title: Benefits of interferon-β and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter: A multicenter study.
abstract: BACKGROUND
  The aim of the current study was to catalog genomic and epigenomic abnormalities in newly diagnosed glioblastoma patients and determine the correlation among clinical, genetic, and epigenetic profiles and clinical outcome.
  
  
  METHODS
  This study retrospectively included 68 consecutive patients who underwent surgical treatment and received standard radiotherapy with temozolomide (TMZ)-based chemotherapy. Of a total of 68 patients, 39 patients (57.4%) received interferon (IFN)-β in combination of TMZ.
  
  
  RESULTS
  The genetic and epigenetic alterations frequently observed were EGFR amplification (51.5%), TP53 mutation (33.8%), CDKN2A loss (32.4%), TP53 loss (16.2%), methylation of the MGMT promoter (33.8%) and IDH1 mutation (5.9%). Multivariate analysis revealed that methylated MGMT promoter and the combination of TMZ and IFN-β were independent prognostic factors associated with survival. The median survival time (MST) of the patients who received the combination of IFN-β and TMZ was significantly greater with 19.9 months as compared to the TMZ alone group (12.7 months). Notably, in even patients whose tumors had unmethylated MGMT promoter, the MST prolonged to 17.2 months when receiving TMZ with IFN-β, compared to 12.5 months in those receiving TMZ without IFN-β.
  
  
  CONCLUSIONS
  Taken together, addition of IFN-β for newly diagnosed primary GBM achieved a favorable outcome, particularly in patients with unmethylated MGMT promoter.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Motomura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.forename: Yugo
authors.initials: Y
authors.lastname: Kishida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Higashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakasu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Namba
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D002648:Child; D003131:Combined Modality Therapy; D019175:DNA Methylation; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000077204:Temozolomide
chemical_list: D016899:Interferon-beta; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide