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Abstract
Background: We aimed to evaluate the efficacy of prophylactic cranial irradiation (PCI) in the contemporary management of limited-stage small cell lung cancer (LS-SCLC) and to identify optimal strategies for patient selection.

Patients and methods: This multi-institutional cohort study included patients with LS-SCLC who underwent definitive chemoradiation between 2006 and 2022, all staged using brain MRI and PET. We compared the incidence of brain metastases (BM) and overall survival (OS) between patients who received PCI and those who did not. Additionally, we analyzed the differential effect of PCI across 22 subgroups. BM was classified as either isolated or nonisolated, with cumulative incidence calculated using a competing risk model. Outcomes of salvage treatments for isolated BM were also assessed.

Results: Among the 1,302 study patients, 672 (51.6%) received PCI and 630 (48.4%) did not. During a median follow-up of 30.5 months (range, 4.2-227.2), PCI significantly reduced the cumulative incidence of BM (17.4% vs 27.6% at 2 years; P<.001), primarily by decreasing isolated BM (6.5% vs 16.1% at 2 years; P<.001), but had no significant effect on nonisolated BM. PCI consistently reduced the incidence of isolated BM across all subgroups, which led to improved OS except among patients who achieved complete response (CR) to primary treatment (hazard ratio [HR], 1.03; P=.865). Patients experiencing CR who developed isolated BM and received local salvage treatment achieved an 81.8% remission rate, resulting in OS comparable to those without BM development (HR, 1.10; P=.631). Stereotactic radiosurgery for BM salvage treatment showed superior OS compared with whole-brain radiotherapy or systemic treatment alone.

Conclusions: PCI did not improve OS in patients achieving CR, who demonstrated excellent outcomes with BM salvage treatment. Our findings suggest that MRI surveillance, combined with effective salvage treatment, may serve as a viable alternative for selected patients with LS-SCLC.

Affiliations

Hye In Lee 1, Jae Myoung Noh 2, Tae Hoon Lee 2, Eun Kyung Choi 1, Su Ssan Kim 1, Young Seob Shin 1, Yong Chan Ahn 2, Hongryull Pyo 2, Kyungmi Yang 2, Eunyeong Yang 2, Hong-Gyun Wu 3 4, Joo Ho Lee 3 4, Byoung Hyuck Kim 4 5, Minji Koh 6, Si Yeol Song 1, Hak Jae Kim 3 4 7
11Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
22Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
33Department of Radiation Oncology, Seoul National University Hospital, Seoul, Republic of Korea.
44Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
55Department of Radiation Oncology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
66Department of Radiation Oncology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Republic of Korea.
77Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.