In Reply We thank Dr Simone for his thoughtful comments discussing the clinical value of the FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) multinational study,1 while appropriately highlighting the inherent limitations of retrospective analyses. We agree that there were baseline differences between the stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) cohorts, and these observations were discussed in the article. Patients receiving SRS were more likely to have some positive prognostic factors, including better performance status and fewer brain metastases, as well as some negative prognostic factors, including older age and male sex. On balance, the differences appeared to favor SRS, as evidenced by the propensity score–matched analyses demonstrating more similar overall survival (OS) outcomes than the unmatched data sets.1 These observations were, in fact, expected, given that patients offered first-line SRS rather than the historical standard of WBRT should have been carefully selected. To address imbalances, standard multivariable analyses and propensity score–matched data sets were created (with comparable demographic characteristics for age, sex, year, performance, synchronicity, and number of brain metastases) and compared. These analyses demonstrated superior time to central nervous system (CNS) progression (TTCP) with WBRT but no advantage to WBRT in OS. Similar outcomes were observed in multivariable analyses controlling for the presence of extracranial metastases and extracranial disease control status. In contrast to the framing in the letter, it is reassuring that the hazard ratio for TTCP of 0.38 for WBRT (vs SRS)1 was similar to the landmark randomized clinical trials of SRS with or without WBRT for other solid tumors2 and that the leptomeningeal (10.8%) and neurologic mortality (12.4%) rates1 following SRS were not increased over those reported in historical series of SCLC.3
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Rusthoven CG, Brown PD, Robin TP. Deferring a Change in the Standard of Care for Small Cell Lung Cancer Brain Metastases—Reply. JAMA Oncol. 2021;7(1):135–136. doi:10.1001/jamaoncol.2020.5473
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