Comparative Effectiveness and Safety of Prophylactic Cranial Irradiation Versus Magnetic Resonance Imaging Surveillance in Limited-Stage Small Cell Lung Cancer.

Abstract

Prophylactic cranial irradiation (PCI) has been shown to reduce brain metastasis and prolong survival in limited-stage small cell lung cancer (LS-SCLC) patients who achieve a complete response (CR) or partial response (PR) after chemoradiation therapy (CRT); however, its role in the magnetic resonance imaging (MRI) era remains uncertain. We compared overall survival (OS) and brain metastasis-free survival (BMFS) between PCI and MRI surveillance, and further evaluated the timing of PCI initiation and treatment-related toxicities. We retrospectively analyzed 336 patients with LS-SCLC who achieved CR or PR after first-line CRT at Peking University Cancer Hospital & Institute. Inverse probability of treatment weighting was used to balance baseline characteristics. OS was defined as the time from the start of treatment to death from any cause or to the last follow-up, and BMFS as the time from the start of treatment to the first diagnosis of brain metastasis or to the last follow-up. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test; hazard ratios (HRs) with 95% CIs were obtained from Cox proportional hazards models. Early PCI was defined as 3 to 6 weeks post-CRT, and delayed PCI as 7 to 12 weeks post-CRT. Toxicities, including hematologic and nonhematologic adverse events, were systematically reviewed and compared between groups using χ² or Fisher's exact tests. Between December 2005 and November 2024, 199 patients received PCI and 137 underwent MRI surveillance. At a median follow-up of 58.7 months (IQR, 48.2-69.2), PCI was associated with a longer median OS (70.0 vs 40.5 months: HR, 0.68; 95% CI, 0.49-0.96) and BMFS (not reached vs 15.7 months: HR, 0.57; 95% CI, 0.38-0.86) compared with MRI surveillance. No significant differences were observed in hematologic or nonhematologic adverse events between the PCI and MRI groups. In the timing analysis, early PCI was associated with a lower risk of brain metastasis (HR, 0.33; 95% CI, 0.12-0.94) but not with improved OS (HR, 0.64; 95% CI, 0.30-1.35). PCI was associated with longer OS and BMFS compared with MRI surveillance in LS-SCLC patients who achieved CR or PR after CRT, without an observed increase in clinically recorded treatment-related toxicities. Early PCI was associated with a lower risk of brain metastasis, although no OS benefit was observed, underscoring the need for further trials to optimize patient selection and intervention timing.