title: Radio-chemotherapy improves survival in IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma patients.
abstract: Isocitrate dehydrogenase (IDH) mutations are beginning to drive decisions on therapy for glioma patients. Here we sought to determine the impact of adjuvant treatment in patients with IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma (sHGA) WHO grades III/IV. Clinical data of 109 sHGA patients grades III/IV, in addition to IDH mutation-, 1p/19q-codeletion- and MGMT-promoter methylation status-were retrospectively analyzed. Survival analysis in relation to adjuvant treatment modalities and molecular profiling were performed. Out of 109 patients, 88 patients (80.7 %) harbored IDH mutations, 30 patients had a 1p/19q-codeletion (27.5 %) and 69 patients (63.3 %) exhibited a methylated MGMT-promoter status. At a median follow-up of 9.8 years, 62 patients (57 %) died. The postsurgical treatment included: radio-chemotherapy (RT-CT; 54.5 %), RT alone (19.3 %), and CT alone (22.7 %). The median overall survival (OS) in the entire group was 3.4 years (1.9-6.7 years). Patients who received RT-CT had a significantly longer OS compared with those who underwent RT alone (6.5 vs. 1.2 years, HR 0.35, CI 0.32-0.51, p = 0.011). In the IDH-mutant 1p/19q non-codeleted sHGA subgroup the RT-CT cohort had a significantly longer OS in comparison to the RT cohort (6.4 vs. 1.2 years, HR 2.7, CI 1.1-6.5, p = 0.022). In the stepwise multivariable Cox model for OS of all 88 IDH-mutant sHGA patients, survival was strongly associated with only one factor, namely, adjuvant RT-CT at diagnosis of a sHGA. This retrospective long-term study demonstrates that RT and CT (mostly PCV) significantly improves progression-free and overall survival in IDH-mutant secondary high-grade astrocytoma patients, regardless of 1p/19q-codeletion status.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany. Tareq.Juratli@uniklinikum-dresden.de.
authors.forename: Tareq A
authors.initials: TA
authors.lastname: Juratli
authors.affiliation: Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center/Arthur G. James Cancer Hospital and Richard L. Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Lautenschläger
authors.affiliation: Institute of Neuropathology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Kathrin D
authors.initials: KD
authors.lastname: Geiger
authors.affiliation: Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pinzer
authors.affiliation: German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.|Institute of Radiooncology, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.|Department of Radiation Oncology and OncoRay, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.affiliation: Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.affiliation: Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.|German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Krex
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: 1p/19q-codeletion; IDH mutation; PCV MGMT-promoter status; Radio-chemotherapy; Secondary high-grade astrocytomas