title: Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide.
abstract: OBJECTIVE
  To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT).
  
  
  METHODS
  Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM.
  
  
  RESULTS
  Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR.
  
  
  CONCLUSIONS
  Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Shahed N
authors.initials: SN
authors.lastname: Badiyan
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Markovina
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Simpson
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Robinson
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Todd
authors.initials: T
authors.lastname: DeWees
authors.affiliation: Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: David D
authors.initials: DD
authors.lastname: Tran
authors.affiliation: Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gerry
authors.initials: G
authors.lastname: Linette
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Rohan
authors.initials: R
authors.lastname: Jalalizadeh
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Ralph
authors.initials: R
authors.lastname: Dacey
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Rich
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Chicoine
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dowling
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Leuthardt
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Zipfel
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Albert H
authors.initials: AH
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: jhuang@radonc.wustl.edu.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide