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.

Reduced Mortality and Radiation Necrosis After Surgery With Postoperative Stereotactic Radiation in Patients With Multiple Brain Metastases

“…No patients received upfront WBRT or surgery without stereotactic radiation. 19,20 Outcomes after intracranial treatment included all-cause mortality, neurological death, local failure, radiation necrosis, and development of new brain metastases, classical leptomeningeal disease, or seizures not present at brain metastasis diagnosis. Local failure was defined as using salvage therapy after initial resection or radiotherapy to treat a growing intracranial lesion consistent with progressive tumor.…”

“…34 Neurological death was defined by marked radiographic tumor progression in the brain and corresponding neurological symptoms, leading to death without systemic disease progression or lifethreatening systemic symptoms. 19,20 Cox proportional hazards models were used to obtain hazard ratios for individual predictors. Time to oncological outcomes or last follow-up was calculated from the diagnosis of intracranial involvement.…”

“…In cause-specific Cox models for intracranial outcomes, patients who died were censored at the time of death to estimate the hazard among at-risk patients. 20 Models for all-cause mortality, neurological death, distant failure, leptomeningeal disease, and seizures were adjusted for potential confounders. These included primary tumor histological type; number of brain metastases; maximum pretreatment diameter of the largest metastasis; presence of neurological symptoms at brain metastasis diagnosis; and number of previous systemic therapy regimens (chemotherapy, targeted therapy, and immunotherapy) for metastatic disease.…”

“…Although randomized trials and retrospective studies have also established a role for surgery in single or solitary brain metastases, [17][18][19][20] there is little evidence supporting a survival benefit from surgery among patients with multiple brain metastases. 21 In practice, surgery is typically reserved for patients with controlled extracranial disease (ECD) and metastases that are bulky or causing neurological symptoms refractory to steroids.…”

“…[25][26][27][28][29][30][31] Although fractionated stereotactic radiotherapy (SRT) is a nonsurgical alternative for some bulkier metastases, outcomes associated with SRT alone relative to surgery remain controversial. 20,24,32,33 In this work, we retrospectively compared patients with multiple brain metastases treated with surgery and postoperative SRS/SRT to those treated with SRS/SRT alone in a sizable, contemporaneous cohort. Our study incorporates the largest group of patients with multiple brain metastases treated surgically that has been reported to date.…”