ESTRO 2025 - Abstract Book

S699

Clinical - CNS

ESTRO 2025

Medical Centre Mannheim, Mannheim, Germany. 11 Mannheim Cancer Center, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 12 Department of Radiation Oncology, Ortenau Klinikum Offenburg-Kehl, Academic Teaching Hospital of the Albert Ludwig University of Freiburg, Offenburg, Germany. 13 Department of Radiation Oncology, Klinikum Rechts der Isar, Technical University of Munich (TUM), Munich, Germany. 14 Department of Radiotherapy and Radio Oncology, Philipps University Marburg, Marburg, Germany. 15 Department of Radiation Therapy, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany. 16 Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany; Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany. 17 German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Freiburg, Germany Purpose/Objective: The GLIAA trial investigated the role of re-irradiation for recurrent glioblastoma (rGBM) with a target volume delineation based on either O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) or contrast enhanced T1-weighted magnetic resonance imaging (T1Gd-MRI). Material/Methods: We conducted a prospective, multicenter, randomized trial (NOA 10/ARO 2013-1, DKTK-a., [1,2]). Included were rGBM patients with an in-field recurrence of 1-6 cm, detectable on both FET-PET and T1Gd-MRI. Confirmed histology of glioblastoma was required at initial diagnosis or at recurrence. All patients had received radiotherapy with 59.4 60 Gy at least 6 months prior to inclusion. Patients were treated with high-precision stereotactic re-irradiation with 39 Gy à 3 Gy, 5x/week. Response was evaluated by MRI, and suspected progression was confirmed by FET-PET or histology, where possible. The primary endpoint was progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), locally controlled survival (LCS), recurrence patterns, and toxicity. Results: From November 26 th , 2013, to September 2 nd , 2021, 200 patients were randomized, of which 98 patients in the FET PET arm and 97 patients in the T1Gd-MRI arm were treated per protocol [2]. First, second and third recurrences were included, with multifocal tumors in 54% of patients. Mean total tumor volume was 10.9±11.2 ml. Parallel and sequential chemotherapy, allowed from April 16 th , 2019 onward for 100 patients, was given only to 23 and 18 patients, respectively. Median PFS was 4.2 months (95% confidence interval [CI] 3.8-5.3), the median OS 9.2 months (95% CI 8.3-10.3). Median LCS was 6.5 months (95% CI 6.1-7.1) with a 12-month local tumor control rate of 21%. Patients with tumors <=3 cm had significantly higher PFS (hazard ratio HR=0.64; 95% CI 0.42-0.96; p=0.03), OS (HR=0.50; 95% CI 0.33-0.76; p=0.001) and LCS (HR=0.48; 95% CI 0.31-0.73; p=0.0006). 46.2% of patients recurred in field, 29.9% out-of-field and 17.9% marginal. Aside from radionecrosis, there were 11 radiotherapy-related CTCAE grade 3-4 toxicity events in the first 90 days after treatment, and 10 afterwards. Radionecrosis was documented in 23.6% of cases and appeared to be associated with a tendency towards improved prognosis in a post-hoc analysis (HR = 0.75, 95% CI 0.52-1.08, p=0.12). Conclusion: The GLIAA trial demonstrated based on 200 rGBM patients that stereotactic re-irradiation with 39 Gy in 3Gy fractions is a safe and effective treatment option, achieving a good local tumor control in this vulnerable, pretreated population. Therapy-related toxicity was low and radionecrosis may be a predictor for favorable treatment outcome.

Keywords: re-irradiation, glioblastoma, radionecrosis

References: 1. Oehlke O, Mix M, Graf E, Schimek-Jasch T, Nestle U, Götz I, Schneider-Fuchs S, Weyerbrock A, Mader I, Baumert BG, Short SC, Meyer PT, Weber WA, Grosu AL. Amino-acid PET versus MRI guided re-irradiation in patients with recurrent glioblastoma multiforme (GLIAA) - protocol of a randomized phase II trial (NOA 10/ARO 2013-1). BMC Cancer. 2016 Oct 5;16(1):769. doi: 10.1186/s12885-016-2806-z.