title: Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial.
abstract: OBJECTIVE
  Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG.
  
  
  METHODS
  Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status.
  
  
  RESULTS
  One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months.
  
  
  CONCLUSIONS
  Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
authors.forename: Alvin R
authors.initials: AR
authors.lastname: Cabrera
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Cuneo
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: Frances
authors.initials: F
authors.lastname: McSherry
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Peters
authors.forename: Karen
authors.initials: K
authors.lastname: Allen
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Hoang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chang
authors.forename: Oana
authors.initials: O
authors.lastname: Craciunescu
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: John P
authors.initials: JP
authors.lastname: Kirkpatrick
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D011446:Prospective Studies; D011788:Quality of Life; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab