Risk Factors for Progression and Toxicity after Preoperative Radiosurgery for Resected Brain Metastases: A PROPS-BM Multicenter Cohort Study

Abstract

<h3>Purpose/Objective(s)</h3> Preoperative (preop) stereotactic radiosurgery (SRS) is a feasible alternative to postoperative (postop) SRS with potential benefits in adverse radiation effect (ARE) and meningeal disease (MD) compared to postop SRS. The goal of this study was to determine risk factors for progression and toxicity after preop SRS in an expanded multicenter cohort. <h3>Materials/Methods</h3> Patients with brain metastases (BM) from solid cancers, of which at least 1 lesion was treated with preop SRS and underwent planned resection were included from 6 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included classically radiosensitive or non-solid cancers and prior or planned whole brain radiotherapy (WBRT). SRS dose, fractionation, and interval between preop SRS and surgery was per individual institutional protocol. Intracranial outcomes were estimated using cumulative incidence with competing risk of death. Radiographic MD was categorized as nodular (nMD) or classical "sugarcoating" (cMD). <h3>Results</h3> The cohort consisted of 378 patients with 389 preop SRS treated index lesions. Most patients (61.1%) had a single BM, underwent gross total resection (GTR, 95.4%), and had non-small cell lung (NSCLC, 47.9%), breast (16.1%), or melanoma (11.4%) cancer. Median dose was 15 Gy in 1 fraction to a median gross tumor volume (GTV) of 10.1 cc. Median interval between preop SRS and surgery was 2 days. Median cranial imaging follow-up interval was 9.5 months overall and 17.5 months for alive patients. The 2-year cavity local recurrence (LR) rate was 14.5%. Multivariable analysis (MVA) for LR demonstrated subtotal resection (STR, vs. GTR), single fraction SRS (vs. fractionated), larger GTV, gastrointestinal (GI) primary (vs. NSCLC), active systemic disease, and piecemeal resection (vs. en bloc) to be associated with higher risk of LR. Of note, interval between preop SRS and surgery was not significant. The 2-year any grade ARE rate was 7.7%. MVA for ARE demonstrated only larger planning target volume (PTV) margin expansion as associated with higher risk of ARE. The 2-year rate of MD was 5.6%. Most MD (76%) was classical type, with the remainder being nodular type. MVA for MD demonstrated STR (vs. GTR) and breast or melanoma histology (vs. NSCLC) as associated with higher risk of MD. Of note, posterior fossa location and type of surgical resection were not significant. <h3>Conclusion</h3> Preop SRS demonstrates overall excellent rates of cavity LR, ARE, and MD in this expanded multicenter cohort study. We have identified several tumor and treatment factors that are significantly associated with risk of cavity LR, ARE, and MD after treatment with preop SRS. Minimizing likelihood of STR and treating with fractionated preop SRS for larger higher risk tumors may lead to improved outcomes. A randomized trial of preop versus postop SRS is currently being designed (NRG BN012).