Identification of Factors Associated with Improved Outcomes After Brain Metastasis Surgical Resection in Patients with Oligometastatic Disease

Introduction: The incidence of oligometastatic disease to the brain (OMDB) has increased as local, systemic, and targeted treatments of single brain metastasis have been developed and improved. There is currently limited evidence on which patients with OMDB are good surgical candidates. This study aimed to develop a selection paradigm that facilitates informed decision-making by identifying patients who are most likely to benefit long-term from resection.

Methods: Patients with OMDB, defined as 2-5 brain metastases, who underwent craniotomy at a single-institution were selected for analysis. Multivariable Cox regression identified independent predictors of overall survival. Recursive partitioning analysis (RPA) ranked putative predictors by prognostic importance and created a survival decision tree for patient risk-stratification. Kaplan-Meier analysis validated the risk groups established by the selection strategy.

Results: From 2006-2023, 175 OMDB patients underwent resection of a dominant metastasis, of which 49.1% had 2, 27.4% had 3, 14.3% had 4, and 9.1% had 5 metastases. On Cox regression, patients with longer time from brain metastasis diagnosis to surgery (HR=0.75, p=0.013), gross-total resection (GTR) (HR=0.57, p=0.037), or postoperative checkpoint inhibitor (HR=0.30, p< 0.001), targeted inhibitor (HR=0.53, p=0.023), or radiotherapy (HR=0.39, p< 0.001) treatment were independently associated with longer survival. On RPA, a decision tree with three branched groups was developed based on systemic disease status at surgery and extent of resection (EOR). Survival was different across the groups on Kaplan-Meier analysis (log-rank p-value < 0.001). Patients with both extracranial disease and subtotal resection had shorter survival (median=0.88-years) than all patients without extracranial disease regardless of EOR (median=2.67-years, HR=2.50, p=0.001) and patients with active extracranial disease but GTR (median=1.90-years, HR=2.99, p=0.001).

Conclusion : Patients with OMDB and metastases amenable to GTR or no evidence of extracranial disease may benefit most from surgery. The use of postoperative systemic therapy, including checkpoint inhibitors, targeted inhibitors, or radiotherapy all enhance postoperative survival.