309 - Target Volume Delineation for the Re-Irradiation of Recurrent Glioblastoma: MRI- or PET-Based? Results of the GLIAA Prospective Randomized Trial

I. Popp¹, W. Weber², E. Graf³, M. Mix⁴, R. Wiehle¹, U. Nestle^1,5, T. Schimek-Jasch¹, M. Niyazi^6,7, C. Belka⁶, F. Paulsen⁷, F. Eckert⁷, M. J. Eble⁸, L. König⁸, F. A. Giordano⁹, E. Sperk⁹, F. Momm¹⁰, I. Spehl¹⁰, S. E. Combs¹¹, and A. Grosu^1,12; ¹Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany, ²Department of Nuclear Medicine, School of Medicine, Technical University Munich, Munich, Germany, ³Institute of Medical Biometry and Statistics, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany, ⁴Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany, ⁵Kliniken Maria Hilf, Department of Radiation Oncology, Moenchengladbach, Germany, ⁶Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany, ⁷Department of Radiation Oncology, University Hospital Tübingen, University of Tübingen, Tübingen, Germany, ⁸Department of Radiation Oncology, RWTH Aachen University, Aachen, Germany, ⁹Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, ¹⁰Department of Radiation Oncology, Ortenau Klinikum Offenburg-Kehl, Academic Teaching Hospital of the Albert Ludwig University of Freiburg, Offenburg, Germany, ¹¹Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ¹²German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany

Purpose/Objective(s): The aim of this trial was to investigate the oncological benefit of a re-irradiation based on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) for patients with recurrent glioblastoma (rGBM) as compared to a re-irradiation based on contrast-enhanced T1-weighted magnetic resonance imaging (T1Gd-MRI). Materials/

Methods: GLIAA was a prospective, multicenter, randomized clinical trial (NOA 10/ARO 2013-1, DKTK-a., NCT01252459). Patients with rGBM of 1-6 cm were randomized 1:1 at 14 centers in Germany between a FET-PET-based target volume delineation (experimental arm A) and a T1Gd-MRI-based target volume delineation (control arm B) and received high-precision stereotactic re-irradiation with 39 Gy à 3 Gy, 5x/week. Follow-up was performed by MRI and suspected progression was confirmed by FET-PET or histology, whenever possible. Primary endpoint was progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), locally controlled survival (LCS), recurrence patterns, and safety.
Results: Between November 26, 2013 and September 2, 2021, 200 patients were randomized between FET-PET-based (n=100) and GdT1-MRI-based (n=100) target volume delineation, of whom n=98 and n=97 patients, respectively, were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRT arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39;). Median OS was 9.4 months (95% CI 7.8-11.1) in the FET-PET arm and 9.0 months (95% CI 7.6-10.5) in the GdT1-MRI arm (HR 1.01 [95% CI 0.75-1.37], p=0.92). Median LCS was 6.3 months (95% CI 5.1-7.2) in the FET-PET arm and 6.8 months (95% CI 6.2-7.3) in the GdT1-MRI arm (HR 1.20 [95% CI 0.88-1.62], p=0.25). At 12 months, the local control rate was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). In the PET arm, 45.0% of recurrences were in field, 28.3% out of field, and 21.7% marginal. In the MRI arm, 47.4% relapsed in field, 31.6% out of field, and 14.0% marginal. Radiation necrosis was documented in 25.5% of cases in the FET-PET arm and in 21.6% in the GdT1-MRI arm. There were no adverse events related to the application of the FET tracer.
Conclusion: The GLIAA trial could not identify an oncological benefit of the FET-PET-based rGBM-re-irradiation as compared to the GdT1-MRI-based treatment. Consequently, both imaging modalities remain valid for radiotherapy planning in this case. Both the FET-PET investigation and the re-irradiation were well-tolerated, supporting the safety of this treatment.