PracticeUpdate Oncology May 2019

EXPERT OPINION 20

Stereotactic Radiosurgery vs Whole Brain Radiation for Patients With Four or More Brain Metastases Interview with Michael Lim MD by Aman Shah MD

Dr. Shah: I have a very specific patient scenario and I wanted to tease out the best treatment in this situation. For a patient who has four ormore brainmetastases, what would you say is the difference between, or the reasons to use stereotactic radiosurgery, or whole-brain radiation? Dr. Lim: That’s a great question, and I think that’s something that we, as a field, are still trying to sort out. I can tell you what we understand is, of course, pathology plays an important factor in this. If, for example, someone has small cell lung cancer, we generally have steered those patients towards whole-brain radiation. But if somebody has a good performance status and has a good control, whole- brain radiation may not be the best step for a person. You know, to be clear, it is the standard of care, but there are some toxicities that can happen in patients with whole-brain radiation. And, in the past, the sur- vival was so poor for patients with whole brain, with brain metastases, that often times patients weren’t living long enough to see the side effects of memory problems, concentration problems, and depression. But now, with all these great therapies, we think that patients have a reasonable chance of living a long or longer life, and quality of life has become a very important factor in deciding which therapies to give for patients with multiple brain metastases. In gen- eral, we used to say there was this arbitrary number of five or less, we used to give stereotactic radiosur- gery, but there’s been a study out of Japan where you can give up to 10, and people can have very good local control, and good quality of life. And I assume that number may even go up higher. What I can say is that there have been many different approaches. People have tried surgery for multiple lesions, some people have tried stereotactic radiosurgery alone, some people have tried surgery plus a stereotac- tic boost, people have tried whole-brain radiation followed by stereotactic boosts. You can see the different permutations that are possible for this, but what’s interesting is if you look at these studies as a whole, and you look at survival, survival’s not affected. As long as you use salvage therapy, the survivals are about the same in all these patients, so then, I think quality of life becomes the biggest issue. And so, if someone comes in with a great performance status and has four brain metastases, I’m not saying it’s the right answer, but our practice

preference would be to give patients stereotactic radiosurgery, with the thought that they may need additional stereotactic radiosurgery or whole-brain radiation in the future because we think that quality of life is better that way. Dr. Shah: And how does systemic therapy or immu- notherapy fit into this equation, both in terms of the therapy that the patient might be on influencing what kind of radiation you give them, or the other way around, the synergies between these two. Dr. Lim: So, there are some chemotherapeutic agents that we think can be synergistic, or, in terms of toxic- ity, and so, in general, a lot of people just pause and hold the systemic therapy while patients undergo radiation or the stereotactic radiosurgery. I think what’s been interesting, we’ve seen the news with Jimmy Carter getting stereotactic radiosurgery plus the checkpoint inhibitors, anti-PD-1, and there are case reports, and now, even retrospective studies showing that there’s potentially improved survival in patients who get this combination. The thought is that, if you use stereotactic radiation, for example, it acts as kindling to start a systemic immune response. What it’s ultimately doing is killing some tumor cells to promote antigen release. It’s probably, also, caus- ing damage to activate the myeloid cells to pick up the antigens, and probably just stunning the tumor cells to not be so immunosuppressive. And so, what you’re doing is using a local therapy to essentially start a systemic immune response, and there’s this phenomenon called the abscopal response, where peoples’ tumors in distant sites have been melting away, just by using stereotactic radiosurgery. Dr. Shah: So, if you could just walk us through a clinical scenario of melanoma patient who is most likely going to be quite responsive to immunotherapy, now presents with four or more brain metastases. How would you approach that patient at your institution? Dr. Lim: Well I think, first of all, you want to assess the brain metastases and we want to make sure that

Dr. Lim is Associate Professor of

Neurosurgery, Oncology and

Radiation Oncology, and Director of Brain Tumor Immunotherapy at The Johns Hopkins Hospital in Baltimore, Maryland.

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