title: Phase I trial of simultaneous in-field boost with helical tomotherapy for patients with one to three brain metastases.
abstract: OBJECTIVE
  Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT.
  
  
  METHODS
  The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort.
  
  
  RESULTS
  A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients.
  
  
  CONCLUSIONS
  The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.
authors.affiliation: Department of Oncology, University of Western Ontario and London Regional Cancer Program, London Health Sciences Centre, London, ON, Canada. george.rodrigues@lhsc.on.ca
authors.forename: George
authors.initials: G
authors.lastname: Rodrigues
authors.forename: Slav
authors.initials: S
authors.lastname: Yartsev
authors.forename: Brian
authors.initials: B
authors.lastname: Yaremko
authors.forename: Francisco
authors.initials: F
authors.lastname: Perera
authors.forename: A Rashid
authors.initials: AR
authors.lastname: Dar
authors.forename: Alex
authors.initials: A
authors.lastname: Hammond
authors.forename: Michael
authors.initials: M
authors.lastname: Lock
authors.forename: Edward
authors.initials: E
authors.lastname: Yu
authors.forename: Robert
authors.initials: R
authors.lastname: Ash
authors.forename: Jean-Michelle
authors.initials: JM
authors.lastname: Caudrelier
authors.forename: Deepak
authors.initials: D
authors.lastname: Khuntia
authors.forename: Laura
authors.initials: L
authors.lastname: Bailey
authors.forename: Glenn
authors.initials: G
authors.lastname: Bauman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary*; D015331:Cohort Studies; D016371:Cranial Irradiation / Q000379:methods*; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009864:Ontario; D010166:Palliative Care / Q000379:methods; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012074:Remission Induction; D036542:Tomography, Spiral Computed