P05.35 Intraoperative radiotherapy after resection of brain metastases (INTRAMET) - initial safety/efficacy analysis of a prospective phase II study

Abstract

BACKGROUND: Brain metastases occur in roughly 40% of patients diagnosed with systemic cancer. External beam radiotherapy (to the cavity or whole brain) lowers local recurrence rates but also prolongs the time to (systemic) salvage therapies. We here present initial safety/efficacy data on INTRAMET, a phase II trial that evaluates local efficacy of immediate sterilization of the cavity using intraoperative radiotherapy (IORT). MATERIAL AND METHODS: INTRAMET is a monocentric, open-label, one-arm, prospective, phase II study that includes patients aged 18 years and older with newly diagnosed, resectable brain metastases with a KPS of 50 of better. following resection of the macroscopic tumor, all patients receive IORT with 30 Gy prescribed to the margin of the resection cavity. The primary endpoint is local progression-free survival (L-PFS), secondary endpoints are time to salvage cancer therapy (TTST), overall survival (OS), global (cancer-specific) PFS, cognitive performance, quality of life and dose-limiting toxicities (DLT) defined as wound healing disorders, cerebral hemorrhage, ischemia or radionecrosis requiring surgical intervention. We here report (i) safety and efficacy results of a planned safety/interim analysis after inclusion of 10 patients and (ii) on a pre-planned comparison of TTSTs of IORT-treated patients and of 19 patients treated with surgery and postoperative radiotherapy (consecutively) within the same timeframe. RESULTS: All patients included in this interim analysis had a pulmonary primary (IORT group: n=7 adenocarcinoma, n=3 squamous-cell carcinoma; control group: n=14 adenocarcinoma, n=3 squamous-cell carcinoma, n=2 large cell neuroendocrine carcinoma). The median follow-up was 7.9 months. No DLT occurred. of the 10 patients receiving IORT, only one had a confirmed local recurrence which occurred synchronous with multiple other new out-of-feld metastases 41 days after treatment. The mean TTST after IORT was 46.2 [27-83] days compared to 61.3 [16-229] days in the control group, with a mean time to cerebral radiotherapy after surgery of 26.8 days. CONCLUSION: IORT for cerebral brain metastases appears to be safe and effective. In addition, the time to systemic therapy trends to be reduced, which is of high impact for palliative care, where patients have very limited survival time.