ASCO Guidelines

An interview with Dr. Marcia Cruz-Correa from the University of Puerto Rico and MD Anderson Cancer Center on the ASCO Resource Stratified Guideline on early detection for colorectal cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Marcia Cruz-Correa from the University of Puerto Rico and MD Anderson Cancer Center, senior author on "Early Detection for Colorectal Cance: ASCO Resource-Stratified Guideline." Thank you for being here today, Dr. Cruz-Correa. Well, thank you very much for the opportunity to speak with you today. So first, can you give us a general overview of what this guideline covers? Absolutely, Shannon. Well, we are very excited to review the content of the guideline. And we put together a summary of the current guidelines out there for patients that are undergoing colorectal cancer screening. With these particular resource, a certified guideline takes, for the first time, into account the place where the colorectal cancer screening is being delivered, which is different from when you read any other colorectal cancer screening guidelines, where normally we assume that all available methodologies are equally distributed regardless of the country or the setting. So in our particular guideline, we really emphasize the fact that, depending on where our clinicians are, they might have differing technologies available. And that's why it's called resource-stratified-guidelines, to help our clinicians and our practicing physicians to understand what would be the best method to be able to implement screening in their own settings. So what are the key recommendations of this guideline? I think that the most important recommendation is that colorectal cancer is a prevalent disease, not only affecting very highly developed countries, but a disease that we're seeing more and more in low-to-middle-income countries. As ASCO is an organization that has members from around the world, being cognizant of the fact that colorectal cancer affects many individuals across different settings, and countries, and continents, for that matter, allows us to provide the most important information which is to consider colorectal cancer screening across the different settings, so not only in the industrialized well-developed first-world country, but also in the low-to-middle-income, or those that are becoming more and more industrialized. So our main recommendation-- it's number one-- that we need consider colorectal cancer screening even in settings where, for many years, the burden of disease was really focused in infectious-driven diseases. Nowadays, we're seeing more and more low-to-middle-income countries where the number one cause of death, it's not an infectious-driven disease, but rather a cancer. And colorectal cancer, it's one of the top cancers that we're seeing in many of the settings. So our number one recommendation is to be cognizant about that so that different countries and different settings, the practitioners consider screening. And our second and most important recommendation is that, the important thing is to consider what you have available in your setting, in your clinical practice. And depending on what you have available, then you can offer the method that could be given to your patient. So it's almost like thinking differently. It's not a one size fits all, but rather it's more or less of a personalized recommendation based on your setting, based on your clinical practice methods available to you. So why is this guideline so important? And how will it change practice? We believe that it's very important, because when you look at guidelines in any published article out there, we read it. And it looks as if everyone had every resource available. And when you're practicing in a low-to-middle-income country, or a place-- it could be a rural area where you have more basic settings or more limited settings-- you might not have that new machine or that new equipment. So then, as a practitioner, you feel that you're not equipped to be able to provide the best care to your patients. So this guideline, it's mirrored after a previous guideline that was put together by the ASCO Clinical Practice Group, where we stratify the type of practice for our-- where our practitioners are providing care. There are four main practice settings. The first one is what we call the basic setting, which is where you have the minimal necessary facilities to be able to evaluate patients and provide first primary care services. The second tier, it's called the limited setting, where you have more clinical facilities, but yet you don't have all the elements, like imaging, for instance, or the specialized surgeon, or the third- or fourth-level specialized technology. Then you have something, the next level would be the enhanced, where you, again, you see more methods and more availability of more clinical instrumentation and facilities. And then final one, which is the fourth level, will be the maximal setting. So in a maximal setting is when you go to a city, a cancer center, for instance, where you have all the specialists, all the imaging, all the endoscopy, and experts that are able to use those equipments and provide the best care. So using that four-level approach, from basic-- and think about, when you think about basic, it's in a rural community maybe in-a-low-to-middle income or developing country, places where you have a general surgeon. And you may have a primary physician. You may have nurse practitioners or nurses that actually provide that first care, first-level care. And then you keep going from there all the way to the maximal setting. So depending where you are, these resource-stratified guidelines will provide the physician and the clinical practitioner with methods that they can implement now. So to give you an example, when you think about colorectal cancer screening, you think about individuals that come to see you because they have no symptoms or they might have some symptoms. Most of the time, they would be asymptomatic individuals that come for a general screening, general visit. So this resource-stratified allows the physician that is practicing at a basic or a limited setting to provide, for the case of colorectal cancer, screening to provide fecal or cold-blood testing. This is a test that has been shown to be effective, that when used in the adequate setting for a patient that is 50 years of age or older, will provide enough sensitivity to diagnose an individual that might have either colorectal cancer or advanced colonic polyps so that that patient can then undergo a confirmatory test such as a barium enema, if you are in a basic setting. Very different, Shannon, when you are in a setting where you have all the instrumentation there-- you as a physician, you could either do a fecal immunological testing to look for, or cold blood. Or you could decide to refer a patient to a colonoscopy. And I think, when you practice in the US, I mean, large or industrialized places like Europe or Australia, you think that everyone has access to endoscopy. And believe it or not, one of the things that we realized when we were looking at all these data, is that in basic settings, setups for colonoscopy for removal of polyps with polypectomy during a colonoscopy are not available. So we took all those factors of clinical facilities, and availability of equipment, and expert physicians to be able to provide adequate care for the patients that are receiving care by our practitioners in the different settings, from basic all the way to enhanced and maximal settings. And finally, how will these guideline recommendations affect the patients? You have asked the most important question. The reason that we put guidelines out there is to guide our physicians, our practitioners to provide the best care that they can regardless of where they are. By providing this information, the ultimate and most important beneficiary of these guidelines is the patients. Right now, in many settings, especially in low-to-middle-income or developing countries, they are not receiving screening or preventive testing. In fact, there are many countries that do not have standardized or institutionalized programs for colorectal cancer screening. So if you don't have a program in place, you can imagine that then a patient would not even be considered for preventive care. So the ultimate and most important beneficiary of this resource-stratified colorectal cancer screening guideline is the patients that we serve. So as countries continue to evolve, and even in a country that is industrialized but where you have limited resources, only access to a basic laboratory, there we can still provide screening. And then the guidelines are written in a way that you can identify the type of practice where you're at. And you can choose between the different methods. And then it guides you as to decide when to refer a patient to a higher level with regards to clinical facilities. So if you're in a basic setting and you get a positive screening test, what do you do with that patient? Are you able to refer to the second level, which will be the limited? Or do you have to refer it all the way to enhanced? So it's almost like it's a guideline, but it's very practical in nature. So our hope is that this will allow our practitioners to feel empowered, to understand that this is a disease that will be affecting their population, the patients that they are taking care of, but furthermore, that they feel empowered to provide the best care, because that's why we practice medicine. And that's the bottom line, the most important reason why this was put together. Great, thank you so much for your work on this important guideline. And thank you for your time today, Dr. Cruz-Correa. Thank you very much for the opportunity, Shannon. And you know, hopefully we'll get many comments from across the different members of the organization across the globe. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Paul Celano from the Greater Baltimore Medical Center on the recently published ASCO Standards on safe handling of hazardous drugs. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Paul Celano from the greater Baltimore Medical Center, lead author on "Safe Handling of Hazardous Drugs: ASCO Standards." Thank you for being here today, Dr. Celano. Thank you for having me. I'm certainly glad to talk about these standards. They're very important to our employees and our patients. So first I want to make the distinction that this publication is not a guideline like we usually cover on this podcast. So can you tell us what standards are and how they differ from guidelines? Well, guidelines really are intended to guide practitioners around recommended care options. They give obviously a lot of latitude to clinical judgment and circumstances. Standards, on the other hand, are really meant primarily for the organization of care and are intended to have a higher level of obligation to help drive either practice or policy or even legislative efforts. So that's really the distinction. And what are the standard statements that are made by ASCO in this publication? The publication really is about safe handling of hazardous drugs. This all came about is because recently there have been a number of national guidelines or standards that have been offered by other organizations, but not specifically oncology or certainly ASCO or the ASCO organization. We felt a need to address the standards that have been put out on the basis of the evidence, so that best practices can be offered. Initially, we did collaborate with other societies, such as the Oncology Nursing Society and the Hematology Oncology Pharmacy Association. That was really the impetus behind making sure that we are, in a sense, congruent with standards that are already being published and discussed, but also to also place in our interpretation of these standards so that they're based on the best evidence that's available. And what qualifying statements are there to note about these standards? Well, I think the best way to look at these standards is there has been recently published or offered what's been called the UST 800 standards, which really incorporate other previous standards by the Pharmacy Association as well as OSHA, the Occupational Safety and Health Association, as well as NIOSH, the American Society of Hospital Pharmacists, Oncology Nursing, etc. So there's a lot of standards that have been offered. And in fact, the ASCO review of this really in a sense agrees with many of the standards that have already been published and offered-- types of exposures, the responsibilities of personnel handling the drugs, the personal protective equipment, how we communicate the hazardous drugs, the training of compounding personnel, how the drugs are dispensed and even transported. So there's lots of things that we really do agree with. I think it's also important to understand that the objectives of this is really to protect personnel and the environment to make sure the standards apply to all personnel who compound hazardous drugs and preparations, all places where hazardous drugs are prepared and stored, transported and administered. So that's really a key part of this. These are a comprehensive program really to prevent worker environmental exposure and to provide the most practical safety environment for all involved. So finally, why are these standards so important? And how will they affect practice? Well, they effect practice in many ways. I mean, the key thing is making sure that our employees, meaning the nurses, pharmacy, the technicians, really everyone involved that they're not unduly exposed to these hazardous drugs. And so that's really the key thing that we're all trying to achieve by this. Now, what really makes the sort of ASCO standards somewhat different or the things that we came into a contention with has to do with the differences that ASCO has come up with in contrast to some of the other standards. And these have to do with really four main areas within these standards. They have to do with medical surveillance, external ventilation, closed system transfer devices, and also proper assignment of our personnel while they may have either trying to conceive or pregnant or nursing. So those areas that in our review, the ASCO review, have come under some question. As an example, medical surveillance, there in some of the standards offered-- not ASCO's-- that there's a number of medical surveillance procedures that have been elucidated, that really we find, number one, have really not any proven value for our employees and generate a lot of confusion in terms of how this process is supposed to be done. Obviously, if one of our employees has some undue exposure, such as a spill of chemotherapy or even just have flat out a concern, then obviously those things will be clearly investigated. But to have general medical surveillance of all employees, really we did not feel was of great value. But also further, we really feel that this is an area where more research needs to be done to better elucidate really what should this process look like and what value are we providing to our employees. Another aspect of this is the use of what are called closed system transfer devices. Currently, there are a number of these devices available that there is interestingly no standard way that these devices have been evaluated. And so it's hard to recommend one device over another, because there is no standards for which they're really being compared. And there certainly have been no studies looking at really any form of health outcome that really help us to direct this to how best to use these devices. And so really, a lot of these objections are more around let's do things in an evidence-based way so we can better know how to best direct our practices. Another area of concern in terms of ASCO standards have been the implementation of external ventilation in either containment secondary engineering controls or other situations. And the challenges is that HEPA filters are probably appropriate for collecting solid or aerosolized particles, but don't capture vaporized drugs. But there's little data available on the ability of hazardous drugs to vaporize within the workplace environment and what those hazards really are. And so again, it's is a call for more research to have an optimal environment for preparing these drugs and without having to place undue burdens in terms of external ventilation. Another area is options for alternative duties for workers who are actively trying to conceive or are pregnant or breastfeeding. And these we recognize can be special burdens to small practices looking to implement alternative duty programs. There is a lot of controversy regarding the potential level of risk that really these workers really have. And basically our stance has been that we should have a policy that identifies alternative work options for workers who are trying to conceive, are pregnant or are breastfeeding, and that this information needs to be conveyed to these employees at the time of their hire so they understand what their risks are and what their options are within the workplace. Again, trying to make sure everyone is well informed and aware of what the work environment they're in and as their life circumstances change what they can do to change with this. I think the key is that we all feel that this is an area that we should have continued research on. And our standard, certainly ASCO's standards will continue to evolve as more and more research and evidence becomes available. Thank you so much for taking the time to explain these standards to us today, Dr. Celano. You're welcome. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague

An interview with Dr. Valerie de Haas from Princess Máxima Center for Pediatric Oncology in the Netherlands on "Initial Diagnostic Workup of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the CAP and ASH Guideline." ASCO fully endorses the CAP-ASH guideline on initial diagnostic work-up of AL and includes some discussion points according to clinical practice and updated literature. 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] Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Valerie de Haas from Princess Máxima Center for Pediatric Oncology in the Netherlands, lead author on "Initial Diagnostic Workup of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the CAP and ASH Guideline." Thank you for being here today, Dr. de Haas. Thank you. So first, can you give us a general overview of what this guideline covers? Well, yes. The laboratory evaluation of patients who are suspected of having acute leukemia is very complex, and it has evolved significantly with the incorporation of advanced laboratory techniques. The traditional backbone of initial workup of AL, of acute leukemia, is composed of ctyomorphology, cytochemistry, immunophenotyping, and molecular cytogenetics. These techniques are the backbone of the initial diagnostic workup of acute leukemia. This is leading to risk stratification and fine tuning of the therapy by molecular signatures. The advanced molecular diagnostics, such as next-generation sequencing, has become more important in the diagnosis and in the risk stratification of acute leukemia. This guideline is meant for both pediatric and adult patients, and it was initially published in 2017. This year, we reviewed this guideline, and we have taken into account two important developments. First, since 2017, we've seen that there are major advances in molecular techniques and also that we can identify and validate new molecular markers. And those two events have contribute to a better risk stratification. And the second development is the effect that the WHO classification was revised in 2017 which also has led to new risk recoveries and refined subclassifications. So what are the key recommendations of this guideline? Well, in total, we have reviewed 27 guideline statements by the ASCO endorsement expert panelists. And discussion points are used to summarize issues that were identified from the updated literature. The ASCO expert panel determined that the recommendations from the guideline as published in 2016 are clear, thorough, and they are based upon the most relevant scientific evidences. We fully endorse the CAP-ASH guideline on initial diagnostic workup of acute leukemia. And we decided to include some discussion points according to clinical practice and according to the updated literature. In fact, we identified four categories of key recommendations. The first one is the initial diagnostics focusing on basic diagnostics and determination of risk parameters. This concerns, in total, about 11 guideline recommendations, and they give an overview of the initial workup varying from the collection of the clinical history of the patient to initial basic diagnostics by cytomorphology, flow cytometry and molecular cytogenetic analysis of peripheral blood, bone marrow, and cerebrospinal fluids. Secondly, the second category were molecular markers and MRD detection, and they were addressed by 10 of the recommendations. And these recommendations give a structural overview of the molecular and cytogenetic workup for acute lymphoblastic leukemia versus acute myeloid leukemia identifying different prognostic markers. Also, the detection of MRD is taken into account in this recommendation. There is a major difference between children and adults, and this part is given most attention in the discussion part as the developments have been major during the past few years. The third one is the context of referral to another institution with expertise in the management of acute leukemia. This is addressed by four recommendations, emphasizing the point that referral to an institution with specific expertise is of major importance for the central workup of acute leukemia. And finally, the final reporting and report keeping is reflected in three recommendations, mainly supporting conclusions from 2017 which were describing the fact that the complete report with basic diagnostics in one central report should be available within 48 to 72 hours. And this should be followed by complete, final, comprehensive report in one or two weeks. So can you tell us about those discussion points that were made and why the panel decided to include these? The discussion points include mostly issues regarding diagnostics that involve flow cytometry and molecular techniques as addressed in part one and two of the guidelines. We think that the cytomorphologic assessment is essential for initial diagnosis of acute leukemia. Multicolor flow cytometry using 8 to 10 colors has led to a better distinction between myeloids, lymphoid, and mixed lineage blast origin. Even when the number of cells are limited, for instance in CNS involvement, fine needle aspirate of extramedullary leukemic infiltration, or skin biopsy for leukemic cutis. Also, it was suggested to better assess the central nervous system involved in leukemia. The expert panel recommends the immunophenotyping studies as an additional detection technique next to the cytomorphological examination of cytospins and particularly for those with a low level involvement of acute leukemia that cannot be well addressed by a morphologic examination only. The TDT immunohistochemistry staining of cytospins has alternatively been used for detection of CNS disease in AML and evaluation of CSF by multicolor flow cytometry has been recently adopted in some centers. Flow cytometry, using at least six, but we now use in some laboratories, even 8 to 10 colors has led to a much more specific in tentative diagnosis. And this has improved the detection of CNS involvement. The use of molecular tools, for instance, polymerase change reaction, PCR, NGS for low-level CSF involvement is still under study, and therefore, we did not recommend this in our discussion. Regarding the molecular markers and MRD detection, the discussion here was mainly based upon the results of translational research supported by better molecular detection techniques. And those molecular diagnoses have been developing in the past few years with the inclusion of many more molecular markers. And they included one of the key diagnostic criteria in the revised WHO classification, which was revised in 2017. And we made substantial changes that have been made in the ASH-CAP guidelines concerning molecular diagnostics. Those newly identified targets by advanced molecular techniques give possibilities for better risk stratification. Some examples of better molecular characterization of acute lymphoblastic leukemia are, for instance, additional testing for MLL translocations. Furthermore, we can look in patients with T-ALL for NOTCH1, and FBXW7 mutations. The Ikaros family zinc finger gene, the IKZF1 gene is frequently deleted in adults as well in children with B-ALL. And it was shown to have an independent prognostic significance and was also associated with poor clinical outcome. In the current text of the current risk that the protocols IKZF1 should be regularly included in the screening panels for all ALL patients. If we look for examples for better characterization of AML, acute myeloid leukemia, we have found an increasing number of additional cytogenetic aberrations, like for instance FLT3 ITD which is associated with poor outcome. Another example is appropriate mutational analysis for kids, which can be detected both in adult patient as pediatric patients with a confirmed core binding factor acute myeloid leukemia. So this is myeloid leukemia with a translocation A21, RUNX1, or inversion 16. This recommendation is very strong in adults, whereas in children, this prognostic fact impact remains unclear. So there have been proven several publications which refer to a similar prognosis for children and others who refer to a poor prognosis in comparison to known mutated genes. So we suggest to test for this mutation in adults, especially, but also in children to learn from it. Finally, emerging evidence supports molecular studies as principle test for monitoring minimal residual disease of acute leukemia. And there are several key molecular markers that are included in the initial workup, which will be carried on for monitoring MRD, for instance, PML- RAR-alpha, RUNX1-RUNXT1, CBFB-MYH11, and NPM1, CEBP-alpha and others. Beside those aforementioned markers, it's very important to screen for other molecular markers that have predictive or prognostic value in the individual. And it is possible to use them for MRD. We have found a recent consensus from the European Leukemia Net MRD Working Group, who was proposing that for detection of molecular MRD, and they refer the RT PCR platform to NGS and digital PCR platforms. Although all those molecular techniques have been developed very quickly and it is very tempting to use them for initial diagnostics, currently, not all laboratories will have all those techniques available. So the expert panel strongly advises understanding to make distinction between diagnostic that are needed in the first phase to start treatment and subsequently, treatment stratification, in contrast to the usual dose findings in a broader research. For instance, available karyotyping, FISH, PCR techniques, if possible, NGS can be used in the initial start of treatment, whereas techniques like whole exome sequencing, whole genome sequencing, RNA sequencing, and epigenomic studies are meant for a broader research. And finally, how will these guideline recommendations affect patients? Well, in the end, the patients will receive better and especially, more personalized treatment. If we have results available within two weeks from diagnosis, it will be possible to better identify which basis will better benefit from more intensified and more personalized treatment, whereas others may need less intensive treatment with less toxicity. If you use traditional techniques to do this supported by molecular techniques like karyotyping, FISH, and PCR techniques, and in the end, following MRD to see which patients are responding to treatment, MRD detection will help to identify these patients and stratify them finally to the best treatment. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. de Haas. OK. Thanks a lot. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

An interview with Dr. Elena Stoffel from University of Michigan on Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion. This PCO addresses identification and management of patients and family members with possible predisposition to pancreatic adenocarcinoma. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast Series. Is my name Shannon McKernin and today, I'm interviewing Dr. Elena Stoffel from the University of Michigan, lead author of "Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion." Thank you for being here today, Dr. Stoffel. I'm delighted to join you. So first, can you tell us what a professional clinical opinion is and why this topic is so important to ASCO? Well, a provisional clinical opinion is a statement that ASCO puts out when we are seeing trends that are relevant to the care of our patients but that may not necessarily have the level of evidence needed to include in a true clinical guideline. This particular provisional clinical opinion that deals with the management of patients with pancreatic cancer and their families is based on some new data that has been published regarding the prevalence of inherited factors influencing pancreatic cancer risk. So what are the key statements of this Provisional Clinical Opinion or also known as a PCO? This particular provisional clinical opinion, which is about just the inherited susceptibility to pancreatic cancer, was prompted by several recent publications, which found that the prevalence of genetic predisposition among patients with pancreatic cancer was much higher than we had originally anticipated. And this is relevant because in talking about pancreatic cancer as one of the deadliest cancers in both in the United States and worldwide, we are very interested in finding ways to reduce the morbidity from this cancer to patients and their families. And this particular provisional clinical opinion addresses the role that genetic risk assessment should have in the care of pancreatic cancer patients and also the role for clinical genetic testing, as well as the risks and benefits of pancreatic cancer screening for at risk family members. What considerations are there for having these conversations with patients and their families? Well, many times when we see families affected with cancer, one of the questions they have is what is the likelihood that this will happen to other individuals in our family and what can we do to prevent cancers in other family members. And I think what's important here is that review of the data from multi-gene panel genetic testing in unselected individuals diagnosed with pancreatic cancer identified pathogenic germline variants in 1 out of every 10 individuals. And this is really important because when you think about it, if 1 out of every 10 patients with pancreatic cancer develop their cancer in the setting of a genetic predisposition syndrome, this has tremendous implications for management both for them as well as for their family members. One of the most common inherited cancer syndromes identified in families affected with pancreatic cancer is hereditary breast ovarian cancer associated with mutations of BRCA1 and BRCA2. As you know, there are definite screening recommendations we make for individuals who carry these genetic alterations. And certainly if a family member is diagnosed with a genetic alteration, then that has an impact for cancer screening and management. Furthermore, there are emerging data about the utility of pancreatic cancer screening in high risk individuals. And while there's still some controversy about how to screen individuals at risk for pancreatic cancer, certainly there are some emerging data suggesting that this may have a role for early detection. And finally, the panel included a discussion section on the limitations of the research and future directions. So what are the key points of this section? I think that what we're learning is with genetic testing, and particularly with multi-gene panel testing, we are we often find unexpected results. Certainly variants of uncertain significance are not uncommon when multi-gene panel tests are used. And being able to interpret the clinical significance of some of these genetic test results can pose some challenges, especially for clinicians who don't have specific expertise in genetics. Certainly being able to deal with the volumes of patients who need genetic testing who are also battling pancreatic cancer, we want to make sure that we have the resources to be able to offer genetic testing to everyone who needs it. And finally, in talking about screening for pancreas cancer, while there are some studies that have demonstrated that screening with MRIs and/or endoscopic ultrasounds has led to early detection and down staging of cancers in some cases, larger studies are needed to be able to refine more specifically who and how to screen individuals at risk for pancreas cancer. Great. Thank you so much for taking your time today to discuss this PCO with us, Dr. Stoffel. Thank you very much for having me. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Jennifer Griggs from University of MIchigan on Adjuvant Endocrine Therapy for Women with Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update. This guideline provides recommendations on extended adjuvant therapy. on particular, use of aromatase inhibitors in women who had completed five years of adjuvant endocrine therapy. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Jennifer Griggs from the University of Michigan, senior author on "Adjuvant Endocrine Therapy for Women with Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update." Thank you for being here, Dr. Griggs. And thank you for the opportunity to talk about this focused update to the guidelines on extended adjuvant therapy. I would, of course, like to thank all my co-authors in the ASCO guidelines team for their contribution to this effort. So first, can you give us a general overview of what this guideline covers and their research which informed this focus update? Yes. First of all, the goal of the guideline was to give an update to the previous guidelines on this topic. And we specifically focused on extended adjuvant therapy. In particular, the aromatase inhibitors in women who had completed five years of adjuvant endocrine therapy. And it goes without saying, but it's worth reminding our listeners that the guideline is restricted only to post-menopausal women with hormone receptor-positive breast cancer. And, of course, our guidelines are only as good as the data upon which we rely. So for this guideline, six phase III randomized controlled trials met the pre-specified eligibility criteria for the updated systematic review and provide the evidence base for the guideline recommendations on the duration of aromatase inhibitor therapy. Each of the trials used the standard doses of the drugs that we use in practice today. So I'm not going to say the doses of each of the medications. So I'm going to go briefly over those six trials and just describe them so everybody's up to date with how the studies were designed. So briefly, the first trial I'll describe is MA17R, which compares letrozole to placebo for five years in over 1,900 women who had already received 4.5 to six years of adjuvant therapy with an AI, proceeded in most women by treatment with tamoxifen. The second study is NSABP B-42. And this also compares letrozole to placebo in nearly 4,000 women who'd completed five years of endocrine therapy with either five years of an aromatase inhibitor or up to three years of tamoxifen followed by an aromatase inhibitor, for a total of five years. The third study that we looked at is the DATA trial, which stands for the Different Durations of Adjuvant Anastrozole Therapy. This trial compared six years of adjuvant anastrozole with three years of adjuvant anastrozole in over 1,600 women after two to three years of adjuvant tamoxifen. The fourth trial out of the six is the IDEAL trial, the Investigation on the Duration of Extended Adjuvant Letrozole. This study randomized over 1,800 women to either 2 and 1/2 or five years of letrazole after five years of tamoxifen, an AI, or a combination in sequence of tamoxifen and an AI. So very similar study designs. The fifth study is the ABCSG-16 trial, the Austrian Breast Cancer Study Group Trial 16, which randomized nearly 3,500 women following four to six years of adjuvant therapy with tamoxifen and AI or a sequence of tamoxifen and then an AI, to either two or five years of anastrozole as extended therapy. And finally, the study of letrozole extension, or the SOLE trial, randomized over 4,800 women with node-positive breast cancer who had completed five years of adjuvant endocrine therapy to receive either continuous letrozole for five years or five years of an intermittent schedule of letrozole given nine months on and three months off in years one to four and on continuously for a year or five. So I know that's a lot to take in, but I do think it was important for our audience to understand the six trials that were included. These were all large studies, randomized, and patients had completed five years of adjuvant endocrine therapy. And then, were randomized either to placebo or different durations of an aromatase inhibitor or a placebo. For all of these studies, it's important to know that the primary outcome was disease-free survival. Overall survival and adverse events where secondary outcome. Great. So given that research and those trials, what are the key recommendations for this guideline update? Five key recommendations are included in this focused update to the previous guidelines. And they are for women with node-negative breast cancer, extended adjuvant aromatase inhibitor therapy can be offered for up to a total of five years of adjuvant therapy. Recommendations are based on considerations of recurrence risk using our usual established prognostic factors. However, since the recurrence risk is lower, the benefits are likely narrower in node-negative patients. The guidelines panel recommends that women with low-risk, node-negative tumors should not routinely be offered extended adjuvant therapy. Now, that might sound vague. We did not make recommendations using genomic profiling results because we don't have sound data to support such views that we felt were strong enough to integrate genomic testing results. Our second recommendation is that women with node-positive breast cancer should be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine therapy. And that means combined tamoxifen and aromatase endocrine therapy. That's the total that we meant to recommend. Third recommendation is that women receiving extended adjuvant endocrine therapy should receive no more than 10 years of total treatment. The fourth recommendation is when given as prevention of secondary or contralateral breast cancer, the risk of second breast cancers based on prior therapy should inform the decision to pursue extended therapy. So what this means is specifically, a woman who has had a bilateral mastectomy will not reap the benefit of preventative therapy with endocrine therapy. The fifth recommendation is that extended therapy carries ongoing risks and side effects, and these should be weighed against the potential absolute benefits of longer treatment in a shared decision-making process between the clinical team and the patient. Specifically, to date, none of the studies have shown improvement in overall survival with longer duration aromatase inhibitor therapy. As such, the recommendations, therefore, an extended adjuvant AI therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers. So why is this guideline so important and how will it change practice? The importance of this guideline rests in the fact that it supports what many clinicians and patients are already doing in practice. The second is it recommends against durations of endocrine therapy longer than 10 years in the absence of data supporting such a practice. So it's our thought that doctors and patients and other care providers, nurse practitioners, physician assistants, primary care doctors, are already practicing what we're recommending, and it supports doing so. And the second is that for those providers and patients who aren't sure that 10 years is enough, this guideline suggests that 10 years is sufficient. We don't have any data supporting giving more than 10 years. And the third recommendation is that this guideline really supports the need for shared decision-making, given the absence of data supporting an improvement in overall survival. So finally, since you did mention shared decision-making, how does this guideline recommendation affect patients? Well, the panel strongly believes that the tailored decision-making process is key in the decision to recommend extended adjuvant therapy. So tailoring on disease factors plays a role in the recommended duration of therapy. Obviously, since we stratified by high-risk and low-risk and what treatment's been received specifically. And if a woman's had bilateral mastectomy, she's not going to benefit from the risk reduction that's achieved with giving somebody extended therapy. But in addition to disease factors, patient preferences and tolerance of therapy should inform clinician and patient decision-making. Again, since none of the studies have shown improvement in overall survival with longer duration of AI therapy, patients and their medical providers need to make decisions based on an awareness that the benefits include, specifically prevention of distant recurrence and prevention of second breast cancers. And the importance of those benefits is going to vary according to a patient and how she views her life going forward and how bad her side effects have been, how well she tolerates the therapy. From my own personal point of view, as a breast oncologist, I believe two things. Number one, we should provide aggressive support for managing symptoms in patients who are most likely to benefit from extended therapy. That is, we should not stop therapy early if she is very likely to benefit if we haven't maximized control of her symptoms. There are many things we can do to improve symptoms and we shouldn't just stop therapy because she's not tolerating treatment if we haven't done the most that we can to improve her quality of life and her symptoms. Conversely, my hope is that we are not doggedly persisting in recommending prolonged therapy in a patient who has a fear of recurrence but who has little to gain from extended therapy. In the latter case, high quality information support is more therapeutic than extended therapy with a medication that's proven, in randomized controlled trials and in her own personal experience, to decrease her quality of life with marginal, if any, medical benefit. Thank you so much for the overview of this guideline today and thank you for your time. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

An interview with Dr. Scott Morgan from the Ottawa Hospital and University of Ottawa on "Hypofractionated Radiation Therapy for Localized Prostate Cancer: an ASTRO, ASCO, and AUA Evidence-Based Guideline." This guideline provides recommendations on hypofractionated external beam radiation therapy for localized prostate cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Scott Morgan from the Ottawa Hospital and University of Ottawa, lead author on "Hypofractionated Radiation Therapy for Localized Prostate Cancer: an ASTRO, ASCO, and AUA Evidence-Based Guideline." Thank you so much for being here today, Dr. Morgan. It's my pleasure, Shannon. I'm happy to take part in the podcast and hopefully share the highlights of the guideline with your listeners. So first, can you give us a general overview of what this guideline covers? Yeah. So the guideline covers really hypofractionated external beam radiation therapy, which is a treatment for localized prostate cancer, and for the non-radiation oncology folks in your audience, I think it's important to begin by placing the guideline sort of in its context and going over some of the terminology that we use as radiation oncologists. So external beam radiotherapy, it's a standard treatment-- standard local treatment option for men with localized prostate cancer. It gives outcomes which are really equivalent to those of radical prostatectomy or brachytherapy, which are the other two standard local treatment options. And traditionally, it's given in small daily fractions over several weeks and the usual daily fraction size is 1.8 to 2 Gray per day. And this is called conventional fractionation. And that really translates into a course of about seven and a half to nine weeks of treatment. And so that total dose which is delivered in those daily treatments, five days a week, is about 76 to 80 Gray. And that's what we call conventional or standard fractionation. And there's a theoretical framework in radiation medicine and there's some evidence to accompany that that suggests that prostate cancer is quite sensitive to radiation fraction size. And just to give a brief primer, for any tissue, cancerous or non-cancerous, there's a sensitivity to fraction size and it's characterized by something called the alpha-beta ratio. And for prostate cancer, that's felt to be low compared to most other cancers, the alpha-beta ratio, and indeed, it's thought to be lower than the adjacent dose-limiting normal structure, which is the rectum. And so an implication of that is that hypofractionation, and by that we mean daily fraction size of more than 2 Gray, might improve the therapeutic ratio of radiation therapy in localized prostate cancer. Now the guideline-- and I think it's important to emphasize this-- it draws a distinction between what we call moderate hypofractionation and ultra-hypofractionation. Clearly, fraction size is a continuous variable, so any subdivision that we might make is necessarily a bit arbitrary, but it turns out that at least in clinical practice, there's been really two distinct approaches to hypofractionation that have arisen. And one of these is moderate hypofractionation and that's an approach where the fraction size is modestly higher than 2 Gray per fraction, and in the guideline, it's been defined as a fraction size between 2.4 and 3.4 Gray, whereas ultra-hypofractionation, this is defined in the guideline as a fraction size greater than 5 Gray. And it's also been referred to in the literature as extreme hypofractionation or Stereotactic Body Radiation Therapy, SBRT, or SABR, Stereotactic Ablative Radiation Therapy. But in any case, we are talking here about, with ultra-hypofractionation, with radical courses of treatment that are often delivered over as few as five fractions, often on an alternate day approach over two or two and a half weeks. And so the guideline really was largely motivated by the publication of a number of randomized trials, including four large-scale trials in the past two years that have compared conventionally fractioned radiation therapy and moderately hypofractionated radiation therapy. So that is really what stimulated the guideline, which was the evidence concerning moderately hypofractionated radiation therapy. But at the same time, there has been an increasing use in routine clinical practice that's been observed of ultra-hypofractionated radiotherapy, so the decision was made to make recommendations on it as well. So ASTRO, American Society for Radiation Oncology, in collaboration with ASCO and the AUA, convened a panel of radiation oncologists, medical physicists, urologists, radiation oncology resident, patient representative, and a systematic review of the literature was conducted and their recommendations have been made on the basis of this systematic review. So the aim was to provide recommendations on use of both moderate hypofractionation and ultra-hypofractionation, in particular with reference to oncologic outcomes, toxicity, and quality of life. So we didn't directly consider health economic endpoints, though clearly the very nature of hypofractionation is such that there are potential advantages in terms of cost and convenience for patients. And what are the key recommendations of this guideline? We separated the key recommendations into three main groups and the first set of recommendations pertains to moderate hypofractionation, and these are generally based on the highest-quality evidence. So they could be viewed as the strongest recommendations in the guideline. And the second set of recommendations concern ultra-hypofractionation. They're somewhat less strong given they're based on somewhat weaker evidence. And then the third set of recommendations relate to some of the technical aspects of the planning and delivery of hypofractionated radiation therapy. So, dealing with the moderate hypofractionation recommendations first, arguably the most important recommendation of the guideline is that the panel has recommended that in patients with localized prostate cancer who are candidates for external beam radiation therapy, moderate hypofractionation should be offered. And this is graded as a strong recommendation. It's based on high-quality evidence and it applies to patients across all risk groups. So it applies to patients with low-risk prostate cancer who require active treatment or who have declined active surveillance and it also applies to patients with intermediate-risk or high-risk localized prostate cancer. And why really does it apply to all these groups? It's essentially because these groups are well-represented in the trials of moderate hypofractionation. And the trials have shown that moderate hypofractionation really gives similar outcomes in terms of efficacy to conventional fractionation. Now one caveat I guess that I should say is that the trials generally only looked at radiation therapy to the prostate rather than radiation therapy to the prostate as well as the pelvic lymph nodes. So the panel's recommendations regarding moderate hypofractionation don't apply to the scenario where the clinician has decided to include the pelvic lymph nodes in the radiation therapy volume. The panel also made recommendations with respect to toxicity and quality of life, and specifically, they did recommend that men should be counseled about a small increased risk of acute gastrointestinal toxicity, typically rectal toxicity, with moderately hypofractionated radiation therapy. And they should also be counseled that moderately hypofractionated radiation therapy has a similar risk of late GI toxicity and also has a similar risk of both acute and late GU toxicity compared to conventional fractionation. The only difference was seen in acute GI toxicity. And I think it's probably worth dwelling on this a little bit more. Probably the most granular data on acute GI toxicity comes from the CHHiP trial. This was a trial from the UK. It was far and away the largest randomized trial of moderate hypofractionation versus conventional fractionation. And they followed the amplitude of GI toxicity very carefully over the short and long term and what they did found was that in the early weeks, there was greater peak acute GI toxicity with moderate hypofractionation, but this difference had really disappeared by about 18 weeks after the start of radiotherapy. So within a few months, there was no difference, and afterwards, there was no consistent difference in long-term GU or GI toxicity across these trials. Now I guess I should mention that, at the current time, that the median follow-up of most of these trials is between five and six years, so arguably, the last word hasn't been written. The panel also offered conditional recommendations on particular moderate hypofractionation regimens. There were multiple different regimens that were evaluated but most were not compared head-to-head. And the panel preferred two particular regimens-- 60 Gray and 20 fractions over four weeks or 70 Gray and 28 fractions over five and a half weeks, as these were the two regimens that were evaluated in the largest populations. And of these two, likely the strongest evidence supports 60 Gray and 20 fractions, given it was used in two different trials and it was used across all risk groups and with or without concomitant hormonal therapy. So those were the recommendations regarding moderate hypofractionation. So moving to ultra-hypofractionation, again, this is talking about fraction size of at least 5 Gray, typically a course of as few as five fractions over perhaps two or two and a half weeks. I think it's important to say that, at the time we were preparing this guideline, there were no published efficacy or toxicity data from randomized trials comparing ultra-hypofractionation and conventional fractionation. So the strengths of the recommendations made by the panel is correspondingly lower than was the case for moderate hypofractionation. But having said that, there are several prospective non-randomized studies that have been published and have documented safe delivery of ultra-hypofractionation for appropriately-selected patients and pretty good biochemical control and low toxicities have been observed in these studies. But again, relatively few have follow-up beyond five years. So what the panel recommended was that in men with low-risk prostate cancer-- and the bulk of the data to date for ultra-hypofractionation has been in this group-- panel conditionally recommended that in those who decline active surveillance and choose active treatment with radiation therapy, that ultra-hypofractionation may be offered as an alternative to conventional fractionation. Again, this is a conditional recommendation. In men with intermediate-risk prostate cancer, the panel has conditionally recommended that ultra-hypofractionation may be offered as an alternative to conventional fractionation but it's strongly recommended in this group that these patients be treated as a part of a clinical trial-- and there are several clinical trials ongoing-- or as part of the multi-institutional registry. And then finally, in patients with high-risk localized prostate cancer, there was really insufficient comparative evidence for the panel to suggest offering this outside of a clinical trial or outside of a registry. Regarding particular regimens, that the panel again made a conditional recommendation that a schedule of 35 Gray to 36.25 Gray and five fractions delivered to the planning target volume could be offered and that it recommended against consecutive daily treatments for this schedule. So I think it's again important to note that compared to moderate hypofractionation, the ultra-hypofractionation literature is really substantially less mature and it is evolving rapidly. And therefore, a short-term update of this guideline to address new data pertaining specifically to ultra-hypofractionation is likely going to be necessary. And then I mentioned there was a third set of recommendations and these pertain to the technical aspects of planning and delivering radiation therapy. And these probably are not of core interest to your audience, but briefly, the guideline recommends that in the planning of hypofractionated radiotherapy, that normal tissue constraints and target volumes derive from published reference standards the use and that image guidance and intensity modulation at one form or another are recommended in delivering hypofractionated radiotherapy. Great. Thank you for the overview of those guideline recommendations. So why is this guideline so important and how will it change practice? Yeah. I guess the first point to make is that the guideline potentially can inform the care of a very large number of patients. Across North America, about 200,000 patients a year are diagnosed with prostate cancer and its far and away that the most prevalent non-dermatologic cancer in men and it's the third-leading cause of cancer death in men, at least in North America. So the vast majority of those 200,000 men are diagnosed with localized disease at the time of presentation and therefore they're potentially treatable with radiation therapy and therefore the guideline is relevant to these patients. Prior to the publication of the trials that motivated this guideline, the overwhelming majority of these men who chose external beam radiotherapy as their primary treatment have been treated with conventionally fractionated therapy. In other words, seven and a half to nine weeks of treatment. And already, since the publication of these trials-- the trials of moderate hypofractionation-- we're talking really about moderate hypofractionation because I think that is where the guideline will have its impact, at least in the short term. In the jurisdiction where I practice in Canada, practice has already substantially changed in light of these trials, and I think a large majority of patients with localized prostate cancer choosing external beam radiation therapy are now typically being treated with a moderately hypofractionated approach, typically a four-week schedule. So it will be interesting to see if a similar change is occurring or will occur over time in the United States, particularly informed or potentially informed in part by this guideline. And then finally, with respect to ultra-hypofractionation, I think again I have to note that this is a very dynamic space in terms of evidence and there are a number of large-scale trials looking at ultra-hypofractionation and comparing it to either conventional fractionation or moderate hypofractionation that are in progress or near to reporting. And so again, an update of the guideline in the short-term as data emerges from these studies will likely be important and it may ultimately influence practice as well on a large scale. And finally, how will these guideline recommendations affect patients? So I think in the short term, that the recommendation that has the potential to impact patients in the greatest way is the recommendation regarding moderate hypofractionation. And the guideline really recommends that this is a management approach that substantially reduces the treatment burden without compromising treatment efficacy and without increasing the risk of long-term side effects. So in my view, the move to moderately hypofractionated radiation therapy is a win for patients with localized prostate cancer who choose radiation therapy as their primary treatment modality. And so moderate hypofractionation really represents about a halving of the overall treatment time in some patients. And those who live, for example, in rural or remote areas and who need to travel considerable distance to have their treatment, a halving of treatment time is significant. But I think even more generally, halving of treatment time is significant for patients regardless of where they live. And clearly there are also benefits potentially in terms of cost and also benefits in terms of for the health care system but those really weren't specifically studied in the guideline. Great. Thank you so much for your time today, Dr. Morgan, and thank you for your work on this important guideline. My pleasure, Shannon, and thank you for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Carole Fakhry from Johns Hopkins School of Medicine on the ASCO endorsement of the CAP guideline on human papillomavirus (HPV) testing in head and neck carcinomas. Read the full guideline at www.asco.org/head-neck-cancer-guidelines The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Carole Fakhry from Johns Hopkins School of Medicine, lead author on Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the CAP Guideline. Thank you for being here today, Dr. Fakhry. Thanks for having me. So first, can you give us a general overview of what this guideline covers? Sure. This guideline serves to guide multi-disciplinary clinicians in the evaluation of head and neck cancers. And it really starts to clarify which HPV tests to order and when. Also discusses some of the imitations of using surrogate HPV testing in specific situations. The College of American Pathology Guidelines were recently published and we are providing an endorsement with certain classifications and discussions of nuances that we as a committee felt were important and clinically significant, specifically, aspects that could alter clinical care. So what are the key recommendations of this guideline? So first and foremost, the key recommendation is that HPV tumor detection should be performed in oropharynx tumors and not for non-oropharynx tumors. An important aspect of that is that HPV tumor testing should not be altered based on sex, race, age, or smoking history. Another important recommendation is that the term "high-risk" only be used when HPV-specific testing is performed. That would establish the tumor is ideologically related to the infection human papillomavirus. In the absence of HPV-specific testing, we recommend that the term HPV-related tumors be used, and that p16 deserving for oropharynx tumors only. And can you tell us a little bit about the qualifying statements made on some of these recommendations, and why the expert panel decided to include these? Sure. So one of the qualifying statements that we did make was a generalized one, and the one that I kind of just touched upon, that the term "high-risk HPV" should only be used in situations when HPV-specific testing was performed. And that's because sometimes things are p16 positive but not necessarily HPV-related or etiologically related to the infections. So as a committee, we wanted to make sure that that was clear. In light of that, one of the recommendations from the CAP Guidelines was that for tissue specimens presenting with medistatic squamma cell carcinoma of unknown primary and cervical upper, or mid-jugular, chain lymph nodes, pathologists should perform p16 in situ hybridisation. They also had added a note saying that additional high-risk HPV testing on p16-positive cases should be performed for tumors located outside of level two or three in the neck, and/or for tumors with keratinizing morphology. So in the qualifying statement, our committee felt that p16 immunohistochemistry alone was not sufficient in the scenario of an unknown primary cancer. We can get false positives and tumors that are p16-positive but not related to HPV. Can arise in situations of metastasis from the skin cancers, salivary gland malignancies, or even lung primaries. Therefore, in the case of an unknown primary, we would recommend HPV-specific testing. What other important consideration that our committee felt was important to clarify was that in the unknown primary, whether or not a tumor is felt to have keratinizing or non-keratinizing morphology, that HPV-specific testing should be done. And the reason for that is that the pathologists acknowledge that considering a tumor keratinizing or non-keratinizing may be a difficult distinction for most pathologists, and that discerning HPV status may actually be easier and may help hone in on the diagnosis. And as part of this, what we did was we created an algorithm which simplified the College of American Pathologists algorithm for HPV detection. So there are fewer nodes in terms of HPV detection. And in general, for oropharynx tumors, we recommend starting a p16 immunohistochemistry. We endorse the 70% cutoff used on immunohistochemistry for p16. And if it's an oropharynx tumor with greater than 70% p16 staining, then that can be considered an HPV-related squama cell carcinoma. For non-oropharynx tumors, we don't ever recommend HPV tumor status evaluation. And then for unknown primary, whether or not it's a level 2 or 3, starting with p16 is adequate, but if it is p16-positive, that needs to be followed up with HPV-specific testing to be deemed HPV-related. In the College of American Pathology algorithm, acknowledging that determining HPV status can be complex, there are more nodes and more decisions that could be made in terms of discerning what's HPV-related and what's not. And so our committee tried to distill it down and simplify the algorithm. And finally, how will these guideline recommendations affect patients? So it is recommended that patients with oropharynx cancer be tested for HPV. And so this really helps their clinicians determine how to best test their tumors. In cases that are not so clear that are not oropharynx tumors, it also helps to guide their clinicians in terms of the when and how to test their tumors. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Fakhry. Thanks for having me. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Justin Bekelman from University of Pennsylvania Perelman School of Medicine on the ASCO endorsement of the AUA/ASTRO/SUO Guideline on the management of localized prostate cancer. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Justin Bekelman from University of Pennsylvania Perelman School of Medicine, lead author on "Clinically Localized Prostate Cancer: ASCO Clinical Practice Guideline Endorsement of an AUA/ASTRO/SUO Guideline." Thank you for being here today, Dr. Bekelman. Thanks for having me. First, can you give us a general overview of what this guideline covers? Sure. So this guideline addresses the key question about what is the current best practice available for the management of localized prostate cancer. It's an endorsement guideline, which means it reinforces the recommendations offered by the American Urologic Association, ASTRO, SUO, which is the Society of Urologic Oncology. In April of 2017, these three groups got together to release a joint evidence-based practice guideline on clinically localized prostate cancer. And then, now more recently, in 2018 ASCO assembled a panel to review those policies, update them, and endorse them as appropriate. So this guideline has over 60 recommendations. So I'm not going to ask you to read through all of them. But can you talk about some of the key topics and discussion points that was added by the ASCO expert panel? Yeah, absolutely. I'd like to highlight four areas. The first area-- panel endorsed guideline recommendations on active surveillance for men with low risk Gleason 6 prostate cancer, what's called grade 1 prostate cancer now. The panel also felt it reasonable to add that ASCO has also produced a guideline on active surveillance which provides more context and counsel for clinicians and patients. It also includes a discussion of how surveillance might be considered for men with low volume Gleason 3+4, or what's called grade 2 cancers. And so I would reference that ASCO guideline on active surveillance for folks who are interested in that. Second, panel updated the recommendation regarding the length of androgen deprivation therapy or hormone therapy for men with higher risk clinically localized prostate cancer. Prior recommendations considered 24 to 36 months to be appropriate. And that's what's captured in the 2017 guidelines from the AUA, ASTRO, and SUO. But new evidence released after those guidelines were published from two trials-- one called RADAR and one called PCS IV trial-- shows that 18 months may be equivalent and permissible, and thus these trials should be followed really closely. But that's really interesting, provocative information for patients as they consider adjuvant hormone therapy for high risk cancers when they're receiving radiation. Third, the panel describes two really high impact quality of life studies comparing surgery, external beam radiation, and brachytherapy that were published in JAMA in 2017, again, after the AUA guideline was published. These two studies are actually summarized in the discussion of the panel findings. And they are an excellent reference for both clinicians and patients as they consider the potential benefits and harms of the various treatments for prostate cancer. The last one I'd want to highlight to the audience is the panel's recommendations regarding cryosurgery. And even though the original guidelines stated that selected patients are candidates for cryosurgery, the panel found that there was insufficient evidence to support the use of cryosurgery for clinically localized prostate cancer. So those are four highlights from the evidence based review. And why is this guideline so important? And how will it change practice? This guideline represents the most up to date consensus recommendations from the major professional societies that represent clinicians-- the surgeons, the radiation oncologists, the medical oncologists-- who counsel and treat men with prostate cancer. So it's a really important initial original guideline and then a really important endorsement. I think it will change practice by highlighting what the current best practice standards of care are for clinically localized prostate cancer. And finally, how will these guideline recommendations affect patients? I think this guideline will have an immediate impact on important questions that patients and their clinicians want answered. I think that's how the panel actually took its role, is thinking, how can we both endorse and provide further evidence that would be patient centered as we considered these guidelines. So this endorsement and the guidelines, they ask questions like, how should we conduct shared decision making with our patients to offer the highest chance that treatment decisions will be concordant with our patient goals of care? That's number one and so crucial. Who is appropriate for active surveillance? A top topic for men facing clinically localized prostate cancer. What are the differences and side effects among the major treatments for clinically localized prostate cancer, mostly focused on surgery and radiation? The endorsement updates the latest data through 2017 and even in 2018 with really patient-centric information about what patients might expect with each of these treatments. Even what are the aspects of prostate cancer care that represent the highest quality? And how might patients assess that? What are the most important aspects of survivorship? So the endorsement and recommendations from the original guidelines themselves hit on each of these. And I think that patients will find them very interesting and insightful. Great. Thank you so much for your time today. And thank you for your work on this important guideline, Dr. Bekelman. Oh, my pleasure. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

An interview with Dr. Randy Taplitz from UC San Diego Health on the guideline update which addresses antimicrobial prophylaxis for adult patients with immunosuppression associated with cancer and its treatment. Read the full guideline at www.asco.org/supportive-care-guidelines The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Randy Taplitz from UC San Diego Health, lead author on Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. Thank you for being here, Dr. Taplitz. Thank you. So first, can you give us a general overview of what this guideline covers? Yes. I mean, I think we're all aware that infection in the setting of neutropenia associated with cancer chemotherapy is really a major cause of morbidity in these patients. And it's also important to be aware that prevention and appropriate management of febrile neutropenia and infection should thus be a critical focus in cancer care. So the focus of this particular guideline was to evaluate the risk and benefits of antimicrobial prophylaxis in these patients and really to determine evidence-based best practices for prevention of infection and how to go about doing that. So In this guideline, what we do is we identify the groups at risk for febrile neutropenia and really recommend settings for which prophylaxis with antibacterial, antifungal, antiviral medications are indicated. And then as well make recommendations for consideration of vaccination and other measures such as respiratory etiquette, and hand hygiene, and the like that will help reduce the risk of infection in these vulnerable patients. So since this is an update of a 2013 guideline, what are the major changes? And can you tell us a little bit about the research that informed this update? Yes. Really, when you update a guideline, one is informed by review of articles that encompass, in this setting, randomized clinical trials as well as meta analysis of interventions to prevent microbial infections in patients with neutropenia or other types of immunosuppression. And one example of this-- I think one of the better examples-- is we reviewed a large meta analysis of antibiotic prophylaxis in neutropenic patients after chemotherapy that showed that for fluoroquinolone prophylaxis resulted in really significant reductions in all cause mortality and febrile episodes, particularly in patients who were high risk, meaning the hematologic malignancy population and stem cell transplant population. And in that particular population, in fact, the number needed to treat to prevent one death was 29. So therefore, in that high risk population, really as with prior guidelines, the fluoroquinolone prophylaxis is recommended. However, we also reviewed other articles that include emerging data on some of the risks of fluoroquinolone prophylaxis. So for instance, the effect of fluoroquinolone on the intestinal microbiome and its association with selection of fluoroquinolone-resistant bacteria such as Gram-negative rods, as well as selection of organisms such as Clostridium difficile and enterococcus. And then we also reviewed fluoroquinolone toxicities. So what is added to this guideline are some qualifying statements alerting clinicians to really be aware for these concerns and to consider what the clinical spectrum of things like Clostridium difficile infection, et cetera, look like. In terms of antifungal prevention, including pneumocystis prevention, we really haven't made any major changes to this guideline with the exception that in this new guideline, the panel has also started looking at complications associated with immunotherapy and actually makes a suggestion that people consider pneumocystis prophylaxis in the setting of prolonged steroid use when it's used to treat immune-related adverse events that we've begun to see in increasing numbers associated with agents like checkpoint inhibitors and other immunotherapies. In terms of viral infections, the updated guidelines recommend risk assessment for hepatitis B reactivation and then treatment in accordance with other ASCO guidelines and yearly influenza vaccine, as well as really endorsing other vaccines as described in the Infectious Disease Society of America Guideline for Vaccination in Immunocompromised Hosts. So really, those are the main new events since 2013. And what are the key recommendations of this guideline? So the key recommendations-- the first thing is what we call a risk assessment. So after-- what one does is carefully assess, really, what the risk of febrile neutropenia is. And that includes assessment of patient, what the cancer is, and what the treatment-related factors are. And then after they're risk adjusted and risk assessed, then we take, in turn, different forms of prophylaxis that we consider. And so the first one that we always consider is antibiotic prophylaxis against bacterial infections. And the recommendation is still with the fluoroquinolone. And that's recommended for most patients who are at high risk for febrile neutropenia or profound, really prolonged neutropenia, such as those getting therapy for AML, or myelodysplastic syndrome, or stem cell transplant recipients, particularly with myeloablative regimens. In the lower risk groups, such as those with most solid tumors, fluoroquinolone prophylaxis is not recommend. In terms of antifungal prophylaxis, what is recommended is an oral triazole or Micafungin-- for patients, again, at risk for profound protracted neutropenia such as that AML, MDS, stem cell transplant group during that period of neutropenia. When the risk of invasive aspergillus is high, such as in patients with AML or MDS during the neutropenia period while getting chemotherapy, then the consideration of a mold-active triazole is recommended and in addition should be considered in the context of stem cell transplant recipients with graft versus host disease. In terms of PCP prophylaxis, PCP preventive therapies are recommended for those at high risk for PCP, which include those on greater than what we say 20 milligrams of prednisone equivalent a day for over a month, or based on purine analog use. Viral prophylaxis for HSV is recommended for seropositive patients undergoing allogeneic stem cell transplant or leukemia induction. And then as I mentioned before, patients at risk for hepatitis B reactivation are recommended treatment with a nucleoside reverse transcriptase inhibitor. And this is more carefully discussed in the ASCO Provisional Clinical Opinion on Hepatitis-B Virus Screening for Patients With Cancer Before Therapy. It's also recommended that a yearly flu vaccine is given to patients as well as given to family, household contacts, and health care workers. Other vaccination recommendations are as per the Infectious Disease Society of America Guidelines for Vaccination of Immunocompromised Hosts. And then the other things that are recommended are really review and repeat recommendation of adherence with hand hygiene, with respiratory etiquette, which is recommended and really required for all health care workers. And that out patients with neutropenia from cancer chemotherapy should avoid high risk activities, which include really contact with environments that have high concentration of fungal spores such as construction and demolition, high intensity gardening, et cetera. So those are really a summary of the key recommendations of this guideline. And finally, how will these guideline recommendations affect patients? I think it's important to remember that to ensure best practices on infection prevention, the literature needs to be reviewed frequently and guidelines need to be updated. I don't think that these current guidelines will dramatically change the preventive strategies that are used for patients, with the exception of perhaps a few extra vaccines-- some newer indications for pneumocystis prevention, hepatitis B reactivation prevention, those kinds of things. However, I think in reviewing the literature, it becomes clear what will we will need to be thinking about in the coming years, what we will need to be assessing. And a couple of those things are the dramatic increase in the use of immune-based therapies and how that will affect infection risk in patients with or without neutropenia. We need to be considering the effects of routine antibiotic prophylaxis on the microbiome and the risks that that might incur. And we need to really understand how new vaccines can be utilized. So yeah, I think these areas are really ripe for research and need to be followed closely to ensure optimization of these preventive strategies for our patients in the future. Thank you for your time today, Dr. Taplitz. You're quite welcome. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer this show to a colleague.

An interview with Dr. Naren Ramakrishna from University of Florida Health Cancer Center at Orlando Health on the guideline update which addresses management of brain metastases for patients with human epidermal growth factor receptor 2–positive advanced breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines