Radiation Therapy for Brain Metastases: ...

An interview with Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, VA, Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, FL, and Dr. Vinai Gondi from Northwestern Medicine Cancer Center Warrenville and Proton Center in Warrenville, IL, authors on "Radiation Therapy for Brain Metastases: American Society of Clinical Oncology Guideline Endorsement of the American Society for Radiation Oncology Guideline." An ASCO endorsement panel endorsed the "Radiation Therapy for Brain Metastases: an ASTRO Clinical Practice Guideline," and the authors review the endorsement process and key points in this episode. Read the full guideline endorsement at www.asco.org/neurooncology-guidelines.

TRANSCRIPT

Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts.

My name is Brittany Harvey, and today I'm interviewing Dr. David Schiff, from the University of Virginia Medical Center in Charlottesville, Virginia, Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, Florida, and Dr. Vinai Gondi from Northwestern Medicine Cancer Center Warrenville and Proton Center in Warrenville, Illinois, authors on 'Radiation Therapy for Brain Metastases: American Society of Clinical Oncology Guideline Endorsement of the American Society for Radiation Oncology Guideline'.

Thank you for being here, Dr. Schiff, Dr. Vogelbaum, and Dr. Gondi.

Drs. Schiff, Vogelbaum, and Gondi: Our pleasure.

Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guideline products and ensures that the ASCO conflict of interest policy is followed for each guideline product.

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

Dr. David Schiff: No relevant disclosures, Brittany.

Brittany Harvey: Thank you. And Dr. Vogelbaum, do you have any relevant disclosures that are related to this topic?

Dr. Michael Vogelbaum: I have no relevant disclosures.

Brittany Harvey: Thank you. And Dr. Gondi, do you have any relevant disclosures that are related to this topic?

Dr. Vinai Gondi: Brittany, my only relevant disclosure is that I served as vice-chair of the guidelines that we're discussing today, but otherwise, no relevant disclosures.

Brittany Harvey: Excellent! Thank you all. So, then starting us off, Dr. Schiff, what is the scope of this guideline endorsement? And how does it intersect with the recently published 'Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline'?

Dr. David Schiff: Sure. A little bit of background, from the start of the joint ASCO and SNO guideline effort, we had the participation of radiation oncologists, in addition to neurosurgeons, medical oncologists, and neuro-oncologists.

As we were getting underway, ASTRO reached out asking to participate formally as well. They had been planning to update their brain metastasis guidelines but were a year or two away from getting started. And they recognized it would be redundant for them to create comprehensive guidelines that covered chemotherapy, immunotherapy, and surgery as our guidelines were poised to do.

By participating with ASCO and SNO, they were able to have their task force focus specifically on key questions related to radiation oncology practices. In particular, the ASTRO project went into considerable depth on issues of radiation and radiosurgery dose, fractionation schemes, and the risk of radiation complications.

These were areas that our guidelines didn't address. Several members of the ASTRO task force including their chair, Paul Brown, and co-chair Dr. Gondi were members of our committee, and we added Dr. Brown as a co-chair to our committee when ASTRO came on board. The overlap between our two groups helped ensure that our recommendations were in harmony.

Brittany Harvey: So, then, Dr. Vogelbaum, can you provide us with an overview of how the ASCO guideline endorsement process works?

Dr. Michael Vogelbaum: Sure, Brittany. So, as Dr. Schiff mentioned, ASCO had convened a guidelines panel to develop the new 'Treatment for Brain Metastasis: ASCO-SNO-ASTRO Guideline'. And this was a multidisciplinary panel that he and I co-chaired and was anchored by a guideline specialist from ASCO, Hans Messersmith, and the process was that we had evaluated recent literature pertaining to the treatment of the brain metastases, and so, we had a very good understanding of what was supported by high-quality evidence and what was not there yet, as a group. So, when ASTRO came to ASCO and asked whether or not we would be interested in endorsing their guidelines, we were already prepared with all the evidence.

And so, the same panel got together again, to evaluate the ASTRO guidelines. And we did this, again, in a very structured manner. We reviewed the guideline questions and recommendations, compared them to the evidence, and went through the same type of review and polling process that we had when we had developed our own original guidelines.

In the end, we had a conversation with the ASTRO guidelines leadership about some of the points that we raised questions about, and we were able to reach an accommodation that allowed us to fully endorse the ASTRO guidelines.

Brittany Harvey: Thank you, Dr. Vogelbaum for that overview of the endorsement process. So, then, Dr. Gondi, what are the key recommendations of the ASTRO guideline?

Dr. Vinai Gondi: Thank you, Brittany. As Dr. Schiff and Dr. Vogelbaum outlined, ASTRO commissioned a list of key questions that they sought to address specifically to inform the radiotherapeutic management of brain metastases. And to address these questions, ASTRO not only convened a panel of expert radiation oncologists across the country but also engaged with the Agency for Healthcare Research and Quality (AHRQ) to create a comparative effectiveness evidence review, in addition to our own high-level evidence review to address these questions.

The four key questions that were addressed in the ASTRO guidelines are:

Number one: What are the indications for stereotactic radiosurgery alone for patients with intact brain metastases?

Number two: What are the indications for observation, preoperative radiosurgery or post-operative radiosurgery, or whole-brain radiotherapy in patients with resected brain metastases?

Number three: What are the indications for whole-brain radiotherapy for patients with intact brain metastases?

Number four: What are the risks of symptomatic radionecrosis with whole-brain radiotherapy and/or stereotactic radiosurgery for patients with brain metastases?

The recommendations that were made are based on a high-level review of a considerable amount of literature over the past several years that addressed these specific questions. I would encourage the listeners to this podcast to read through the guidelines to understand the specific nuances of each of those recommendations.

Brittany Harvey: Excellent! Thank you for that overview. Then, in addition to what Dr. Gondi just said, Dr. Vogelbaum, were there any additional points of discussion raised by the ASCO endorsement panel?

Dr. Michael Vogelbaum: Brittany, yes, there was an area of discussion where we needed to interact with the ASTRO guidelines leadership, as I mentioned earlier, and it really related to that key question one that Dr. Gondi described, which is what are the indications for SRS alone for patients with intact brain metastasis.

The approach that had been strongly endorsed by ASCO was that there would be a multidisciplinary approach to decision making. And really the benefit of that, the value of that radiosurgery really comes in the form of the interaction between the radiation oncologist and the neurosurgeon.

The way that the original proposal had been formulated, there was a size cut-off that was higher than we thought was appropriate for really endorsing that kind of conversation between the radiation oncologist and the neurosurgeon.

And so really, we proposed that we bring that cut-off down further, there actually was another subpart to the guideline that had looked at a lower cut-off, but did not specifically call out that interaction between the neurosurgeon and the radiation oncologist. And we felt it would be more appropriate to insert that at that cut-off rather than the larger lesion cut-off.

And after a conversation, there was agreement, that was really the only guideline or subpart of the guidelines where there was any real debate or discussion. For the rest of it, the comments that came up from the panel were easily addressed and it really just came down to this one modification. And fortunately, ASTRO agreed, and we were able to go ahead and complete the endorsement.

Brittany Harvey: Great! It's great that this was able to be a complete endorsement of that guideline. So, then, Dr. Gondi, in your view, what is the importance of this guideline endorsement? And how will it affect ASCO members?

Dr. Vinai Gondi: Thank you, Brittany. A number of responses to that. Number one is, as Dr. Vogelbaum, outlined the purpose of these guidelines was meant to be patient-centric and patient-focused, that we had patient champions who had navigated, who are part of the guideline development team, but also to be multidisciplinary. And so, the type of input and feedback we received from the ASCO team was super valued and valuable, as we were formulating these guidelines and Dr. Vogelbaum outlined a good example.

Number two, it had been almost a decade since the last guidelines had come out from ASTRO related to brain metastases management. And much has happened in our field over the past several years that has been practice-changing. We have several novel and innovative radiotherapy technologies and techniques, such as the emergence of radiosurgery, the use of novel radioprotectants, such as hippocampal avoidance, and memantine, but also the emergence of innovative and novel neurosurgical interventions and CNS active systemic therapies.

So, the modern management of brain metastases has really undergone quite a revolution over just the past few years, and it is important that these guidelines be updated to reflect those changes, but also to inform radiation oncologists on the contemporary management of brain metastases and in evidence-based care.

So, we believe that these guidelines will significantly impact ASCO members. Certainly, those who are radiation oncologists, as brain metastases are some of the most common patients that radiation oncologists manage in the community and in academic centers, but also for other members of ASCO medical oncologists, surgeons to understand sort of the nuances of radiotherapy management that is evidence-based, so they can have a patient-centered, patient-focused, multidisciplinary discussion with their radiation oncologist as well.

Brittany Harvey: Those are excellent points for clinicians on the management for brain metastases. So, then finally, Dr. Schiff, Dr. Gondi just mentioned how these guidelines are patient-centric. So, how will these guideline recommendations impact patients with brain metastases?

Dr. David Schiff: Yeah, well, I think what I'm about to say is really going to echo what Dr. Gondi just said. You know, 20 years ago, patients diagnosed with brain metastases were typically immediately referred to a radiation oncologist, they almost always got whole-brain radiation therapy, the median survival was about four months, and many, if not most patients, died from their brain metastases.

The situation has really changed recently. With the rapid advances in management from new therapies, and well-designed clinical trials in recent years, outcomes have markedly improved, it's probably less than a quarter of patients now who succumb to their intracranial disease. But at the same time, decision-making for patients has become much more complicated.

Nowadays, medical oncologists may reach out initially to neurosurgeons for consideration of radiosurgery or surgical resection, or in some circumstances utilize systemic therapy as a first step.

Conversely, a patient might see a neurosurgeon first, who may or may not be aware that there's appropriate immunotherapy or targeted agent that might make sense prior to going on to radiosurgery.

It's obviously a challenge for sub-specialists to keep up with all the emerging clinical trial data and new drugs. Our two sets of guidelines provide a roadmap for physicians of different expertise to help determine what types of therapies or referral should be considered when brain metastases are found. The end result of all this is improved control of intracranial disease and improved quality of life for the patients.

Brittany Harvey: Absolutely. Those are key points. It's excellent to see these guidelines, and the overarching 'Treatment for Brain Metastases: ASCO-ASTRO-SNO Guideline' be published. So, I want to thank you all for your time today, Dr. Schiff, Dr. Vogelbaum, and Dr. Gondi. Thank you for all of your work on these guidelines.

Dr. Michael Vogelbaum: My pleasure.

Dr. Vinai Gondi: Thank you for having us.

Dr. David Schiff: Thank you, Brittany. It was great to participate in this important project.

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline endorsement go to www.asco.org/neurooncology-guidelines.

You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.