Intraoperative radiotherapy after resection of newly diagnosed brain metastases in adult patients - results of a prospective phase II trial (INTRAMET).

Abstract

Brain metastases occur in approximately 20% of cancer patients. Surgical resection followed by radiotherapy is a standard approach for symptomatic lesions. Intraoperative radiotherapy (IORT) enables immediate irradiation of the resection cavity and may facilitate treatment integration. We conducted a prospective phase-II-trial to evaluate the efficacy and safety of low-energy X-ray IORT following resection of brain metastases. INTRAMET was an open-label, single-arm study enrolling patients with suspected brain metastases between 2017 and 2022. Following resection and frozen-section confirmation of metastatic disease, IORT was delivered to the resection cavity using a mobile low-energy X-ray device. A dose of 30 Gy was prescribed to the applicator surface. Primary endpoint was local control. Secondary endpoints included distant brain control, overall survival, time to initiation of subsequent systemic therapy, and treatment-related adverse events. Thirty-five patients were included. Median follow-up was 25.7 months. Median patient age was 64 years, and 68.6% of metastases originated from lung cancer. Local control was 94.3% (95% CI, 82.9-98.8%), while distant brain control was 57.1% (95% CI, 40.7-72.4%). Median overall survival was 43.6 months. Radionecrosis occurred in 20% of patients, predominantly low grade; no grade 4 or 5 IORT-related toxicities were observed. Leptomeningeal dissemination outside the irradiated field occurred in 8.6% of patients. Median time to initiation of subsequent systemic therapy was 45 days. IORT to the resection cavity was associated with favorable local control and an acceptable safety profile. It may represent a feasible alternative to postoperative stereotactic radiosurgery in selected patients.