title: IDH mutation and MGMT promoter methylation are associated with the pseudoprogression and improved prognosis of glioblastoma multiforme patients who have undergone concurrent and adjuvant temozolomide-based chemoradiotherapy.
abstract: OBJECTIVE
  This study aimed to investigate the potential association between IDH mutation and O6-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy.
  
  
  METHODS
  A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis.
  
  
  RESULTS
  Of the 157 GBM patients, 145 (92.36%) patients, including 38 patients with psPD, 38 patients with early progression (ePD), and 69 patients with non-progression (non-PD), were followed up for six to 56 months. We identified a higher rate of MGMT promoter methylation and IDH1 mutation in psPD patients compared with ePD patients (P=0.002). In addition, MGMT promoter methylation and IDH1 mutation predicted a high probability of psPD development in GBM patients (P=0.001 and P<0.001, respectively). MGMT promoter methylation, IDH1 mutation, Karnofsky performance score (KPS) ≥70, and psPD were associated with a significantly longer overall survival of GBM patients (P=0.001, 0.001, 0.002, and P<0.001, respectively). Both of MGMT promoter methylation and IDH mutation had a cumulative effect on the OS of GBM patients. GBM patients with psPD (39.2±2.1months, P<0.001) had a longer median survival (MS) than GBM patients with ePD (11.9±1.1months) or with non-PD (24.4±2.4months).
  
  
  CONCLUSIONS
  MGMT promoter methylation and IDH1 mutation were associated with PsPD and predicted a longer median survival in GBM patients after TMZ-based chemoradiotherapy. Genetic analyses of the MGMT promoter and IDH1 may allow us to effectively treat GBM patients.
authors.affiliation: Department of Neurosurgery, Navy General Hospital, Beijing 100048, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Navy General Hospital, Beijing 100048, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Navy General Hospital, Beijing 100048, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China. Electronic address: hjzyysw@163.com.
authors.forename: Xuezhen
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D059186:Chemoradiotherapy, Adjuvant; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D011401:Promoter Regions, Genetic; 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; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Chemotherapy; Glioblastoma; IDH mutation; MGMT; Molecular genetics; Pseudoprogression