Brain metastasis burden and management in patients with small cell lung cancer in Canada: a retrospective, population-based cohort study.

Background: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada.
Methods: This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018. Data were analysed between June 2, 2022, and December 20, 2023. Patients with second cancer diagnosis were excluded. Patients were identified and data retrieved from the Institute for Clinical Evaluative Sciences (ICES) databases. Kaplan-Meier and multivariable Cox regression analyses were performed to compare OS between patient cohorts stratified by disease stage, BM diagnosis, and intracranial treatment modality. Propensity score-matching based on age, disease stage, time to BM, and receipt of chemotherapy was performed to compare OS between intracranial treatment modalities.
Findings: 8705 patients were included (male: 4433, female: 4272). Median age at diagnosis was 68 years (interquartile range, IQR, 61-75). Median OS of all patients was 7.46 months (95% confidence interval, CI, 7.23-7.69). 32% (n = 2686) of patients developed BM (synchronous, 43.7%; asynchronous, 56.3%) with median OS of 9.76 months (95% CI, 9.36-10.22). 102 (4%), 1654 (62%), and 930 (35%) patients received stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or no treatment, respectively, for their BM in the first-line setting or after prophylactic cranial irradiation (PCI). In propensity score-matched analyses, OS from time of BM diagnosis was non-inferior between SRS- and WBRT-treated cohorts among patients who did not receive PCI (hazard ratio, HR, 0.68, 95% CI, 0.44-1.06, p = 0.091, n = 86) and in favour of SRS for those who received PCI prior to BM development (HR, 0.47, 95% CI, 0.31-0.72, p = 0.0042, n = 112).
Interpretation: OS for patients with SCLC remains poor, and many patients present with BM. With careful selection, patients with SCLC and BM may benefit from SRS treatment. Future research should incorporate information on burden of intracranial disease and novel immunotherapies.
Funding: None.
Competing Interests: IBM declares honoraria from Bristol-Myers Squibb, Agence Unik, AstraZeneca, and Merck. IBM is on the Advisory board for InSightec and received trainee funding from Takeda, AstraZeneca, and BMS as well as research funding from AstraZeneca. BHL declares institutional grants from AstraZeneca and Pfizer and honoraria and support for travel/attending meetings from AstraZeneca. AS received a research grant and acted as a consultant for Elekta/Elekta AB and BrainLab. AS received Honoraria for educational seminars from Elekta/Elekta AB, Varian, BrainLab, AstaZeneca, Seagen Inc, Cerapedics, and CarboFIX. AS was reimbursed for travel expenses by Elekta/Elekta AB, Varian, and BrainLab. AS received research grants from Seagen Inc and is Vice President for the International Stereotactic Radiosurgery Society. SD has received grant funding from the Canadian Institutes of Health Research, Gratitude 10, the Canadian Cancer Society, the Calum Macbeth fund and the Keenan Chair in Surgery. SD received royalties from Oxford University Press. SD reports support for travel and accommodation from the Congress of Neurological Surgeons and the American Association of Neurological Surgeons. SD participated on a data safety monitoring board or advisory board for the Subcortical Surgery Group and XPan Medical. SD is the Provincial Lead for CNS Cancers at Ontario Health, Cancer Care Ontario. SD receives research support from the Keenan Chair in Surgery. KG, AWE, SC, and KKWC declare no competing interests.
(© 2024 The Author(s).)