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Final Results of the Prospective Biomarker Trial PETra: [11C]-MET-Accumulation in Postoperative PET/MRI Predicts Outcome after Radiochemotherapy in Glioblastoma.

Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. annekatrin.seidlitz@uniklinikum-dresden.de. National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany. OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site, Dresden, Germany. Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. German Cancer Research Center (DKFZ), Department of Radiology, Heidelberg, Germany. Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Institute of Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, New York. Department of Chemistry and Food Chemistry, TU Dresden, Dresden, Germany. Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Dresden, Germany. German Cancer Research Center (DKFZ), Heidelberg, Germany.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2021;(5):1351-1360
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Abstract

PURPOSE This prospective trial investigates the association of time to recurrence (TTR) in glioblastoma with [11C]methionine (MET) tracer uptake before postoperative radiochemotherapy (RCT) aiming to guide radiotherapy boost regions. EXPERIMENTAL DESIGN Between 2013 and 2016, 102 patients with glioblastoma were recruited. RCT was performed with concurrent and adjuvant temozolomide to a total dose of 60 Gy. Tumor residues in postresection PET and MRI were together defined as gross tumor volumes for radiotherapy treatment planning. [11C]methionine (MET)-PET/MRI was performed before RCT and at each follow-up. RESULTS The primary hypothesis of a longer TTR for patients without increased tracer accumulation in postoperative MET-PET was confirmed in 89 patients. With 18.9 months (95% confidence interval, 9.3-28.5 months), median TTR was significantly (P < 0.001) longer for patients without (n = 29, 32.6%) as compared with 6.3 months (3.6-8.9) for patients with MET accumulation (n = 60, 67.4%) in pre-RCT PET. Although MRI often did not detect all PET-positive regions, an unfavorable impact of residual tumor in postsurgical MRI (n = 38, 42.7%) on TTR was observed [4.6 (4.2-5.1) vs. 15.5 months (6.0-24.9), P < 0.001]. Significant multivariable predictors for TTR were MRI positivity, PET-positive volume, and O6-methylguanine DNA methyltransferase (MGMT) hypermethylation. CONCLUSIONS Postsurgical amino acid PET has prognostic value for TTR after RCT in glioblastoma. Because of the added value of the metabolic beyond the pure structural information, it should complement MRI in radiotherapy planning if available with reasonable effort, at least in the context of maximal therapy. Furthermore, the spatial correlation of regions of recurrence with PET-positive volumes could provide a bioimaging basis for further trials, for example, testing local radiation dose escalation.