dr. Gregory Riely from Memorial Sloan Kettering Cancer Center in New York, New York, authors on Therapy for Stage IV Non-Small-Cell Lung Cancer with Driver Alterations: American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) Guideline Update. Thank you for joining me today, Drs. Leighl, Robinson, Riely. DR. ANDREW ROBINSON: Thank you for having us. DR. NATASHA LEIGHL: Thanks for having us, Brittany. 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. Leighl, do you have any relevant disclosures that are related to this guideline topic? DR. NATASHA LEIGHL: I don't have relevant disclosures, but I do have institutional research funding from a number of companies, including Amgen, ARRAY, AstraZeneca, EMD Serono, Guardant Health, Eli Lilly, Merck, Pfizer, Roche, and Takeda, and personal fees from Bristol-Myers and MSD, which are unrelated. Thanks. BRITTANY HARVEY: Thank you. And Dr. Robinson, do you have any relevant disclosures that are related to this guideline? DR. ANDREW ROBINSON: I do not have any relevant disclosures related to this guideline. My institutional list of research funding is not as extensive as Dr. Leighl's, but is still fairly extensive and includes many of those companies. BRITTANY HARVEY: And Dr. Riely, do you have any relevant disclosures? DR. GREGORY RIELY: I receive institutional research funding from Novartis, Roche, Genentech, GlaxoSmithKline, Pfizer, Moradi, Merck, and Takeda. But those are my only disclosures. BRITTANY HARVEY: Thank you all. Then let's get into some of the content of this guideline update. So this guideline is an update of an earlier ASCO guideline on the systemic treatment of patients with stage IV non-small cell lung cancer, which was then divided into two companion guidelines, one on systemic therapy treatment options for patients without driver alterations, which was published in 2020, and then this one for patients whose cancer has driver alterations. So Dr. Robinson, can you give us a general overview of what this particular guideline covers? DR. ANDREW ROBINSON: Thank you, Brittany. It was a great experience to be part of this important guideline and an honor. As you mentioned, this guideline is on treatment of stage IV non-small cell lung cancer patients with driver mutations. And it's a companion guideline to the earlier guideline published on treatment of stage IV non-small-cell lung cancer without driver mutations. The guideline followed a robust evidence gathering and evaluation process as a standard for ASCO-Ontario Health guidelines. In this case, we ended up reviewing several phase III trials, as well as many earlier phase studies and specific driver mutation groups. If we look back to 2017, there were four driver mutation group recommendations included in the guideline. We now have recommendations for seven different oncogenes, as well as some recommendations that are specific not only for the oncogene involved, but also the specific mutation within that gene. The non-driver mutation guideline is referenced as well frequently in this guideline, as many of the treatment options that are recommended in that guideline are also appropriate for patients with driver mutations, with the exception of a couple of key mutation groups such as EGFR. Recommendations in the guideline are qualified as weak, moderate, or strong, and the level of evidence for each recommendation is given. For many of these novel agents, the evidence is relatively low in comparison to what we are used to with recommendations based on phase II trials without comparator arms, and with surrogate endpoints for patient benefits such as response rates and duration of response, as opposed to quality of life and overall survival. Nonetheless, it was felt appropriate to include many of these agents in the recommendations, with the caveat that the level of evidence is weak or non-evidence-based. One of the recommendations in the introduction to these guidelines is to continue with studies such as phase III clinical trials in many of these settings, in order to move from an informal consensus-based recommendation, to a recommendation based on moderate to high quality evidence. We hope oncologists and their patients will find these guidelines useful. BRITTANY HARVEY: Great. Then, as you just mentioned, this guideline focuses on seven targets, EGFR, ALK, ROS1, BRAF, RET, MET, and NTRK. I'd like to review those key recommendations for each of those targets. So first, Dr. Robinson, what is recommended for patients with stage IV non-small-cell lung cancer and an epidermal growth factor receptor mutation? DR. ANDREW ROBINSON: Thank you. In terms of stage IV EGFR mutation positive lung cancer, the recommendations in the 2017 guidelines were to use tyrosine kinase inhibitors upfront, such as gefitinib, afatinib, or erlotinib, and to follow that with osimertinib if a mutation was found in T790M, or chemotherapy depending on what was available. In the current treatment guideline, we have recommendations not only for first and second line treatment, but also some acknowledgment and recommendations for treatment of patients with EGFR mutations other than the classical exon 19 deletion mutation or LA58R. For patients with a classical EGFR mutation, several strategies have been shown to be superior to first generation tyrosine kinase inhibitors in the first line setting. And the panel strongly recommended osimertinib to be used as first line therapy with a high level of evidence, based on the FLAURA clinical trial. This demonstrated not only an overall survival benefit, but a quality-of-life benefit. Other strategies that have been shown to benefit include dacomitinib as first line therapy, gefitinib plus chemotherapy as first line therapy. Erlotinib/bevacizumab and erlotinib/ramucirumab are also options with a lower level of evidence, as they have not been shown yet to be associated with improved overall survival. But they are associated with improved progression-free survival. Most of the recommendations, other than osimertinib, are really recommendations for what to pursue if osimertinib is not available. If we move to patients with sensitizing but non-classical EGFR mutations, the evidence is certainly much more sparse, as are these patients. And the recommendation was for afatinib first line or osimertinib was also considered an option based on phase II data. For patients with EGFR exon 20 insertion mutations, recommendation at this time was not to use a targeted agent first line, but to default to the non-driver mutation guidelines. For second line therapy, after tyrosine kinase inhibition stops benefiting, the recommendation was to use doublet platinum chemotherapy with or without bevacizumab. The atezolizumab/bevacizumab/carboplatin/paclitaxel combination was acknowledged as an option based on an exploratory analysis of the phase III EMPOWER trial, but this was considered exploratory and this regimen was not strongly recommended until further evidence accrues. BRITTANY HARVEY: OK, thank you. Then Dr. Leighl, what is recommended for patients with stage IV non-small-cell lung cancer and ALK rearrangement? DR. NATASHA LEIGHL: So for patients with ALK rearranged stage IV lung cancer, in the first line setting, next generation ALK inhibitors alectinib or brigatinib should be offered to patients. This is based on randomized trials comparing these to first generation inhibitors, crizotinib specifically, demonstrating better outcomes including progression-free survival and better intracranial activity. If you live in a region where alectinib and brigatinib are not available, earlier inhibitors like crizotinib or ceritinib should be offered again based on high quality evidence randomized trials demonstrating that these are better than chemotherapy. In the second line setting, if your patient has received alectinib or brigatinib first line, lorlatinib may be offered. If your patient received an earlier generation inhibitor crizotinib, they should be offered alectinib, brigatinib, or ceritinib, again based on randomized trials. And later, lorlatinib third line may be offered. It's also important to remember that in this group of patients, chemotherapy, especially pemetrexed-based chemotherapy, is very active. And we would refer you to the ASCO-Ontario Health non-driver mutation guidelines for chemotherapy recommendations when targeted therapy is no longer an option. I should also note that when we drafted these guidelines, we did not yet have results of the first line lorlatinib study, the CROWN study, where we found that lorlatinib was also superior to crizotinib, the first generation inhibitor. This is currently under review by the US FDA. So while it's not recommended in our guideline, we may see this added to future guidelines in our next guideline update. BRITTANY HARVEY: Great. Thank you. And then, what is recommended for patients with ROS1 rearrangement? DR. NATASHA LEIGHL: So for patients with ROS1 rearranged stage IV lung cancer, in the first line setting, specific ROS1 inhibitors, crizotinib or entrectinib may be offered. Because this is based on very impressive response rates and prolonged duration of response and patient benefit, in single arm studies, we have to recognize that alternatives may also include standard treatment based on the ASCO non-driver mutation guidelines, as well as other target agents, such as ceritinib or lorlatinib, that may be offered. If, though, your patient has progressive disease and previously received non-targeted therapy, targeted therapy with crizotinib, ceritinib, or entrectinib, can certainly be offered. Also, if your patient has received ROS1 targeted therapy in the first line setting, standard treatment based on the ASCO non-driver mutation guidelines should be offered also with consideration of clinical trials. BRITTANY HARVEY: And then additionally, what is recommended for patients with stage IV non-small-cell lung cancer and an NTRK fusion? DR. NATASHA LEIGHL: Thanks, Brittany. For patients with stage IV disease and an activating NTRK fusion, entrectinib or larotrectinib may be offered in the first line setting based on single arm studies, including patients with lung cancer and very dramatic response rates and prolonged duration of response. However, standard treatment based on the non-driver mutation guideline chemotherapy-based may also be offered in the second line setting. If NTRK targeted therapy was given first line, standard treatment with chemotherapy-based options may be offered second line based on the non-driver mutation guideline. If NTRK targeted therapy, though, was not given in the first line setting, entrectinib or larotrectinib may be offered to your patient. And I think at this point, we really don't know what the optimal sequence is for these patients. But I think it's very clear from the data that we do have, that we want to try and identify this target and get patients on targeted therapy as soon as possible in the course of their disease. BRITTANY HARVEY: Great. Then Dr. Riely, can you review what the guideline recommends for patients with stage IV non-small cell lung cancer and a BRAF mutation? DR. GREGORY RIELY: Thank you, Brittany. I'll highlight that the BRAF mutation guideline pertains specifically to those patients with BRAF V600E mutations. The other BRAF mutations that we observed, we don't have sufficient data to make recommendations. But for those patients with BRAF V600E alterations, again, based on the quality of the data and the type of data available, the guidelines recommend consideration of first line use of dabrafenib with trametinib. This is a consideration rather than a should recommendation, given the absence of randomized clinical trial evidence. But nonetheless, we recommend that they be considered in the first line setting. If, in fact, you choose to use a non-targeted approach in the first line setting, then the guidelines do recommend consideration of dabrafenib with trametinib in the second line setting. So it's, again, the first line setting, dabrafenib/trametinib combination. Or, if not used in the first line setting, then recommendation dabrafenib/trametinib in the second line setting. BRITTANY HARVEY: OK, then, what is recommended for patients with stage IV non-small-cell lung cancer and a MET mutation? DR. GREGORY RIELY: Again, specific for MET, we're talking about MET exon 14 alterations rather than MET amplification with other mutations, which we might call emerging targets. So for patients with metastatic exon 14 altered non-small cell lung cancer, the recommendation is for the use of capmatinib or tepotinib. These are newer MET inhibitors that have recently been approved. And again, the guidelines recommend that they should be considered in the first line setting. If, however, you choose to use non-targeted therapies in the first line setting, then MET directed therapy such as capmatinib or tepotinib should be considered in the second line setting. BRITTANY HARVEY: And then the final target addressed in this guideline, what is recommended for patients with stage IV non-small cell lung cancer and RET rearrangement? DR. GREGORY RIELY: RET rearrangements are relatively uncommon, but important in a subset of patients with non-small cell lung cancer. And we have MET targeted agents that are available. The current guidelines recommend that in the first line setting, we consider the use of selpercatinib. And in the second line setting, if patients have not previously received a RET inhibitor, one should consider selpercatinib in that context. Patients who have received a targeted therapy in the first line then conventional chemotherapy with or without immunotherapy or bevacizumab should be considered. I will note that the guidelines were finalized prior to the approval of pralsetinib, and pralsetinib is another RET inhibitor with similar data in this context. BRITTANY HARVEY: Great. Thank you all for reviewing those recommendations. So Dr. Robinson alluded to this earlier, but Dr. Riely, could you describe what emerging targets the panel reviewed but were unable to make recommendations for at this time? DR. GREGORY RIELY: The development of treatments in patients with non-small cell lung cancer has really proceeded at a breakneck pace over the past 10 years. We've seen newer alterations identified, new drugs tested in those populations, and new drugs approved in relatively rapid succession. We have a number of targets that are currently being studied with new drugs, but we don't quite have enough data yet and the drugs aren't yet approved, so they can't be included in the guidelines. Some of these targets include KRAS G12C, recently seen a number of direct KRAS inhibitors that have been developed and seem to have activity in that group of patients. And that's a hot area to look forward to. We've also seen that patients with EGFR exon 20 insertions don't seem to benefit from currently available EGFR TKIs at the standard recommended dose. And so we don't have recommendations for their utilization here, but there are new drugs that are being developed to target this group of patients. Similarly, patients with HER2 mutations seem to not benefit from available therapies, but there are drugs that are being developed, and we look forward to seeing more data in that context. Finally, patients with NRG1 fusions are another emerging target, but we don't have good recommendations yet or good drugs yet. BRITTANY HARVEY: Great. Understood. So then, Dr. Robinson, in your view, why is this guideline important, and how will it impact clinical practice? DR. ANDREW ROBINSON: Well, this guideline is important because it's taking a problem that we see in the real world, which is patients with lung cancer with an ever-expanding number of driver mutations, and trying to give recommendations for the integration of new therapies with standard clinical practice. It's important that I've highlighted that for most of these mutations, without phase III evidence, the recommendations were to consider the targeted agent as first line therapy. But also, if it's not given first line, to use it in subsequent lines. And I think we need to recognize that these targeted agents, it's most important that patients get these drugs at some point in their care, even if we don't know exactly what the optimal point in their care is. The guideline was sort of the first one in lung cancer, where we've taken a number of these rare mutations and examined the phase II data, and will likely be the template for what is going forward with an ever-expanding number of medications. So hopefully, we get a bit of standardization out of it. Hopefully, we've highlighted some of the areas that are still unclear and can be a template for the next round of targeted therapy guidelines. BRITTANY HARVEY: Definitely, it's an ever-changing landscape. So finally, Dr. Leighl, what do these updated guideline recommendations mean for patients with stage IV non-small-cell lung cancer? DR. NATASHA LEIGHL: So this is really great news. And as Dr. Riely and Dr. Robinson have highlighted, in just a very short number of years since 2017, we've made tremendous progress. We have at least three new targets, many new treatments for almost every class of targeted therapy indication in lung cancer. And most of these new targets are their oral therapies or pills. And many of them should now be offered to patients as first or second line treatment instead of chemotherapy. So for patients, this really means many more will be able to enjoy a chemotherapy-free world, or at least a chemotherapy-free period for a time. I think it's really important for patients and the oncology team to remember that genomic testing is essential. And it's an essential part of the stage IV non-squamous, non-small-cell lung cancer diagnostic process, and in some places, you know, any non-small-cell lung cancer. And this may be a very important part of the process. And it really doesn't depend on clinical factors like smoking. It's really about your pathologic diagnosis or in your tumor sample. So it's really key that we make sure that patients get their samples tested as soon as possible in their lung cancer journey, preferably with comprehensive profiling so we can identify any of these targets, if our patients have them, and then get them onto the right treatment as fast as possible. If there isn't enough tissue for testing, liquid biopsy has emerged as a potential alternative. And I think it's so important for patients and oncology professionals to remember that PD-L1 expression, which is an important marker for immune therapy, is not enough. At least a quarter of our patients with PD-L1 expression that suggests immunotherapy should be an option, in fact, have these actionable genomic targets. And we do know that in these patients, targeted therapy should come first. So again, tremendous progress, many exciting opportunities for our patients to be chemo-free for much longer. And again, important to get the right test as soon as possible so we can get you onto the right treatment as soon as possible. BRITTANY HARVEY: Great. Well, thank you all for reviewing the extensive literature associated with this guideline and developing these recommendations, and for taking the time to speak with me today, Dr. Leighl, Dr. Riely, and Dr. Robinson. DR. GREGORY RIELY: Thank you. DR. ANDREW ROBINSON: You're welcome, and thanks a lot to the ASCO staff for doing all of the work in sort of herding the cats that are oncologists, as well as getting all the references and the deep literature searches for us. DR. NATASHA LEIGHL: Agreed. Thanks so 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/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.

An interview from Dr. Larissa A. Korde from the National Cancer Institute and Dr. Dawn L. Hershman from Columbia University on "Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline." This guideline covers the optimal use of neoadjuvant therapy for women with invasive, non-metastatic breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines. Transcript ASCO: 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 podcast.asco.org. My name is Brittany Harvey, and today I am joined by Dr. Larissa Korde from the clinical investigations Branch of the Cancer Therapy Evaluation Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute in Bethesda, Maryland, and Dr. Dawn Hershman from the Herbert Irving Comprehensive Cancer Center at Columbia University in New York, New York, co-chairs on Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. Thank you for being here Dr. Korde and Dr. Hershman. DR. LARISSA KORDE: Thank you for having us. DR. DAWN HERSHMAN: Yes, thank you. 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 on-line with the publication of the guideline in the Journal of Clinical Oncology. Dr. Korde, do you have any relevant disclosures that are related to this guideline topic? DR. LARISSA KORDE: I do not. BRITTANY HARVEY: And Dr. Hershman, do you have any relevant disclosures that are related to this guideline topic? DR. DAWN HERSHMAN: No, I do not. BRITTANY HARVEY: Great, thank you both. Then, Dr. Hershman, to kick off the content of the guideline, first, can you give us a general overview of the scope and the purpose of this guideline? DR. DAWN HERSHMAN: Yeah, sure. In breast cancer, we have seen a plethora of studies looking at neoadjuvant therapy for breast cancer. And as we've learned over time, that neoadjuvant therapy has focused on the role of, really, response as a predictive marker and whether or not the improvement in a pathologic complete response rate translates into benefit in terms of long-term outcome. And the fact that several studies have shown that has really increased our interest in looking at pathologic complete response rate and its predictive value. So part of the guideline is really to help us really elucidate as the understanding of biology of breast cancer has evolved over time, what scenarios where neoadjuvant therapy is the best choice for patients, and what the real purpose of neoadjuvant therapy is. So the guidelines' purpose is really to help us develop recommendations concerning the optimal use of neoadjuvant therapy, whether it be chemotherapy, endocrine therapy, or targeted therapy for a variety of different biologic subtypes. And I think the overarching principle is that the expert panel strongly advocated for a multidisciplinary team in the management of these patients. Specific guidelines really go into details about each of the scenarios where we would use this therapy. BRITTANY HARVEY: Great. Then I'd like to review some of those key recommendations that you just mentioned for our listeners. So Dr. Korde, which patients with breast cancer are appropriate candidates for neoadjuvant systemic therapy? DR. LARISSA KORDE: So when we sat down to write this guideline, we thought through this question in many different ways. But we basically ended up sort of dividing patients by breast cancer subtype and then coming up with recommendations separately for each subtype. So broadly speaking for triple negative breast cancer patients and for HER2-positive breast cancer patients, we felt that the kind of most important triage point is that in both those diseases, there are effective treatments that can be used in the adjuvant setting in patients who do not have a pathologic complete response to neoadjuvant therapy. And so broadly speaking, it's those patients where there would be an adjuvant therapy decision point, or recommendation in whom the neoadjuvant response is important. Those would be the patients in whom we would most strongly recommend neoadjuvant chemotherapy. In ER-positive disease, we looked at both chemotherapy and endocrine therapy in the neoadjuvant setting. And we know that both of these can improve response. Pathologic complete response is less common in patients with ER-positive disease. But there are also benefits to neoadjuvant treatment in those patients in terms of being able to reduce the size of the surgery, reduce potentially morbidity from surgery, and then also in terms of being able to convert patients who were not lumpectomy candidates from mastectomy to lumpectomy. And so in the guideline we outline the scenarios for ER-positive patients in which neoadjuvant therapy would be recommended as well. BRITTANY HARVEY: Great, got it. Then Dr. Hershman, what do the guidelines say about how clinicians should measure response in patients receiving neoadjuvant chemotherapy? DR. DAWN HERSHMAN: Yes, so patients undergoing neoadjuvant therapy should really be monitored by their provider at each visit with a clinical examination at regular intervals. And we really felt that the role of breast imaging was really for patients where there was some clinical suspicion of progression during that therapy to ensure that patients were not progressing during treatment. And ultimately, the best modality for imaging was the modality that was most effective at the point of diagnosis, whether it be mammogram, ultrasound, or MRI, that should be the imaging modality used at follow up. We did not feel that there were any specific blood markers or tissue based markers at this time that should be used for monitoring patients undergoing neoadjuvant therapy. Much of that is done for clinical trial purposes, but not so much in the clinic. And that when patients had completed their treatment, pathologic complete response rate is the most important outcome and would be really assessed at the time of surgery as the absence of any invasive disease in either the breast or the lymph nodes. But in order for that to be good for clinical decision making, it's really imperative that the clinician and the surgeons make sure that the tissue is removed that is suspect to begin with, so to make sure that the clips that defined where the tumor was evaluated and that the tumor bed is clear of any evidence of disease. BRITTANY HARVEY: Great, that's helpful information. So then, Dr. Korde, you mentioned that the recommendations are divided up by biologic subtypes. So what are those neoadjuvant systemic therapy regimens recommended for the following patient population-- so first, those with triple negative breast cancer, second, those with HER2-negative hormone receptor positive breast cancer, and then finally, for those with HER2-positive disease? DR. LARISSA KORDE: So maybe we can divide this up a little. Let's start with the triple negatives. For triple negative breast cancer patients who are embarking on neoadjuvant chemotherapy, and that would be patients with clinically node positive disease, and/or at least T1C disease, and again, with the thought that the goal is really to think about whether adjuvant therapy recommendations would be altered based on PAP CR. But in that setting, we recommended that patients be offered an anthracyclines and taxane containing regimen. We also found data supporting the use of carboplatin with neoadjuvant therapy for the purpose of increasing the likelihood of PCR. So we noted that while there is good data showing that PCRs increase with carboplatin, there is more conflicting data regarding the effect of carboplatin on long-term outcomes. Although, hopefully, new clinical trials that are ongoing now or that are in follow up may clarify this question a little bit more. We felt at the time that we wrote the guideline, and certainly, this is potentially an evolving topic. But at this point, we felt that there was insufficient evidence to recommend routinely adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early stage breast cancer. And again, there may be more data on this upcoming in the next few years. So maybe Dawn can take the next category, the HER2-negative hormone receptor positive patients. BRITTANY HARVEY: Yeah, that would be great. DR. DAWN HERSHMAN: Absolutely. So we felt for this population of patients that neoadjuvant chemotherapy could be used instead of adjuvant chemotherapy in any patient where the chemotherapy decision could be made without the benefit of having the results from the surgical pathology data, or any results from the specific genomic testing. So if the decision was made that the patient was going to need chemotherapy regardless, that would be a patient that could get it neoadjuvantly. We felt that for postmenopausal patients with hormone receptor positive HER2 negative breast cancer that neoadjuvant endocrine therapy with an aromatase inhibitor could be offered to either increase local regional treatment options, if there was no intent for surgery, endocrine therapy could be used for Disease Control. So in a patient where they really were not a good surgical candidate, we could offer this therapy to try to control their disease. For premenopausal patients with hormone receptor positive HER2-negative disease, we did really not feel that neoadjuvant endocrine therapy should be routinely offered outside of a clinical trial. Because in this scenario, there really wasn't enough evidence to offer this approach. BRITTANY HARVEY: And then Dr. Korde, do want to finally address those patients with HER2-positive disease? DR. LARISSA KORDE: Absolutely. So in patients with HER2-positive disease that is either node positive or high risk node negative, we felt it would be appropriate to offer neoadjuvant therapy with either an anthracycline and taxane containing regimen, or a non-anthracycline-based regimen in combination with targeted therapy. And we did feel that targeted therapy should include trastuzumab and may also include pertuzumab. For patients with smaller tumors, really those in whom it's unclear whether the more aggressive for on-chemotherapy regimens or even any chemotherapy at all is needed, for example, those with very small tumors, T1A and T1B, we did not feel that neoadjuvant should be routinely offered. And we did note that in those patients with smaller tumors, an alternative regimen, the APT regimen of paclitaxel and Trastuzumab is something that has been studied in the adjuvant setting. But again those patients with these very small node negative tumors, in general, would not be routinely offered neoadjuvant chemotherapy. BRITTANY HARVEY: Great, thank you both for reviewing those neoadjuvant systemic therapy approaches for those specific patient populations. So Dr. Hershman, in your view, what is the importance of this guideline? And how will it impact clinical practice? DR. DAWN HERSHMAN: Yeah, that's an excellent question. I think as our data has shown more and more studies where there's a benefit to giving adjuvant treatment based on the response of patients in the neoadjuvant setting to get additional benefit long-term amongst patients with residual disease, I think that these guidelines really can help clinicians to understand those scenarios where we know we can maximize treatment. I think ultimately the goal of neoadjuvant therapy is that it gives us opportunities to both escalate treatment in patients that are at high risk that don't have great responses, and de-escalate therapy in patients that have outstanding responses. And so I think this will help clinicians understand what those benefits are. BRITTANY HARVEY: Definitely. It seems like it will provide some clarity for those scenarios. So finally, Dr. Korde, how do you envision that these guideline recommendations will affect patients with non-metastatic breast cancer? DR. LARISSA KORDE: Well, I think building on Dr. Hershman's answer to the previous question, really, the key here is to be able to personalize or tailor the therapy for individual patients. So in those patients whose disease is very high risk, or did not respond to initial therapy, patients can be given appropriate escalation of treatment. And for patients who have an excellent response to treatment in the neoadjuvant setting can potentially be spared other treatments. And so I think that the main use of neoadjuvant treatment and the use of this guideline in terms of how it affects patients is being able to offer the most appropriate therapy for each patient. BRITTANY HARVEY: Great, well, thank you both for your work on this guideline on neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer. Appreciate your leadership on this guideline. And I want to thank you also for taking the time to speak with me today, Dr. Korde and Dr. Hershman. DR. DAWN HERSHMAN: Thank you. DR. LARISSA KORDE: Happy to be here. Thanks so 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.

An interview with Dr. Megan E. Daly from the University of California, Davis on "Radiation Therapy for Small Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline." An ASCO Expert Panel reviewed an ASTRO guideline on radiation therapy for SCLC and determined it was clear, thorough, and evidence based. ASCO endorsed the ASTRO guideline with a few discussion points, which Dr. Daly reviews in this podcast. Read the full guideline endorsement at www.asco.org/thoracic-cancer-guidelines. TRANSCRIPT PRESENTER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcast.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. Megan Daly from the University of California Davis, Co-Chair and lead author on "Radiation Therapy for Small Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline." Thank you for being here, Dr. Daly. DR. MEGAN DALY: Thank you. Glad to be here. 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 panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Daly, do you have any relevant disclosures that are directly related to this guideline topic? DR. MEGAN DALY: I do not. BRITTANY HARVEY: Great. Thanks so much. So generally, can you give us an overview of what this guideline endorsement addresses and how the ASCO guideline endorsement process works? DR. MEGAN DALY: This guideline was designed to provide an endorsement of a very comprehensive guideline provided by the American Society of Radiation Oncology addressing the use of radiation therapy for small cell lung cancer. The guideline endorsement process involved us developing a team of physicians, both medical oncologists and radiation oncologists, to review and assess the ASTRO guideline and make recommendations and clarifications for the ASCO audience. So our guideline panel met several times by teleconference. We carefully reviewed the guidelines with assistance from the ASCO staff. We reviewed each individual recommendation within the ASTRO guideline, including the supporting evidence and the final recommendations, and provided clarifying comments, when necessary. The entire guideline panel had to vote and reach a consensus on each individual recommendation from the ASTRO guideline to form a final consensus. And ultimately in the case of this guideline, we largely agreed with the excellent ASTRO guideline that had already been produced. So this was largely a process of confirming and endorsing ASTRO's guideline product. We also, then, provided a written paper that provides some additional clarification in context for ASCO's audience. BRITTANY HARVEY: Great. So you just touched on some of the recommendations of the guidelines. So what were those key recommendations of this guideline? DR. MEGAN DALY: So this guideline was specifically addressing the use of radiation therapy for small cell lung cancer, both limited-stage and extensive-stage small cell lung cancer. So the key recommendations that came out of both the ASTRO guideline and ASCO's recommendation of ASTRO's guidelines were first that radiation therapy should be used for most patients with limited-stage small cell lung cancer, confirming standard practice, and that doses of 45 gray in twice daily fractionation remain the standard of care, but alternative schedules delivering 60 to 70 gray over a single fraction are also reasonable. The guideline also addressed that stereotactic radiation is an appropriate consideration for early-stage node-negative limited-stage small cell lung cancer. The guideline also addresses the use of prophylactic cranial irradiation and continues to recommend the use of prophylactic cranial irradiation for fit patients with limited-stage small cell lung cancer while recommending shared decision making for other patients, including those with extensive-stage disease or patients who might have contraindications to PCI for limited-stage small cell lung cancer. And finally, the guideline also addressed the use of consolidated thoracic radiation in extensive-stage small cell lung cancer, providing a recommendation that it be considered for well-selected patients with extensive-stage disease. BRITTANY HARVEY: OK, and then you mentioned earlier that there were select scenarios in which the panel offered clarifying comments. So in which sections did the ASCO expert panel decide to offer those clarifying comments? DR. MEGAN DALY: Our clarifying comments were largely simply to provide clarification in several of the recommendations. For example, in recommendation 1.2, where ASTRO recommends that it's important to maintain the dosage and timing of chemotherapy with radiation and that timing is more critical for accelerated dose intensive radiation, we clarified that dose intensive radiation would be referring to twice daily hyper-fractionated regimens. We also provided clarification that ultracentral tumors refer to those where a planning target volume is overlapping or touching the proximal bronchial tree, the esophagus, and trachea within the recommendation that those tumors, even when early stage might better be addressed by fractionated, rather than a stereotactic radiation. And finally, for recommendation 4.4, it states for patients with extensive-stage small cell with a response to chemotherapy and immunotherapy and residual disease in the thorax, thoracic radiation to 30 gray and 10 fractions within six to eight weeks can be considered. And we provided clarification that that would be six to eight weeks of completion of the chemotherapy and prior to maintenance immunotherapy. BRITTANY HARVEY: Great. Then it sounds like those notes will be key for the ASCO audience in interpreting and implementing these recommendations. So in your view, what is the importance of this guideline endorsement? And how will it affect ASCO members? DR. MEGAN DALY: So I believe this guideline endorsement and the initial ASTRO guideline are both very important in providing guidance to both radiation oncologists and medical oncologists who routinely treat small cell lung cancer patients in their practice. The small cell lung cancer space is constantly changing, and there have been some major developments in small cell lung cancer within the last 5 to 10 years, most notably surrounding the use of prophylactic cranial irradiation and extensive-stage disease. There's also a number of interesting ongoing clinical trials looking at the use of consolidated thoracic radiation in extensive-stage disease. And many practitioners have questions about how to use radiation in the landscape of changing systemic therapies, for example, the integration of immunotherapy into extensive-stage disease, as well as how to integrate newer irradiation technologies like stereotactic radiation into the treatment of small cell lung cancer. So I believe that this guideline endorsement, as well as the original guidelines, can provide valuable guidance to the ASCO community in how to treat these patients in their daily practice. BRITTANY HARVEY: Great. And then finally, how do these guideline recommendations impact patients with small cell lung cancer? DR. MEGAN DALY: Hopefully, these guideline recommendations will help patients with small cell lung cancer receive standard of care latest treatments incorporating radiation. And there's a number of areas where radiation has been shown to improve survival in small cell lung cancer. So we absolutely want to make sure that our patients are receiving the best possible care that incorporates all available treatment modalities and incorporates all the latest data. BRITTANY HARVEY: Great. Well, thank you so much for your work on this guideline endorsement, and thank you for taking the time to speak with me today, Dr. Daly. DR. MEGAN DALY: Yeah, Brittany, thank you so much. Glad to be here. 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/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.

An interview with Dr. Katherine S. Virgo from Emory University in Atlanta, GA on "Initial Management of Non-Castrate Advanced, Recurrent or Metastatic Prostate Cancer: ASCO Guideline Update." This guideline updates recommendations for initial hormonal management of non-castrate advanced, recurrent, or metastatic prostate cancer. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines. TRANSCRIPT PRESENTER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Katherine Virgo from Emory University, lead author and co-chair on initial management of non-castrate advanced, recurrent, or metastatic prostate cancer, ASCO guideline update. Thank you for being here, Dr. Virgo. DR. KATHERINE VIRGO: Thank you, Brittany. 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. Virgo, do you have any relevant disclosures that are directly related to this guideline topic? DR. KATHERINE VIRGO: No, I do not. BRITTANY HARVEY: OK, thanks. Then let's delve into some of the guideline content. What prompted this update of the initial management of non-castrate advanced, recurrent, or metastatic prostate cancer guideline, and what is the scope of the update? DR. KATHERINE VIRGO: Well, the update of the 2007 version of the guideline was largely prompted by the many Phase III randomized clinical trials that had been completed or were nearly complete in the non-castrate space. It was believed that the results of these trials might permit revisiting previous recommendations regarding intermittent versus continuous androgen deprivation therapy and early or immediate versus deferred androgen deprivation therapy. As you might imagine, it took quite some time to gather and review 13 years of literature for each of the study questions from the original 2007 guideline. So in the interim, a sufficient number of randomized clinical trials reached completion to also inform recommendations regarding the use of newer therapies in combination with androgen deprivation therapy as initial therapy for men with metastatic disease, such as docetaxel, abiraterone, enzalutamide, and apalutamide, and thereby also update another existing ASCO guideline authored by Morris et al in 2018, which previously only provided guidance on the use of docetaxel and abiraterone for men with metastatic disease. BRITTANY HARVEY: Great, yeah, definitely a large volume of literature to review there. So then you talked about the recommendations. So I'd like to go through some of those. For men with metastatic non-castrate prostate cancer, what are the recommended standard initial treatment options? DR. KATHERINE VIRGO: So docetaxel, abiraterone, enzalutamide, and apalutamide, each when administered with androgen deprivation therapy, represent four separate standards of care for non-castrate metastatic prostate cancer. The use of any of these agents in any particular combination or in any particular series cannot yet be recommended. That said, we were able to make a recommendation for each agent individually. So I'll go through those recommendations now, first for docetaxel. So for men with metastatic non-castrate prostate cancer with high-volume disease who are candidates for treatment with chemotherapy, the addition of docetaxel to androgen deprivation therapy should be offered. Here, high-volume disease is defined per the charted trial as four or more bone metastases, one or more of which is outside of the spine or pelvis, and/or the presence of any visceral disease. Second, for abiraterone, for men with high-risk de novo metastatic non-castrate prostate cancer, the addition of abiraterone to androgen deprivation therapy should be offered per the latitude trial. For men who are considered low-risk, androgen deprivation therapy plus abiraterone may be offered for the STAMPEDE trial. Third, for enzalutamide, androgen deprivation therapy plus enzalutamide should be offered to men with metastatic non-castrate prostate cancer, including those with de novo metastatic disease and those who have received prior therapies, such as radical prostatectomy or radiation therapy for localized disease. Enzalutamide plus ADT has demonstrated short-term survival benefits, such as PSA progression-free, clinical progression free, and overall survival when compared to androgen deprivation therapy alone for men with metastatic non-castrate prostate cancer per the ENZAMET trial. And finally, fourth, androgen deprivation therapy plus apalutamide should be offered to men with metastatic non-castrate prostate cancer, including those with de novo metastatic disease or those who have received prior therapy, such as radical prostatectomy or radiation therapy for localized disease, per the TITAN trial. Thus in summary, to your initial question, all of the recommendations were phrased as "should be offered" except in the case of androgen deprivation therapy plus abiraterone for men with low-risk de novo metastatic non-castrate prostate cancer, for which the recommendation was phrased as "may be offered," as the evidence was not as strong as for the other recommendations. BRITTANY HARVEY: Great, thank you for reviewing those standard initial treatment options for men with metastatic non-castrate prostate cancer. So then what does the guideline say regarding combination therapy for men with non-castrate locally advanced non metastatic prostate cancer? DR. KATHERINE VIRGO: So here, androgen deprivation therapy plus abiraterone and prednisolone should be considered for men with non-castrate locally advanced non-metastatic prostate cancer, rather than castration monotherapy, due to the failure-free survival benefit for the STAMPEDE trial. We were unable to make a recommendation for men with high-risk non-metastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both, as it's currently unclear whether enzalutamide in the 160-milligram dose plus leuprolide improved metastasis-free survival compared to enzalutamide monotherapy or placebo. The recruitment is complete for the ongoing Phase III EMBARK trial, which is designed to answer this question. The results are not available yet. BRITTANY HARVEY: Great. Then how does the guideline address early or immediate androgen deprivation therapy versus deferred therapy for men with non-castrate locally advanced non-metastatic prostate cancer? DR. KATHERINE VIRGO: So here, early or immediate androgen deprivation therapy may be offered to men who initially present with non-castrate locally advanced non-metastatic disease who have not undergone previous local treatment, and are either unwilling or unable to undergo radiotherapy, based on evidence in one meta-analysis of a modest but statistically significant benefit in terms of both overall survival and cancer-specific survival among the larger population of men with locally advanced non-metastatic disease. Unfortunately, we were unable to make a recommendation for men with PSA relapse after local treatment. Though existing studies suggest a potential overall survival benefit, additional research is needed, as such studies were underpowered. BRITTANY HARVEY: And then finally, for men with biochemically recurrent non-metastatic disease, what are the recommendations for intermittent androgen deprivation therapy versus continuous androgen deprivation therapy? DR. KATHERINE VIRGO: So intermittent therapy may be offered to men with high-risk, biochemically recurrent non-metastatic prostate cancer after radical prostatectomy and/or radiotherapy, based on evidence and meta-analyses of the non-inferiority of intermittent androgen deprivation therapy when compared to continuous androgen deprivation therapy, with respect to overall survival. This is further supported by evidence from four meta-analyses testing superiority. And here, high-risk biochemical recurrence after radical prostatectomy is defined as a PSA doubling time less than one year or a pathologic Gleason score of 8 to 10. High-risk biochemical recurrence after radiation therapy has a different definition, here defined as an interval to biochemical recurrence of less than 18 months or a clinical Gleason score of 8 to 10. BRITTANY HARVEY: Thank you for reviewing all those recommendations and the evidence supporting them. It's very interesting to hear where you were able to make recommendations and where you weren't. So in your view, what is the importance of this guideline, and how will it change practice? DR. KATHERINE VIRGO: As mentioned earlier, the previous version of the guideline was 13 years old. And practice, as you might imagine, has changed considerably in the interim. Though consensus documents have been issued by other organizations since that time, it was important, given ASCO's global audience, to provide up-to-date, evidence-based guidance for the organization's worldwide membership. Practice patterns of most clinicians based at large university medical centers likely approximate the guidance provided in the ASCO guideline update, at least with respect to the treatment of men with de novo metastatic high-risk or high-volume disease. Some may be surprised by the current lack of evidence for the use of docetaxel among patients with de novo metastatic low-volume disease. The new guidelines should be particularly useful for community-based clinicians, who may not be as actively involved in clinical trial enrollment. BRITTANY HARVEY: Definitely. And then finally, how will these guideline recommendations impact patients with prostate cancer? DR. KATHERINE VIRGO: So patients will be impacted in three ways. First, the guidelines should be helpful to patients in understanding the various treatment options available to them, depending on the extent of their disease and any previous treatment they may have already received. The guidelines also highlight treatment options that should not be offered to patients who have certain characteristics and hopefully assist patients with adjusting their treatment expectations. Second, the cost table in the guidelines should also be helpful to patients, as it provides some idea of how costs vary by the type of treatment received, while also indicating when a less costly generic equivalent is available. And finally, third, the guidelines suggest that patients be counseled about the potential side effects associated with androgen deprivation therapy, such as depression, dementia, stroke, myocardial infarction, deep venous thrombosis, hot flush, fatigue, and nausea. Side effects vary by type of androgen deprivation therapy, as well as by age and patient comorbidities. Knowing up-front that such side effects are possible can assist patients in having more informed conversations with their physician when treatment discussions are underway. BRITTANY HARVEY: Great. Then it sounds like these guidelines have a real impact for both community oncologists and for patients. So I want to thank you for your leadership on the development of these evidence-based guidelines, and thank you for taking the time to speak with me today, Dr. Virgo. DR. KATHERINE VIRGO: 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/genitourinary-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.