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

## TL;DR

Reirradiation for recurrent glioblastoma is safe and may improve survival when combined with anti-VEGF therapy.

## Contribution

Demonstrates the safety and efficacy of reirradiation combined with anti-VEGF therapy for recurrent glioblastoma.

## Key findings

- Reirradiation had no grade 3–5 acute adverse events and 16.9% radiation necrosis, mostly grade 2.
- Anti-VEGF therapy reduced radiation necrosis risk and improved treatment outcomes.
- Concomitant systemic therapy was linked to significantly longer progression-free survival.

## Abstract

•Reirradiation for rGBM was safe with no grade 3–5 acute adverse events.•Radiation necrosis (RN) occurred in 16.9% of patients, mostly grade 2.•Anti-VEGF therapy reduced RN risk and improved treatment efficacy.•Concomitant systemic therapy was linked to significantly longer PFS.•No benefit for dose intensification beyond current recommendations.

Reirradiation for rGBM was safe with no grade 3–5 acute adverse events.

Radiation necrosis (RN) occurred in 16.9% of patients, mostly grade 2.

Anti-VEGF therapy reduced RN risk and improved treatment efficacy.

Concomitant systemic therapy was linked to significantly longer PFS.

No benefit for dose intensification beyond current recommendations.

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.

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).

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).

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.