A Phase 3 Randomized Controlled Trial of Post-Surgical Stereotactic Radiotherapy Versus Surgically Targeted Radiation Therapy with GammaTile for Treatment of Newly Diagnosed Metastatic Brain Tumors.

TPS2092 Background: Optimal management for brain metastases (BM) is crucial for outcomes of patients with metastatic cancer. The size of the BM often drives the treatment approach, with larger, symptomatic BM considered for resection followed by adjuvant stereotactic radiotherapy (SRS). SRS improves local control over resection alone. While adjuvant SRS is a well-developed standard of care for surgical BM, there are downsides that warrant consideration for alternative strategies. Local recurrence occurs in approximately 20-30% of patients, with delays to receiving adjuvant SRS associated with worse outcomes. Additionally, up to 20% of patients develop radiation necrosis. BM patients would benefit from improvements in these outcomes. GammaTile (GT Medical Technologies) is an FDA-approved device that consists of four cesium-131 radiation-emitting seeds in a collagen tile. Tiles are placed to line the cavity immediately after BM resection. This brachytherapy approach has a number of potential benefits, including an immediate start of radiation after resection when the disease burden is at a minimum; optimization of radiation dosimetry; and direct visualization of the cavity time of tile placement. Additionally, patients do not need to return as an outpatient for radiation treatment of the surgical lesion. Methods: This is a phase III trial with a 1:1 randomization between GammaTile brachytherapy and post-resection SRS of previously untreated BM with stratification based on patient age, duration of extracranial disease control, number of metastases, histology, maximal lesion diameter, and use of immunotherapy. The primary end point is surgical bed recurrence-free survival. Secondary end points include overall survival, physical function, neurocognitive status, quality of life, and safety. Adult patients with 1 to 4 newly diagnosed BM with a single index lesion (between 2.0 cm and 5.0 cm) planned for surgical resection are eligible. Previous and/or concurrent treatment with systemic therapies is permitted. Patients must have a Karnofsky Performance Status score of ≥70 and have stable systemic disease or reasonable systemic treatment options with a life expectancy of ≥6 months. Past radiation or surgical therapy to the index lesion or the newly diagnosed non-index lesion(s) is exclusionary, however up to 2 prior courses of SRS treatment to previously diagnosed BM are allowed if at least 15 mm from the index lesion. As of February 3 2024, 87 patients have enrolled and 80 have been randomized across 17 sites, out of a total accrual goal of 180 patients. This is a multicenter randomized controlled trial funded by GT Medical Technologies (NCT04365374). The study opened for enrollment in April 2021. The DMC last reviewed the trial in October 2023 and recommended that the trial continue as planned. Clinical trial information: NCT04365374 .