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. 2025 Aug;174(1):243-252.
doi: 10.1007/s11060-025-05042-9. Epub 2025 May 1.

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

Sina Mansoorian  1   2   3 , Manuel Schmidt  3   4 , Thomas Weissmann  1   3 , Daniel Delev  3   5 , Dieter Henrik Heiland  3   5 , Roland Coras  3   6 , Jenny Stritzelberger  3   7 , Marc Saake  3   8 , Daniel Höfler  1   3 , Philipp Schubert  1   3 , Charlotte Schmitter  1   3 , Sebastian Lettmaier  1   3 , Irina Filimonova  1   3 , Benjamin Frey  1   3 , Udo S Gaipl  1   3 , Luitpold V Distel  1   3 , Sabine Semrau  1   3 , Christoph Bert  1   3 , Chukwuka Eze  2   3 , Stephan Schönecker  2   3 , Claus Belka  2   3 , Ingmar Blümcke  3   6 , Michael Uder  3   8 , Oliver Schnell  3   5 , Arnd Dörfler  3   4 , Rainer Fietkau  1   3 , Florian Putz  9   10
Affiliations

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

Sina Mansoorian et al. J Neurooncol. 2025 Aug.

Abstract

Purpose: 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.

Conclusion: 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.

Keywords: Chemoradiation; Glioblastoma; Prognostic factors; Radiotherapy; Recurrence; Reirradiation; Tumor volume.

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Conflict of interest statement

Declarations. Conflict of interest: The authors state that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Kaplan–Meier plot of overall and progression-free survival for the re-irradiation cohort (n = 71). Vertical bars represent censored cases
Fig. 2
Fig. 2
Effect of residual contrast-enhancing tumor at the beginning of re-irradiation on overall survival. The optimal threshold was determined by maximally selected rank statistics. P-value of 0.005 adjusted for multiple testing. Vertical bars represent censored cases
See this image and copyright information in PMC

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