Session Item

Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). We did this study to evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for completely resected BM.

In this investigator-initiated, single-arm, open-label, phase 2 trial, adult patients (aged 18 years or older) with one completely resected supratentorial BM in the presence of up to 10 lesions suggestive of BM were recruited. All patients were treated with 50 kV portable linear accelerator using spherical applicators into the surgical cavity with a prescribed dose of 18 Gy to a depth of 1 mm. The primary endpoints were actuarial LC and BDC (LC associated with the absence of new distant BM). Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). A Simon two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to the second stage. We report the final analysis of the first stage after a minimum follow-up (FU) of 6 months was completed for all alive patients. Data set was locked on June 15, 2021. This trial is registered with ClinicalTrials.gov, number NCT03789149.

Between June 11, 2019, to November 17, 2020, 10 patients were accrued. The primary tumors were lung cancer in four patients, breast cancer and melanoma, each in two patients, and colon and endometrial cancer, each in one patient (Table 1). The median clinical and imaging FU was 11.2 (IQR 8.2-22.7) and 9.7 (ICR 6.0-14.3) months, respectively. One patient had local failure 3 months after IORT and three patients died due to extracranial progression during the FU period. Median LC was not reached and median BDC was 5 months (95% CI 2.37-7.62). The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. The incidence of LF at 6 and 12 months, with death as a competing risk, was 10%. The incidence of DBF at 6 and 12 months, with death as a competing risk, was 50% and 70%, respectively. All patients who developed DBF were salvaged with focal stereotactic radiotherapy during the FU time, with no failure with leptomeningeal carcinomatosis. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN 10 months after IORT. There were no patients with wound dehiscence.

IORT for completely resected BM is associated with a promising high local control and low risk of RN, reaching the pre-specified criteria to proceed to the second stage and warranting further studies.