Intracranial radiotherapy with or without immune checkpoint inhibition for brain metastases: a systematic review and meta-analysis

BACKGROUND: With the development of immunotherapy in recent years, the prognosis of patients is expected to improve due to immune checkpoint inhibition (ICI) combined with radiotherapy (RT). However, studies on combination therapy (ICI + intracranial RT) have reported inconsistent results, and it is unclear whether the combination has increased toxicity. By analyzing the latest relevant literature, we performed a meta-analysis to further clarify the effectiveness and safety of intracranial RT combined with ICI in patients with brain metastases (BMs). METHODS: We searched PubMed, Embase and the Cochrane Library for published studies that compared the efficacy and safety of intracranial RT combined with ICI versus intracranial RT alone in the treatment of BMs. Overall survival (OS), local brain failure (LBF), distant brain failure (DBF), and radiation necrosis (RN) were pooled with the use of the hazard ratio (HR) or odds ratio (OR). RESULTS: A total of 26 retrospective observation cohort studies were included, and over 1,500 patients who received ICI and intracranial RT were evaluated. Compared with intracranial RT alone, RT combined with ICI significantly improved OS in patients with BMs [HR =0.55, 95% confidence interval (CI): 0.48–0.64, P<0.001 when OS was defined from the date of diagnosis of BMs; HR =0.45, 95% CI: 0.39–0.52, P<0.001 when OS was defined from the date of RT], though the risk of RN was similar to that of RT alone (HR =1.27, 95% CI: 0.58–2.79, P=0.55). However, significant improvement in LBF and DBF was not obtained with RT combined with ICI (1-year LBF: OR =1.71, 95% CI: 0.38–7.67, P=0.48; LBF: HR =0.49, 95% CI: 0.28–0.87, P=0.01; 1-year DBF: OR =1.05, 95% CI: 0.47–2.33, P=0.90). CONCLUSIONS: ICI combined with intracranial RT confers a significant OS benefit for patients with BMs without significantly increasing treatment-related toxicity, but further research regarding the specific details of combined treatment application is needed to improve the survival and quality of life of patients with BMs.