Outcomes of a feasibility and safety trial of tile-based radiation therapy with cesium-131 followed by external beam radiation therapy with concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma (NCT05342883).

Abstract

2011 Background: Standard of care (SOC) of Glioblastoma (GBM) includes maximal safe resection followed by external beam radiation therapy (EBRT) with concomitant temozolomide (TMZ). This typically begins 4-6 weeks after surgery, during which rapid early progression (REP) occurs in ~50% of patients and is associated with worse survival, especially in unmethylated GBM (median OS ~13 months as per BN007). SOC treatment in BN007 showed ~38% ≥grade 3 treatment-related adverse events (TRAEs). GammaTile (GT Medical Technologies, Inc., Tempe, AZ), a tile-based radiation therapy (TBRT) with cesium-131 sources, immediately initiates radiation at resection, eliminating the 4-6-week delay. Methods: This is a prospective, single arm, open-label feasibility study across 15 US centers with a primary aim of assessing the safety and feasibility of combining resection + TBRT with an abbreviated course of EBRT with concurrent and adjuvant TMZ for newly diagnosed molecular GBM. Eligible patients were ≥18 years old; only patients with IDH-wildtype were included in survival analysis. MGMT and IDH underwent central lab review. Feasibility was defined as percent of patients who started EBRT+TMZ between 21-35 days post-surgery. Safety was assessed by incidence of ≥grade 3 TRAEs. REP was centrally reviewed. Additional aims included PFS and OS estimated using Kaplan-Meier. A planned sample size of 61 was chosen to ensure feasibility could be estimated with a ±10% degree of precision. Results are presented based on the modified intent to treat (mITT) population (enrolled patients who had surgery and confirmed GBM). Results: From 8/2022-8/2025, 70 patients were enrolled and had surgery; 67 of whom had confirmed GBM. Table 1 presents baseline characteristics. Median follow-up was 12.4 months. 93% started EBRT+TMZ; 74% started 21-35 days post-surgery. The median (range) of days from surgery to EBRT+TMZ was 29 (23-70) days. There were no delays due to EBRT planning. 39% of patients experienced a ≥grade 3 TRAE: 22% of patients were related to surgery only, 18% to radiation only, and 13% to surgery and radiation. 6.0% of patients showed REP. Median OS for patients with unmethylated MGMT was 16.5 months vs. 28.0 months for patients with methylated MGMT. The median PFS for patients with unmethylated MGMT was 9.3 months vs. not yet met for patients with methylated MGMT. Conclusions: Feasibility and safety are in line with SOC. REP had a notable reduction compared to literature. OS is encouraging. These data provide the basis for a phase 3 randomized trial (NCT07195591). Clinical trial information: NCT05342883 . Baseline characteristics. Parameter Detail n 67 Age, median 66 Male:Female, n 42:25 Ethnicity (Non-Hispanic), n 61 Race (White), n 56 EOR – GTR:not GTR, % 66:34 IDH-wildtype:mutated, n 66:1 MGMT promoter methylated:unmethylated, n 28:39