Up-Front Stereotactic Radiosurgery an Option for SCLC Brain Mets

Largest Study of Its Kind

Megan Brooks

June 10, 2020

A new retrospective study provides some of the strongest support yet for considering first-line stereotactic radiosurgery (SRS) over whole-brain radiotherapy (WBRT) in carefully selected patients with brain metastases from small-cell lung cancer (SCLC), the researchers say.

As expected, WBRT was superior to focused SRS in lengthening the time to disease progression in the brain. However, this advantage did not appear to provide an improvement in overall survival (OS).

Dr Chad Rusthoven

"This study suggests that the trade-offs inherent to first-line SRS without WBRT, including a shorter time to new brain metastases without an apparent difference in overall survival, may be similar to other settings where SRS alone is already well established," lead author Chad Rusthoven, MD, told Medscape Medical News.

Up-front SRS may be "particularly attractive for SCLC patients with limited brain metastases and those at a higher risk of developing neurocognitive toxicity from WBRT, including older patients and those with a poor baseline performance status," said Rusthoven, of the Department of Radiation Oncology, University of Colorado School of Medicine, Aurora.

Results of the FIRE-SCLC study ― the largest analysis of first-line SRS for patients with SCLC brain metastases ― were published online June 4 in JAMA Oncology.

The coauthors of an editorial in JAMA Oncology say the FIRE-SCLC study investigators should be "commended for conducting this important work and also for highlighting the inherent limitations of retrospective data.

"Even after multivariable adjustment, OS may not be directly compared between the SRS and WBRT groups because selection bias is likely," caution Cecile Le Pechoux, MD, and Antonin Levy, MD, PhD, from Institut Gustave-Roussy, in Villejuif, France.

"Impressive" Outcomes

The researchers analyzed the outcomes of 710 patients (mean age, 68.5 years; 75% men; Karnofsky Performance Status score, ≥90) who underwent first-line SRS without prior treatment with WBRT or prophylactic cranial irradiation. They compared the SRS outcomes with outcomes of a cohort of 219 patients treated with first-line WBRT for SCLC brain metastases.

The SRS outcomes are "encouraging," with median OS of 8.5 months, median time to central nervous system (CNS) progression (TTCP) of 8.1 months, and median CNS progression-free survival (PFS) of 5.0 months, the study investigators say.

The outcomes are "particularly impressive" in patients with a single brain metastasis (median OS and TTCP, 11.0 months and 11.7 months, respectively), they note.

They found no significant differences in OS or TTCP after SRS in patients with two to four lesions and those with five to 10 lesions.

Median OS was 8.7 months with two to four lesions, 8.0 months with five to 10 lesions, and 5.5 months with 11 or more lesions. Corresponding median TTCP was 6.8, 6.1, and 4.7 months.

Local failures after SRS were rare. Most CNS progression occurred in the form of new lesions, which is in line with what's been shown with SRS in other settings.

In propensity score–matched analyses that compared SRS with WBRT, median OS was higher with SRS (6.5 months vs 5.2 months with WBRT; P = .003). Median TTCP was improved with WBRT (SRS, 9.0 months vs WBRT, not reached; hazard ratio, 0.38; 95% confidence interval, 0.26 – 0.55; P < .001), with no significant difference in CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79).

The results were similar in multivariable analyses that compared SRS and WBRT, including subgroup analyses that controlled for extracranial metastases and extracranial disease control status.

Benchmark Data

"Although these retrospective data should not be used to conclude that OS is superior with SRS, the findings of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP, are similar to other settings in which SRS alone is well established by multiple randomized clinical trials," the researchers write.

These data, they say, provide a "benchmark for SRS outcomes and offer support to first-line SRS as a treatment option in carefully selected patients with small cell lung cancer."

In a news release, senior author Tyler Robin, MD, University of Colorado School of Medicine, notes that paradigms for the treatment of SCLC are "evolving," with the integration of immunotherapy into SCLC management, less use of WBRT, and guideline updates advising routine brain MRI surveillance for all patients.

"These changes may be expected to increase the identification of small-cell lung cancer patients with limited brain metastases who may be candidates for first-line SRS," said Robin.

SRS made mainstream headlines in 2015 when former President Jimmy Carter was successfully treated for melanoma brain metastases with it. At the time, SRS was relatively new. The approach is more targeted and less toxic than traditional WBRT. Carter was treated at Emory University in Atlanta, Georgia.

SRS is now widely available in the United States, but adoption has been slow, Rusthoven told Medscape Medical News.

"Delayed adoption of SRS for SCLC is related to a number of factors, including a concern for short-interval CNS progression with SCLC histology and the historical exclusion of SCLC patients from the landmark randomized trials that established SRS alone," he said.

"We hope that this study will contribute to an increased interest in the role of SRS for carefully selected SCLC patients and that it will offer support to ongoing and developing prospective clinical trials evaluating first-line SRS alone for SCLC," Rusthoven added.

Prospective Data "Eagerly" Needed

The French editorial writers say prospective data are "eagerly needed" for this patient population.

SRS, they conclude, "might be a promising treatment option" for patients with SCLC with brain metastases, but larger studies are needed, as prophylactic cranial irradiation or prophylactic-intent WBRT has been shown to improve survival. "Hopefully, the work of Rusthoven et al will be used for the development of further prospective trials in patients with SCLC with brain metastases," they write.

The study was funded by a grant from the University of Colorado Cancer Center. Rusthoven has received research funding from Takeda outside the submitted work as well as honoraria for educational talks from Genentech and AstraZeneca outside this work. The original article contains a complete list of author disclosures. Le Pechoux has received institutional honoraria for participation in advisory boards from AstraZeneca, Nanobiotix, and Roche; institutional honoraria for participation to educational meetings from Amgen, AstraZeneca, Medscape, and Eli Lilly and Company; and personal honoraria from prIME Oncology for participation in educational meetings. Levy has disclosed no relevant financial relationships.

JAMA Oncol. Published online June 4, 2020. Abstract, Editorial

Follow Medscape Oncology on Twitter for more cancer news: @MedscapeOnc.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.