Proton Stereotactic Radiosurgery for Brain Metastases: A Single-Institution Analysis of 370 Patients

Int J Radiat Oncol Biol Phys. 2018 Jul 15;101(4):820-829. doi: 10.1016/j.ijrobp.2018.03.056. Epub 2018 Apr 4.

Abstract

Purpose: To report the first series of proton stereotactic radiosurgery (SRS) for the treatment of patients with single or multiple brain metastases, including failure patterns, survival outcomes, and toxicity analysis.

Methods and materials: This was a single-institution, retrospective study of 815 metastases from 370 patients treated with proton SRS between April 1991 and November 2016. Cumulative incidence estimates of local failure, distant brain failure, and pathologically confirmed radionecrosis and Kaplan-Meier estimates of overall survival were calculated. Fine and Gray and Cox regressions were performed to ascertain whether clinical and treatment factors were associated with the described endpoints.

Results: The median follow-up from proton SRS was 9.2 months. The 6- and 12-month estimates of local failure, distant brain failure, and overall survival were 4.3% (95% confidence interval [CI] 3.0%-5.9%) and 8.5% (95% CI 6.7%-10.6%), 39.1% (95% CI 34.1%-44.0%) and 48.2% (95% CI 43.0%-53.2%), and 76.0% (95% CI 71.3%-80.0%) and 51.5% (95% CI 46.3%-56.5%), respectively. The median survival was 12.4 months (95% CI 10.8-14.0 months) after proton SRS. The most common symptoms were low-grade fatigue (12.5%), headache (10.0%), motor weakness (6.2%), seizure (5.8%), and dizziness (5.4%). The rate of pathologically confirmed radionecrosis at 12 months was 3.6% (95% CI 2.0%-5.8%), and only target volume was associated on multivariate analysis (subdistribution hazard ratio 1.13, 95% CI 1.0-1.20).

Conclusions: To the best of our knowledge, this is the first reported series of proton SRS for the management of brain metastases. Moderate-dose proton SRS is well tolerated and can achieve good local control outcomes, comparable to those obtained with conventional photon SRS strategies. Although proton SRS remains resource-intensive, future strategies evaluating its selective utility in patients who would benefit most from integral dose reduction should be explored.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / radiation effects
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary*
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Necrosis / pathology
  • Proportional Hazards Models
  • Proton Therapy / adverse effects
  • Proton Therapy / methods*
  • Proton Therapy / mortality
  • Radiation Injuries / pathology
  • Radiosurgery / adverse effects
  • Radiosurgery / methods*
  • Radiosurgery / mortality
  • Retrospective Studies
  • Salvage Therapy
  • Survival Rate
  • Time Factors
  • Treatment Failure
  • Young Adult