Type and timing of systemic therapy use predict overall survival for patients with brain metastases treated with radiation therapy

J Neurooncol. 2021 Jan;151(2):231-240. doi: 10.1007/s11060-020-03657-8. Epub 2020 Nov 18.

Abstract

Introduction: This study aimed to investigate whether systemic therapy (ST) use surrounding radiation therapy (RT) predicts overall survival (OS) after RT for patients with brain metastases (BMs).

Methods: Provincial RT and pharmacy databases were used to review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016 (n = 3095). Multivariate analysis on a randomly selected subset was used to develop an OS nomogram.

Results: In comparison to the 2096 non-recipients of ST after RT, the median OS of the 999 recipients of ST after RT was 5.0 (95% Confidence interval (CI) 4.1-6.0) months longer (p < 0.0001). Some types of ST after RT were independently predictive of OS: targeted therapy (hazard ratio (HR) 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55), cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79), and immunotherapy (HR 0.64, CI 0.37-1.06). Patients who discontinued ST after RT had 0.9 (CI 0.3-1.4) months shorter median OS than patients who received no ST before or after RT (p < 0.0001). In the multivariate analysis of the 220-patient subset, established prognostic variables (extracranial disease, performance status, age, cancer diagnosis, and number of BMs), and the novel variables "ST before RT" and "Type of ST after RT" independently predicted OS. The nomogram predicted 6- and 12-month OS probability and median OS (bootstrap-corrected Harrell's Concordance Index = 0.70).

Conclusions: The type and timing of ST use surrounding RT predict OS for patients with BMs.

Keywords: Brain metastases; Nomogram; Radiation therapy; Systemic therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • Combined Modality Therapy
  • Cranial Irradiation / mortality*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Nomograms*
  • Prognosis
  • Retrospective Studies
  • Salvage Therapy*
  • Survival Rate
  • Time-to-Treatment / statistics & numerical data*
  • Young Adult