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Treatment of Metastatic Carcinoma and Myeloma of the Femur: Joint MSTS/ASTRO/ASCO Guideline Oct 01, 2020

Show notes

An interview with Dr. Felasfa Wodajo from Virginia Cancer Specialists on "The Treatment of Metastatic Carcinoma and Myeloma of the Femur: Joint MSTS/ASTRO/ASCO Guideline." This guideline covers medical oncology, radiation oncology, and surgical recommendations regarding the management of patients with metastatic or myelomatous lesions of the femur. Read the full guideline at www.asco.org/supportive-care-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's 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. Felasfa Wodajo from Virginia Cancer Specialists in Fairfax, Virginia, co-chair on the treatment of metastatic carcinoma and myeloma of the femur, joint Musculoskeletal Tumor Society, American Society for Radiation Oncology, and American Society of Clinical Oncology Guideline. Thank you for being here Dr. Wodajo. Dr. Felasfa Wodajo: Thank you so much Brittany, I really appreciate the opportunity to talk about our joint guideline that is being published as we speak. It's a great opportunity to share the information with your members as well as hopefully patients and members of other societies. Brittany Harvey: Great. Then first I'd like to note that ASCO takes care in the development of its guidelines in ensuring that the conflicts of interest are managed for each guideline. This guideline expert panel was assembled in accordance with the American Association of Orthopedic Surgeons conflict of interest policy implementation for clinical practice guidelines. And the full conflict of interest information for this guideline panel is available online in the full text of the joint guideline on the MSTS website. Dr. Wodajo, do you have any relevant disclosures that are related to this guideline topic? Dr. Felasfa Wodajo: There's one relevant, but not directly conflicting. I'm a consultant for ONKOS Surgical. That's a maker of implants, but mostly for patients who need sarcoma surgery, and they don't make implants for the types of conditions that are in the guideline. Brittany Harvey: OK, well thanks for letting us know. First, can you give us a general overview of what this guideline covers? Dr. Felasfa Wodajo: Sure. The guideline is focused on the effects of metastatic carcinoma or myeloma on the femur. And, as all medical oncologists are aware, metastatic disease to the bone and myeloma are often associated with skeletal pain and sometimes skeletal fractures. Those fractures can occur in any part of the body, spine, of course long bones, and ribs, and so on. But in our world of orthopedic surgery-- I'm a representative from the Musculoskeletal Tumor Society-- the bones and then added complication are not all equal, and some areas have greater morbidity and effect on patient's outcome than others, the femur being a very important one. And we wanted to focus our efforts on discussing the causes and potential treatments of metastatic disease to the femur. Brittany Harvey: And then what are the key recommendations of this guideline? Dr. Felasfa Wodajo: Sure, I'm looking forward to discussing those. I do want to, of course, take a second to acknowledge the hard work that was done by my co-chairs, Dr. Patrick Getty, also from the MSTS, Dr. John Charlson, who was an ASCO co-chair, and Dr. Josh Petit, who is the ASTRO co-chair. And also this gives me a chance to say that this guideline was a joint effort between those three organizations which you already mentioned. The initiative was led by our organization-- the Musculoskeletal Tumor Society, MSTS-- which is a mostly North American, but also international, society of musculoskeletal tumor surgeons, also known as orthopedic oncologists. And therefore, in almost every place that members of our group work, they're working in close association with medical oncologists and radiation oncologists. So we wanted to make sure that the guideline reflects the input of all three specialties since all three specialists are often treating the same patients. And in developing the PICO questions-- which are the underlying questions in developing a guideline-- we made sure that we had co-chairs-- one from each of the societies-- agree on which PICO questions to include in the final literature search. And then finally, the guideline as written, roughly breaks the recommendations down by specialty. It starts off with medical oncology topics, then radiation oncology topics, and then surgical topics. So that's a little bit of background that might be helpful. I also wanted to mention that one of the meta level findings was the paucity or the dirth of literature that directly addressed the question at hand which is, what kinds of treatments can prevent femur fractures, and then which therapies are best for patients with disease in the femur that may or may not lead to fractures. And we started off with a fairly broad net. But as we focused down on the questions, our initial literature search-- which resulted in over 4,000 journal articles-- was winnowed down to a total of 23 papers which had the high enough level of evidence to be included in our guideline production. And therefore, that inevitably a good number of our questions-- not having strong enough evidence to make a strong evidence based recommendation-- and therefore more than half of our recommendations in the end had to be consensus or expert opinion. So let me continue with your original question which is, what are the key recommendations. Well, questions that we were interested in were number one, to what extent can non-surgical treatments of metastatic disease to the femur, or myeloma in the femur, will reduce the risk of fracture. So almost everybody listening to this podcast will know well that bone targeted agents such as the bisphosphonates and denosumab have a strong effect validated in multiple high level randomized and prospective studies in reducing Skeletal Related Events, SREs. As you know, as the listeners also know, Skeletal Related Events is a fairly broad umbrella term, and it includes fracture of any bone as well as hypercalcemia and need for surgery. But like I said earlier on, a compression fracture of a vertebral body which causes back pain but is treated conservatively, and a fracture of the rib, which also causes pain, treated conservatively or nonoperatively, is a very different matter from a femur fracture which always requires surgery in order to allow the patient to ambulate and regain function. Having said that, we were disappointed to find that in much of the literature around bone targeted agents-- of which there is plenty-- there's really very little of it that you can find where they stratify, or at least retort, which bones were fractured. So even though there is a strong literature base supporting reduction skeletal events, we can't really say for sure that the risk of a fracture of a femoral lesion is diminished by both targeted agents. That came out as a consensus statement because this seems to reduce fractures overall, so we left this as a consensus and agreed that BMAs may assist in reducing the incidence of femur fractures. The next item, number three, in our final report recommended that clinicians consider decreasing the frequency of zoledronic acid dosing to 12 weeks instead of the usual, and most common, four week interval. There's actually a fair amount of literature supporting quarterly injections as equally efficacious. That's mostly focused on zoledronic acid. It may be true for [INAUDIBLE]. It may also even be true for denosumab, but the literature didn't support that as yet. But we did make this strong recommendation on our part that clinicians consider reducing the frequency of dosing. If nothing else, because in addition to reducing costs to the patient and time of the patient, we think there may be-- and we put this in our rationale-- there's some chance that some of the unintended side effects of long-term treatment with these bisphosphonate and bismuth therapies such as aseptic necrosis of the jaw and atypical fractures, or brittle bone fractures, of the femur may be reduced with decreased frequency. Extrapolating from the finding that the longer patients are treated, the higher the incidence of these conditions are, especially atypical fractures. So it could be that less frequent dosing is analogous to less length of treatment. So that was an evidence based and strong recommendation. We also then looked at the effect of radiation on bone lesions and whether or not it does reduce risk of fracture. We found, not surprisingly, that the radiation oncology literature really focuses on pain. And it's been proven many times and in multiple studies across many decades that radiation therapy does reduce pain at 80% to 90%. And even re-treatment will reduce pain in up to 50% to 70% of patients. But surprisingly, there's actually very little data out there whether it reduces the risk of fracture. Now we would presume that fracture risk is correlated to bone loss, and that would be radiolucency or loss of calcification on the X-ray. And there are some studies out there which attempt to measure density of bone before and after radiation therapy. And there seems to be some validation, or at least some measurement out there that radiodensity does increase with radiation therapy, and again, we went from that and extrapolated that fracture risk would best be reduced. But that ended up being a consensus statement. And it's actually a fairly important topic. And hope that more studies would be forthcoming on this, because it would be very helpful for us to predict ahead of time whether this patient can avoid a fracture with radiation alone or do they need to go to surgery. Next we talked about how effective or beneficial is radiation after somebody's had surgery. So whether or not they've had a fracture, is there a further benefit to radiation. And here the amount of data was even more disappointing. There's really only two studies that attempt to address this question-- is there a benefit to additional radiation following surgery-- neither one of which was well controlled. They're way out of date and the criteria themselves used in measuring the benefit were not validated. Now we felt, as a work group-- again consisting of medical oncologists, radiation oncologists, and surgical oncologists, in this case orthopedic oncologists-- that the additional morbidity from radiation after surgery is fairly low. So we left that recommendation as that it has some benefit, but that was the consensus only. One item that we elevated from consensus to a moderate strength was the benefit of using multifraction radiotherapy to reduce the risk. There is some data-- again, it may be biased-- that patients who undergo single dose radiotherapy as opposed to multifraction radiotherapy for metastatic lesions have an increased risk of fracture. And it may be associated and it may be that those patients getting single dose radiation were at higher risk or had more rapidly progressing disease. But there may be some signal in that noise, and after evaluating the papers and with the help of our experts in radiation oncology, we elevated that to a moderate strength of recommendation. Then there was a series of questions we tried to address, various surgical techniques and the management of pathology of fractures in the femur and prevention of, and those questions are really more about surgical technique. And these were addressed to our surgical colleagues in large part. I don't know, and I would suspect that the audience of this podcast probably won't be as interested in these questions as the ones we just discussed, so I'll leave those for another time. But I will say a large number of these ended up being also consensus driven evidence. Brittany Harvey: Got it. Well, thank you so much for reviewing those highlights from the multidisciplinary group and the supporting level of evidence. That's very helpful. So in your view, why is this guideline so important and how will it impact clinical practice? Dr. Felasfa Wodajo: So, thank you for the question. I'll answer that in two ways. I think the two items that might be of immediate clinical relevance, and therefore of help to patients and their physicians, is number one, further promulgation of the idea of less frequent dosing of bone targeted agents is equally efficacious. We felt that, if based on our common experiences in our various practices and institutions, that still was not widespread practice. In other words, most patients were still receiving monthly injections of these medications. So we do believe that there is some net patient benefit available to us if those are reduced to quarterly injections for the reasons I mentioned above. So that's one potential immediate release and early improvement that we can expect for patients. I think the other one, to some extent, may be that what I discussed a little while ago about and multifraction versus single fraction therapy. Again, we don't have nationwide survey data to tell us how often those techniques are used. Again, based on this sort of experience of the workup we thought that that may not be widely understood. So those are two immediate clinical benefits that may be there for patients. The other way I would look at is at a meta level. Number one was that this is a cooperative venture in which the design and implementation of the guideline was across three organizations. And many times guidelines do incorporate the viewpoints of people of multiple specialties, and sometimes even patient representatives. But it's also, I think, further valuable to have multiple organizations involved because there's some cross-fertilization opportunities there, other products may arise from that, and then also you get what we hope is promulgation of that information to people of different specialties. In other words, these recommendations don't stay inside the ecosphere of one association. Now when you have multiple organizations working on one project, necessarily it gets more complicated. And there is certainly a heavier administrative burden in getting this project initiated and completed. But hopefully the benefits of that will accrue. The other thing which I'd like to mention is that I think the paucity of high level evidence for the questions we ask-- which we believe are important questions for physicians and patients-- I think hopefully should stimulate the researchers in these fields to accrue more data so that future researchers and clinicians have access to these information. For example, I suspect that in future prospective studies of bone targeted agents-- those studies are ongoing-- new agents will be coming out. Pharma will be looking at how those work for their patients in the future. And we would like to ask that those future researchers include, at a minimum, anatomic data for fractures. In other words, they should unbundle Skeletal Related Events and tabulate fractures as occurring in which part of the bone, and if that resulted in surgery. Those data are there in the records, but if they don't collate them…

Full show notes at the publisher

PARP Inhibitors in the Management of Ovarian Cancer Guideline Aug 13, 2020

Show notes

An interview with Dr. William P. Tew from Memorial Sloan Kettering Cancer Center on "PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline." This guideline provides recommendations on the use of poly (ADP-ribose) polymerase inhibitors (PARPis) for management of epithelial ovarian, tubal, or primary peritoneal cancer. Read the full guideline at www.asco.org/gynecologic-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, at podcast.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. William P. Tew from Memorial Sloan Kettering Cancer Center in New York, New York, lead author on PARP inhibitors and the management of ovarian cancer. Thank you for being here, Dr. Tew.

Dr. William Tew: Thank you, Brittany, for having me.

Brittany Harvey: First, I'd like to note the 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. Tew, do you have any relevant disclosures that are directly related to this guideline topic?

Dr. William Tew: No, I do not.

Brittany Harvey: OK, thank you. Then, can you give us a general overview of what this guideline covers?

Dr. William Tew: Sure. So my co-chair, Elise Kohn, and panel members, and ASCO staff put together a very comprehensive guideline on the use of PARP inhibitors in the management of women with ovarian cancer. And as many of your listeners may know, there has been a rapid speed of phase 3 practice changing trials that have been published and FDA approvals within the last year, and what we wanted to do was to put that all in one document and give guidance on how and when and which PARP inhibitor to use in your specific patient and at what point during the lifecycle of ovarian cancer of when to use it.

So we broke up the guideline into five sections. One is the use of PARP inhibitors as maintenance therapy after first line platinum based treatment in women with stage 3 and 4 ovarian cancer. Second, we looked at maintenance therapy after a second or higher platinum based treatment. Three, the use of PARP inhibitors as treatment for patients with recurrent epithelial ovarian cancer.

We then looked at different combinations of PARP inhibitors, whether it's with chemotherapy or biologics and the data that we have presently on those combinations. And then lastly, we looked at common side effects with PARP inhibitors and offering guidance on how to manage those toxicities.

Brittany Harvey: Great. Then you just mentioned that this covers several different sections, so I'd like to go through each of those sections and review those recommendations for our listeners. So first, what are the recommendations for PARP inhibitors for patients with newly diagnosed epithelial ovarian cancer?

Dr. William Tew: So for women with newly diagnosed ovarian cancer, there's been several studies that have been published in the last year and a half, and we broke this up into the different studies and the different patient populations. First and foremost, we wanted to stress that PARP inhibitors are not recommended for the use in the initial treatment of patients with early stage, meaning stage 1 or 2 ovarian cancer, because there really isn't sufficient evidence to support the use in this population. All of the trials looked at patients with stage 3 or 4 epithelial ovarian cancer and used primarily in the main setting, and what that basically means is that women that have had a complete or partial response to first line platinum based chemotherapy and have response by CT scan or CM 125, when do you use a PARP inhibitor?

Which are the women that you would say PARP inhibitor is going to benefit you with long-term outcome? So our first recommendation is based on a trial-- looking at a drug called olaparib. Olaparib was the first PARP inhibitor published in this population, and in that study, they included women with both germline or somatic pathogenic or likely pathogenic variants in the BRCA1 or BRCA2 gene. And so this is a group of women that you could offer olaparib for.

And generally, that is given at a dosage of 300 milligrams once every 12 hours for up to two years. The second study looked at a drug called niraparib, and in this trial, they included population of all women, regardless of BRCA status. And they offered it to women with high-grade serous or endometrial ovarian cancer. And the FDA has given approval for the use of niraparib for all patients, and that is at a dosage of 200 to 300 milligrams oral daily for three years, with the lower dose given for patients who have a low platelet count or low body weight to prevent the common toxicity of thrombocytopenia.

Then you could consider longer durations in select individuals, but generally, these drugs are given for a limited period of time and continued unless a patient has significant toxicity or progression. The other two studies in the newly diagnosed ovarian cancer population was a study that looked at olaparib with bevacizumab maintenance. This was a study that included patients with germline or somatic mutations and BRCA 1 or 2 and/or genomic instability or homologous repair deficiency, as determined by the myriad my choice test.

And again, this population, a partial or complete response to chemotherapy and their first line therapy should have included bevacizumab. And so if one is on bevacizumab with their platinum based therapy, they should have a response to treatment, one could continue bevacizumab and add the addition of olaparib as a PARP inhibitor. And then the final study that we addressed was called switch therapy, and that we don't really have enough data to support its use, specifically that's with the drug called veliparib, and veliparib was given in addition to the chemotherapy and then continued as a maintenance therapy.

We don't really have sufficient data to suggest this was superior, equal, or less toxic than the approaches discussed above, which is single agent PARP inhibitor or bevacizumab with PARP inhibitor. And it should be noted, also, veliparib is not yet an FDA approved drug and not commercially available.

Brittany Harvey: OK, then what are the recommendations for PARP inhibitors for patients with recurrent epithelial ovarian cancer?

Dr. William Tew: Yeah, and this data has been around a little bit longer, and I think any oncologists that treat them with ovarian cancer are more comfortable with the evidence with these studies. So what we're talking about here is that patients who were in clinical remission and then their ovarian cancer recurs. And the first group of women that we look at is patients that are then retreated with platinum based therapy. Those women that have platinum sensitive disease, and then whether to offer PARP maintenance in the second line or more remission settings.

And there is very good data to support the use of PARP monotherapy in second or greater maintenance. This has been shown with all three commercially available PARP inhibitors, olaparib, rucaparib, and niraparib. We do know that women who have a germline or somatic pathogenic or likely pathogenic variant in the BRCA 1 or 2 genes have the highest benefit of maintenance PARP inhibition, and those patients have the strongest evidence to receive those drug.

So the only other point I wanted to make with current ovarian cancer is if a patient has received a PARP inhibitor in the past, there is no evidence to give a second exposure to PARP inhibitor. Those studies are being developed now, but PARP inhibitor use once in the life cycle is what's recommended. And then there's also evidence to use PARP inhibitor as an actual treatment. So not in the maintenance setting, and the drug most commonly used as one called niraparib or olaparib, and these are patients that have measurable disease or generally have platinum sensitive disease, and those women that have homologous repair deficiency, as determined by the Myriad myChoice test, and again, have platinum sensitive to disease do have benefit for treatment with PARP inhibitors.

Brittany Harvey: OK, then, so you just mentioned this, but is it correct that PARPi therapy for epithelial ovarian cancer should not be repeated over the course of treatment?

Dr. William Tew: Right now, that is what we recommend. All of the studies that looked at the use of PARP inhibitors disqualified women who have had prior PARP inhibitors. So as of now, we don't have any evidence to support the use of repeated PARP inhibition.

Brittany Harvey: And what does the guidelines say about using PARP inhibitors in combination with chemotherapy or other targeted agents?

Dr. William Tew: There are many studies going on currently looking at the use of PARP inhibitors in combination with immunotherapy, chemotherapy, and other targeted agents, but currently, at least in the recurrent setting, there is no data to support its use in combination with another anti-cancer treatment. Now, of course, in the context of a clinical trial, this would be very reasonable, and we encourage clinical trial participation.

The only studies that looked at PARP in combination with other anti-cancer treatments are in the first line setting, as I discussed earlier, including PARP inhibitors with bevacizumab, as in the case with olaparib or PARP inhibitors with chemotherapy, as is often the case with veliparib.

Brittany Harvey: OK, thank you. And then how should clinicians manage the adverse effects associated with PARP inhibitors?

Dr. William Tew: I think the first and foremost thing is to be aware of the specific side effect profile of each PARP inhibitor, because they can vary slightly between parts. The most common side effects include fatigue, nausea, change in appetite, and effects on the blood counts, and we gave guidance on each of those specific side effects. As far as the effects on the blood counts, anemia, I'd say, is one of the more common side effects across all PARPi's, and the use of blood transfusions is generally recommended if patients are symptomatic and their hemoglobin is below 8 to 7.

And then for neutropenia, usually, this requires hold of dosing, and we did not encourage the use of growth support, although it may be used in certain settings when the drugs on hold. And then the final cytopenia issue is the issue with platelets, and this is unfortunately very common side effect with niraparib. And we discussed earlier about starting at a lower dose, 200 milligrams of niraparib based on a weight and platelet count to help temper the degree of thrombocytopenia. But with thrombocytopenia, clearly, the drugs sometimes need to be held or discontinued if it's significant.

And with cytopenias, we do recommend close observation of laboratory blood work, particularly in the first month of use of PARP inhibitors, and then always being mindful if patients are on PARP inhibitors for prolonged periods of time that there has been reports of treatment related myelodysplastic syndromes and leukemias and that should be further worked up if there is any evidence of dysplasia.

Brittany Harvey: So then, what is the importance of this guideline in your view, and how will its implementation affect clinical practice?

Dr. William Tew: Well, I think this is the most up-to-date and comprehensive guideline on PARP inhibitors and will help, both clinicians and patients, understand all the practice changing studies, the populations, and the settings they will use, and all these studies that were published over the last five years. I think this last year we've seen such a rapid growth of clinical trial results and FDA approvals that this manuscript, I think, successfully puts them all together in table form and brief recommendations to better treat and provide proper management to your patients with ovarian cancer.

Brittany Harvey: And then finally, how will these guideline recommendations impact patients with ovarian cancer?

Dr. William Tew: We were very fortunate to have two patient advocates as part of our panel, and what they told us was that these recommendations will help them understand the scientific trials, will put in context when to use PARP inhibitors, and also to prepare them for those conversations that they have with their clinicians in discussing if they're a good candidate for a PARP inhibitor now or in the future. So we're really proud of that, that we were able to get our patients perspective in developing these guidelines.

Brittany Harvey: Definitely. Well, thank you for your work on these important and timely guidelines and for taking the time to join me on the podcast today, Dr. Tew.

Dr. William Tew: My pleasure. Thank you so much, Brittany, for having me.

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/gynecologic-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.

Metastatic Pancreatic Cancer Guideline Update Aug 05, 2020

Show notes

An interview with Dr. Davendra Sohal from the University of Cincinnati, and Dr. Daniel Laheru from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins on "Metastatic Pancreatic Cancer: ASCO Guideline Update." This update covers new information on targeted therapies for metastatic pancreatic cancer. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines

Transcript

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

My name is Brittany Harvey, and today I'm interviewing Dr. Davendra Sohal from the University of Cincinnati, and Dr. Daniel Laheru from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, co-chairs on Metastatic Pancreatic Cancer, ASCO Guideline update. Thank you for being here, Dr. Sohal and Dr. Laheru.

Hi, Brittany. Thank you for inviting us.

Happy to be here. Thanks.

First, I'd like to note that ASCO takes great care in 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. But Doctor Sohal, do you have any relevant disclosures that are directly related to this guideline topic?

No, I do not have anything directly in conflict. Thank you.

And Dr. Laheru, do you have any relevant disclosures that are related to this guideline topic?

Thank you, Brittany. I do not either.

Great. Than delving into the guideline content, Dr. Laheru, can you tell us what prompted an update to this guideline?

Yeah, sure. So what has been seen in almost every cancer is that with careful understanding of the molecular alterations of individual cancers, that targeted therapies have been developed for almost every cancer. And so for pancreas cancer, we have not had an opportunity in the past to use targeted therapies. Because for pancreas cancer, many of the genetic alterations that are found in other cancers are not seen in pancreas cancer. And so the guidelines were updated based on new evidence of the use of certain targeted therapies for pancreas cancer.

Then Dr. Sohal, what are the key updates that were made to the recommendations in this guideline iteration?

So the key updates relate to the so-called targeted therapies, the genomic-driven therapies that have now come up with evidence that pertains to pancreatic cancer as well. The overarching update is that every patient with metastatic pancreatic cancer who is a candidate for treatment should have tumor or somatic, the so-called somatic genomic profiling, as well as germline genomic testing, because these can lead to treatment recommendations.

And those treatment recommendations include PD-1 checkpoint inhibitor therapies for microsat light instability high tumors, track the TRK fusion inhibitors, such as larotrectinib and entrectinib for track fusions in tumors. And PARP inhibitors, such as olaparib for germline BRCA1 or BRCA2 mutations to be used as maintenance therapy after stable disease on platinum-based therapy.

Then Dr. Laheru, can you speak to the importance of this guideline and how it will drive changes to clinical practice?

Yes. So as Dr. Sohal said, these specific genetic alterations, the mismatch repair deficiency, the use of PARP inhibitors for BRCA1, BRCA2 germline mutations or somatic mutations that are pathologically significant, and for the NTRK fusion transcripts, even though these mutations for pancreas cancer are quite unusual, less than 5%, for example, for NTRK fusion transcripts, 5% to 10% for BRCA1, BRCA2 germline mutations, and probably 1% or 2% for a mismatch repair deficient pancreas cancer, the committee felt that we should inform the larger cancer community that even though these mutations are uncommon, if they are found, they could be very important for individual treatment for pancreas cancer.

And so this is why we really felt that it was time to provide an update, because of the recent information with the olaparib maintenance and with the NTRK inhibitors for the NTRK fusion transcripts.

Great. And then finally, Dr. Sohal, how do you envision that this guideline update will affect patients?

I think it expands our armamentarium for pancreas cancer patient management. It affords opportunities for better treatments, targeted therapies, which have hopefully higher efficacy and lower toxicity than standard chemotherapy, even though, as Dr. Laheru said, the proportion of patients being eligible for these therapies may be only around 5%. Still, in a disease where there are not many options, every 1 in 20 patients can get these therapies based on tumor genomic profiling and/or germline testing.

And the other slightly different but associated topic is that if germline testing finds something in the patient, a bad gene, then obviously, that patient's blood relatives can be tested for that germline finding, and there may be implications for further testing and surveillance of family members.

Well, thank you both for your work on this metastatic pancreatic cancer guideline update. And thanks for taking the time to speak with me today, Dr. Sohal and Dr. Laheru.

It's our pleasure, Brittany. Thank you very much.

Certainly. Thank you so much.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/gastrointestinal-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.

Hepatitis B Virus Screening and Management for Patients with Cancer Prior to Therapy Provisional Clinical Opinion Update Jul 27, 2020

Show notes

An interview with Dr. Jessica Hwang from MD Anderson Cancer Center and Dr. Andrew Artz from City of Hope Cancer Center on "Hepatitis B Virus Screening and Management for Patients with Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update." This update presents a clinically pragmatic approach to HBV screening and management that calls for universal HBV serological testing of patients at the onset of anticancer therapy. Read the full PCO at www.asco.org/supportive-care-guidelines

Transcript

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 Hwang from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, and Dr. Andrew Artz from the City of Hope Comprehensive Cancer Center in Duarte, California, co-chairs on hepatitis B screening and management for patients with cancer prior to therapy, ASCO provisional clinical opinion update. Thank you for being here, Dr. Hwang and Dr. Artz.

Thank you for inviting us.

Thank you so much.

First, I'd like to note that ASCO takes great care in the development of its guideline products and ensuring that the ASCO conflict of interest policy is followed. The full conflict of interest information for this provisional clinical opinion panel is available online with the publication in the Journal of Clinical Oncology. Dr. Hwang, do you have any relevant disclosures that are related to this topic?

Well, I have received some research funding from Gilead, a maker of a hepatitis drug in the past.

And, Dr. Artz, do you have any relevant disclosures?

I have no relevant disclosures.

OK, then so, Dr. Artz, so this provisional clinical opinion, or PCO, on hepatitis B screening and management for patients with cancer prior to therapy was first published in 2010 and then last updated in 2015. What prompted this update to the PCO?

This PCO guidance, more broadly, is necessary because the hepatitis B status for most patients is actually unknown at the time they're starting cancer therapy. In 2015, the PCO though suggested that we limit hepatitis B screening to patients who were at most risk for hepatitis B reactivation, if they were hepatitis B carriers, so those receiving anti-CD20 antibodies, such as rituximab or stem cell transplant. But for the remaining patients, most patients receiving cancer therapy, the guidance was to survey patients about their close contacts or exposures to hepatitis B and determine if formal hepatitis testing should ensue.

This 2020 PCO represents an evolution in our understanding of hepatitis B screening and the dangers of hepatitis B after anticancer therapy. We've learned from studies, including those done by my colleague, Dr. Hwang, that questionnaires to detect hepatitis B are not very effective or practical. We also have accumulating information that many of our anticancer therapies pose a significant danger for hepatitis B related complications in hepatitis B infected patients. We believe appropriate monitoring and treatment, as outlined in the PCO, will reduce these dangers.

So given that new information, I'd like to discuss the updated statements for the PCO. So first, Dr. Hwang, for patients who will receive systemic anticancer therapy, who should be tested for HBV and how should they be tested?

That's a great question, Brittany. Thanks. I think that the data is really clear now that all patients with cancer anticipating systemic anticancer therapy should be tested for hepatitis B virus. That includes all solid tumor patients, as well as hematologic malignancy patients.

And they can be tested with a simple blood test. The hepatitis B virus can be tested by three blood tests for hepatitis. It's the hepatitis B surface antigen, HBsAG, or the hepatitis B core antibody. There are two types of this. It's either the IgG or the total IG, which shows, if positive, could indicate a patient has past infection. There is a IgM version of that core antibody test. And that tells, if positive, tells whether a patient has acute infection. So for our purposes, it's recommended that the IgG or total IG is used and not the IgM, because we are interested in whether a patient has past infection.

So the third test is a hepatitis B surface antibody. And this is a protective antibody. So if positive, it shows that a patient has had some exposure in the past or perhaps a vaccination in the past. And so this is a good test to have positive.

So then what does the PCO state for patients with chronic HBV infection?

Patients with chronic HBV infection, that is those patients with a positive hepatitis B surface antigen test, these patients really should have very close monitoring during as well as after anticancer therapy. These patients will need antiviral therapy prophylactically prior to enduring as well as after the cancer treatment. They should also see a clinician experienced in the management of hepatitis B, whether it's a hepatologist, a gastroenterologist, an infectious disease specialist, or maybe a primary care doctor who's experienced in treating and caring and monitoring for patients with hepatitis B. That's really important for these patients with a chronic hepatitis B, because they are at high risk of developing complications during and as well as perhaps even shortly thereafter of receiving systemic anticancer therapy.

And then what does the PCO state for patients with past HBV infection?

This is a really good question. The patients with past HBV infection are those who have a negative hepatitis B surface antigen and a positive hepatitis B core antibody. This represents maybe some 6% at least of the US population. It could be much higher. So this is a sizable group of patients. And it's really important to know that it is sort of a tailored approach.

So patients with past HBV infection who are anticipated to receive one of the high risk anticancer therapies that Dr. Artz mentioned just a few moments ago, namely stem cell transplantation or maybe one of the anti-CD20 monoclonal antibodies, these patients are at really high risk of reactivation. So these patients would need a very close monitoring plan. They would need their hepatitis B and liver test monitored during their anticancer therapy. And most often they would need antiviral prophylaxis before, during, and even after their immunosuppressive therapy ends.

So there are patients, of course, who don't receive these high-risk therapies. So that is patients with past HBV infection who are receiving anticancer therapy that's not a stem cell transplant and not an anti-CD20 monoclonal antibody. These patients could be monitored carefully. They could have hepatitis B and/or liver testing monitoring during anticancer therapy. And if they have any elevations in their surface antigen or their ALT, then they could have further hepatitis B testing to see if they have any evidence of complications from their hepatitis B. So that's in general what the PCO recommends for these two groups.

Well, thank you for reviewing those highlights from the PCO. So Dr. Artz, what is the importance of this PCO and how will its implementation impact practice?

Thank you for the question. This PCO I feel dramatically simplifies the challenge of hepatitis B screening by proposing universal hepatitis B testing, as Dr. Hwang outlined, at a defined point in time. That is at the initiation of therapy.

And clinicians have really struggled with hepatitis B testing for lots of different reasons. They're difficulties in knowing who to screen, how to screen, in part because the data have started to emerge that many of the therapies may pose some risks and the prior suggestion that we use questionnaires, but there wasn't a standard set of questionnaires that we could use if we wanted to identify people based on risk factors of acquiring hepatitis B. So this led to a lot of confusion on testing.

I think by standardizing this makes it considerably easier. And also, the guidance from the PCO is better harmonized with other organizations, such as the Centers for Disease Control and our Liver Society colleagues who actually participated in the panel. And so now the guidance clinicians receive are more consistent across organizations. So I think this will allow doctors and health care systems overall to now invest in the implementation of hepatitis B screening, rather than the question about who should we do it and can we do it and when should we do it, but rather more on the implementation to help patients.

Great. And then finally, what is the impact of this updated PCO for patients?

Well, I'll take the first part of that. I believe that the implementation should permit safer systemic anticancer therapy by reducing hepatitis B related complications. Whenever patients have complications or there's even uncertainty about whether hepatitis might be contributing, this also can lead to delays in our treatments. If we know in advance and we appropriately manage and monitor this, we should have fewer treatment delays as well. Dr. Hwang, I know, might also have some comments on this.

Thanks. I do have a few general comments beyond the cancer care implications. And I'd like to say I think that hepatitis B testing and then the results of that and sharing that information with patients is really important. Letting patients know their hepatitis B status, especially if they're positive, empowers them to seek further care, get connected with a hepatitis B specialist person who's experienced in managing hepatitis B, and also to look around the local environment to their household and close contacts because hepatitis B is a virus that is transmitted from person to person through blood-borne sexual transmission and close family or household contact.

So I think it's important for patients to know their status to protect themselves during cancer therapy, as Dr. Artz mentioned, but just in general for good health care for themselves and for those around them. And in addition, I think that it's important for the family members and those close contacts to then get screened and perhaps even consider getting vaccinated if they haven't been vaccinated.

Well, thank you both for your hard work on updating this PTO and for taking the time to speak with me today, Dr. Hwang and Dr. Artz.

Thank you, Brittany.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full provisional clinical opinion go to www.asco.org/supportive-care-guidelines. This PCO also has a companion cancer.net podcast episode. Cancer.net is the patient information website of ASCO. And we encourage you to learn more by tuning into their episode. You can find their podcast and all ASCO podcasts at podcast.asco.org.

You can also find many of our guidelines, PCOs, 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.

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers Guideline Update Jul 14, 2020

Show notes

An interview with Dr. Charles Loprinzi from Mayo Clinic in Rochester, MN on "Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update." This update incorporates new evidence into recommendations for the prevention and treatment of chemotherapy-induced peripheral neuropathy in adults with a history of cancer. Read the full guideline at www.asco.org/survivorship-guidelines

TRANSCRIPT

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. Charles Loprinzi from the Mayo Clinic in Rochester, Minnesota, lead author on prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers, ASCO guideline update. Thank you for being here, Dr. Loprinzi.

It's my pleasure to participate.

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 of our guidelines. The full conflict of interest information for this guideline panel is available online with the publication in the Journal of Clinical Oncology. Dr. Loprinzi, do you have any relevant disclosures that are related to this guideline topic?

Well, that's always the perception, I think. Let me mention a couple of things. I've been intimately involved with research with chemotherapy-induced neuropathy for about 20 years or so, and have looked at a lot of the different drugs and treatments that we considered in this guideline.

I consulted for companies that have interest in neuropathy, including Asahi Kasei Pharma, Disarm Therapeutics, Metis Pharmaceuticals, PledPharma, and NKMax America. But other than that, I do not have anything else to note there.

Great, thanks. So first, what prompted an update to this guideline on the prevention of management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers?

Well, it's been about five years since we did the initial guideline. It is a very prominent problem-- I think probably one of the most prominent chronic problems we get associate with chemotherapy. You get acute problems like nausea and vomiting, but those go away. But this can be a prominent problem that can last for years.

There have been about 40 new trials for looking at prevention of neuropathy while you're giving chemotherapy, or treatment of neuropathy after you receive the chemotherapy and looking at ways to try to treat that. About 40 new trials have been published since we did the last guideline. So it was decided that it's time to look at this again to see what's new, what's not new, and sort things out.

So with that new information that the guideline panel looked at, what are the recommendations for prevention of chemotherapy-induced peripheral neuropathy?

OK. So for prevention-- and we're talking about you're about to give chemotherapy that has neurotoxic properties, if you will. Not all chemotherapies cause neurotoxicity. And by neurotoxicity, I'm talking about numbness, tingling, pain, usually in distal extremities. Hands and feet is where it usually starts. But that's what we're talking about here.

And the bottom line answer, which is similar to what it was five years ago, is that there is no proven means for being able to prevent this problem other than not giving the chemotherapy that can cause the problem. And we usually want to give the chemotherapy to try to kill the cancer process. So there is no proven means.

There is, however, suggestive evidence for a few things. And each of these need more research to really clarify the risks of doing them and that benefits from. One of these things is something called cryotherapy or cold therapy. And you put cold therapy on hands and feet, causes less blood flow, and slows the metabolism somewhat while the person is getting chemotherapy. And there's suggestive evidence that helps, although not proof.

There is another thing that's somewhat related to that, and it's called compression therapy, where if you put tight surgical gloves on a hand while you're getting the chemotherapy, decreasing blood flow when there's a lot of chemotherapy in the blood-- again, suggestive evidence. But there is things where they've actually combined these things with both doing cryotherapy and some compression.

And the third thing is exercise. There are data suggestion that exercise can decrease the amount of neuropathy that patients get. Again, no proof for any of those three things, but more research is needed in that area.

Thanks for reviewing those recommendations for prevention. What are the recommendations for treatment approaches for chemotherapy-induced peripheral neuropathy?

So I think we have two things in here. One of them is what about when you're giving chemotherapy to a patient-- neurotoxic chemotherapy-- and you're planning to give, let's say, 12 cycles of paclitaxel, a common drug that we give for 12 cycles once a week-- one-week cycles, so dose once a week for 12 weeks, and it causes neurotoxicity. And you might be six or seven or eight doses in, and the patient's getting fairly significant neuropathy. And you're worried about giving more of that chemotherapy because it might cause more neuropathy, which may not go away for months or years after it is finished.

So in that setting, the decision, the recommendation, is for the doctor to think about how much additional benefit are we going to get from continuing onto the 12 cycles from the 8 cycles or 6 cycles wherever we are, and decide how much, if this is given in the adjuvant setting where you're trying to cure a person.

They've had surgery. They've had-- the cancer has been removed, and you can see that there's a risk of recurrence, and you're giving chemotherapy to try to decrease the risk of recurrence, what percentage benefit will it get if you go on to 12 cycles? Is that 1% additional benefit that the patient wouldn't get recurrence? Or is it 10%? Is it 5%? Is a 15%? So helping to sort that through, and then talking to the patient about that, and then making a decision. Do I continue on with the planned full dose of their chemotherapy?

The other aspect is what about treatment of a patient who is finished with their chemotherapy, and now they have the neuropathy? And, again, for some types of chemotherapy drugs, their neuropathy continues to get worse for about three months after you've did the last dose of chemotherapy. It's not because you stop the chemotherapy that it makes the neuropathy get worse. But it's rather, in my mind, that it takes three months to get full manifestations of the neuropathy for drugs such as oxaliplatin.

So in that setting, there is one drug that is a winner, if you will, called duloxetine. It does improve things statistically significantly. It doesn't improve them a whole lot. But it does work, and it's been shown in repetitive studies for that. So that's the one recommended approach there.

There are three things where there is suggestive evidence of benefit. And, again, exercise fits in that category. There is some suggestion that patients who exercise will get benefit and get improvement. There are some data that acupuncture will cause some improvement. And there are some data that something called scrambler therapy, a type of cutaneous neuro stimulation process will help decrease neuropathy in those situations. Again, for all three of them, the committee was unable to say yes, we-- was unable to say that we have scientific proof that these work. But there's suggestive evidence that they might provide some benefit.

So with these updated recommendations, in your view, what is the importance of this guideline and its relevance for practicing clinicians?

I think it's-- again, it's a big problem in practice for patients-- oncologists as they're seeing patients, and for the patients themselves, and to find what we do know works, and what we know doesn't work, and what we think might be helpful is helpful for patients. It's helpful for patients to hear this and know this.

It's helpful for physicians to be able to say, yes, we looked at all the data. There were 42 more studies, and most of them didn't show benefit, unfortunately. Here's the ones that did show benefit, and here's the ones that are suggestive evidence, or some things like exercise is probably a reasonable thing to go with. Even though it needs more study, it's probably a reasonable thing for people to do, because we don't exercise enough in this country.

And then finally, you've touched on this a bit, but how will these guideline recommendations impact patients?

I think that just kind of as we said. You know, whatever the doctors can understand better about it, the clinicians there, and then relate that back to the patients themselves is the best way. Is it possible for the patients, and there are some very bright patients out there who could read the medical literature and take a look at this and read it on their own? Yes. Sure. Why not? But that's how I think. Understanding-- getting the physicians to-- scientists to understand what we do know, and then getting that word on to the patients and their families in this setting.

Great. Well thank you for your work on this important guideline update and for taking the time to speak with me today, Dr. Loprinzi.

You're welcome.

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/survivorship-guidelines. This guideline also has a companion cancer.net podcast episode. Cancer.net is a patient information website of ASCO, and we encourage you to learn more by tuning into their episode.

You can find their podcast and all ASCO podcasts at podcast.asco.org. You can also find more ASCO 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.

Antiemetics Guideline Update Jul 13, 2020

Show notes

An interview with Dr. Paul J. Hesketh from Lahey Hospital and Medical Center in Burlington, MA on "Antiemetics: ASCO Guideline Update." This update addresses antiemetic prophylaxis in patients treated with checkpoint inhibitors and incorporates new data since the last guideline publication. Read the full guideline at www.asco.org/supportive-care-guidelines

TRANSCRIPT

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. Paul Hesketh from Lahey Hospital and Medical Center in Burlington, Massachusetts, co-chair of antiemetics, ASCO Guideline update. Thanks for joining me, Dr. Kesketh.

Hello, Brittany. I'm very happy to have the opportunity to join in today's podcast.

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. Hesketh, do you have any relevant disclosures directly related to this guideline topic?

No, I do not have any relevant disclosures.

So, Dr. Hesketh, what prompted an update to this an antiemetics guideline, which was last published in 2017?

Well, as you know, Brittany, each guideline panel is instructed by ASCO to regularly review the evolving literature and other information, looking for any significant developments that are relevant to that specific guideline. And since our last update in 2017, there has been a tremendous expansion in the use of checkpoint inhibitors for a variety of different neoplastic diseases. Although they're often used alone, increasingly, the checkpoint inhibitors were being added to a variety of chemotherapy regimens. And as this was occurring, concerns were being expressed by some oncologists that corticosteroids, a critical component of many antiemetic regimens, might be contraindicated when checkpoint inhibitors were being added to chemotherapy regimens given the potential immunosuppressive possibility for corticosteroids. So the panel felt that an update was indicated to try to address this issue as well as providing information on new antiemetics, antiemetic regimens, and to try to categorize the medic potential of the many new anticancer agents that have been approved since our last update.

Great. So you touched on a couple things there. So first, how does the guideline address antiemetic prophylaxis in patients treated with checkpoint inhibitors?

Well, the search that we conducted for this guideline found 10 relevant publication on checkpoint inhibitors. The search reaffirmed the panel's conclusion that all currently available checkpoint inhibitors really have minimal emetic potential when used as monotherapy. And really, no prophylactic antiemetics are required when an individual checkpoint inhibitor is used.

When used in combination with chemotherapy, two phase III trials were particularly instructive in helping to formulate our guidelines. Both trials were conducted in adult patients with non-small cell lung cancers treated with a platinum based doublet with or without the Program Death 1, PD-1 inhibitor pembrolizumab. And they recommended in both those studies that all patients receive dexamethasone as a component of the prophylactic antiemetic regiment. And of note, in both studies, superior efficacy outcomes were noted in the PD-1 inhibitor containing harms. Therefore, the panel feels that there is really no clinical evidence at present to warrant emission of dexamethasone from guideline compliant prophylactic antiemetic regiments when checkpoint inhibitors are administered to adults in combination with chemotherapy.

And then you touched on also antiemetic regimens that were updated. Given the new information about olanzapine, what recommendations were updated?

Well, olanzapine is a very interesting drug. It's a second generation antipsychotic which, very interestingly, has significant antiemetic properties. And the updated guidelines reaffirms the role of olanzapine as part of antiemetic prophylaxis when one administers highly emetogenic chemotherapy regimens. And it also can be very useful as a rescue agent in patients developing emesis despite appropriate prophylaxis.

So the new studies that were published since our last update have demonstrated the value of adding olanzapine to a 5-HT3 receptor antagonist, dexamethasone, and an NK-1 receptor antagonist used in the setting of high dose chemotherapy when used with hematopoietic stem cell transplantation. In addition, the prior recommendations only specified a 10 milligram dose of olanzapine as the only option. We now have data from an updated study that a 5 milligram dose is an acceptable alternative to the 10 milligram dose when used in the setting of highly emetogenic chemotherapy.

Great. Thanks for reviewing that information. So what in your view is the importance of this guideline for clinical practice?

Well, we have made really enormous progress in developing effective means to prevent treatment induced nausea and vomiting in patients with cancer. Each update of the guidelines, the current version included, have provided additional valuable insight for clinicians to help further limit the frequency of this potential side effect of cancer treatment. The most important aspect of the current update will be providing reassurance to clinicians that effective antiemetic prophylactic regimens do not need to be compromised when the new checkpoint inhibitors are administered in combination with emetogenic chemotherapy regiments. In addition to the new information on olanzapine, the update also notes the addition of useful new IV formulations of aprepitant and the combination agent netupitant and palonosetron. In addition, we have information on the use of fosaprepitant and as an option when an NK-1 receptor antagonist is indicated in the pediatric setting.

And then finally, how do you view that these recommendations will impact patients?

Well, we know from many patient surveys that treatment induced nausea and vomiting are among the most dreaded potential side effects that patients worry about when they think about starting cancer treatment, especially if they're going to be receiving chemotherapy. So fortunately, we now have extremely effective and well tolerated antiemetic regiments for all treatment settings. However, patients will only benefit if these evidence-based regimens are utilized in a manner consistent with the ASCO guidelines. So we hope that this guideline update will provide useful information for ecology providers to really optimize the prevention of nausea and vomiting in patients receiving various emetogenic type of treatment regimens.

Well, thank you so much for your work on this ASCO guideline update on antiemetics and for taking the time to speak with me today, Dr. Hesketh.

Thanks very much, Brittany. Happy to do so.

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 in iTunes or the Google Play store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

Treatment of Locally Advanced Esophageal Carcinoma Guideline Jun 22, 2020

Show notes

An interview with Dr. Manish Shah from New York Hospital Weill Cornell Medical Center on "Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline." This guideline provides evidence-based recommendations on treatment options for patients with locally advanced esophageal adenocarcinoma and squamous cell carcinoma. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines

Transcript

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. Manish Shah from New York Hospital Weill Cornell Medical Center, lead author on "Treatment of Locally Advanced Esophageal Carcinoma," ASCO guideline. Thank you for being here, Dr. Shah.

I'm so pleased to be here on this podcast for ASCO with you, Brittany. I'm very pleased to talk about this guideline and its significance to the oncologic community and to our patients.

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. But Dr. Shah, do you have any relevant disclosures that are directly related to this guideline topic?

No, I have no conflicts as it relates to this topic. I do have research funding from Merck, Boston Biomedical, Oncolys, BMS, and Acelis, and no other conflicts and nothing specific to locally advanced esophageal cancer.

Thank you. Then let's dive into this guideline. First, can you give us an overview of what this guideline covers?

Sure. This guideline covers the management of locally advanced esophageal cancer, both adenocarcinoma and squamous cell cancer, because management of these diseases is very complicated, primarily as the epidemiology of this disease has shifted over the past several decades. About 20 to 30 years ago, squamous cell cancers of the esophagus was the predominant disease subtype. About 90% of patients that we would see with esophageal cancer were of squamous cell histology.

However, with the rise in Barrett's esophagus and adenocarcinoma of the distal esophagus and GE junction, now, about 50% of esophageal cancers are adenocarcinoma histology. This distinction is important because, while the two diseases have significant overlap and treatment options, there are differences in sensitivity to various therapies. The guideline attempts to tease out these distinctions to provide the best evidence-based practice recommendations for the community.

Great. So you mentioned that this covers both adenocarcinoma and squamous cell carcinoma. So what are the key recommendations of this guideline for patients with locally advanced esophageal adenocarcinoma?

Sure. So for both squamous cell cancer and adenocarcinoma of the esophagus, locally advanced disease, the first and key recommendation is that multimodality therapy is considered and offered to both disease histologies. It's very important that these patients are treated through a multidisciplinary approach that involves a surgeon, typically a thoracic surgeon, but sometimes a general surgical oncologist as well, as well as a radiation oncologist and a medical oncologist.

For adenocarcinoma of the esophagus, which is really becoming the most common type, the primary recommendation is that patients with locally advanced esophageal adenocarcinoma receive either preoperative chemotherapy with radiation or perioperative chemotherapy. Because there is no comparative study for these two options, we also provide a clinical vignette to help readers understand some of the key features that may sway one to one treatment versus another.

For example, large bulky tumors where an R1 resection is more likely may be better suited for chemoradiotherapy, followed by surgery. An R1 resection, of course, is where the microscopic margin might still be positive. Additionally, patients who may not have a three-hole or a thoracic surgery as part of their surgical plan may not have an adequate lymph node dissection. That might be another reason to consider chemoradiotherapy, followed by surgery.

And what is recommended for patients diagnosed with locally advanced esophageal squamous cell carcinoma?

Yes. For squamous cell cancer, we recognize that these tumors are much more sensitive to radiotherapy. So the options that are recommended here, based on the evidence available, is that patients who receive preoperative chemotherapy and radiation or definitive chemotherapy and radiation, meaning chemotherapy and radiation with or without surgery. These are the recommendations for squamous cell cancer.

So why is this guideline important, and how will it change practice?

So we hope that our guideline will provide some clarity on a very murky field. The study suggests that there are several options available for patients with locally advanced esophageal squamous cell cancer and adenocarcinoma. And the guideline helps us frame the question and frame how we think about these options in offering patients the best practice that we can with regard to the available data. Additionally, the guideline may help define future research questions as well, as the gaps in knowledge are clear based on the guideline.

For example, there are patients, a significant number of patients, who have a complete response to chemotherapy and radiation. Should all of these patients have immediate surgery, or can surgery safely be delayed? That's an ongoing question that is being examined in rectal cancers. And also, there is some data in esophageal cancer as well. And that might be an important question to ask, moving forward, for example.

Great. And then finally, how will these guideline recommendations affect patients?

We hope that through the guideline process and understanding the nuances of how to treat patients with locally advanced esophageal cancer, that based on histology, based on the size and bulk of the tumor, based on the likelihood of an R1 resection, or based on even the surgical approach, that patients will receive more uniform therapy and therapy that is more tailored to their particular condition and situation. In the end, we hope that patients will receive the right care and ultimately have better outcomes because their care is more uniform.

It sounds like these guidelines could have a real impact for patients. So thank you for your work on these treatment of locally advanced esophageal carcinoma guidelines and for taking the time today to speak with me, Dr. Shah.

Thank you. It's a pleasure to be here.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. 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.

Management of Cancer Cachexia Guideline May 20, 2020

Show notes

An interview with Dr. Eric Roeland from Massachusetts General Hospital Cancer Center on "Management of Cancer Cachexia: ASCO Guideline." This guideline provides evidence-based recommendations on the clinical management of cancer cachexia in adult patients with advanced cancer. Recommendations are made on both pharmacologic and nutritional interventions. Read the full guideline at www.asco.org/supportive-care-guidelines

My name is Brittany Harvey, and today I'm speaking with Dr. Eric Roland from Massachusetts General Hospital Cancer Center. Lead author on Management of Cancer Cachexia, ASCO Guideline. Thank you for being here, Dr. Roland.

Well thank you very much.

Before we get into the content of this guideline, I want to note that all conflict of interest disclosure information for the expert panel is available online with the publication of the guideline in the Journal of Clinical Oncology.

Dr. Roland, do you have any conflicts of interest to disclose?

Yes, within the last two years, I've served as a consultant for Asahi Kasei Pharmaceuticals, DIG Consulting, Napo Pharmaceuticals, American Imaging Management, Immuneering Corporation, and Prime Oncology. I've also served on advisory boards for Herron Pharmaceuticals and Vector Oncology. And I serve as a member on the Data Safety Monitoring Boards for Oragenics, Kalyra Pharmaceuticals, and [INAUDIBLE] Life Sciences Pharmaceutical Company.

Thank you. Then first, can you give us a general overview of what this guideline covers?

Sure. We performed a systematic review of the literature regarding available evidence for nutritional and pharmacologic interventions for cancer cachexia. Specifically, we searched PubMed and the Cochrane Library for randomized controlled trials and systematic reviews published between 1966 in 2019. We focused our review on adult patients with advanced or incurable cancer. And given the highly variable nature of cancer cachexia, we specifically evaluated the endpoints of loss of appetite or anorexia, body weight, and lean body mass, or skeletal muscle. Our targeted audience included clinicians as well as patients and caregivers.

Can you provide us with a little background on cancer cachexia?

Yes, first I think it's incredibly important for us to define cancer cachexia, especially given its prevalence in cancer care. Traditionally, cancer cachexia has been defined as a certain amount of weight loss over a defined time period. However, cachexia is much more complicated than weight loss alone. It is a multifactorial syndrome characterized by loss of appetite, weight, and skeletal muscle, which leads to fatigue, functional impairment, increased treatment related toxicity, poor quality of life, and even reduced survival. And as clinicians, we need to try to identify any reversible causes contributing to cachexia and treat them. This of course, includes treating the underlying cancer when possible.

Additionally, it's essential for patients to receive optimal palliation of all symptoms that may be interfering with the intake of calories, such as pain, nausea, vomiting, constipation, diarrhea, and depression. Therefore, as clinicians, we need to work in teams of experts that might include expertise in pain, palliative care, nutrition, physical occupational therapy, and mental health where available.

We also need to introduce and discuss the term, cachexia, with our patients and their caregivers, who often have never heard of it before. They may not understand that this term is unique and very different from weight loss alone. I personally have found that describing the unique nature of cachexia and providing the information to patients and caregivers can be very helpful.

Additionally, we need to recognize that food is a very complicated issue. And when we engage patients and caregivers around issues of food, we need to recognize that there are informational needs, but there are also emotional needs. And as clinicians, we help patients and caregivers gain access to evidence based information and interventions, but we equally need to ensure that they receive emotional support. Food represents hope and control in an uncontrollable situation. And not being able to eat or feed a loved one can cause severe distress.

Therefore, we need to engage patients and caregivers regarding these emotional issues and make sure they feel heard. We can also reach out to our mental health colleagues, such as social workers and psychologists, who may help us support patients and caregivers in this difficult issue.

Then, what are the key recommendations covered in this guideline?

With regard to our systematic review, we identified 20 systematic reviews and 13 additional randomized controlled trials. And from this data, we made the following recommendations. First, we found limited data supporting the integration of dietary counseling with or without oral nutritional supplements. However, given the lack of harm and the critical role of educating patients and caregivers, we felt it was important to support referring patients with incurable cancer and loss of appetite and/or body weight to registered dietitian for assessment and counseling.

It's critical for patients and caregivers to learn about practical and safe approaches to feeding. Specifically, registered dietitians may help develop strategies, such as shifting away from three larger meals per day towards frequent high protein, high calorie, nutrient dense snacks. Dietitians can also address questions regarding specific diets, including fad diets and unproven or extreme diets.

Moreover, clinicians should not routinely offer enteral tube feeding or parenteral nutrition to manage cachexia in patients with incurable cancer. A short term trial of parenteral nutrition may be offered to a very select group of patients, such as patients with a reversible bowel obstruction, or short gut, or issues with malabsorption, but otherwise reasonably fit. We also can consider discontinuing previously initiated enteral parenteral nutrition near the end of life, as it is associated with net harm at that time.

With regard to pharmacologic interventions, there are no FDA approved drugs to treat cancer cachexia. Yet there is sufficient data to support two pharmacologic interventions associated with improvements in appetite and/or body weight. And these include progesterone analogs, such as megestrol acetate and corticosteroids. The optimal dose and timing of each drug remains unknown.

Regarding megestrol acetate, data support its role in improving appetite, modest weight gain, and improvement in quality of life. However, the weight gain associated with megestrol acetate is primarily fat and not skeletal muscle. We also need to be aware of side effects of megestrol acetate, including an increased risk of thromboembolic events, edema, adrenal insufficiency, and even an increased risk of death.

As for corticosteroids, the first published double-blind randomized study dates back all the way to 1974, which showed an improvement in appetite and sense of well-being. However, clinicians are aware of the multiple side effects associated with corticosteroid use, that often limit initiation and timing of their use. Additionally, the weight gain associated with corticosteroids is not skeletal muscle.

As important as it is to know what drugs are evidence based, it is also important to note what pharmacologic approaches are not supported by evidence. There are many agents that have been evaluated in clinical trials without any evidence to support an improvement in cancer cachexia outcomes.

One such drug that frequently is asked about is dronabinol or the general class of cannabinoids. Insufficient data was available to recommend dronabinol or medical cannabis, and they have notable side effects, including altered mental status and a higher risk of falls. Especially in the elderly.

Why is this guideline important? And how will it impact practice?

Cachexia is a very common clinical entity and causes lots of distress for patients and caregivers. Oftentimes, the issues regarding nutrition and weight loss can be the central focus of clinical appointments and conversations with oncologists. We need to ensure that patients and caregivers have access to evidence based information and recognize that some interventions may be associated with more harm than benefit.

And finally, you've just spoken to this a bit, but how will these guideline recommendations affect patients?

Primarily, I think these cancer cachexia guidelines will serve as a great educational resource. They will also allow patients to better understand the risks associated with some of the pharmacologic interventions. I also think it's critical to define the current state of evidence in cancer cachexia, as we have many new exciting clinical trials evaluating novel agents in the setting.

Furthermore, as a cancer community, we need to ensure that interventional trials are focused on clinically meaningful endpoints, such as improvements in appetite, muscle mass, and quality of life. We also need to encourage a rigorous but expedited approval of these agents, given the lack of any FDA approved drugs in this setting.

Lastly, we need to recognize this is a multi-modal syndrome that requires the help and expertise of our interdisciplinary colleagues. Supporting our patients and their caregivers with this very difficult syndrome requires as much help as possible.

Great. Thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Roland.

Thank you so much, Brittany. I would also like to recognize and thank ASCO for its support of these guidelines, the talented ASCO staff, and the experts who contributed. Most of all, I'd like to recognize our patients and their caregivers.

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-cancer-guidelines.

This guideline also has a companion, cancer.net podcast episode. Cancer.net is the patient information website of ASCO. And we encourage you to learn more by tuning into their episode. You can find their podcast and all ASCO podcasts at podcast.asco.org. 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.

Lung Cancer Surveillance After Definitive Curative-Intent Therapy Guideline May 07, 2020

Show notes

An interview with Dr. Benjamin Levy from Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital on "Lung Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline." This guideline provides recommendations to clinicians on radiographic imaging and biomarker surveillance strategies after definitive curative-intent therapy in patients with stage I-III non–small-cell lung cancer and small-cell lung cancer. Read the full guideline at www.asco.org/thoracic-cancer-guidelines

Transcript

Hi. My name is Clifford Hudis, and I am the CEO of the American Society of Clinical Oncology, as well as the host of the ASCO in Action podcast. About twice a month, I interview thought leaders in health care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues. You can find the ASCO in Action podcast on Apple Podcasts or wherever you are listening to this show, and you can find all nine of ASCO's podcasts which cover a wide range of educational and scientific content, and offer enriching insight into the world of cancer care at podcast.asco.org.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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. Benjamin Levy from Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, author on "Lung Surveillance After Definitive Curative Intent Therapy ASCO Guideline." Thank you for being here, Dr. Levy.

Thanks for having me.

So first, can you give us a general overview of what this guideline covers?

Yeah, I think that the general broad stroke intent of this consensus paper was to provide evidence-based guidelines and recommendations for practicing clinicians on what the optimal radiographic imaging and biomarker surveillance strategy should be for patients who received definitive curative intent therapy, and specifically for patients with stage I through III non-small-cell lung cancer, or patients who have received curative intent therapy for a limited-stage small-cell lung cancer.

And importantly, this expert panel comprised a multidisciplinary team, and this included not only medical oncologists, but surgical oncologists, pulmonologists, radiologists, a general internist, a patient representative. So we had, I think, the relevant stakeholders to make the best recommendations we could based on the evidence. And we really framed our recommendations by answering five questions, and I think we can get to the five questions at a later time during this cast, but we try to answer these five questions in a systematic way. And really looked at the type-- was an evidence-based or was it informal consensus? What was the evidence quality? Was it low, was it intermediate, or was it high? And then finally, the strength of the recommendation.

And importantly, we tried to answer these questions based on the evidence. We did a literature search, which culminated in a systematic review of more than-- close to 1,200 studies of which 14 studies were identified, and these 14 studies included meta-analysis, randomized control trials, case-controlled trials, and retrospective studies, and really by doing this, we wanted to come up with important guidelines. I think these guidelines are coming on the heels of a lot of confusion about what is the optimal surveillance strategies post-curative intent therapy for our lung cancer patients? So we recognize this confusion and tried our best to create guidelines that were reasonable to follow, and hopefully it can change practice.

Great. So you just mentioned that there were five key questions that you looked at for this guideline.

Yeah.

Could you elaborate on what those questions are and the key recommendations of the guideline?

Sure. So the crux of our recommendations, again, come on these five questions, and just a summary of these questions. One, what should be the frequency of surveillance imaging post-curative intent therapy? Two, what is the optimal imaging modality? Three, are there any patient factors such as performance status or age limits that would preclude surveillance? Four, is there a role for circulating biomarkers and surveillance? And then five, is there-- or what is the role of brain MRI imaging for surveillance of curative intent patients both non-small cell and small-cell?

And just briefly in terms of-- I'll maybe go over briefly just the answers to these questions that we tried to hash out in this consensus work-- for the question, what should be the frequency of surveillance imaging? We recommended that patients should undergo surveillance imaging for recurrence every six months for two years. We then recommend that patients should undergo surveillance imaging for detection of new primary lung cancers annually after the first two years.

And in question 2, what is the optimal imaging modality? We recommended a diagnostic chest CT that included the adrenals with contrast, that's preferred, or without contrast when conducting surveillance for recurrence during the first two years post-treatment. We did state that there was no evidence of any added benefit for CT of the abdomen and pelvis over a chest CT through the adrenals, that surveillance. We then, again, similar answer to recommendation 1, we do recommend a low dose screening for chest CT when conducting surveillance for new lung primaries after those first two years. And then I think importantly, we take a hard stand on PET scans as part of the answer to question 2, where we really should not be using PET scans as a surveillance tool in the surveillance starting post-curative intent therapy.

Question 3, are there any patient factors such as performance status or age limits that would preclude surveillance? And for us, we make the recommendation that surveillance imaging may be permitted in some patients who are clinically unsuitable, have multiple medical comorbidities, or unwilling to undergo further treatment. Doesn't make a lot of sense to offer surveillance imaging if patients are stating that they're not going to undergo any further treatment. We also state that age should not preclude surveillance imaging, but there needs to be a consideration for overall health status and chronic medical conditions and patient preferences.

Question 4 was, is there a role for circulating biomarkers in surveillance? And this is probably one of the more confusing parts of surveillance. Many physicians are still using CEA to monitor for a recurrence, and we really take a hard stand and say that clinicians should not be using circulating biomarkers as surveillance strategy for the detection of recurrence in patients who've undergone curative intent treatment, but we also do state that there is emerging data looking at ctDNA that may change this over the next four or five years, but we're certainly not there yet. So standard of care should not be-- to be using anything like that.

And then question 5 is, are there-- or what is the role for brain MRI for surveillance in patients with both non-small-cell and small-cell? And our recommendations are a little nuanced here. We did say for patients with stage I through III non-small-cell lung cancer, clinicians should not be using a brain MRI for routine surveillance after curative intent therapy, and patients who have undergone curative intent treatment for small-cell and did not receive prophylactic cranial radiation, this is where we do say clinicians should offer a brain MRI every three months for the first year and then every six months for the second year for surveillance. So a little bit different surveillance strategies for patients whether you're small-cell or non-small-cell.

So those are the broad stroke overviews of the recommendations that we put together in this consensus statement.

And then can you speak to the importance of this guideline and these recommendations and how they will impact practice?

I think that ASCO recognized how much confusion there was post-curative intent therapy. So I think this is the reason why these guidelines are so important. We need to keep in mind that health care resources that are utilized and be mindful of that. There's no real role for routine imaging less than the intervals that we're describing as they may obviously not be in touch with health care utilization and cost.

The other thing is this idea that patients are getting scans so frequently that we're picking up on a lot of false positive information that can't be used, and so we recognize that as well. So I think that on the heels of the confusion coupled with cost considerations, as well as what we're picking up on frequent scans, we do have to make recommendations that will hopefully unify and harmonize practice across the country to better suit patients and also evidence-based practice. I think that's really important.

And finally, how will these guideline recommendations affect patients?

Yeah, I think patients hopefully, if physicians follow these guidelines, will be receiving the appropriate interval. I mean, look, we understand that two-thirds of patients with lung cancer who relapse will present with metastatic disease and that there have been limited data thus far on what should be the optimal interval for scans. But we understand also that patients who do relapse could present with potentially curable lung cancer, and in addition, there's been recent data to suggest that even patients with limited metastatic disease who was detected on recurrence may be cured or may have improved survival with certain strategies like local ablative therapy.

So we hope that these guidelines can be firmly cemented into the practice for clinicians so that the appropriate interval is selected, but that also patients can benefit from these appropriately timed-out scans to improve outcomes for them.

Great. Thank you for your work on these guidelines, and thank you for taking the time today to give an overview to our listeners, Dr. Levy.

Thank you so much.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/thoracic-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 have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Guideline Apr 23, 2020

Show notes

An interview with Dr. Jessica Geiger from Cleveland Clinic on "Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline." This guideline provides evidence-based recommendations addressing diagnosis, surgery, radiation therapy, and systemic therapy for patients with squamous cell carcinoma of unknown primary in the head and neck. Read the full guideline at www.asco.org/head-neck-cancer-guidelines.

Transcript

[MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

[MUSIC PLAYING]

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. Jessica Geiger from Cleveland Clinic, author on Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck ASCO guideline. Thank you for being here, Dr. Geiger. Thanks, Brittany, for the invitation and the opportunity.

First, can you tell our listeners what is squamous cell carcinoma of unknown primary in the head and neck and what this guideline generally covers?

Sure. So cancer of unknown primary or carcinoma of unknown primary in the head and neck is metastatic squamous cell carcinoma found in cervical lymph nodes. And importantly, there's a lack of a primary mucosal tumor that's identified. So these patients comprise about 5% of all head and neck cancers. And it poses a challenge for all members of the treatment team, both from a diagnostic perspective but as well as treatment management; what is the best way to proceed for treatment with these patients? Now this guideline provides an up-to-date and evidence-based management for recommendations. And these recommendations are based on published literature. But where the data is lacking in the literature, expert panel consensus was utilized to provide recommendations. I'd like to discuss some of the key recommendations of this guideline. First, with regard to diagnosis of squamous cell carcinoma of unknown primary in the head and neck, what are the challenges, and what are the recommendations from the guideline?

The diagnostic challenges come about when a patient presents with a neck mass. They often have imaging, a clinical exam. But again, about 3 to 5 percent of patients, we will be unable to locate where this tumor started. Squamous cells don't show up in the lymph nodes by themselves. They came from somewhere else. And part of the reason that this makes a diagnostic challenge if we're not able to readily see where the primary tumor is, oftentimes, it's very small in size. And so it's not picked up by imaging or by a physical exam. Also, these are sometimes difficult anatomic locations to evaluate. So all of this can pose a challenge to coming up with the right diagnosis. Now some of the recommendations for diagnosing these patients, obviously, we need to have a complete history and physical exam. And this physical exam should include a fiberoptic laryngoscopy, so a good lab endoscopy exam looking at all of the mucosal tissues, trying to find abnormalities, trying to see where exactly this cancer started. Now in order to make the diagnosis of squamous cell carcinoma, obviously, a biopsy needs to be done, and that is in the neck, where these suspicious nodes are. Either a fine needle aspiration or a core needle biopsy is recommended within these guidelines. The guidelines also indicate when to do additional pathologic testing. So this is for high-risk HPV, especially in neck nodes that are in level two or three. If high risk HPV testing is negative, then we give recommendations regarding Epstein-Barr virus testing, so looking to find is this nasopharynx primary cancer and then, of course, imaging guidelines. So the image modality of choice is a contrast enhanced CT of the neck, not just to elucidate and better evaluate the nodal burden of disease, which the patient presents with, but also to investigate for evidence of a mucosal primary. Now if that fails to produce a primary then we give recommendations regarding PET scans.

And then what are the recommendations for surgery for a squamous cell carcinoma of unknown primary in the head and neck?

There are many recommendations that we go into to address the surgical approach to a cancer with unknown primary. Now the previous question asked about diagnosis included in the surgical recommendations in our guidelines for diagnostic surgical interventions. So we can sort of branch point or divide recommendations for surgery, whether it's a diagnostic or a therapeutic procedure. And then in the therapeutic procedures, we can look more in detail at what surgery is recommended for a primary or the mucosal, and then how to how do we address the neck? So first, as part of diagnosis with surgery, all patients need a complete operative evaluation of the upper aerodigestive path. And this includes directed biopsies. So the surgeon goes in the operating room, gets a good look around. Any suspicion for any possible cancer is biopsied, as opposed to blind biopsies or random biopsies, which are not recommended.

Now the recommendations for surgery also include when to do tonsillectomies and what tonsillectomies to do. So are these palatine tonsillectomies or lingual tonsillectomies? Do we perform them or recommend them on the ipsilateral side, or what is the role for a contralateral or even bilateral tonsillectomy? And I won't go into the specifics because they're all-- all the different scenarios are laid out within the guidelines, but the recommendations are based on the patient's nodal burden. So do they have bilateral lymph nodes; do they have lymph nodes just on one side; how big they are, that all plays a role into the recommendations regarding surgical intervention. Now if mucosal primary tumor is identified, there are clear recommendations and guidelines that every effort to clear the disease with negative margin is of paramount importance. So we're talking about a definitive oncologic surgery in this case. And the reason we want to stress that negative margins are the goal is because we're trying to avoid trimodal therapy. So we're trying to get to a good surgical resection. A positive margin left behind is likely going to lead to recommendations for postoperative radiation with the addition of radiosensitizing chemotherapy, which is what we do not want. We want to try to avoid toxicities with trimodal therapy.

That brings me to then surgical management of the neck and the guidelines set forth in this document. So recommendations for neck surgical management are broken into whether the patient has what we consider small volume disease versus large volume disease. So for small volume disease, small lymph nodes on one side of the neck, we recommend a multidisciplinary discussion whether or not the patient should be best served with a definitive surgery involving a neck dissection or if they should have definitive radiotherapy. Again, our goal is to avoid trimodal therapy. So if there's obvious gross extranodal extension seen on imaging, then they would be best served with a primary radiation approach, as opposed to surgical. Similarly, any large volume disease, obviously, gross extranodal or extracapsular extension, definitive chemo radiotherapy is favored. Now a comment on management of the neck, if you're suspecting an oropharynx primary, which is the majority of cancer of unknown primaries of the head and neck, we give specific recommendations regarding what levels to routinely surgically dissect, levels IIa, III, and IV in that instance.

In your discussion of the surgical recommendations, you began to touch on the radiation recommendations. Could you elaborate on those recommendations from ASCO on radiation therapy for this patient population? Of course. And again, when you refer back to the guideline and the recommendations, there are even more specific recommendations regarding when and how to use primary radiotherapy or adjuvant radiotherapy in this setting. So I'm not going to go into great detail for every single recommendation that is provided, but a nice overview is, basically, if a patient is receiving radiotherapy as the primary definitive management of cancer of unknown primary, obviously, we recommend treatment should be given to gross nodal disease but also to neck regions and mucosal anatomic regions, which are considered at risk for containing microscopic disease. So it's not just good enough to radiate what we see on imaging but also to consider the areas around it, the nodal echelons and other mucosal areas where there could be cancer. So for example, an HPV-related disease where it's likely oropharynx unilateral disease, there are specific locations to include. And this is also the same for HPV-negative disease. Now if we're worried about a possible nasopharynx cancer in the setting of E-Barr or EBV-positive disease, the mucosal radiotherapy can be limited to just the nasopharynx, but you want to radiate bilateral necks, level II through IV, and include the retropharyngeal lymph nodes.

There are specific recommendations where unilateral versus bilateral neck irradiation is recommended. And again, I just encourage the listeners to refer back to the guideline itself for these specific instances. Also included within the radiotherapy guidelines and recommendations are specific doses. What doses do you use? Where do you use these doses? And these doses are extrapolated from known and well established evidence for traditional head and neck squamous cell carcinoma in which we know where the primary is, also, when to give post neck dissection kind of in the adjuvant setting, again, all extrapolated from known head and neck squamous cell carcinoma but very specific and laid out within the guidelines.

And what does the expert panel recommend for systemic therapy for squamous cell carcinoma of unknown primary in the head and neck?

Similarly, when we devised the recommendations for radiotherapy for this disease, the use of systemic therapy, when to use it, when to add it to radiation is also extrapolated from the head and neck guidelines and evidence for known head and neck cancer. So we recommend adding chemotherapy to definitive radiotherapy in advanced nodal disease, and we've defined what advanced nodal disease is based on the AJCC 8th Edition. So in HPV-negative disease, this is N2 or N3, in HPV-positive disease, multiple ipsilateral lymph nodes. If a lymph node is greater than three centimeters, we recommend adding chemotherapy to radiation in the definitive setting. Now, specifically, the chemotherapy that we recommend is cisplatin. Again, this is based on well-established studies and evidence in head and neck cancer. So patients who are medically fit and able to receive cisplatin, that is the treatment of choice. There are also recommendations regarding resected cancer of unknown primary. So with evidence of extranodal capsular extension, we recommend the addition of, again, cisplatin chemotherapy to postoperative radiotherapy, again, extrapolated from well-established head and neck studies. And then, again, if you are concerned that this is an Epstein-Barr-related nasopharynx cancer, stages II through IVA, again, AJCC 8th Edition, we recommend the addition of chemotherapy to radiation in those settings as well.

Great. This guideline covers a lot of ground and many recommendations. Can you speak to why this guideline is important and how you envision it will impact practice? So this guideline is important because a fair amount of patients will be presenting with cancer of unknown primary. We stress through this guideline that this is very evidence-based recommendations and guidelines with a focus on a multidisciplinary approach to how to treat these patients.

And finally, how will these guideline recommendations affect patients?

Well, hopefully, this guideline will provide reassurance to patients that no matter where they are receiving treatment, they are receiving quality standard of care management, again, largely driven by evidence. And it doesn't matter whether they're treated by locally practicing experts and specialists or at a large institution, they're being treated by the standard of care that is accepted across the board.

Well, thank you for your time today, Dr. Geiger, and for working on these comprehensive guidelines. You're very welcome. Thanks, Brittany.

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 and iTunes or the Google Play Store. If you have enjoyed what you've heard today, please write and review the podcast and be sure to subscribe so you never miss an episode.

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