title: Hypofractionated stereotactic radiosurgery with concurrent bevacizumab for recurrent malignant gliomas: the University of Alabama at Birmingham experience.
abstract: BACKGROUND
  Nearly all patients with malignant glioma will have disease recurrence. Our purpose was to define the treatment toxicity and efficacy of concurrent bevazicumab (BVZ) with hypofractionated stereotactic radiosurgery (SRS) of relatively larger targets for patients with recurrent MG.
  
  
  METHODS
  A retrospective review of 21 patients with recurrent malignant glioma (18 glioblastoma, 3 WHO grade III glioma), treated at initial diagnosis with surgery and standard chemoradiation, was performed. All patients had concurrent BVZ with hypofractionatedSRS, 30 Gy in 5 fractions, with or without concurrent chemotherapy (temozolomide or CCNU).
  
  
  RESULTS
  Median patient age was 54 years, median Karnofsky Performance Status was 80, and median target size was 4.3 cm (range, 3.4-7.5 cm). Eleven patients (52%) had previously failed BVZ. One patient had grade 3 toxicities (seizures, dysphasia), which resolved with inpatient admission and intravenous steroids/antiepileptics. Treatment-related toxicities were grade 3 (n= 1), grade 2 (n= 9), and grade 0-1 (n= 11). Kaplan-Meier median progression-free survival and overall survival estimates (calculated from start of SRS) for GBM patients (n= 18) were 11.0 and 12.5 months, respectively. Concurrent chemotherapy did not appear to show any statistically significant efficacy benefit or have any propensity for toxicity.
  
  
  CONCLUSIONS
  BVZ concurrent with hypofractionated SRS was well tolerated by this cohort of patients with relatively larger targets. Ongoing randomized trials with more moderate radiotherapy dosing may help establish the efficacy of this regimen, though intricacies of this approach, including patient selection, radiation target volume delineation/size, and optimal radiation dose, will need further evaluation.
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Grant M
authors.initials: GM
authors.lastname: Clark
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McDonald
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Louis B
authors.initials: LB
authors.lastname: Nabors
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Hassan
authors.initials: H
authors.lastname: Fathalla-Shaykh
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Xiaosi
authors.initials: X
authors.lastname: Han
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Willey
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: James M
authors.initials: JM
authors.lastname: Markert
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Barton L
authors.initials: BL
authors.lastname: Guthrie
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: Markus
authors.initials: M
authors.lastname: Bredel
authors.affiliation: University of Alabama at Birmingham Radiation Oncology , Birmingham, Alabama (G.M.C., A.M.M., C.D.W., M.B., J.B.F.); University of Alabama at Birmingham Neuro-Oncology , Birmingham, Alabama (L.B.N., H.F.-S., X.H.); University of Alabama at Birmingham Neurosurgery , Birmingham, Alabama (J.M.M., B.L.G.).
authors.forename: John B
authors.initials: JB
authors.lastname: Fiveash
keywords: bevacizumab; glioblastoma; hypofractionated radiation; radiosurgery; recurrent