Challenging WBRT: SRS Efficacy in SCLC Brain Metastases

Ayal Aizer, MD, MHS

While stereotactic radiosurgery (SRS) represents the standard-of-care instead of whole brain radiotherapy (WBRT) for patients with limited brain metastases, this standard does not extend to small cell lung cancer (SCLC) due to concerns about neurologic decline and death. A phase 2, multi-institutional, prospective study (NCT03391362) sought to investigate these paradigms.

Researchers conducted a clinical trial involving 100 patients with SCLC with 1 to 10 brain metastases, treating them with SRS instead of WBRT. The primary goal was to compare neurologic death rates between this group and historical data on patients treated with WBRT.

The results showed a lower neurologic death rate (11%) than expected compared with historical controls. This suggests that SRS may be a viable option for patients with SCLC and brain metastases, offering a potentially less harmful treatment approach without significantly increasing the risk of neurologic complications.

In an interview with Targeted Oncology^TM, Ayal Aizer, MD, MHS, head of the division of central nervous system radiation oncology at Brigham and Women’s Hospital/Dana-Farber Cancer Institute, discussed the study, its findings, and the changing paradigms for the treatment of brain metastases in SCLC.

Targeted Oncology: What unmet needs exist in this patient population?

Aizer: Patients with small cell lung cancer and brain metastases have historically been managed with whole brain radiation, which targets the entirety of the brain and can lead to some downstream negative consequences, like problems with memory, balance issues, or other toxicities. For most other cancers, there have been good data that allows physicians to and other clinicians to use targeted radiation for patients with a limited number of metastases. But all those studies excluded patients with small cell lung cancer. For pretty much every randomized study evaluating the omission of whole brain radiation in lieu of targeted approaches, patients with small cell lung cancer were excluded. There is a strong need to evaluate whether similar paradigms can hold true in this population.

What were you evaluating in this study?

We wanted to determine if stereotactic or targeted radiation to the brain in patients with small cell lung cancer and brain metastases, which are limited in number, can be done in an effective and safe way without causing significant harm to the patient or compromising their cancer-related outcomes. What we wanted to determine was, are we putting patients at risk of neurologic decline and death by leaving out the rest of the brain from the radiation field?

The study methodology was a single-arm, phase 2, prospective study of 100 patients where all patients received stereotactic or targeted radiation to the brain. We monitored a number of outcomes in that population, namely neurologic death, which was the primary outcome, but also things like how often did they develop new brain metastases? How often did we need to give additional radiation? How often did leptomeningeal disease develop? And ultimately, is this a good strategy for patients? Are we putting patients at significant risk as a result of leaving out the rest of the brain?

Could you summarize your efficacy findings?

What we found is that neurologic death rates were relatively low in patients who have small cell lung cancer brain metastases and receive targeted radiation. We had anchored what we expected to see for neurologic death, based on historical controls, managed at our institution with whole brain radiation. What we saw was that the rates of neurologic death with stereotactic radiation did not exceed the rate that we had seen historically with whole brain radiation. Given the confidence intervals around that assessment, we felt comfortable that we were not putting patients at significant risk by leaving out the rest of the brain.

The tricky part is that historically, there has been a role for prophylactic cranial radiation in patients with small cell lung cancer where even if they do not have brain metastases, treating the entirety of the brain in some settings and in some studies, has been thought to be advantageous. But that led to concern with leaving out the rest of the brain in that population. What we found from our study is a strong suggestion that stereotactic radiation may be applicable and appropriate for some patients.

What would you consider to be the biggest implications of these findings?

I think the main takeaway is that at this moment, we still do not know which is the best option for patients with small cell lung cancer and brain metastases. We are going to await 2 randomized trials, which will more definitively answer that question. I think what our study shows, and what some other data that is mainly retrospective shows, is that it is probably reasonable to offer stereotactic radiation for patients with small cell lung cancer who have never received prophylactic cranial radiation and who have a limited number of brain metastases, as long as they understand the limitations of the data and understand the nuances of both approaches, be it stereotactic or whole brain radiation. If that patient and clinician feel that the most optimal approach is stereotactic radiation, then our study does support that concept and gives providers comfort with allowing patients to receive radiation in such a manner.

What are the next steps moving forward from this research?

I think what this study establishes and demonstrates is that stereotactic radiation is likely a viable option. It is likely reasonable to consider it likely to offer some benefit. But what it does not do is compare with what some will consider to be the standard-of-care, which is full brain radiation. This is where randomized data would be most helpful. Thankfully, there is some data that has been presented, and a larger study which is still accruing that will most definitively answer this question. But I think the next step would be to look at the randomized data and see which is truly the better option.

If the paradigm in small cell lung cancer follows that of almost every other cancer that we manage that goes to the brain, we would potentially see that stereotactic approaches are better for patients, if they have a limited number of tumors. It allows them to spare so much of the toxicity that we sometimes see with whole brain radiation. Our study certainly supports that notion, but it is the randomized studies that will give us the definitive answer.

REFERENCE:

Aizer A, Bi WL, Catalano PJ, et al. Stereotactic radiosurgery in patients with small cell lung cancer and 1-10 brain metastases: A multi-institutional, phase II, prospective clinical trial. J Clin Oncol. 2024;42(suppl 16):abstr 2020. doi:10.1200/JCO.2024.42.16_suppl.2020