Clin Oncol (R Coll Radiol). 2026 Feb 14;52:104084. doi: 10.1016/j.clon.2026.104084. Online ahead of print.
ABSTRACT
AIMS: Brain metastases (BMs) represent the most common intracranial tumours in adults with advanced solid cancers, significantly impacting morbidity and mortality. While the emergence of systemic therapies such as immunotherapy (IT) and targeted therapy (TT) has improved survival outcomes, the interaction of these modalities with stereotactic radiotherapy/radiosurgery (SRS/SRT) remains poorly explored. This study aims to evaluate the safety, local control (LC), and efficacy of combining SRS/SRT with IT or TT in patients with BM.
MATERIALS AND METHODS: This prospective, monocentric study (“RaBITT Trial”) analysed patients with BM treated with SRS/SRT using the CyberKnife system (Accuray) between May 2020 and May 2023. Patients received IT or TT in conjunction with SRS/SRT. Outcomes assessed included LC, overall survival (OS), disease-free survival (DFS), and next-line systemic treatment-free survival (NEST-FS). Toxicity, including radionecrosis and haemorrhage, was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Statistical analysis employed Kaplan-Meier curves and univariate (UVA) and multivariate (MVA) regression models.
RESULTS: We analysed 45 patients with a total of 225 BMs. The LC rate at 1 and 2 years was 85.7% and 79.8%, respectively. The overall response rate was 85.3%, with 56 complete responses (CRs). Multivariate analysis identified a higher biological effective dose with an α/β ratio of 10 and prescription isodose as predictors of CR. DFS rates at 1 and 2 years were 37.1% and 27.5%, respectively, while OS rates were 52.5% and 44.7%, respectively. NEST-FS rates at 1 and 2 years were 35.9% and 25.5%, respectively. Toxicity analysis revealed a radionecrosis rate of 20% for patients (6.7% of total lesions), with most cases being asymptomatic. Intralesional haemorrhage occurred in 1.7% of lesions, predominantly in melanoma and lung cancer patients.
CONCLUSION: The combination of SRS/SRT with IT or TT yields high rates of LC and overall response with a manageable safety profile, emphasising the importance of personalised dosimetric planning and careful toxicity monitoring. Despite promising outcomes, the study’s monocentric nature and limited sample size highlight the need for multicenter trials with extended follow-up to optimise treatment strategies and better understand long-term risks and benefits.
PMID:41791143 | DOI:10.1016/j.clon.2026.104084
