title: Increased subventricular zone radiation dose correlates with survival in glioblastoma patients after gross total resection.
abstract: OBJECTIVE
  Neural progenitor cells in the subventricular zone (SVZ) have a controversial role in glioblastoma multiforme (GBM) as potential tumor-initiating cells. The purpose of this study was to examine the relationship between radiation dose to the SVZ and survival in GBM patients.
  
  
  METHODS
  The study included 116 patients with primary GBM treated at the Johns Hopkins Hospital between 2006 and 2009. All patients underwent surgical resection followed by adjuvant radiation therapy with intensity modulated radiation therapy (60 Gy/30 fractions) and concomitant temozolomide. Ipsilateral, contralateral, and bilateral SVZs were contoured on treatment plans by use of coregistered magnetic resonance imaging and computed tomography. Multivariate Cox regression was used to examine the relationship between mean SVZ dose and progression-free survival (PFS), as well as overall survival (OS). Age, Karnofsky Performance Status score, and extent of resection were used as covariates. The median age was 58 years (range, 29-80 years).
  
  
  RESULTS
  Of the patients, 12% underwent biopsy, 53% had subtotal resection (STR), and 35% had gross total resection (GTR). The Karnofsky Performance Status score was less than 90 in 54 patients and was 90 or greater in 62 patients. The median ipsilateral, contralateral, and bilateral mean SVZ doses were 48.7 Gy, 34.4 Gy, and 41.5 Gy, respectively. Among patients who underwent GTR, a mean ipsilateral SVZ dose of 40 Gy or greater was associated with a significantly improved PFS compared with patients who received less than 40 Gy (15.1 months vs 10.3 months; P=.028; hazard ratio, 0.385 [95% confidence interval, 0.165-0.901]) but not in patients undergoing STR or biopsy. The subgroup of GTR patients who received an ipsilateral dose of 40 Gy or greater also had a significantly improved OS (17.5 months vs 15.6 months; P=.027; hazard ratio, 0.385 [95% confidence interval, 0.165-0.895]). No association was found between SVZ radiation dose and PFS and OS among patients who underwent STR or biopsy.
  
  
  CONCLUSIONS
  A mean radiation dose of 40 Gy or greater to the ipsilateral SVZ was associated with a significantly improved PFS and OS in patients with GBM after GTR.
authors.affiliation: Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Chen
authors.forename: Hugo
authors.initials: H
authors.lastname: Guerrero-Cazares
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.forename: Eric
authors.initials: E
authors.lastname: Ford
authors.forename: Todd
authors.initials: T
authors.lastname: McNutt
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kleinberg
authors.forename: Michael
authors.initials: M
authors.lastname: Lim
authors.forename: Kaisorn
authors.initials: K
authors.lastname: Chaichana
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quinones-Hinojosa
authors.forename: Kristin
authors.initials: K
authors.lastname: Redmond
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D002552:Cerebral Ventricles; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D050397:Radiotherapy, Intensity-Modulated; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
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