A biologically effective dose-based framework for integrating LDR brachytherapy and EBRT in glioblastoma treatment.

Purpose: Radiation therapy is a core component of the standard of care (SOC) for glioblastoma (GBM), yet outcomes remain poor. Rapid early progression (REP) between maximal safe resection and start of external beam radiation therapy (EBRT) is associated with reduced survival. The GESTALT trial (NCT05342883) investigates whether initiating low-dose-rate brachytherapy (LDRBT) at time of resection can mitigate rates of REP prior to EBRT. This work presents a framework for integrating LDRBT and EBRT to deliver a composite biologically effective dose (BED) distribution comparable to SOC and demonstrates its feasibility for clinical use.

Methods: A voxel-level optimization framework was developed to account for LDRBT BED when planning EBRT. The method was applied to generate EBRT plans for 34 GESTALT trial patients following resection and intraoperative implantation of GammaTile® cesium-131 LDRBT devices. Plan quality metrics and doses to organs at risk (OAR) were compared to trial requirements to demonstrate feasibility and safety.

Results: Mean composite target dose coverage was statistically equivalent to prescribed doses while achieving similar dose conformity as SOC EBRT delivered using modern techniques. Composite dose constraints for OARs were met in most cases, with constraint violations observed in fewer than 10% of patients for any individual structure.

Conclusion: These findings demonstrate the feasibility of a novel approach to account for LDRBT when optimizing EBRT to deliver a desired composite BED. These results support earlier initiation of radiation with LDRBT for GBM and establish a basis for forthcoming analyses of clinical outcomes and model performance in the GESTALT trial.