Study on the Safety and Efficacy of Biological Target Radiotherapy Based on 11C-MET PET/CT in Patients with Newly Diagnosed Glioblastoma

Abstract

<h3>Purpose/Objective(s)</h3> The purpose of this study was to evaluate the safety and efficacy of biological target area (BTV) defined by ¹¹C-methionine positron emission tomography / computed tomography (¹¹C-MET PET/CT) in postoperative radiotherapy for glioblastoma. <h3>Materials/Methods</h3> This study is a single-arm, open, single-center exploratory clinical study. Patients with newly diagnosed glioblastoma confirmed by pathology in our center were enrolled. The initial biological target area (BTV) was delineated on the basis of the area of high metabolism of ¹¹C-MET PET/CT. Finally, the BTV included the highly increased area of ¹¹C-MET PET/CT metabolism and comprehensively considered the abnormal signal areas on multimodal magnetic resonance imaging. BTV dose escalation with a simultaneous or increased in late course. Oral chemotherapy of temozolomide was given concurrently, and temozolomide adjuvant chemotherapy was given for 6 cycles after simultaneous radiotherapy and chemotherapy. The primary clinical study endpoints were safety, progression-free survival (PFS), and the secondary study endpoints were overall survival (OS) and 1 year survival (OS-1). The Common Terminology Criteria for Adverse Events (CTCAE) version 5. 0 was used to evaluate the adverse reactions. Folstein Mini-Mental Status Exam (MMSE) was used to evaluate the cognitive function of the patients. <h3>Results</h3> A total of 18 patients with assessable glioblastoma were enrolled from November 22, 2018 to June 2, 2021. The median follow-up period was 14.4 months (7.9months-37.2months). The median BTV dose was 74 Gy (64 Gy-75 Gy), and the median CTV dose was 60 Gy (50.1 Gy-60 Gy). The median dose of CTV1 was 46 Gy (30 Gy-50.1 Gy), and the median dose of CTV2 was 14 Gy (8 Gy-23.4 Gy). The median PFS was 10.1 months (95%CI:7.25-12.95). The main acute adverse events were hematological adverse events. Grade 1 leukopenia occurred in 5 patients (27.8%), and no grade 2 leukopenia was observed.4 patients (22.2%) developed grade 2 gastrointestinal reactions (nausea, vomiting, anorexia). One patient (5.6%) had advanced cognitive decline (MMSE score ≤ 26). No other hematological adverse events and non-hematological adverse events such as radiation brain necrosis were observed. OS-1 is 85.6%. The median OS was not reached. <h3>Conclusion</h3> BTV based on ¹¹C-MET PET/CT images guided dose-escalated radiotherapy has a good short-term effect in the treatment of newly diagnosed glioblastoma patients, and the incidence of adverse reactions is low, safe and tolerable. The long-term effect still needs longer follow-up and a large sample of clinical studies.