title: Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis.
abstract: OBJECTIVE
  Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma.
  
  
  METHODS
  173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection.
  
  
  RESULTS
  Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis.
  
  
  CONCLUSIONS
  High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.
authors: Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. percylee@mednet.ucla.edu
authors: Percy
authors: P
authors: Lee
authors: Wietse
authors: W
authors: Eppinga
authors: Frank
authors: F
authors: Lagerwaard
authors: Timothy
authors: T
authors: Cloughesy
authors: Benjamin
authors: B
authors: Slotman
authors: Phioanh L
authors: PL
authors: Nghiemphu
authors: Pin-Chieh
authors: PC
authors: Wang
authors: Patrick
authors: P
authors: Kupelian
authors: Nzhde
authors: N
authors: Agazaryan
authors: John
authors: J
authors: Demarco
authors: Michael T
authors: MT
authors: Selch
authors: Michael
authors: M
authors: Steinberg
authors: Jung Julie
authors: JJ
authors: Kang
mesh_terms: D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D002552:Cerebral Ventricles / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000502:physiology / Q000528:radiation effects*; D011879:Radiotherapy Dosage