Radiotherapy or systemic therapy versus combined therapy in patients with brain metastases: a propensity-score matched study

Abstract

Aim: This study aimed to evaluate the clinical benefits of systemic therapy (ST) combined with stereotactic radiosurgery (SRS) for brain metastases (BM).

Methods: The patient data were extracted from the institutional disease database from 2016 to 2021. Surgical and whole-brain radiotherapy cases and poor Karnofsky performance status (KPS < 70) were excluded. The eligible patients were divided into monotherapy (SRS alone or ST alone) and combined therapy (SRS and ST, combined within a month). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of death and intracranial progression. The propensity score for selecting treatment was calculated based on existing prognostic covariates. Two groups were matched 1:1 and compared for intracranial progression-free survival (PFS) and overall survival (OS).

Results: We identified 1605 patients and analyzed 928 (monotherapy: n = 494, combined therapy: n = 434). In a multivariable model, the combined therapy was independently associated with improved PFS and OS relative to the monotherapy. At the median follow-up of 383 days in the matched dataset, the combined therapy group showed significantly longer PFS (median, 7.4 vs. 5.0 months, P < 0.001) and OS (median, 23.1 vs. 17.2 months, P = 0.036) than the monotherapy group. The overall intracranial progression and mortality risk was reduced in the combined therapy group, with an estimated HR of 0.70 and 0.78.

Conclusions: Combined therapy exhibited longer PFS and OS than monotherapy in BM patients. The results support the recent trend toward combining systemic and local therapies, encouraging future clinical trials.

Keywords: Brain metastases; Immunotherapy; Radiosurgery; Radiotherapy; Systemic therapy; Targeted therapy.