ESTRO 2024 - Abstract Book

S875

Clinical - CNS

ESTRO 2024

Material/Methods:

We conducted a prospective, multicenter, randomized trial (NOA 10/ARO 2013-1, DKTK-a., [1]). rGBM patients with a detectable recurrence of 1-6 cm no earlier than 6 months after initial radiotherapy with 59.4-60 Gy were randomized at 14 centers in Germany. Patients were randomized 1:1 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. Randomization was centralized, computerized and stratified using a minimization algorithm. 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, differences between target volumes, quality of life, safety and toxicity. The trial was approved by the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM - Germany) and is registered with ClinicalTrials.gov (NCT01252459), the German Clinical Trials Register (DRKS00000634) and the European Clinical Trials Database (EudraCT-No. 2012-001121-27). From November 26, 2013, to September 2, 2021, of 271 patients assessed for eligibility, 200 were randomized between FET-PET-based (n=100) and GdT1-MRI-based (n=100) target volume delineation. Of these, n=98 patients in the FET-PET arm and n=97 patients in the T1Gd-MRI arm 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). Local control rate at 12 months was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). In 60 patients with progression in the experimental arm, 45.0% of recurrences were in field, 28.3% out of field, and 21.7% marginal. In 57 patients with progression in the control 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. Out of 239 patients who received the FET tracer, 9 reported 13 adverse events and 3 reported 5 SAEs in the timespan of 7 days after FET-PET. No event was related to the application of the FET tracer. Results:

Conclusion:

This trial could not demonstrate an advantage of FET-PET-based re-irradiation in comparison to the GdT1-MRI based treatment in rGBM patients. Therefore, clinicians may choose any of these two modalities for target volume delineation in this setting. Stereotactic re-irradiation with 39 Gy in 3 Gy fractions was shown to be a safe and effective treatment option for rGBM. The FET-PET investigation was well tolerated in all cases. Since only FET-PET positive patients were included, the results of this trial have no impact on the diagnostic role of FET-PET in differentiating tumor progression from post-therapeutic changes.

Keywords: re-irradiation, glioblastoma, FET-PET/MRI