title: A phase I dose escalation study of hypofractionated IMRT field-in-field boost for newly diagnosed glioblastoma multiforme.
abstract: OBJECTIVE
  To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost.
  
  
  METHODS
  Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy.
  
  
  RESULTS
  All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy.
  
  
  CONCLUSIONS
  Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.
authors.affiliation: Department of Radiation Oncology, UC Davis School of Medicine, Sacramento, CA 95817, USA. arta.monjazeb@ucdmc.ucdavis.edu
authors.forename: Arta M
authors.initials: AM
authors.lastname: Monjazeb
authors.forename: Deandra
authors.initials: D
authors.lastname: Ayala
authors.forename: Courtney
authors.initials: C
authors.lastname: Jensen
authors.forename: L Douglas
authors.initials: LD
authors.lastname: Case
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ellis
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McMullen
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Tatter
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Lesser
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D010033:Otitis Media; D011446:Prospective Studies; D011832:Radiation Injuries / Q000150:complications; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D015996:Survival Rate