title: Temporal relationship of post-operative radiotherapy with temozolomide and oncologic outcome for glioblastoma.
abstract: To determine the impact of delay between surgery and radiotherapy on overall survival (OS) in temozolomide treatmented patients with the incorporation of O6-methylguanine-DNA methyltransferase (MGMT). From 2000 to 2012, 345 consecutive glioblastoma patients were treated with surgery, radiotherapy, and temozolomide at our institution. A Cox-regression model was constructed using significant univariate parameters, known prognostic factors including MGMT, and the interval from surgery to radiotherapy (≤ 2, 2-5, and ≥ 6 weeks). Survival rates were calculated by Kaplan-Meier methods. Cox-regression was utilized to calculate adjusted hazard ratios (HR). The median survival for the entire cohort was 12.2 months. The 1 year actuarial OS was 43.1 %, 53.3 %, and 64.3 % (p = 0.11), for intervals from surgery to radiotherapy of ≤ 2, 2-5, and ≥ 6 weeks, respectively. Patients radiated within 2 weeks post-surgery were more likely to have older age (p = 0.03), treated with 2D techniques (p < 0.001) and dose <36 Gy (p < 0.001), undergo a biopsy only (p < 0.001), KPS of <70 (p < 0.001), severe pre-radiotherapy neurologic symptoms (p = 0.04), and bilateral disease (p = 0.02). Multivariate analysis including MGMT status demonstrated a significant detriment in delaying radiotherapy (≤ 2 weeks as reference); 3-5 weeks (HR 2.80 [0.72-10.89], p = 0.14), and >6 weeks (HR 3.76 [1.01-14.57], p = 0.05). We report the first analysis on the survival impact of delaying post-operative radiotherapy for temozolomide treated glioblastoma patients with MGMT information. Our data does not support the OS benefit previously seen in delayed RT when correcting for important covariates. We demonstrate a survival detriment with delaying RT post-surgery greater than 6 weeks on multivariate analysis.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 22, New York, NY, 10065, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Spratt
authors.forename: Michael
authors.initials: M
authors.lastname: Folkert
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Zumsteg
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Chan
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beal
authors.forename: Philip H
authors.initials: PH
authors.lastname: Gutin
authors.forename: Elena
authors.initials: E
authors.lastname: Pentsova
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D015331:Cohort Studies; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000379:methods*; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide