Ctni-14. neoadjuvant stereotactic radiosurgery (nasrs) for large brain metastases (brm): results of an international multicenter phase ii trial

Abstract BACKGROUND We conducted an international multi-center phase II trial evaluating NASRS for BrM. We hypothesized that radiation necrosis (RN) would be lower than post-operative cavity radiotherapy since the tissues receiving the highest radiation dose are resected in NASRS. METHODS BrM patients with 1 index lesion ( >2 and <5 cm in greatest diameter) suitable for resection, and 9 or less additional BrM (< 3 cm in greatest diameter, not requiring resection) were recruited across 3 centres. SRS was administered a median 3 (range: 2-21) days prior to surgical resection. A single fraction of 15-21 Gy was delivered, targeting the index tumor with a 2mm margin. From a sample of 30 patients, the primary endpoint was the 1-year rate of grade 2+ (G2+) RN from the index lesion. Secondary endpoints included local failure (LF), leptomeningeal disease (LMD) and overall survival (OS). RESULTS We enrolled 35 patients [Mean age (SD): 58.9 (12.9) years, 46% female] between 2018 and 2022. The most common primary histologies were lung (40%), and gastrointestinal (20%) cancers. The median BrM volume prior to surgery was 16.6 cc (range 3.2 -38.0); median index lesion size was 3.2 (range: 1.9-4.5) cm. All participants received planned protocol treatment; n = 30 are currently available for 1 year outcomes. No patients developed G2+ RN; 5 had a LF (1-year rate 38%) at 5-12-months following surgery, all of whom had an en-bloc resection. One patient each developed classic LMD and pachymeningeal failure 3 and 11 months after surgery, respectively. Median OS was 11.5 months. CONCLUSION No patients in our study experienced G2+ RN. The 1-year rate of LF was higher than anticipated, indicating the potential benefit of considering a higher radiation dose or larger margins for improved outcomes.