title: Radiotherapy plus concomitant temozolomide in primary gliosarcoma.
abstract: Clinical guidelines for gliosarcoma (GSM) are poorly defined and GSM patients are usually treated in accordance with existing guidelines for glioblastoma (GBM), with maximal surgical resection followed by chemoradiation with temozolomide (TMZ). However, it is not clear yet if GSM patients profit from TMZ therapy and if O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is crucial. We retrospectively evaluated 37 patients with histologically proven, primary GSM who had received radiation therapy since the temozolomide era (post-2005). Twenty-five patients (67.6 %) received combined chemoradiation with temozolomide, and 12 cases (32.4 %) received radiation therapy alone. Molecular markers were determined retrospectively. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses. All cases were isocitrate dehydrogenase 1 (IDH1) wildtype, MGMT promoter methylation could be observed in 33.3 % of the assessable cases (10/30) and TERT promoter mutation was seen in a high frequency of 86.7 % (26/30). The influence of TMZ therapy on overall survival (OS) was significantly improved compared with cases in which radiation therapy alone was performed (13.9 vs. 9.9 months; p = 0.045), independently of MGMT promoter methylation. The positive effect of TMZ on OS was confirmed in this study's multivariate analyses (p = 0.04), after adjusting our results for potential confounders. In conclusion, this study demonstrates that concomitant TMZ together with radiation therapy increases GSM-patient survival independent of MGMT promoter methylation. Thus, GSM can be treated in accordance to GBM guidelines. MGMT promoter methylation was infrequent and TERT promoter mutation common without influencing the survival rates. The mechanisms of TMZ effects in GSM are still not fully understood and merit further clinical and molecular-genetic and -biological evaluation.
authors.affiliation: Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Sebastian.adeberg@med.uni-heidelberg.de.|Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. Sebastian.adeberg@med.uni-heidelberg.de.|Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Sebastian.adeberg@med.uni-heidelberg.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Adeberg
authors.affiliation: Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.|Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Bernhardt
authors.affiliation: Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.|Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Semi Ben
authors.initials: SB
authors.lastname: Harrabi
authors.affiliation: Department of Neurosurgery, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.|Department of Radiation Oncology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.|Institut für Innovative Radiotherapie (iRT), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Ingostädter Landtraße 1, Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Diehl
authors.affiliation: Department of Neuropathology, University Hospital of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.affiliation: Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.|Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany.|Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rieken
authors.affiliation: Department of Neurosurgery, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Unterberg
authors.affiliation: Department of Neuropathology, University Hospital of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.|Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany.|Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D059248:Chemoradiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D018316:Gliosarcoma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008866:Microsurgery; D008875:Middle Aged; D015999:Multivariate Analysis; D019635:Neurosurgical Procedures; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C509186:TERT protein, human; D019098:Telomerase; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Gliosarcoma; IDH1; MGMT; Radiation therapy; TERT; Temozolomide