SURG-65. Neoadjuvant fractionated radiosurgery leads to shorter interruption in systemic therapy following craniotomy in patients with melanoma brain metastases

Abstract INTRODUCTION In comparison to postoperative stereotactic radiotherapy (SRT) for brain metastases, preoperative (neoadjuvant) SRT is postulated to decrease risks of leptomeningeal carcinomatosis and radiation necrosis. Another potential benefit may be shortened time to (re)starting systemic therapy, which could improve oncologic outcomes. We aimed to determine the potential impact of neoadjuvant stereotactic radiotherapy on time to post-operative systemic therapy initiation and oncologic outcomes including distant metastatic melanoma disease control. METHODS Patients with melanoma brain metastases (MBM) treated surgically between 2013-2024 at a single institution were analyzed. Patients were grouped based on timing of SRT (neoadjuvant versus adjuvant) and excluded if they did not receive postoperative systemic therapy. Progression free survival (PFS) was defined as time from surgery to progression of non-operated brain lesion(s) (D-PFS), development of new intracranial (N-PFS) or extracranial metastases (EC-PFS). The interval between surgery and (re)initiation of systemic therapy was determined. RESULTS There were 16 patients in the neoadjuvant group and 18 in the adjuvant group. Preoperative MBM-Graded prognostic assessment variables were similar between groups. Most patients underwent fractionated radiotherapy, receiving a median 24Gy (range 14-30Gy) in median three (range 1-5) fractions. Despite a shorter interval to (re)initiating systemic therapy following neoadjuvant SRT (4.0 vs 6.5 weeks, p=0.022), times to D-PFS (72.9 vs NR weeks, p=0.36), N-PFS (10.4±29.8 vs 114.7±62.9 weeks, p=0.08) and EC-PFS (101.4±26.9 vs 133.1±13.4 weeks, p=0.77) did not differ between groups. There were similar rates of D-PFS (46.7% vs 27.8%, p=0.30), N-PFS (68.8% vs 55.6%, p=0.50) and EC-PFS (31.3% vs 44.4%, p=0.50) noted between neoadjuvant and adjuvant groups, respectively. Overall survival was similar between neoadjuvant and adjuvant groups (26.9±4.5 and 37.5±4.9 months, respectively). CONCLUSION Neoadjuvant SRT for melanoma brain metastases allows for faster postoperative (re)initiation of systemic therapy after craniotomy for MBM. Beneficial impact on oncologic outcomes was not demonstrated in this limited cohort.