Imaging patterns of glioblastoma progression: Comparative analysis of sequential proton boost versus conventional photon therapy

Singer L, Gött H, Vu VD, Engenhart-Cabillic R, Eberle F, Dohmen H, Jensen A, Lang S, Stein M, Uhl E, Dörfler A, Struffert T, Schmidt M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 8

Journal Issue: 1

DOI: 10.1093/noajnl/vdag116

Abstract

Background: Glioblastoma is the most aggressive brain tumor, with a 5-year survival rate of only 8%. Radiotherapy plays a crucial role in multimodal treatment. With novel therapy approaches emerging, we evaluated specific imaging patterns of progression in patients treated with a sequential proton boost after standard radiochemotherapy. Methods: We analyzed data from 144 patients with histologically confirmed glioblastoma (CNS-WHO grade4), 94 received a sequential proton boost, and 50 underwent conventional photon radiation. Tumor progression (TP) was confirmed histologically or according RANO criteria. MRI segmentation was automated using CE-marked AI software, tumor voxels were classified by location (inside or outside the clinical target volume [CTV]) and CBV-perfusion status (inclusion-zone). Results: At progression, the proton group showed significantly larger contrast-enhancing tumor volumes outside the CTV (P = .007), focused in the CTV-PTV-transition-zone (P = .004) with no significant difference inside the CTV (P = .43). Subgroup analysis revealed greater extra-CTV volumes in MGMT-unmethylated (P = .019), TERT-mutant (P = .004), and RTK II subtype patients (P = .044). Metabolically active tumor tissue showed no significant differences between groups, inside or outside the CTV (P = .15 and.30). Conclusion: Sequential proton boost therapy was associated with a distinct spatial pattern of radiographic progression, characterized by increased contrast enhancement beyond the CTV, especially in the CTV-PTV-transition-zone, without a corresponding rise in metabolic activity. These findings are hypothesis-generating and may reflect radiobiological range-edge effects or treatment-related tissue responses rather than true TP. Prospective studies integrating dosimetric and metabolic data are warranted to elucidate underlying mechanisms.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Eberhard Karls Universität Tübingen Germany (DE)

How to cite

APA:

Singer, L., Gött, H., Vu, V.D., Engenhart-Cabillic, R., Eberle, F., Dohmen, H.,... Schmidt, M. (2026). Imaging patterns of glioblastoma progression: Comparative analysis of sequential proton boost versus conventional photon therapy. Neuro-Oncology Advances, 8(1). https://doi.org/10.1093/noajnl/vdag116

MLA:

Singer, Ludwig, et al. "Imaging patterns of glioblastoma progression: Comparative analysis of sequential proton boost versus conventional photon therapy." Neuro-Oncology Advances 8.1 (2026).

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