title: Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients.
abstract: OBJECTIVE
  Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ).
  
  
  METHODS
  We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis.
  
  
  RESULTS
  Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82).
  
  
  CONCLUSIONS
  With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall survival for HRT and SRT with concurrent TMZ among elderly patients, suggesting the need for a randomized trial to compare these regimens directly.
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nils D
authors.initials: ND
authors.lastname: Arvold
authors.affiliation: Harvard Radiation Oncology Program, Boston, Massachusetts.
authors.forename: Shyam K
authors.initials: SK
authors.lastname: Tanguturi
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ayal A
authors.initials: AA
authors.lastname: Aizer
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Eudocia Q
authors.initials: EQ
authors.lastname: Lee
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Nayak
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Laura W
authors.initials: LW
authors.lastname: Christianson
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Horvath
authors.affiliation: Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Dunn
authors.affiliation: Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Golby
authors.affiliation: Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts; School of Public Health, Yale University, New Haven, Connecticut.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Claus
authors.affiliation: Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: E Antonio
authors.initials: EA
authors.lastname: Chiocca
authors.affiliation: Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts. Electronic address: bmalexander@lroc.harvard.edu.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Alexander
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D057216:Propensity Score; D012189:Retrospective Studies; D015983:Selection Bias; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide