In this study, we provide a comprehensive clinical and molecular biological characterization of radiation-induced gliomas (RIG), including a risk assessment for developing gliomas. A cohort of 12 patients who developed RIG 9.5 years (3-31 years) after previous cranial radiotherapy for brain tumors or T-cell acute lymphoblastic leukemia was established. The derived risk of RIG development based on our consecutive cohort of 371 irradiated patients was 1.6% at 10 years and 3.02% at 15 years. Patients with RIG glioma had a dismal prognosis with a median survival of 7.3 months. We described radiology features that might indicate the suspicion of RIG rather than the primary tumor recurrence. Typical molecular features identified by molecular biology examination included the absence of Histon3 mutation, methylation profile of pedHGG-RTK1 and the presence of recurrent PDGFRA amplification and CDKN2A/B deletion. Of the two long-term surviving patients, one had gliomatosis cerebri, and the other had pleomorphic xanthoastrocytoma with BRAF V600E mutation. In summary, our experience highlights the need for tissue diagnostics to allow detailed molecular biological characterization of the tumor, differentiation of the secondary tumor from the recurrence of the primary disease and potentially finding a therapeutic target.

Center for Pediatric Neuro Oncology University Hospital Motol 5 Uvalu 84 15006 Prague 5 Czech Republic

Department of Neurosurgery 2nd Faculty of Medicine Charles University Prague and University Hospital Motol 5 Uvalu 84 15006 Prague 5 Czech Republic

Department of Oncology 2nd Faculty of Medicine Charles University Prague and University Hospital Motol 5 Uvalu 84 15006 Prague 5 Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine Charles University Prague and University Hospital Motol 5 Uvalu 84 15006 Prague 5 Czech Republic

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University Prague and University Hospital Motol 5 Uvalu 84 15006 Prague 5 Czech Republic

Department of Radiology 2nd Faculty of Medicine Charles University Prague and University Hospital Motol 5 Uvalu 84 15006 Prague 5 Czech Republic

Division of Pediatric Glioma Research Hopp Children's Cancer Center Heidelberg Germany

German Cancer Research Center Heidelberg Germany

National Center for Tumor Diseases NCT Heidelberg a partnership between DKFZ and Heidelberg University Hospital Heidelberg Germany

Prague Brain Tumor Research Group 2nd Faculty of Medicine Charles University and University Hospital Motol 5 Uvalu 84 15006 Prague 5 Czech Republic

Proton Therapy Center Czech Budínova 1a 180 00 Prague Czech Republic

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