title: Large volume re-irradiation with bevacizumab is a feasible salvage option for patients with refractory high-grade glioma.
abstract: BACKGROUND
  Clinical studies of re-irradiation (ReRT) for relapsed high-grade glioma (HGG) have generally reported the use of small volume ReRT techniques such as stereotactic radiosurgery in selected patients with isolated focal relapse. This study reports the outcome with large-volume ReRT to manage the more common mescenario of extensive diffuse relapse of HGG.
  
  
  METHODS
  All HGG patients managed with an overlapping second course of radiation therapy (RT) for refractory progression of HGG between October 2009 and April 2013 were included. ReRT was initially used with bevacizumab (BEV), then used when disease was refractory to BEV, and finally used upfront with BEV-naïve patients. Tumor volume (GTV) and specific RT dosimetry factors, including the target volume treated (PTV), and cumulative RT dose maximum (Dmax), were analyzed. Median survival post ReRT was calculated using the Kaplan-Meier method and SPPS v19 software.
  
  
  RESULTS
  Eighteen HGG participants with refractory, bulky contrast-enhancing disease received ReRT. Thirteen participants had a maximum tumor diameter >5 cm, and median GTV was 54 cm3. Seven participants had BEV-refractory disease, and 8 participants were BEV naïve. ReRT dose was 35-40 Gy in 15 fractions; median PTV was 133 cm3, and median Dmax was 98.2 Gy. Median survival post ReRT for all participants was 8 months (95%CI, 5.8-10.2 months); with 10 months and 3 months for the BEV-naïve and BEV-refractory participants, respectively (P= .024). Two early participants, who were managed without BEV, were later salvaged with BEV, including one who required craniotomy for radiation necrosis at 6 weeks post RT. No other significant morbidity was reported.
  
  
  CONCLUSIONS
  ReRT combined with BEV is a feasible salvage treatment option for diffuse refractory HGG.
authors.affiliation: Northern Sydney Cancer Centre , Royal North Shore Hospital , Sydney , Australia (M.B., C.G., M.K., L.G., H.W.); Northern Clinical School, Sydney Medical School , University of Sydney , Sydney , Australia (M.B., C.G., H.W.).
authors.forename: Michael
authors.initials: M
authors.lastname: Back
authors.affiliation: Northern Sydney Cancer Centre , Royal North Shore Hospital , Sydney , Australia (M.B., C.G., M.K., L.G., H.W.); Northern Clinical School, Sydney Medical School , University of Sydney , Sydney , Australia (M.B., C.G., H.W.).
authors.forename: Cecelia E
authors.initials: CE
authors.lastname: Gzell
authors.affiliation: Northern Sydney Cancer Centre , Royal North Shore Hospital , Sydney , Australia (M.B., C.G., M.K., L.G., H.W.); Northern Clinical School, Sydney Medical School , University of Sydney , Sydney , Australia (M.B., C.G., H.W.).
authors.forename: Marina
authors.initials: M
authors.lastname: Kastelan
authors.affiliation: Northern Sydney Cancer Centre , Royal North Shore Hospital , Sydney , Australia (M.B., C.G., M.K., L.G., H.W.); Northern Clinical School, Sydney Medical School , University of Sydney , Sydney , Australia (M.B., C.G., H.W.).
authors.forename: Linxin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Northern Sydney Cancer Centre , Royal North Shore Hospital , Sydney , Australia (M.B., C.G., M.K., L.G., H.W.); Northern Clinical School, Sydney Medical School , University of Sydney , Sydney , Australia (M.B., C.G., H.W.).
authors.forename: Helen R
authors.initials: HR
authors.lastname: Wheeler
keywords: bevacizumab; glioma; re-irradiation; salvage