Minimizing Intracranial Disease Before Stereotactic Radiation in Single or Solitary Brain Metastases

Abstract

BACKGROUND AND OBJECTIVES: Stereotactic radiotherapy (SRT) in multiple fractions (typically ≤5) can effectively treat a wide range of brain metastases, including those less suitable for single-fraction stereotactic radiosurgery (SRS). Prior prospective studies on surgical resection with stereotactic radiation have focused exclusively on SRS, and retrospective studies have shown equivocal results regarding whether surgery is associated with improved outcomes compared with SRT alone. We compared resection with postoperative cavity SRT or SRS to SRT alone in patients with 1 brain metastasis, while including patients receiving SRS alone as an additional reference group. METHODS: We studied 716 patients in a retrospective, single-institution cohort diagnosed with single or solitary brain metastases from 2007 to 2020. Patients receiving whole-brain radiotherapy were excluded. Cox proportional hazards models were constructed for overall survival and additional intracranial outcomes. RESULTS: After adjustment for potential confounders, surgery with cavity SRT/SRS was associated with decreased all-cause mortality (hazard ratio [HR]: 0.39, 95% CI [0.27-0.57], P = 1.52 × 10−6) compared with SRT alone, along with lower risk of neurological death attributable to intracranial tumor progression (HR: 0.46, 95% CI [0.22-0.94], P = 3.32 × 10−2) and radiation necrosis (HR: 0.15, 95% CI [0.06-0.36], P = 3.28 × 10−5). Surgery with cavity SRS was also associated with decreased all-cause mortality (HR: 0.52, 95% CI [0.35-0.78], P = 1.46 × 10−3), neurological death (HR: 0.30, 95% CI [0.10-0.88], P = 2.88 × 10−2), and radiation necrosis (HR: 0.14, 95% CI [0.03-0.74], P = 2.07 × 10−2) compared with SRS alone. Surgery was associated with lower risk of all-cause mortality and neurological death in cardinality-matched subsets of the cohort. Among surgical patients, gross total resection was associated with extended overall survival (HR: 0.62, 95% CI [0.40-0.98], P = 4.02 × 10−2) along with lower risk of neurological death (HR: 0.31, 95% CI [0.17-0.57], P = 1.84 × 10−4) and local failure (HR: 0.34, 95% CI [0.16-0.75], P = 7.08 × 10−3). CONCLUSION: In patients with 1 brain metastasis, minimizing intracranial disease specifically before stereotactic radiation is associated with improved oncologic outcomes.