Reirradiation for recurrent glioblastoma: the significance of the residual tumor volume.

Objective: Recurrent glioblastoma has a poor prognosis, and its optimal management remains unclear. Reirradiation (re-RT) is a promising treatment option, but long-term outcomes and optimal patient selection criteria are not well established.

Methods: This study analyzed 71 patients with recurrent CNS WHO grade 4, IDHwt glioblastoma (GBM) who underwent re-RT at the University of Erlangen-Nuremberg between January 2009 and June 2019. Imaging follow-ups were conducted every 3 months. Progression-free survival (PFS) was defined using RANO criteria. Outcomes, feasibility, and toxicity of re-RT were evaluated. Contrast-enhancing tumor volume was measured using a deep learning auto-segmentation pipeline with expert validation and jointly evaluated with clinical and molecular-pathologic factors.

Results: Most patients were prescribed conventionally fractionated re-RT (84.5%) with 45 Gy in 1.8 Gy fractions, combined with temozolomide (TMZ, 49.3%) or lomustine (CCNU, 12.7%). Re-RT was completed as planned in 94.4% of patients. After a median follow-up of 73.8 months, 88.7% of patients had died. The median overall survival was 9.6 months, and the median progression-free survival was 5.3 months. Multivariate analysis identified residual contrast-enhancing tumor volume at re-RT (HR 1.040 per cm3, p < 0.001) as the single dominant predictor of overall survival.

Conclusions: Conventional fractionated re-RT is a feasible and effective treatment for recurrent high-grade glioma. The significant prognostic impact of residual tumor volume highlights the importance of combining maximum-safe resection with re-RT for improved outcomes.