title: MGMT gene promoter methylation as a potent prognostic factor in glioblastoma treated with temozolomide-based chemoradiotherapy: a single-institution study.
abstract: OBJECTIVE
  Recently, cells deficient in O(6)-methylguanine-DNA methyltransferase (MGMT) were found to show increased sensitivity to temozolomide (TMZ). We evaluated whether hypermethylation of MGMT was associated with survival in patients with glioblastoma multiforme (GBM).
  
  
  METHODS
  We retrospectively analyzed 93 patients with histologically confirmed GBM who received involved-field radiotherapy with TMZ from 2001 to 2008. The median age was 58 years (range, 24-78 years). Surgical resection was total in 39 patients (42%), subtotal in 30 patients (32%), and partial in 17 patients (18%); only a biopsy was performed in 7 patients (8%). Postoperative radiotherapy began within 3 weeks of surgery in 87% of the patients. Radiotherapy doses ranged from 50 to 74 Gy (median, 70 Gy). MGMT gene methylation was determined in 78 patients; MGMT was unmethylated in 43 patients (55%) and methylated in 35 patients (45%). The median follow-up period was 22 months (range, 3-88 months) for all patients.
  
  
  RESULTS
  The median overall survival (OS) was 22 months, and progression-free survival (PFS) was 11 months. MGMT gene methylation was an independently significant prognostic factor for both OS (p = 0.002) and PFS (p = 0.008) in multivariate analysis. The median OS was 29 months for the methylated group and 20 months for the unmethylated group. In 35 patients with methylated MGMT genes, the 2-year and 5-year OS rates were 54% and 31%, respectively. Six patients with combined prognostic factors of methylated MGMT genes, age ≤50 years, and total/subtotal resections are all alive 38 to 77 months after operation, whereas the median OS in 8 patients with unmethylated MGMT genes, age >50 years, and less than subtotal resection was 13.2 months.
  
  
  CONCLUSIONS
  We confirmed that MGMT gene methylation is a potent prognostic factor in patients with GBM. Our results suggest that early postoperative radiotherapy and a high total/subtotal resection rate might further improve the outcome.
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jaeho
authors.initials: J
authors.lastname: Cho
authors.forename: Jun Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chang
authors.forename: Dong Suk
authors.initials: DS
authors.lastname: Kim
authors.forename: Kyu Sung
authors.initials: KS
authors.lastname: Lee
authors.forename: Chang-Ok
authors.initials: CO
authors.lastname: Suh
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020266:Radiotherapy, Conformal; D012086:Reoperation; D012189:Retrospective Studies; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide