P15.16.a 11c-methionin pet for radiotherapy treatment planning in patients with rapid early progression after glioblastoma surgery: prospective phase ii trial

Abstract BACKGROUND Treatment of glioblastoma, the most aggressive primary brain tumor in adults, is multimodal with radiotherapy (RT) involved in almost of patients after the initial surgery. According to rare retrospective studies, progression is unfortunately seen on planning MR (called Rapid Early Progression, REP), performed usually up to 1 week before RT initiation, in a few tens of percent of patients, with no proven effect of waiting time to RT. REP was proved to be an independent negative prognostic factor. The optimal treatment of patients with REP is unknown and has not yet been studied in detail. The aim of this ongoing prospective phase II clinical trial (Eudra CT number 2020-000640-64) is to evaluate the effect of 11C-Methionin PET scan used for RT planning of glioblastoma patients with REP in order to prolong progression-free survival (PFS, primary outcome). Here we present the initial experience after the enrollment of first 26 patients out of the 67 planned. MATERIAL AND METHODS We included patients with Glioblastoma, IDHwt or Astrocytoma, IDHmt, WHO gr. IV, who developed REP and are fit for concurrent chemoradiotherapy. REP is evaluated by comparison of planning MRI and early postoperative MRI and is defined as 1) increase in postoperative residuum by ≥ 25% in any direction, 2) appearance of a new contras enhancing lesion (T1w MRI), 3) unequivocal progression of the enhancing lesion (e.g., in the case of multifocal glioblastoma where only the main tumor has been removed and the retained satellite has progressed). Patients were treated according to the Stupp or Perry protocol based on their age, and respective overall condition. Treatment response was evaluated using RANO criteria. Target volumes for RT were constructed as follows: Gross tumor volume: tumor cavity + enhancing lesion on T1w MRI + 11C-MET PET with 1.3 tumor-to- BACKGROUND ratio. Clinical target volume: GTV plus modified 2cm. The study is powered to prove increase of PFS from 4.9 months (historical cohort of patients with REP who had median overall survival of 10.7 months) to PFS 8 months. RESULTS A total of 26 patients were evaluated so far, 14 were treated according to Stupp protocol, the rest with an abbreviated course of RT in 15 fractions. The median follow up is 9.7 months. The median volume of GTV-MR was 22.2ccm (range 1.7-110.6ccm), the median volume of GTV-MET was 8.4ccm (range 0.3-46.3ccm). Median PFS was 5.6 months (6months-PFS of 46%) with a difference between those who underwent Perry protocol (8.5 months) and Stupp protocol (4.2 months). Median OS was 14 months (12months OS of 51%). CONCLUSION 11C-MET PET may be valuable in target definitions for RT of glioblastoma patients with REP. Volumetric studies, patterns of failure and quality of life will be important secondary outcomes.Supported by the Ministry of Health of the Czech Republic, grant NU20-03-00148.