Permanent carrier-embedded cesium-131 brachytherapy for the salvage treatment of previously irradiated, recurrent brain metastases

Abstract BACKGROUND Salvage of recurrent of previously-irradiated brain metastases (rBrM) is a significant clinical challenge. High local failure rates are seen following salvage resection without adjuvant re-irradiation, while reirradiation is associated with high radionecrosis rates. Salvage surgery plus intraoperative Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced integral brain dose versus re-irradiation. METHODS A prospective registry of consecutively treated patients with rBrM after prior stereotactic radiosurgery (SRS) was analyzed. Following maximal-safe resection and intraoperative viable-disease confirmation, cavities were implanted with commercially-available, collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies). Prescribed dose was 60Gy at 5mm from the cavity. RESULTS Twenty patients underwent 24 operations with Cs131 implantation in 25 cavities. Previous SRS occurred a median of 358d preoperatively (range=56-1334). Median maximum preoperative diameter was 3.0cm (range=1.1-6.3) and enhancing volume was 9.5cm3 (range=0.6-69.7). Gross- or near-total resection was achieved in 60% of lesions. A median of 16 Cs131 seeds (range=6-30), with a median activity of 3.5U/seed were implanted. Maximal preoperative diameter and enhancing volume were weakly associated with the number of implanted seeds (correlation coefficients=0.50, 0.41, respectively). There was one postoperative wound dehiscence in a multiply resected and irradiated patient with hydrocephalus. With median follow-up of 12.5 months, 2 tumors recurred (one in-field, one marginal) resulting in a 1-year progression incidence of 9.8% (95%CI=0.0-23.2). Radiographic seed migration was identified in 7/25 cavities (28%) on surveillance scans ranging from 1.9-11.7 months post-implantation, without clinical sequelae. CONCLUSIONS With >1 year of follow-up, intraoperative brachytherapy with commercially-available Cs131 implants was associated with a high rate of local control and a favorable toxicity profile. Modest correlation between preoperative tumor geometry and implanted tiles in the context of high associated cost suggests a need to optimize planning criteria. A randomized trial of salvage resection with or without Cs131 is ongoing (NCT04690348) to assess the incremental benefit of brachytherapy.