Reirradiation of recurrent glioblastoma: Results from a single-center retrospective cohort study

Abstract

Purpose: The management of recurrent glioblastoma (rGBM) remains a clinical challenge, with only limited therapeutic options available to date. Reirradiation may offer a progression-free survival (PFS) benefit in selected cases, but data are scarce.

Methods: Consecutive patients from the last 10 years with GBM (CNS WHO grade 4, IDH-wildtype) who underwent at least one additional course of cranial radiotherapy for suspected or histopathologically confirmed rGBM at a tertiary neuro-oncological center were retrospectively analyzed. The primary endpoint was PFS, secondary endpoints included reirradiation-related adverse event rates, with a particular focus on radiation necrosis (RN).

Results: Fifty-nine patients were included with a median follow-up (range) of 8.7 (0.5-48.0) months after reirradiation. The median time to first recurrence was 15 (4-89) months, with the majority occurring in-field (59.7 %). The EQD2_⍺/β=10 ranged from 31.3-80.2 Gy with a median prescription dose of 42 Gy. Reirradiation was combined with systemic therapy in 81.4 % of patients. No grade 3-5 acute reirradiation-related adverse events were observed. RN was diagnosed in 16.9 % of patients (80 % grade 2 and 20 % grade 3), with a notably low rate in those receiving anti-VEGF therapy parallel to reirradiation. RN risk was independent of reirradiation volume or dose (p = 0.15 and 0.43, respectively). The disease control rate following reirradiation was 83.6 % and the median PFS was 5.9 (0.5-48.0) months. Concomitant chemotherapy or anti-VEGF therapy was significantly associated with improved outcomes (p = 0.049), whereas smaller reirradiation volumes demonstrated a non-significant trend towards longer PFS (p = 0.23).

Conclusion: In this retrospective analysis, reirradiation for rGBM was feasible and safe, conferring a potential PFS benefit in selected patients. Bevacizumab emerged as a particularly promising combination partner, contributing to both RN prevention and enhanced efficacy.

Keywords: Glioblastoma; Radiation necrosis; Recurrence; Reirradiation.

Fig. 1

Overview of patient selection. Patients were included if they had received radiotherapy in the primary setting and at least one additional course of cranial radiotherapy for suspected or histopathologically confirmed recurrent glioblastoma (n = 59). GBM: glioblastoma; WHO: World Health Organization; CNS: central nervous system.

Fig. 2

Clinical outcome after reirradiation for recurrent glioblastoma. (a, b, c, d) Kaplan-Meier curves of progression-free survival (PFS) in the first 24 months depending on (a) time to initial progression < 18 months (orange) versus > 18 months (green), (b) age at recurrence ≤ 60 years (pink) versus > 60 years (gray), (c) dose prescription in EQD2_⍺/β=10 < 42 Gy (red) versus ≥ 42 Gy (blue) as well as (d) concomitant administration of systemic treatment (chemotherapy or VEGF-targeting agents in purple versus none or other treatments in yellow). Log-rank test (two-tailed); dashed lines indicate 95 % confidence intervals; p-values are shown in the corresponding graphs. (e) Distribution of best radiographic tumor response after reirradiation as per mRANO. (f) Dot plot showing reirradiation PTV sizes in cm³ (up to 100 cm³) depending on radiographic tumor response as per mRANO (green: SD, PR, CR; purple: PD). Mann-Whitney test; p-values are depicted in the graph. VEGF: vascular endothelial growth factor; mRANO: modified Response Assessment in Neuro-Oncology; PTV: planning target volume; SD: stable disease; PR: partial response; CR: complete response; PD: progressive disease; CTX: chemotherapy; DCR: disease control rate. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)