title: Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme.
abstract: BACKGROUND
  Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE) radiotherapy improved tumor control and survival in GBM patients.
  
  
  METHODS
  We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction) and conventional doses (60 Gy), respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ) were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated.
  
  
  RESULTS
  Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS) of patients who received DE radiotherapy was 15.2 months (95% confidence interval [CI] =11.0-18.6), while median OS of the latter cohort was 18.4 months (95% CI =12.5-31.4, P=0.253). Univariate analyses of clinical and dosimetric parameters among the DE cohort demonstrated a trend of longer progression-free survival, but not OS, with incremental radiation doses to the ipsilateral SVZ (hazard ratio [HR] =0.95, 95% CI =0.90-1.00, P=0.052) and proportion of ipsilateral SVZ receiving 50 Gy (HR =0.98, 95% CI =0.97-1.00, P=0.017).
  
  
  CONCLUSIONS
  DE radiotherapy did not improve survival in patients with GBM. Incorporation of ipsilateral SVZ as a radiotherapy target volume for patients with GBM requires prospective validation.
authors.affiliation: Division of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Grace
authors.initials: G
authors.lastname: Kusumawidjaja
authors.affiliation: Division of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Patricia Zhun Hong
authors.initials: PZ
authors.lastname: Gan
authors.affiliation: Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore.
authors.forename: Whee Sze
authors.initials: WS
authors.lastname: Ong
authors.affiliation: Department of Radiology, Division of Radiation Oncology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
authors.forename: Achiraya
authors.initials: A
authors.lastname: Teyateeti
authors.affiliation: Department of Radiology, Division of Radiation Oncology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
authors.forename: Pittaya
authors.initials: P
authors.lastname: Dankulchai
authors.affiliation: Division of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Daniel Yat Harn
authors.initials: DY
authors.lastname: Tan
authors.affiliation: Division of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Eu Tiong
authors.initials: ET
authors.lastname: Chua
authors.affiliation: Division of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Kevin Lee Min
authors.initials: KL
authors.lastname: Chua
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Chee Kian
authors.initials: CK
authors.lastname: Tham
authors.affiliation: Division of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Fuh Yong
authors.initials: FY
authors.lastname: Wong
authors.affiliation: Division of Radiation Oncology, National Cancer Centre, Singapore; Duke-NUS Graduate Medical School, Singapore.
authors.forename: Melvin Lee Kiang
authors.initials: ML
authors.lastname: Chua
keywords: dose escalation; glioblastoma multiforme; intensity-modulated radiotherapy; subventricular zones