ASCO Guidelines

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Patient-Centered Standards for Medically Integrated Dispensing: ASCO/NCODA Standards Dec 09, 2019

Show notes

An interview with Dr. Melissa Dillmon on the Patient-Centered Standards for Medically Integrated Dispensing: ASCO/NCODA Standards. The interview covers the findings of the systematic review, which were consistent with the NCODA patient-centered standards for patient relationships and education, adherence, safety, collection of data, documentation and other areas. NCODA standards were adopted and used as basis for these ASCO/NCODA standards. Additional information is available at www.asco.org/mid-standards.

Management of Osteoporosis in Survivors of Adult Cancers with Nonmetastatic Disease Guideline Sep 18, 2019

Show notes

An interview with Dr. Charles Shapiro from Mount Sinai Hospital in New York and Dr. Joan Neuner from Medical College of Wisconsin, co-chairs of "Management of Osteoporosis in Survivors of Adult Cancers with Nonmetastatic Disease: ASCO Clinical Practice Guideline." This guideline includes recommendations on assessing risk factors and interventions, including pharmacologic and nonpharmacologic options. Read the full guideline at www.asco.org/survivorship-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 healthcare 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.

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 of the shows, including this one, at podcast.asco.org. My name is Shannon McKernin and today on the ASCO Guidelines Podcast, I'm interviewing Dr. Charles Shapiro from Mount Sinai Hospital in New York, and Dr. Joan Neuner from the Medical College of Wisconsin, Milwaukee, co-chairs of management of osteoporosis in survivors of adult cancers with non-metastatic disease ASCO clinical practice guideline. Thank you for being here, Dr. Shapiro and Dr. Neuner.

Thanks a lot.

Pleasure to be here.

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

This guideline covers very important topics, that of osteoporosis and that of cancer survivorship. It's the coalescence of these two common problems that is the impetus for this guideline. It covers risk factors and what you can do as a cancer survivor to mitigate your risk. It covers screening and identification of the best test to use to measure your bone density, and it covers how to treat or pull the trigger for anti-osteoporosis drugs based on the guidelines that are contained within the document.

And what are the key recommendations for this guideline?

So we developed this guideline with three key guideline questions in mind. And they really required a fairly extensive search of the literature to address them. And we did that by looking to some of the literature outside of cancer in osteoporosis screening in other patients as well. So I'll sort of talk about it in terms of the three key questions. So the first question we had was, which patients with non-metastatic cancer are at increased risk for developing osteoporotic fractures? So that first question was, which patients are we really addressing in this guideline? And how do we assess whether they're at potentially increased risk? So in response to that, we strongly recommend that oncologists teaming with other physicians, including primary care doctors like myself, evaluate their patients to determine whether they're high risk. And so we provide a lot of details in an extensive document. But in our bottom line, we have a summary of the most common and the most severe risk factors. And those include things like advanced age, current smoking, excessive alcohol consumption, and a history of prior fractures, so already showing that they're at high risk for fractures. So we recommend you look to that list. And then add in your own clinical judgment, particularly about patients who have added risks from their cancer treatments. And so we do also talk about those patients. And in particular, we call out patients with specific anticancer therapies, for example, aromatase inhibitors given to breast cancer patients, antiandrogens or GnRH agonists given to breast cancer and prostate cancer patients and call out how they're at particular risk. And finally, in response to this question, we also recommend that you consider using a risk assessment tool. And here, I mention that we had to look to the non-cancer literature. So here, the WHO actually developed something called the Fracture Risk Assessment Tool, or FRAX. And we do recommend that you use this tool or something like it to help you to assess whether your patient is at high risk. And those are readily available on the web. Search FRAX-- F-R-A-X-- to use it. And, of course, we have links in the guideline. So that addresses the first question, which again was, which patients are at increased risk? And we have a list of risk factors that you should be considering and some references, particularly FRAX, to help you with thinking about those risk factors and how important any specific risk factor is. Our second question really dovetailed right on that. And that was, how should patients who are at increased risk, you've identified as part of that first question, to be at increased risk for osteoporotic fractures be screened? And here again, we look to the standard recommendations for patients who don't have cancer as well. And there are two ways that you could move towards, should you screen your patient or not? One could be your patient had one of those risk factors that we talked about and are listed in the document. The other is you use that FRAX tool and patients are more than average risk. And then we recommend patients be screened using one of the standard screening tools. The most common one, is called dual X-ray absorptiometry. And I want to specifically mention central dual X-ray absorptiometry, which means that the test is done on the hip and the lumbar spine. Those are readily available. All major medical centers have them, and many clinics have them as well. And so we do recommend that for screening. And then we offer some specifics about how frequently you might screen, because that's another question that often comes up. And so then our final question is once you determine that your patient is at high risk because their bone density test and/or their FRAX test shows that patients are at high risk, we do encourage talking to them about treatment options. And the first thing I want to say is essentially everyone that our guideline addresses, which is all patients who currently have or who are survivors of non-metastatic cancer, that they should consume a diet with adequate calcium and vitamin D. And so that's generally considered to be 1,000 to 1,200 milligrams of calcium and at least 800 to 1,000 IUs, international units, of vitamin D. We also strongly recommend exercises and call out some specifics. That you want to work on balance, flexibility, and resistance, if possible. And that you quit smoking and limit alcohol consumption. All very good things for the body generally, but also very good for the bones. Obviously, the meat of this guideline is also about pharmacologic intervention specifically. And since Dr. Shapiro treats so many patients with this, I'm going to ask him if he wants to comment further on specifics about pharmacologic treatments, when you think patients should get them.

So thanks, Joan. So pharmacologic interventions include RANK ligand inhibitors, like Denosumab or IV or oral bisphosphonates. So clearly, if your patients are at risk, that means a hip fracture predicted at 3% or more or a non-hip vertebral fracture at 20% or more-- and you get these numbers from the FRAX calculator and other calculators in common usage-- then you pull the trigger and use one of these agents. Now we couldn't distinguish between the agents in terms of what's one was preferred. It depends on patient preference, comfort with the doctor in terms of how comfortable the doctor is using the agent, and other factors that go into the decision about which biphosphonate to use. Generally, the IV Zoledronic Acid and sub-cu Denosumab are used in the cancer populations. But oral biphosphonates can be used as well.

And why is this guideline so important? And how will it change practice?

Well, this guideline is so important because we know from survey studies that osteoporosis and preventing osteoporosis and treating osteoporosis in the cancer survivor population is underutilized. And this is an important point, because many people, especially with breast and prostate cancer and colorectal cancer and bone marrow transplants, will be long-term survivors. And we don't want to cure a patient just to have them fracture 10 or 20 years later. So that's the importance of the guideline. So it's the recognition that osteoporosis is treated the same, whether you're a cancer survivor or not. But the cancer treatments we use in routine practice can cause osteoporosis and bone loss. And that's the importance of this recommendation, as well as the particulars of who's at risk, the risk factors, screening, and pulling the trigger for treatment. So that's basically in a nutshell, why this guideline is so important and how it will change practice, because we hope that the guideline stimulates us, as health practitioners, to screen our patients for osteoporosis, recognize risk factors, and how to pull the trigger on treatment to prevent or treat osteoporosis in this population. It doesn't matter who follows patient, but the patient has to know who's going to follow the bone density and treatment for osteoporosis, whether it's comfort that an oncologist has with the whole process of screening and risk factors and pulling the trigger for bisphosphonates or Denosumab or endocrinologists, the rheumatologist, the primary care physician. The patient's got to know who's going to be responsible for what aspects of care, survivorship care. And this is a big part of survivorship care. So the treatment summary, which is a document that the patients get and is given to the primary care provider, should specify who will take responsibility for what aspects of survivorship care. And this is a big aspect of survivorship care, osteoporosis screening and treatment, if necessary. So it doesn't matter who does it, as long as it gets done.

I would jumped in if I could, Charlie.

Yes, so please jump in.

So I guess the only other point that I wanted to make about how it might change practice is osteoporosis guidelines have been out since the late '90s, early 2000s. And so many patients probably have thought about osteoporosis and their risk in the past. But I did want to note that there have been a number of studies in the last five years showing that in primary care-- so family medicine and general internal medicine, like I practice-- that we're actually ordering fewer bone densities than we did in the past. And all the reasons for that aren't clear. Perhaps it's because of some concerns about the rare side effects of some of these medicines. Perhaps it's because the guidelines aren't clear because the data is not clear about how often we should test people who don't seem to be at high risk once they've had a first test. But nonetheless, there seems to already be some effects of this that the hip fractures, which had been decreasing are starting to look like they're rising again.

So it really is important then if we're not going to screen very frequently everybody, that we are screening the people who really need it. And so then this guideline it calls that out that these are patients who because either their cancer treatment and the debilitating nature of that in some cases or the specific medications puts them at particular risk. Those are the ones that we can't omit this.

Great. Finally, how will these guideline recommendations affect patients?

You know, I think we're hoping that this will help in the care of cancer survivors and spark people to use things like survivorship care plans. Or if those don't work in your institution, other ways to make clear what the patients who are survivors are at risk for, both related to their cancer and outside their cancer, so that we can all work as teams of health care providers to make sure all of the things on those lists addressed. So we're hoping that with some very clear recommendations about how to address bone health that we can help those teams serve patients that they can. Obviously, it can also provide some really essential information for patients who are wondering what the things that need to be wondering about in this new phase of survivorship after cancer that they're dealing with.

Dr. Shapiro, did you have anything to add to that question?

Hopefully, we can prevent fractures in our cancer survivors by following these guidelines. It's really important that we prevent osteoporosis and hip fractures and vertebral fractures, because we don't want to cure the patient just that saddle them with osteoporosis and breaking a hip or breaking vertebral body 10 or 20 years down the line. So this will hopefully affect patients positively. And we intended the guideline to be for patients in terms of risk factors. And if you need a biphosphonate or anti-osteoporosis drug, then it's clear indications in the document who gets it and who doesn't. So I think that the effect we hope would be great on patients, that part of general health is osteoporosis screening. And just because you're a cancer patient doesn't absolve you from participating in all the health recommendations, including osteoporosis screening.

As with all ASCO Survivorship Guidelines, we do hope that this one informs many conversations between patients, survivors, and providers. Thanks to your overview here today and your work on this guideline, more clinicians will be informed of the risk factors and possible interventions for osteoporosis and survivors of non-metastatic cancers. So I want to thank you both for coming on the podcast to discuss this guideline with me today.

Thanks for having us.

Yes, thank you.

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. And if you've enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe, so you never miss an episode.

Use of Endocrine Therapy for Breast Cancer Risk Reduction Guideline Sep 03, 2019

Show notes

An interview with Dr. Kala Visvanathan from Sidney Kimmel Comprehensive Cancer Center, and Johns Hopkins Bloomberg School of Public Health on the guideline update. This update adds anastrozole to the options of pharmacologic interventions for breast cancer risk reduction based on recent practice changing data. Read the full guideline at www.asco.org/breast-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.

Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Kala Visvanathan from the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, and Johns Hopkins Bloomberg School of Public Health, co-first author on "Use of Endocrine Therapy For Breast Cancer Risk Reduction: ASCO Clinical Practice Guidelines Update." Thank you for being here, Dr. Visvanathan.

Thank you as well for having me.

So can you tell us about the phase III randomized trial, which provided the signal for this update?

Yes. This was the IBIS-II trial that was reported out by Cuzick, et al in 2014. It was a double-blind, randomized placebo-controlled trial that assessed the safety and efficacy of Anastrozole, the aromatase inhibitor Anastrozole, at 1 milligram per day for five years. And the primary endpoint was the reduction of the incidence of breast cancer in postmenopausal women at increased risk of developing breast cancer. The trial itself was reported out with a median follow up of five years and the intention-to-treat analysis actually revealed that 85 women in the placebo group and 40 women in the Anastrozole group had developed both invasive and noninvasive breast cancer. What it showed was that there was a reduction in the incidence of breast cancer of 53% overall. It included both invasive and non-invasive breast cancer after a seven-year followup. And importantly, in subgroup analysis, similar to the other hormone endocrine therapy prevention trials, it also showed that the reduction in breast cancer risk among invasive cancers was limited to those individuals with ER-positive and PR-positive tumors. And the reduction in breast cancer incidence was among hormone-positive breast cancers. Another interesting point to mention here was that the five-year adherence was only slightly less in the Anastrozole arm compared to placebo. So it was well tolerated. And that was 68% in the Anastrozole group compared to 72% in the placebo group. And in all the subgroup analysis, there was no significant difference, except when they stratified by hormone replacement, women who had no prior hormone replacement, they saw a clear risk reduction. And this was not seen in women with prior hormone replacement therapy.

And so what are the key recommendations for the update of this guideline?

So based on these results, the update really adds Anastrozole as another option for endocrine prevention in women at increased risk. So specifically, we say that Anastrozole 1 milligram per day orally for five years should be discussed as an alternate to tamoxifen, raloxifene or exemestane in postmenopausal women for the reduction of breast cancer in women at increased risk. We also clarify further who are the women most likely to benefit from Anastrozole or the other endocrine prevention drugs. And these are women diagnosed with atypical hyperplasia, either ductal or lobular, or lobular carcinoma in situ or women with an estimated five-year risk of at least 3% based on the NCI Breast Cancer Risk Assessment tool or a 10-year risk of at least 5% based on the IBIS Tyrer-Cusick Risk Calculator. But we also give parameters for other risk models, and that is a relative risk of at least four times the population risk for women in the age group 40 to 45 and two times that of the population age group from 45 to 69. I think this is an important part of the recommendations, because up till now, the recommendations for women at increased risk have really followed the eligibility criteria for these trials, which were often a five-year risk, for example, of 1.7% in the NSABP trials. And here, we're trying to really highlight the importance of considering this women at higher risk where there is a clear benefit when you look at benefit-risk ratios. We also talk about the fact that Anastrozole should not be prescribed in women who are premenopausal and that it is really important that both patients and health care providers discuss the benefits and risks of Anastrozole along with the other risk-reduction agents when they are considering prescribing this. And then lastly, the importance of talking about specific adverse effects of Anastrozole, because here we're talking about a population of women at increased risk who are cancer free. And that includes baseline fracture risk, a measurement of bone mineral density as well as other adverse effects like joint stiffness, arthralgias, vasomotor symptoms, hypertension, dry eyes and vaginal dryness. So we think it's important that they have this discussion with women before the study.

So what are some of the clinical considerations for the use of endocrine prevention pharmaceutical agents for breast cancer risk reduction?

So in this guideline, we have introduced this section called Clinical Considerations to try to tackle some of the challenging questions that providers have when considering prescribing endocrine prevention. So I urge people to have a look at this section, because it's really a question-answer format. So one of the things we talk about first is what I just alluded to, how do you identify women at risk, where the benefit of endocrine prevention outweighs the risks? And we go through different risk calculations, and we give examples of clinical patients who fit into these risk categories. The second thing, which I think is an important thing, is we talk about a new study that came out while we were preparing this guideline update. And this was by De Censi, et al. And it's been published in the JCO on low-dose tamoxifen. This was a randomized trial in women with intra-epithelial neoplasia. So this includes women with atypical hyperplasia, lobular carcinoma, or ductal carcinoma in situ. So slightly different population. And the women were randomized to tamoxifen at 5 milligrams a day-- so this is 1/4 of the standard 20-milligram dose-- or placebo for three years. So remember-- or endocrine prevention trials were for five years. So this was a shorter duration. And then a median followup of five years, they reported out the results, and they saw half the number of neoplastic events, so DCIS or invasive cancer, compared to placebo. So the results were very comparable to the original NSABP-P1 trial and very promising. So the further I think, what has been a sometimes prevented uptake of these agents, has been the adverse effects of tamoxifen, for example, equal to uterine cancer. And in this study, they did not see an increase in the number of serious adverse effects, including deep venous thrombosis and endometrial cancer. They still saw an increase in hot flashes. So I think this is very promising data and could be an alternate option for some patients, where side effects are a problem or they're reticent to take prevention given the side effects. Another thing we tackle is the question of age when you start recommending hormone prevention. And here, this relates to we talk about at 70, not so much that you would stop it at 70, but at that age or 70 or above, you would actually make sure you're taking into consideration their life expectancy. So they should have a life expectancy of 10 years or greater. And you're also taking into consideration their breast cancer risk. So the question there was, is there an upper age limit for endocrine risk reduction therapy? And we think that, at least the panel thought that, in women 70 years of age or older, you should actually consider both the short-term risk. It should be at least in the range of 1% or more per year. So that would be women with atypical hyperplasia, a family history, or some with carcinoma in situ. We want to make sure they're active and that they have a life expectancy of 10 or more years. Another question we tackled here was, what is the duration of endocrine therapy in this setting for breast cancer risk reduction? And this comes in the context that now, in the treatment setting, a subset of women are given, for example, tamoxifen for more than five years. In terms of data, with the exception of raloxifene, where we do have longer-term data that is greater than five years, in women at increased risk of breast cancer from the osteoporosis prevention trial, where we see that even with women taking raloxifene for more than five years still have a benefit in terms of the breast cancer risk reduction. We don't really have data for any of the other agents in the preventive setting. So there is currently no data from randomized trials that any of these agents, except for raloxifene, should be given for longer than five years. And that is in the setting of women with osteoporosis. And then the last question that we tackle is to look at how you decide between taking an aromatase inhibitor endocrine prevention therapy or a SERM. And this is really only in postmenopausal women, because we still only have one option for premenopausal women, and that is tamoxifen. Here, we just go through step by step sort of the process of thinking about the side effects for each of these agents. And in the context of the woman who is considering endocrine therapy and tailoring it to their age, what symptoms they have, or other comorbidities.

Finally, how will these guideline recommendations affect conversations between providers and women at increased risk for breast cancer?

So I think, firstly, these guidelines, again, bring attention to breast cancer prevention and the need for us as a community, both providers and women, to move this field forward. And what do I mean by that is we need to be more systematic about identifying women who are truly at increased risk and then subsequently having these discussions with them about the options available. And so I think this guideline adds another agent to the list of agents we now have that can be used to reduce breast cancer risk or breast cancer incidence and also provide the opportunity to-- we look at this and think about how we might incorporate discussions on breast cancer risk reduction into clinical practice. We do also want to stress the importance of discussions on lifestyle factors or risk reduction in addition to these agents. So I think hopefully this guideline helps to, again, refocus attention on the issue and encourage both women to ask their providers about their breast cancer risk and then providers to re-look at this question about breast cancer prevention and how to identify those who are at risk and then discuss endocrine prevention in those at higher risk. I think this is particularly important as we think about our aging population and the increase we are expecting in breast cancer over the next 10 to 20 years. And then also, as we think about breast cancer is now the number-one cancer diagnosed, well, the prevention becomes even more important.

Great. Thank you for your work on this guideline. It sounds like there may be many important conversations which happen between women and their providers based on the work and the research about breast cancer risk reduction. So thank you again for coming on the podcast to share with us today, Dr. Visvanathan. Thank you. I would like to thank ASCO for having these podcasts and also shining a light on breast cancer prevention and getting this information out to its listeners.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer Guideline Update Aug 05, 2019

Show notes

An interview with Dr. Anna Falanga on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guideline Update." The guideline revises several previous recommendations. Most notably, direct oral anticoagulants (DOACs) have been added as options for VTE prophylaxis and treatment.

Read the full guideline at www.asco.org/supportive-care-guidelines

Find all of ASCO's podcasts at podcast.asco.org

TRANSCRIPT

Hi, my name is Clifford Hudis and I am the CEO of ASCO and 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 9 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

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

Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Anna Falanga from the hospital Papa Giovanni XXIII in Bergamo, Italy. Senior author on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guidelines Update." Thank you for being here today, Dr. Falanga.

Yes, thank you. I am very happy to talk on the update of the ASCO VTE guidelines.

So this guideline was first published in 2007 with an update in 2013 and a reaffirmation in 2015. So what prompted this 2019 update?

Thanks for this first question. I think that an update was urgently needed at this time. You know, before, the ASCO guidelines were published in 2007. And then an update was made in 2013, and the second one in 2015. But in 2015 was basically a confirmation of the previous 2013 update. Now the update was urgently needed, because in the very recent years there has been even more evidence of the relevance and impact of a venous thromboembolism in the cancer patients. But in addition, and very importantly, new data from prospective randomized clinical trials with the new drugs for the management of VT in the oncological patients have become available. In particular, as you know, low molecular weight heparins were largely used in the setting of the treatment and trauma prophylaxis in the cancer patients. And actually, the low molecular weight tapering have been the standard of treatment for many years. However, recently the results of prospective randomized clinical trials of direct oral anticoagulant, particularly, the anti-Xa inhibitors, Edoxaban and Rivaroxaban, for cancer associated with [INAUDIBLE] treatment support the role of this new oral agent in the VT management in this setting. And this is related to new politics in the VT management in these patients.

So what are the key recommendations for this guideline update?

The main changes to the previous recommendations are first that Rivaroxaban and Edoxiban, the two anti-Xa inhibitors oral anticoagulants have been added as an option for routine treatment in cancer patients in this update. Also, now we may offer thrombo prophylaxis with Apixaban, Rivaroxaban, or low molecular weight tapering to selected high-risk outpatients with cancer. And about other changes of these new guidelines compared to the last one include that patients with brain metastases have been addressed in the VT type treatment sections, whereas before, only patients with the primary tumors were mentioned in the previous edition. And finally, the recommendation regarding long-term postoperative thromboprophylaxis with low molecular weight heparin expanded to patients undergoing a major open or laparoscopic abdominal or pelvic surgery. These are the main changes that all I think are very, very important.

Why is this guideline so important? And how does it affect practice?

Well, I think that the question how these changes affect our practice is a very important question, because I believe that these guidelines reflect the new evidence that we have from the new data. And this data clearly expand our possibility to choose now between the different treatment options in the single patient in the cancer population. For instance, the new data show that treatment with [INAUDIBLE] anticoagulants compared to low molecular weight heparin lower the risk of a recurrent thrombosis. But in some instances there's a higher risk of bleeding, particularly in the gastrointestinal and urinary tract cancer patients. So therefore it is evident that the patient selection and the individualization of a therapy based on the patient characteristics and the type of cancer-- all these become very important. And we have the possibility now to choose between different treatments, or in the same patients we can change from one treatment to the other according to the face of the disease or complications if the patient is in a phase that is assuming chemotherapy with many side effects like nausea and vomiting. Of course, in these cases a parenteral injection is preferable for the management of a venous thromboembolism. Whereas in other instances, a long-term and oral intake is surely more convenient. So it depends also from the level of risk. But now for the six months treatment we can offer different choice of the oral treatment and also for high-risk patients the primary prophylaxis with Apixaban Rivaroxoaban, and a low molecular weight tapering can be chosen.

And what should patients be aware of when it comes to VTE risks and treatments?

I think that patients should be educated about the risk of a cancer associated with VTE. You know, there is that evidence that they are educated about it. And they know a lot better about neutropenia, and the fever associated with this the neutropenic condition and the other side effect. But they know very little about the possibility that they can experience venous thromboembolism. s So I think they should be taught on how to recognize the symptoms and alert their physician. You know, sometimes the symptoms are indistinguishable It can be just a little pain in the calf. And patients must know that these are to be considered important. They must alert their physician to undergo some test-- objective test-- to see if there is a real thrombosis in the leg or not. This is extremely important, because one important consequence of venous thromboembolism of the extremities is a pulmonary embolism that can be also fatal. So they must know about that. Also, I think they should know about the risk of bleeding associated with the anticoagulant treatment, and also that this risk of bleeding can be different in the different type of tumors. Finally, I think that also they must be told about the once they have, for instance, and episode of venous thromboembolism they have to receive a treatment for that, and these are usually six months to the minimum, and then we'll decide. So they must know what these are the efficacy and the safety profiles of the different drugs. They must know the differences in the route of administration and the other characteristics of the drug. So I think that their shared decision with the patients of the type of treatment must be an integral part of the decision making and is certainly desirable.

Great. It sounds as though there's some important considerations for patients and important conversations which may be prompted by this guideline. So thank you for taking your time to discuss this with me today, Dr. Falanga.

I thank you very much for this interview and talk that our colleagues and also the patients will be happy with these new guidelines of ASCO. Thank you.

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. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Medication-Related Osteonecrosis of the Jaw Guideline Jul 22, 2019

Show notes

An interview with Dr. Noam Yarom, Dr. Charles Shapiro, Dr. Deborah Saunders and Dr. Doug Peterson on "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." This guideline addresses the prevention and management of MRONJ in patients with cancer. This guideline is intended for oncologists and other physicians, dentists, dental specialists, oncology nurses, clinical researchers, oncology pharmacists, advanced practitioners, and patients with cancer. Read the full guideline at www.asco.org/supportive-care-guidelines

Find all of the ASCO podcasts at podcast.asco.org

TRANSCRIPT

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

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today, I'm interviewing a panel of authors from "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." So could I have you each introduce yourselves for the listeners today?

Thank you, Shannon. I'm Dr. Deborah Saunders. I'm the president of the International Society of Oral Oncology and was the section head for the Systematic Review on "Medication-Related Osteonecrosis of the Jaw," with MASCC and ISOO. I was a proud part of the steering committee and one of the authors.

Thank you, Debbie. My name is Dr. Douglas Peterson. I am professor of oral medicine in the School of Dental Medicine at the University of Connecticut Health Center in Farmington, Connecticut. I am also a faculty member in the Head and Neck Cancer Oral Oncology Program at the university's Neag Comprehensive Cancer Center. I'm a member of the steering committee for this clinical practice guideline and one of the co-authors as well. In addition, and as of June 2019, I have been serving as chair elect during this next year for ASCO's Clinical Practice Guidelines committee.

Thank you, Doug. My name is Noam Yarom. I'm an all medicine specialist from the Sheba Medical Center in Tel Aviv University in Israel. I'm serving as a culture of this guideline, and it is a pleasure to be with you today.

Thanks, Noam. I am Dr. Charles Shapiro, professor of medicine at the Mt. Sinai Hospital in New York. And I'm co-chair of the guideline "Medical-Related Osteonecrosis of the Jaw." And I'm happy to be here.

Thank you all for being here today to discuss this guideline on the podcast. So first, can you give us a general overview of what this guideline covers.

Sure. So you know, ASCO and MASCC, as well as ISOO decided that it would be great to provide a practical evidence-based approach in a multidisciplinary type setting to address this important topic that impacts all of our professions, that being medication-related osteonecrosis of the jaw. It's terminology and its definition and the path that's varied and even part of this publication identifies the need for us to move forward with a concise definition and similar terminology, that being medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw is defined as the presence of an exposed or bone that is probable by a probe in a patient that has a history or is undergoing present use of a bone-modifying agent. This being in the absence of any patients having received any radiation to the head and neck and the absence of metastatic lesions to the jaw. The importance of us identifying this definition and agreeing on the terminology allows us to move forward in future publication to better compare outcome and provide better prevention and treatment for our patients moving forward.

And what are the key recommendations of this guideline?

There are six clinical questions associated with this clinical practice guideline as well as a series of recommendations built within each of the clinical questions. Clinical question one is directed to the preferred terminology and definition for osteonecrosis of the jaw, both of the maxilla and the mandible, as associated with pharmacologic therapies in oncology patients. The panel recommends that the term medication-related osteonecrosis of the jaw, MROJ, be used when referring to bone necrosis associated with pharmacologic therapies. As Dr. Saunders has described, the definition contains three key elements-- current or previous treatment with a bone-modifying agent or angiogenic inhibitor, exposed bone, or bone that can be probed through an intra or extra-oral fistula in the maxillofacial region and that has persisted for longer than eight weeks. And third, no history of radiation therapy to the jaws and no history of metastatic disease to the jaws. Clinical question two is directed to specific steps that should be taken to reduce the risk of MRONJ. The recommendation begins with emphasizing the absolute importance of interprofessional communication of the oncology team with the dental team in advance of initiating the bone-modifying agent. For patients with cancer who are scheduled to receive a bone-modifying agent in a non-urgent setting, a comprehensive oral care assessment, including dental examination and periodontal examination and an oral radiographic exam when feasible to do so should be undertaken prior to initiating the BMA therapy. Once the dental care plan has been developed, it should be discussed with the dental team, the patient, and the rest of the oncology team and then implemented based on medically necessary dental procedures. These procedures should be performed prior to the initiation of the bone-modifying agent. Once the bone-modifying agent is implemented, there should be ongoing followup by the dentist on a routine schedule, for example, every six months following initiation of the BMA therapy. It's also important to realize that there are a series of modifiable risk factors which should be emphasized with the patient. For example, poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes mellitus, and tobacco use are all factors that have been associated with development of a MRONJ. All of these modifiable risk factors should be addressed, where appropriate, with the patient in advance of the bone-modifying agent. As far as elective dental alveolar surgery, these procedures, if they are not medically necessary, for example, extractions or alveoloplasties or implants, they should not be performed during active therapy with a bone-modifying agent being given at an oncologic dose. Now, exceptions to this may be considered when a dental specialist with expertise in prevention and treatment of MROJ has reviewed the benefits and risks of the proposed invasive procedures with the patient and the oncology team. In general, however, elective dental alveolar surgical procedures should be deferred while the patient is undergoing active therapy with a bone-modifying agent. If the dental alveolar surgery is performed, the patient should be evaluated by a dental specialist on a systematic and frequently scheduled basis, for example, every six to eight weeks until there is full mucosal coverage of the surgical site. And once again, communication between the dental team and the rest of the oncology team is absolutely paramount in assuring ongoing comprehensive care of the patient. Interestingly, there are still questions in the literature relative to whether or not there should be temporary discontinuation of bone-modifying agents prior to dental alveolar surgery. Unfortunately, there remains insufficient evidence to support or refute the need for discontinuation of the bone-modifying agent prior to dental alveolar surgery. And so the administration of the bone-modifying agent may be deferred at the discretion of the treating physician, in conjunction with discussion with the patient and the oral health provider. So it really becomes an individual judgment call by the treating physician relative to whether or not to temporarily discontinue the bone-modifying agent prior to dental alveolar surgery. Clinical question three involves the staging of MROJ. There are a number of well-established staging systems in the literature addressing severity and extent of MROJ. For example, the 2014 American Academy of Oral and Maxillofacial Surgeons Staging System is one example. Another example is the National Cancer Institute's Common Terminology Criteria For Adverse Events. And there is a 2017 International Task Force on O and J Staging System for MROJ that is available as well. So there are at least three well-established, widely utilized staging systems for MROJ. Having said this, it's important in the view of the panel that the same staging system should be used throughout an individual patient's MROJ course of care. And optimally, the staging should be performed by a clinician experienced with the management of MROJ. Clinical question four involves management of MROJ directly. Here, the recommendations talk in terms of initial treatment of MROJ, which is centered in conservative measures. Now, these conservative measures may include antimicrobial mouth rinses, antibiotics if clinically indicated, effective oral hygiene, and conservative surgical intervention such as a removal of a superficial bone spicule. In cases, however, of refractory MROJ, more advanced MROJ, aggressive surgical interventions, for example, mucosal flap elevations, bloc resections of necrotic bone may be used if MROJ is persisting and severely affects function despite conservative initial treatment. Clinical question five involves bone-modifying agents and whether they should be temporarily discontinued after a diagnosis of MROJ has been established. And once again, there is insufficient evidence to support or refute the discontinuation of the bone-modifying agents after a diagnosis of MROJ has been established. The bone-modifying agent may be deferred at the discretion of the treating physician, again in discussion with the patient and the oral health care provider. And finally, clinical question six involves what outcome measures that should be utilized in clinical practice to describe the response of MROJ lesion to treatment. During the course of MROJ treatment, the dentist, dental specialist, should communicate with a medical oncologist in an ongoing way, both the objective and subjective status of the lesion. The guideline presents a scale that can be utilized to describe the trajectory of the MROJ-- resolved, improving, stable, or progressive. The clinical course of MROJ may impact both local and systemic treatment decisions relative to the cessation or the recommencement of bone-modifying agents. So once again, it becomes very, very important that the ongoing interprofessional communication relative to the clinical course of MROJ-- resolved, improving, stable, or progressive-- be discussed with the oncology team.

Great. Thank you, Dr. Peterson. So on that last note, how can oncologists, dental specialists, and dentists all work together to manage medication-related osteonecrosis of the jaw?

Throughout these guidelines, we do emphasize the importance of collaboration among the cancer care team, dentist, and dental specialists in order to coordinate care and modify risk factors. It is very important that cancer care team and the dental care team speak the same language. Therefore, we spend time on clarifying the definitions, the diagnostic criteria, and staging of MROJ. As been said earlier, we have developed a new system to evaluate the response to treatment, which is based both on objective findings and symptoms. By using this scale, oncologists and dentists would be able to communicate more easily for the benefit of the patients. We emphasized the need for multidisciplinary discussion in a few critical points throughout the course of bone-modifying agent therapy. And it is most important in case of a planned oral surgery in a patient without MROJ or before aggressive surgical treatment of refractory MROJ.

And how will these guideline recommendations affect patients, and what should they talk to their doctors about?

There are a number of things that patients, providers, dental specialists, and medical oncologists can do to lessen the risk and prevent MROJ. Because the key to MROJ is prevention. Once MROJ is established, it's difficult to treat, impacting a patient's quality of life. So we want to prevent, reduce the risk of developing MROJ. Patients can do a number of things-- pursue good oral hygiene, stop smoking, or reduce smoking, and control their diabetes, for example. Those things lessen the risk of MROJ. Providers, dental providers, dental specialists, who are specialized in the area or providers, dentists otherwise in the community, when they encounter a patient that's contemplating bone-modifying agents, they can do what's called a complete dental screening exam, which involves a complete examination of the mouth, Panorex X-rays and X-rays as clinically indicated. We want to identify work in the mouth that needs to be repaired before initiating bone-modifying agents. That way, we don't have to deal with an emergent situation when it could be preventable prior to bone-modifying agents, because one of the single highest risk factors for MROJ is emergent dental work while you're on bisphosphonate or another anti-resorptive agent-- bone-modifying agents. So a dental screening exam is critical to prevent or reduce the risk of MROJ. And medical oncologists have a role too in communication with the dental specialists and really think hard about the indications for bone-modifying agents, whether it be for osteoporosis, whether it be for metastatic disease, and whether it be for anti-cancer effects.

And finally, where can both patients and clinicians go to get more information on this topic or to find a dentist or a dental specialist?

Now, as far as websites, ASCO, MASCC, and ISSO all have websites you can go to to find out more information about MROJ.

Yeah, I think that's great advice. Our links for additional information are listed in the Clinical Practice Guideline as well. This is a really first step at a framework in trying to manage a side effect that affects our patients but is very multidisciplinary. And like Dr. Shapiro was saying, really the best way to prevent this is with proper communication between the dentist and the oncologist and making the patient aware of what is needed prior to commencement of these treatments.

Well, it certainly sounds as though there are some important considerations for clinicians and patients. And I really hope that this guideline is widely read and makes a real impact on the management of osteonecrosis and the communication between oncologists, dental specialists, and dentists. So from me and all of our listeners, thank you all for coming on the podcast today to discuss "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline."

Thank you. Thank you for having us. Thank you very much for this opportunity to contribute to this important discussion. Thank you for allowing me to participate in this important podcast.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer Update Jun 17, 2019

Show notes

An interview with Dr. Lynn Henry from University of Utah Huntsman Cancer Institute on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." This guideline update includes data from the MINDACT and TAILORx trials to clarify the recommendations for patients with hormone receptor-positive, HER2 not overexpressed, axillary node-negative early breast cancer.

Read the full guideline at www.asco.org/breast-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. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin. And today, I'm interviewing Dr. Lynn Henry from the University of Utah Huntsman Cancer Institute, lead author on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you for being here today, Dr. Henry. Thank you very much for the invitation. So this guideline was updated to incorporate new data from the TAILORx and the MINDACT trials. So can you give us an overview of these trials and their results? Sure. So patients with hormone receptor-positive, HER2 negative breast cancer, are generally treated with anti-estrogen treatment and are sometimes also recommended to have chemotherapy. Since these tumors don't always respond well to chemotherapy, tests have been developed that provide more information about how much benefit, in terms of reduction of the likelihood of cancer coming back, an individual patient is likely to get from treatment with chemotherapy. It is important that the benefit of a treatment outweighs the risk of toxicity from the treatment. Two of those tests are called Oncotype DX and MammaPrint. And they have recently been tested in large clinical trials. So TAILORx is a large prospective trial that tested the Oncotype DX assay. In the Oncotype DX assay, a tumor is tested to get more information about how likely a cancer is to return and how much benefit the patient is likely to get from chemotherapy. Scores on this assay can range from 0 to 100. Previously, a study showed that patients whose tumors had scores of 10 or less, and who received five years of anti-estrogen treatment, were very unlikely to have their tumors return. So chemotherapy is not recommended for them. For patients with higher scores, above 30, we also already knew that chemotherapy is likely to decrease the chance of cancers in those patients, and, so, therefore, we generally recommend chemotherapy for women with higher scores. In the TAILORx trial, the recently reported trial, more than 6,700 women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer had their tumors tested and were found to have Oncotype DX recurrent scores between 11 and 25, which is in that intermediate range or at the higher end of the low range. Before this trial was conducted, many people with tumors like these, in the intermediate range, were treated with both chemotherapy and endocrine therapy because we weren't sure how much benefit they would obtain from chemotherapy, and we didn't want to leave out a potentially helpful treatment. In this trial, patients were randomized, or randomly assigned by a computer, to treatment with chemotherapy followed by endocrine therapy or to treatment with endocrine therapy alone. The trial was mainly looking at whether leaving out chemotherapy would increase the likelihood of invasive cancer returning. And, luckily, overall, the trial showed that the likelihood of cancer returning in those patients who got endocrine therapy alone, without chemotherapy, wasn't significantly different compared to those who were treated with chemotherapy followed by endocrine therapy. They also looked, specifically, at the group of women who were 50 years of age or younger. So mostly premenopausal women. Now, this was an exploratory question, meaning it provides information that may be correct, but it hasn't been as fully tested as the main question about what do we do for all women? In these younger women, there appeared to be some benefit from chemotherapy in those whose tumors had scores from 21 to 25, and, also possibly, in those whose tumors had scores from 16 to 20. Therefore, we still consider giving chemotherapy to younger women with Oncotype DX scores in the middle range, from 16 to 25, but not to women over age 50. So that was the TAILORx trial. The MINDACT trial was a bit different. It was testing the MammaPrint assay and the trial also included primarily women with hormone receptor-positive, HER2 negative breast cancer. But in this case, most women's sorry lymph nodes were negative, although a few women had up to three lymph nodes involved. In that trial, patient's risk of disease recurrence was assessed in two ways. First, it was assessed based on clinical factors. So the size of the tumor, how many lymph nodes were involved, and the estrogen receptor, progesterone receptor, and HER2 receptors. Second, it was assessed based on genomic factors-- that was using the MammaPrint test. So if patients were low for both clinical factors and genomic factors, they only were treated with anti-estrogen therapy. If they were high for both clinical factors and genomic factors, then they were treated with chemotherapy followed by anti-estrogen therapy. However, if they were high for one and low for the other, then they were randomized to either endocrine therapy alone or chemotherapy followed by endocrine therapy. So it was a little bit of a confusing trial. In the MINDACT trial, those patients who were thought to be high risk based on their clinical risk, so the size of the tumor, the number of lymph nodes, but then found to be low risk on the MammaPrint assay. They found that there was no benefit to treatment with chemotherapy in terms of how likely a woman was to develop distant metastatic disease. And if they were low risk, based on the clinical assessment, then there didn't appear to be a benefit of actually doing the test, the assay, because chemotherapy wouldn't be recommended for the patient, regardless of the results. So that was the MINDACT trial. So what are the new and updated recommendations for the guideline? Yes, so in this guideline, we, based on the TAILORx trial, we made new recommendations for use of the Oncotype DX results. All of these results apply to women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer. So for women older than age 50, if they have an Oncotype score of 25 or lower, then clinicians may offer endocrine therapy and no chemotherapy. However, for women age 50 or under, if they have an Oncotype score of 15 or lower, 15, then, clinicians may offer endocrine therapy and no chemotherapy. But if the score is 16 to 25, then chemotherapy can be considered in addition to endocrine therapy. So it made a difference in that gray area in the middle. For all women with score 26 to 30, chemotherapy may be considered. And for scores above 30, chemotherapy should definitely be considered. The data from the MammaPrint trial actually aren't that new. Results from that trial were originally published in 2016. However, that was after the original guideline was published, so we wanted to add these results to these updated guidelines for completeness. For a patient with hormone receptor-positive, HER2 negative, node-negative breast cancer, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then treatment with chemotherapy can be avoided. If a patient is thought to be at low clinical risk, the MammaPrint should not be used as chemotherapy can be avoided regardless. And for a patient with hormone receptor-positive, HER2 negative breast cancer, but who has one to three positive lymph nodes, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then it is possible that chemotherapy could be avoided, especially if only one lymph node is involved. So I think the bottom line for this part is that both of these tests-- there are now women who previously would have been recommended to have chemotherapy that maybe now we can avoid chemotherapy based on using these assays on their tumors. So why are these changes so important and how will they affect practice? Yes, that's a good question. Before the publication of the TAILORx trial, we had good information about how to treat patients who had either very low or very high Oncotype scores. But we really weren't sure how best to treat those patients who scores fell in the middle. Now, we have important information to guide decisions about chemotherapy for patients with intermediate scores. For many patients with scores in this range, these new results mean they will be able to avoid chemotherapy and just get endocrine therapy. While these results don't give us answers for every patient, they do provide more information that oncologists can use when having discussions with patients about the benefits and risks of chemotherapy. And what does this mean for patients with early-stage invasive breast cancer? And what should they talk to their doctors about? So as a result of both of these trials, we now have additional tools that can help oncologists provide more individualized treatment recommendations for patients and really assess whether or not chemotherapy, in addition to endocrine therapy, is likely to provide benefits. Knowing which patients' tumors will respond to chemotherapy can help some patients avoid unwanted side effects from a treatment that's not likely to actually give them much benefit. Now, these tests aren't appropriate for everyone and don't provide all the answers, but they are an important step in the right direction for providing more personalized treatment for women newly-diagnosed with certain types of breast cancer. Patients should talk with their doctors about whether these tests are right for them when they're making important decisions about whether or not they should receive treatment with chemotherapy. Great. Thank you, Dr. Henry, for this informative overview of the guideline. Keeping these clinical practice guidelines updated is really crucial and it takes a lot of careful thought to ensure these recommendations represent the evidence. So thank you for coming on the podcast to discuss the "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you very much for the opportunity to talk with you today. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Potentially Curable Pancreatic Adenocarcinoma Guideline Update Jun 10, 2019

Show notes

An interview with Dr. AloK Khorana from Cleveland Clinic on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." This guideline update adds another treatment regimen to the options for patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy.

Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines

See all of ASCO's podcasts at www.asco.org/podcasts

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Alok Khorana from The Cleveland Clinic, lead author on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." Thank you for being here today, Dr. Khorana. Thank you for having me. So this guideline was first published in 2016. And then we saw an update in 2017. And now we've just updated it again. So can you tell the listeners what has prompted these updates? In the world of pancreatic cancer, this has been an evolution in adjuvant treatment, which is sort of a surprise, because we've been treating pancreatic cancer in a very similar fashion over the past several decades. And between the 1990s and until just a few years ago, there hasn't really been much progress in terms of what to do with pancreatic cancer patients after they've had their cancer resected. It's pretty clear that these patients should not have just the surgery, that they should have additional treatment after the surgery. And for decades, the standard treatment after surgery was either 5-fluorouracil or gemcitabine, but most oncologists are opting for gemcitabine. The two recent updates of the ASCO Guidelines reflect two large randomized trials that have been published in this area. The first changed-- added a new standard of care, which was a doublet adjuvant therapy with gemcitabine and capecitabine. And the reason for this most recent update is the publication of a large randomized trial of adjuvant FOLFIRINOX for patients with pancreatic cancer that was published in December 2018 in "The New England." And we felt that the results were so compelling that we needed to update the guidelines so oncologists and practitioners would have the most current data to help them make decisions for patients. So for our listeners who may not now, can you tell us what changes have been made to the recommendations in this newest version of the guideline? So this is a guideline on a potentially curable pancreatic adenocarcinoma, which is we are saying these are resectable pancreatic cancer patients. And the guideline update changes primarily one recommendation, recommendation 4.1, which is a listing of additional adjuvant therapy options. As I mentioned earlier, the most common monotherapy option used to be the gemcitabine 5-fluorouracil. And that recently changed to doublet therapy. And we've kept those recommendations, but we've added the modified combination regimen of 5-fluorouracil, oxaliplatin, and irinotecan, which is known as the FOLFIRINOX regimen. And we are making this the preferred regimen for patients in the absence of concerns for toxicity or tolerance. We are still keeping the recommendations for the doublet therapy with gemcitabine capecitabine as well as monotherapy with gemcitabine alone or fluorouracil with cholanic acid. But those are not the preferred regimens, because the data for FOLFIRINOX is much better than prior regimens. Having said that, there are concerns about using such an aggressive regimen and in patients who have undergone a major surgery. So patients have not recovered from operation, then it's reasonable to consider one of the other regimens. But the update primarily focuses on adding adjuvant FOLFIRINOX as the preferred option in the adjuvant setting. And how has this guideline and its updates affected care for patients with pancreatic adenocarcinoma? I think since the results of this trial, the PRODIGY 24 trial came out of post-operative FOLFIRINOX. Almost every oncologist I know that focuses on treating patients with pancreatic cancer has suddenly added its use in patients that respected pancreatic cancer who are healthy enough to tolerate adjuvant FOLFIRINOX therapy. So it's definitely a practice-changing landmark paper. The results of the study were really quite impressive. The use of adjuvant therapy with FOLFIRINOX led to much longer survival than we've seen in any trial of adjuvant therapy of pancreatic cancer, almost 54 months-- or actually just over 54 months, almost 55 months-- in patients who are randomized to the modified FOLFIRINOX group and about 35 months in the gemcitabine alone group. The overall survival at three years was 63% in FOLFIRINOX and nearly 49% in the gemcitabine group. So that's a big difference at three-year survival as well. The one thing clinicians should be aware of is that this adjuvant therapy trial used a modified dose of FOLFIRINOX. They initially started off at the full those, which is 85 milligrams per meter squared of oxaliplatin, 400 mg per meter squared of leucovorin, and 180 milligrams per meter square of irinotecan. But the dose of iriniotecan was reduced part way through the study to 150 milligrams per meter squared, along with, of course, the conventional 2.4 grams or 5-fluorouracil over 46 hours. This modification of the irinotecan dose from 180 down to 150 is what many patients on the study received and was the more tolerable regimen and allowed the study to be completed. So the Guidelines Panel felt quite strongly that when using FOLFIRINOX in the adjuvant setting, we should stick with this modified dose, which is a lower dose of irinotecan at 150 milligrams per meter squared. And I think it's important that clinicians be aware of this distinction. And so taking this into account, many of us have made this recommendation to patients who are healthy enough to tolerate adjuvant FOLFIRINOX. And the hope is that this guideline will inform this ongoing practice as it changes in response to new data. And finally, what trials or new research are you keeping an eye on that may prompt an update for this guideline in the future? The results of another large adjuvant therapy trial are expected, hopefully at ASCO this year. This trial is the APAC trial that utilizes gemcitabine and nab-paclitaxel or Abraxane. This doublet combination is quite widely used in patients with metastatic pancreas cancer, particularly those patients for whom we feel FOLFIRINOX may not be appropriate because of their performance status or functional status. And the hope was that the doublet combination would also have good success in the adjuvant therapy setting and perhaps be a better option than the gem-cape doublet. There has been a press release from the sponsor of that trial, and it looks like the trial was not successful, although the way the press release is worded is rather confusing. So we wait for the full results of that trial to be presented at ASCO before we have an understanding of whether that is an appropriate regimen to use or not in the adjuvant setting. So that's certainly one large trial that many of us have been looking forward to complete sort of the set of ongoing adjuvant therapy trials in this setting. Great. It sounds like there's some really exciting things happening in pancreatic cancer right now. And I look forward to seeing this guideline evolve with the research. So Dr. Khorana, thank you so much for coming on the podcast today and summarizing the Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. Thank you, Shannon. 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. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Use of Biomarkers to Guide Decisions on Adjuvant Therapy for Early-Stage Invasive Breast Cancer Guideline Update May 31, 2019

Show notes

An interview with Dr. Fabrice Andre from Institute Gustave Roussy, Paris Sud University, in Paris, France on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." This update provides updated recommendations on chemoendocrine therapy for patients who present with a hormone receptor positive, HER2 not overexpressed, axillary node negative early breast cancer.

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. Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Fabrice André from the Institute Gustave Roussy in Paris, France, lead author on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early Stage Invasive Breast Cancer. ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." Thank you for being here today, Dr. André. Thank you. So based on the title of this guideline, we know that this update was prompted by the results of the TAILORx trial. So can you tell us more about that trial and what its results were? Yes. So the TAILORx trial was a trial that randomized two treatment modalities, endocrine therapy versus chemotherapy endocrine therapy in patients who presented what we call an intermediate recurrence cohort. So before moving to the results, maybe we can discuss a little bit the background. What we knew from the past is the fact that patients who present a recurrence score below 11 should be treated with endocrine therapy alone, because they have the good outcomes. And patients who present recurrence score that is high, 31 but also can be more on 25, should receive chemotherapy. And we are talking about patients with hormone-receptor receptor positive, HER2-negative early breast cancer without lymph node involvement. And this is extremely important. So to summarize, it's a clinical trial that includes patients with hormone-receptor positive HER2-negative lymph node negative in early breast cancer, who present with recurrence score between 11 and 25. And the question is whether we can avoid adjuvant chemotherapy in these patients who present this intermediate score. So this is the general design and the question. In terms of research, what we have learned. We have learned that for patients above 50 years old, there is no difference between endocrine therapy and chemotherapy followed by endocrine therapy. So it means that this patient or these patients, we would consider endocrine therapy alone. Then, for patients below 50 years old, there was some difference. And I think we go further into the detail. There was some difference favoring the use of chemotherapy in the group of patients who presented with recurrence score from 16 to 25. And so what changes were made to the recommendations in this update of the guideline? So first, what were [INAUDIBLE] the previous guidelines. The previous guidelines were telling the clinician which genetic tests they could use in patients with hormone-receptor positive, HER2-negative early breast cancer. Now, the big change is that we are making guideline to explain how to use the test. And what is new is that we have made three important decisions. So first, for the patient is at the age above 50, now it is recommended clinician may recommend endocrine therapy alone for women older than 50 who present a recurrence score below 26. Before, the recommendation to use endocrine therapy alone was for patient's who present with low recurrence score. So it means now we have broadened-- we have increased the number of patients who could receive endocrine therapy alone and not receive chemotherapy. Then, for patients who present a recurrence score between 16 to 25 and who are below 50 years old, the clinician may offer chemotherapy followed by endocrine therapy, meaning that we are moving from [INAUDIBLE]. This intermediate score between 11 to 25 was what we call a [INAUDIBLE]. There was no recommendation on how to use the recurrence score. So right now, the update from the ASCO guideline is to provide recommendation on which treatment to administer in case a patient presents with intermediate recurrence score, and there are two different situations above 50 years old and below 50 years old. So why are these changes so important and how will they affect practice? So they will affect practice because for many reasons, I will say. In the US, they would affect practice because they increase the number of patients who will not receive adjuvant chemotherapy, because right now, we have an answer from randomized trial that we can avoid chemotherapy in women above 50 and from 11 to 25 recurrence score. So the impact in terms of public health would be that we could have a decrease in the use of chemotherapy or at least a better precision about who should receive adjuvant chemotherapy. Globally, this trial is going to provide an incentive and increase the level of evidence supporting the use of genetic tests. So it's important to remember that in a large number of countries, genetic tests are not reimbursed. But now, because lack of evidence, and here we have a randomized trial showing a level 1 evidence supporting the use of genetic tests. So we have two direct impacts of this trial. The first, inside US, where [INAUDIBLE] colleagues already use genetic tests, it provides better precision on who will receive adjuvant chemotherapy. And it's going to broaden the number of patients who will not receive. And globally, it's prospective randomized trial that we hope is going to incite payers to reimburse the genetic test in patients with early breast cancer. And so what does this all mean for patients with early stage invasive breast cancer? And what should they talk to their doctors about? So for patients with early breast cancer, so what are the messages for the patient? I think for the patient, the key message is that we are moving to precision medicine. We need a medicine that is extremely precise in terms of who should receive which treatments. And now, thanks to this trial, we are going to decrease the number of patients who receive chemotherapy, but also for the ones who will receive adjuvant chemotherapy, the value of the treatment, we need what the treatment provides to the patient is going to be very, very high. So what is important for patients is to understand that because of this trial, when we give them chemotherapy, we will know that the value of this treatment and the expected benefit is going to be higher than what we used to do in the past. So it's really fast forward and more precise medicine that consists in using molecular tests in order to provide or administer treatment with very high value. Great. Thank you Dr. André for your overview of this guideline update. This has been very informative. It's really good to hear that the expert panel has incorporated the latest research into the guideline and has carefully considered the implications for the patients. So thank you for coming on the podcast to discuss the "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx" Thank you. What people don't realize is we did hard work that ASCO doing with all these guidelines, and people are very committed, and they are [INAUDIBLE]. I mean, it's very reassuring for ASCO member to know that there are highly professional people who provide guidelines and it is also reassuring for the patients, for everyone. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

Role of Treatment Deintensification in the Management of p16+ Oropharyngeal Cancer PCO Apr 25, 2019

Show notes

An interview with Dr. David Adelstein of the Cleveland Clinic on the ASCO PCO which provides statements on the role of treatment deintensification in the management of p16+ oropharyngeal cancer. Read the full PCO at www.asco.org/head-neck-cancer-guidelines

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. David Adelstein from the Cleveland Clinic Taussig Cancer Institute. Lead author on "Role of Treatment Deintensification in the Management of p16 Positive Oropharyngeal Cancer: ASCO Provisional Clinical Opinion." Thank you for being here today, Dr. Adelstein. Thank you, Shannon. Before we get started, I'd like to first note the contributions of my panel co-chair, Drew Ridge, and those of all of the other panel members. And I'd like to extend a special thank you to ASCO for their support in allowing us to put this together and specifically Nofisat Ismaila who did a tremendous amount of work in allowing us to complete this provisional clinical opinion. First, can you give us an overview of the clinical issue for this PCO? Sure. So this really came out of the implications of human papillomavirus mediated oropharynx cancer. I think as most of the listeners know, over the last several decades we've recognized the fact that oropharynx cancer has a second ideology, that not all of it is caused by tobacco use, but that the human papillomavirus is now the major ideologic factor in North American and northern Europe. The importance of this is that the human papillomavirus-induced oropharynx cancer is a different disease. It has a number of different characteristics from the kinds of head and neck cancer we've seen in the past. It's a disease that tends to occur in younger patients, patients who are otherwise generally more healthy. It is unassociated with smoking, although it can occur in smokers. But it's much more frequent in nonsmokers. And I think most importantly, it's a disease that has a dramatically better prognosis than the tobacco related disease. Now over the last several decades, our ability to treat advanced head and neck cancer has improved significantly, because we've begun to incorporate non-operative treatments-- chemotherapy and radiation-- and have been more aggressive in our utilization of chemotherapy and radiation with significantly greater success than we had in the past. The problem with this kind of treatment is that it is quite rigorous. And there's a good deal of acute and, more importantly, late toxicity that patients experience from these kinds of approaches. Now as we became more familiar with the importance of HPV associated oropharynx cancer, we realized that there are subgroups of these patients who have cure rates that are in excess of 90%. And the question arose whether the kinds of rigorous chemotherapy and radiation therapy treatments that we were utilizing were really necessary. Was it necessary to cause this much acute and late toxicity in patients who in vast majority of cases were going to be cured of the disease. And it's important, because these are younger patients. And the late toxicities are going to have a major impact on their quality of life for a number of years. What came about was the notion of treatment deintensification, the idea that perhaps it would be possible to deintensify the kinds of treatments we were giving in select patients. It's a very compelling hypothesis for medical oncologists and radiation oncologists. But there are a number of problems as we try to test this hypothesis. The first problem is how do we identify the good risk patients? There are patients with HPV-positive disease who do not do so well-- the heavy smokers and patients with very advanced tumors. And we need to be careful if we're going to be talking about giving less treatment that we don't give less treatment to the patients who have a worse prognosis. We pick the best prognosis patients. There have been a number of what we call risk stratification schemes that have been developed looking at trying to identify the very good prognosis patients-- those patients who are HPV positive who don't smoke and who have relatively limited disease extent. There's not universal agreement on how best to define these patients. All we know is that they do exist, that you can look at patients with these characteristics and see very good outcomes. One of the issues that has come up is how do we utilize the American Joint Committee staging system-- AJCC the 8th edition. One of the things that AJCC 8 did which is new is that it defined a separate staging system for patients with HPV-positive oropharynx cancer, a system which is entirely different than the staging system that we've used for head and neck cancers for many years. This was based on the recognition that the prognosis of patients with HPV-positive disease is so good so that many patients who we would previously have considered to have stage 4 disease are now classified as having stage 1 tumors, because their prognosis is so good. And that can be confusing, because the typical thought process for an oncologist is that a patient with stage 1 disease should be treated with single modality therapy. The reason that the HPV-positive patients have such a good prognosis, however, is that many of them have been treated with combined modality therapies. And to make the assumption that because now they're classified as stage 1 is incorrect. It is they shouldn't be treated with less intensive treatments and can be confusing. AJCC 8th edition is a prognostic robust staging system, but it really doesn't help us in defining treatment. First problem is how best to define patients who are appropriate for deintensification. Second problem is, what do you do to deintensify? What constitutes meaningful deintensification? Well, over the last 10 or 20 years there have been some significant advances in our standard treatments for all head and neck cancers that weren't developed the idea of deintensification. We now have tremendous experience using transoral surgical techniques, which are generally minimally morbid, much less morbid than the former open techniques that previously were used, which allows consideration of surgery for many of these patients where we wouldn't have considered it before. Similarly, intensity modulated radiation therapy has been widely adopted, and d clearly an approach using radiation, which is far less difficult, far less toxic than the former 2D or 3D radiation planning techniques that used to be used. But if we talk about intensification, what kinds of things can we do to deintensify our treatments? Well, one thought is to reduce the radiation dose. Then the question is, how much reduction is reasonable? And how much reduction is going to actually impact on this toxicity? And are our toxicity measuring tools adequate to even detect the difference in reduction of a radiation dose? Many of our toxicity tools are very crude. Perhaps we should be using some of the patient-reported outcome quality of life instruments that are available. Other thoughts are, perhaps one can reduce the size of the radiation therapy field. Can we reduce the dose of the chemotherapy? Can we eliminate chemotherapy? Can we even use less intensive chemotherapy? Generally, the other treatments for this disease have employed high doses of cisplatin, which is a toxic agent. And then there the question has been asked as to whether we can reincorporate minimally morbid transoral surgical techniques in an effort to better pathologically stage patients and define more appropriate adjuvant treatment. Perhaps not all patients need adjuvant radiation or chemotherapy and radiation. All of these approaches are interesting. They're exciting. They're being tested. But all of the experiences is preliminary. And that really brings us to the third and the biggest problem in any deintensification approach. And that's the need to be certain that if we deintensify our therapy, we're not going to compromise outcomes. It would not be acceptable to give less treatment or less intensive treatment if our survival were compromised. And we have to be certain that we don't do this. So what has evolved over the past decade is a whole number of treatment approaches that have some very enthusiastic early results. But these are generally single arm phase 2 reports where there is no comparison to conventional treatment. And they become difficult to interpret, because the results in general are very good. I think what really raised a red flag for us and that really caused us to take notice was the results of the RTOG 1016 trial that we reported last year. And at the same time, the European de-escalate trial, both of which had a similar design. These were studies that were designed in an effort to see if treatment deintensification would be possible by randomly comparing the standard treatment radiation and cisplatin with what was felt to be a less intensive approach-- radiation and concurrent cetuximab. And cetuximab is an accepted agent in the United States for treating head and neck cancer. The assumption here is that the survival would be equivalent when these two arms were compared, but that the toxicity would be improved by giving the less intensive systemic agent-- the cetuximab. The surprise when the study was analyzed was that that assumption was incorrect, that the radiation and cetuximab arm-- the deintensified arm-- actually proved inferior in terms of survival. And this was in both trials-- both the RTOG trial and the trial from Europe. And that was a big note of caution, because it was somewhat unexpected. I think we learned from that kind of a study, from a good randomized-- a large randomized trial-- that even though the outcomes may appear to be good, we need to be very careful about deintensifying our treatment until we're sure that the survival is equivalent. So although it's tempting for the clinician to see these very exciting reports about administering less treatment with the idea of producing less toxicity, the guideline advisory committee for ASCO really thought it was important that we get the message out that this kind of approach is not a treatment standard. This remains an investigational approach, and that the treatment standards for this disease really haven't changed. So what are the provisional clinical opinions that were made by the expert panel? They made several statements. The first was to acknowledge that the idea of treatment deintensification is a very compelling hypothesis, and it does require careful and appropriate testing. The second was that even though we are now better at identifying good prognosis patients, and we've seen some very promising early results, and even though we're now reclassifying patients with previously advanced stage HPV-positive disease as stage 1 or stage 2 tumors, the treatment recommendations for this disease have not changed. And they're based on the results achieved using AJCC 6 and 7. Standard of non-operated management to patients who are eligible to receive cisplatin remains high concurrent radiation and high dose cisplatin given every three weeks. If patients undergoing a surgical resection, then adjuvant chemotherapy and radiation with radiation and high dose cisplatin every three weeks is recommended in those patients with high risk factors of positive surgical margins or external tumor extension. And most importantly, deintensification, though it's a compelling hypothesis, is something that should only be undertaken on a clinical trial. Why is this guidance so important? And how will it affect practice? Well, I think the important thing about this guideline is that it shouldn't affect practice. The practice shouldn't change. The standards of care are not altered. And that for the clinician, this remains something that is exciting, something that should encourage enrollment on a clinical trial, but that we haven't changed treatment standards. And finally, how will this guidance affect patients? So from a patient's point of view, I think there is continued reason for optimism. A patient with the diagnosis of an HPV-positive oropharynx cancer is a patient with a very good prognosis. Patients are increasingly sophisticated. They read about the potential for treatment deintensification, and recognize that this is not something which is an accepted standard. But it should encourage their participation in clinical trials if [INAUDIBLE] is offered. I think ultimately it's a remarkable thing when oncologists can consider the possibility of reducing treatment intensity because the treatment results have been so good. Great. Thank you for your overview of this PCO. And thank you for your time today, Dr. Adelstein. And thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full PCO, go to www.asco.org/head-neck-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer Guideline Apr 15, 2019

Show notes

An intervew with Dr. Nancy Baxter on "Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline." The guideline makes recommendations based on the results of the IDEA collaboration. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines

Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Nancy Baxter from St. Michael's Hospital in Toronto, senior author on "Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Baxter.

Thanks very much, Shannon, for speaking with me. I'm happy to share our work developing this guideline.

So first, can you give us a general overview of what this guideline covers and the studies which provide the evidence?

Absolutely. So use of adjuvant therapy for patients with stage III colon cancer is common, and it's effective. We know that these patients are at substantial risk of recurrence of their disease and that adjuvant therapy can reduce that risk. But we also know that comes with a cost. The most effective adjuvant therapy is FOLFOX or oxaliplatin-containing chemotherapy regimens. And we know that a really substantial number of people will end up with neurotoxicity, with peripheral sensory neurotoxicity, that can be long lasting and certainly affects their quality of life. So the whole question was whether the duration of oxaliplatin-containing chemotherapeutic regimens could be shortened when they're used for adjuvant therapy, so if we could give three months instead of six months. Because we know that if we give three months of therapy, the risk of neurotoxicity is much lower. So if we had the same effectiveness with the shorter duration, then we could spare patients the negative consequences of the agent given for a longer period of time. So in developing these guidelines, we looked at the results of international group of trials, the six trials from the IDEA collaboration. So these were six randomized trials in various jurisdictions that tried to look at this question, so three months of an oxaliplatin-based chemotherapeutic regimen for adjuvant therapy for stage III cancer versus six months duration of therapy. And so there was a planned analysis to bring all of these data together to develop the evidence base to make this recommendation. So our guideline and our systematic review basically identified this is the key piece of literature to base our recommendations and guidelines on. That's essentially the main study, so the meta-analysis of these six randomized controlled trials that formed the basis of the IDEA collaboration. So the IDEA collaboration studies-- there were six individual randomized trials that formed part of the IDEA collaboration. And they were conducted in Italy, Greece, Japan, North America, through CALGB/SWOG, the UK, Denmark, Spain, Australia, Sweden, and New Zealand, as well as France. So data came from, really, around the world. The median age of people in the studies was 64 years of age. And these people had a really good performance status, so almost all of these patients had an ECOG performance status of 0 or 1. So they were healthy patients that were in the study. And so some patients received CAPOX, and some received FOLFOX. That wasn't part of the randomization scheme. Other than the CALGB/SWOG study, this was up to the discretion of the investigator or patient. In the SWOG/CALGB study, only FOLFOX was given. And the authors planned a prespecified subgroup analysis to look at differences between CAPOX and FOLFOX. There was also a prespecified analysis to look at differences based on stage. What they found when they looked at the results was that, overall, the difference between groups in terms of the three months versus six months was that the hazard ratio between these two was 1.07, meaning a small difference between the groups in terms of recurrence or death between three months and six months overall. But because the prespecified confidence interval, noninferiority interval, for the difference in outcome was 1.12, the 95% confidence interval for the hazard ratio was above this. So it was 1.15, indicating that this prespecified noninferiority margin was exceeded. And so the study did not prove noninferiority of the three-month regimen. So we're left with an inconclusive result. So that's why our guidelines don't have a strong recommendation for the three months, because we can't rule out a small but potentially important difference between the two groups in terms of recurrence or death. Now, interestingly, when they looked at the prespecified subgroup analysis, which was looking at CAPOX versus FOLFOX, a difference was found. So they actually found that for FOLFOX chemotherapy, three months of therapy was inferior to six months of therapy, while for CAPOX, actually, three months and six months were the same. So it met the criteria of noninferiority. So these are kind of two different conclusions based on which type of chemotherapy was used. This was surprising to the investigators and was not expected. And certainly, it was not consistent with the randomized trials that we have comparing these regimens. So we therefore did not make any conclusions in our recommendations about CAPOX versus FOLFOX. But this is certainly something that requires further investigation in the future. In terms of stage, we did not find that there was an interaction between T stage or end stage when you looked at the differences between the three and the six month. And that was the prespecified analysis. But in non-prespecified analysis, which was the higher risk versus lower risk categories, you did find this difference where the patients with high-risk disease had inferior disease-free survival with three months versus six months of therapy, while those at low risk of disease, it seemed quite safe to give three months versus six months. So that's a long story. But essentially, because the high risk versus low risk analysis was not prespecified, there's a limitation to how strong our recommendations can be to have three months of therapy. However, given that the hazard ratio associated with three months versus six months of therapy for this lower risk group was only 1.01, indicating they were the same, and the risk of neuropathy was substantially higher with six months, this has led to us making recommendations that the three months of therapy is adequate for patients with low-risk disease after discussion with patients about the possible pros and cons.

And what are the key recommendations of this guideline?

Well, so the recommendations of this guideline do depend on the pathology, so how high risk the patient is. So based on the evidence from the IDEA collaboration, the researchers found that patients who had a high risk of recurrence-- so had T4 disease or heavily node-positive disease, N2 disease-- the six-month duration of therapy was better than the three-month duration of therapy. These studies and the meta-analysis were designed as noninferiority meta-analyses. But it was clear from the results that the three-month duration was inferior when compared to three months for these high-risk patients. So that seems clear, although we know that those patients will also be at more risk of neuropathy. And so that needs to be discussed with patients, as well. So for the second group, which are patients who are at lower risk of recurrence, what we found was there was less of a clear benefit of six months of therapy. The recommendation was that patients who are in this low-risk category-- so T1, T2, or T3 cancers that are N1, so not heavily node-positive-- clinicians can offer three months versus six months of therapy after having a discussion with their patients about the pros and cons of that. So the clinicians can go ahead and offer that to patients and still be within the common guidelines based on evidence for treatment of stage III colon cancer. So because there's some uncertainty after analysis of the IDEA collaboration, one of the really important recommendations that we make is about this shared decision-making approach. So the third recommendation that we make is that oncologists should discuss these factors with their patients who have stage III resected colon cancer and that the duration of therapy needs to take into account the tumor characteristics-- the surgical resection, the number of lymph nodes examined, the comorbidities, the patient functional status, all of these various things-- and there needs to be a discussion of the potential for benefit and the risk of harm based on the duration of therapy. And oncologists definitely discuss these things with their patients. And this just emphasizes how this is yet another component of the discussion that needs to be included, particularly when speaking with low-risk patients who are at substantial risk of harm from neuropathy and are unlikely to benefit greatly by extending chemotherapy to six months.

So why is this guideline so important? And how will it change practice?

Well, I think, until now, the standard recommendation has been six months of FOLFOX or six months of oxaliplatin-based chemotherapy. And again, there are many patients who have quality of life-affecting neuropathy because of this. So for a substantial proportion of patients who present to us with stage III cancer-- so those that are low risk-- I think this provides some options to them. So they can opt for a shorter duration of chemotherapy with a lower risk of toxicity. This saves time. This saves cost to the patient and to the system and potentially improves their quality of life without a great impact on outcome in terms of disease recurrence. So that's a substantial number, a substantial proportion of our patients, who can be treated in this way. So I think that this is a real benefit. Again, oncologists need to have a conversation with their patients about the pros and cons. But this is an option for their patients, whereas from an evidence-based perspective, it wasn't before the publication of the IDEA collaboration.

Finally, how will these guideline recommendations affect patients?

So for patients who have heavily node-positive disease-- so high-risk patients with T4 or N2 disease-- it's not going to affect care. So the expectation would be those patients would be treated with six months of therapy, similar to previous recommendations. So this will be for people who are at lower risk of disease recurrence, so patients with T1 to 3 tumors that are N1 positive, so not heavily node positive. So these patients will have the opportunity to opt for a shorter duration of therapy. So that's a major benefit to patients. Again, it's important that there's a discussion and that patients understand the pros and cons. But this is now an option for them, which is excellent.

Thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

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