Incidence, Risk Factors, and Impact of Immunotherapy on Brain Metastasis in Extensive-Stage Small Cell Lung Cancer Without Baseline Brain Involvement.

Abstract

Brain metastasis is a frequent site of metastasis in extensive-stage small cell lung cancer (ES-SCLC). We investigated the incidence, risk factors, and the impact of immunotherapy on brain metastasis development in patients without initial brain involvement. A prospective cohort of 371 ES-SCLC patients without baseline brain metastasis from January 2012 to December 2023 were included in this study. Competing risk models were used to estimate the cumulative incidence of brain metastasis. Multivariate competing risk regression identified risk factors of brain metastasis. Among 371 patients (chemoimmunotherapy [CIT]: n = 147; chemotherapy alone: n = 224), 25.88% (96/371) developed brain metastasis over a median follow-up of 37.73 months. Brain metastasis was the first site of progression in 17.79% patients (66/371), with 11.32% (42/371) experiencing isolated brain metastasis. The 1-year cumulative incidence did not differ significantly between CIT and chemotherapy-alone groups (26.37% <i>v</i> 19.93%; <i>P</i> = .133). Prophylactic cranial irradiation (PCI) was independently associated with a lower risk of brain metastasis <b>(</b>adjusted subdistribution hazard ratio, 0.431 [95% CI, 0.195 to 0.955]; <i>P</i> = .038). Adding immunotherapy to chemotherapy did not significantly reduce brain metastasis incidence in ES-SCLC patients without baseline brain involvement. PCI remained the sole evidence-based strategy for brain metastasis prevention in this population, underscoring the need for novel CNS-directed approaches.