title: Phase II trial of preoperative chemoradiation with a hyperfractionated radiation boost in locally advanced rectal cancer.
abstract: OBJECTIVE
  The purpose of this phase II study was to prospectively determine the efficacy of preoperative chemoradiation with a hyperfractionated (Hfx) RT boost to 61.8 Gy in locally advanced rectal cancer.
  
  
  METHODS
  Eligibility stipulated that the primary lesion had to be either T4; or T3 and >4 cm or 40% of the bowel circumference. Radiation (RT) consisted of 45 Gy to the pelvis (1.8 Gy per fraction) followed by 1.2 Gy twice daily (to the gross tumor volume) to a total RT dose of 61.8 Gy. There was 5-FU infused at 1 g/m2/24 hours for 4 days during the 1st and 6th weeks of RT (concurrent with the Hfx boost). Surgical resection was planned 4 to 6 weeks later. Adjuvant chemotherapy (bolus 5-FU/leucovorin) was scheduled for 4 cycles at 28-day intervals.
  
  
  RESULTS
  There were 22 patients, ages 22 to 81 years (median, 64) enrolled in the study. Of the 20 patients evaluable for response, 10 (50%) had evidence of clinical downstaging and 5 patients (25%) had > or =90% fibrosis in the resected specimen. With a median f/u of 40 months (7-158), the 4 years actuarial rate for all patients (n = 22) of OS was 64%, of DFS 62%, and of LC 84%. 3/21 patients (14%) had positive margins, all of whom developed a local failure (P < 0.001).
  
  
  CONCLUSIONS
  This regimen of high dose preoperative chemoRT with a Hfx RT boost (to 61.8 Gy) in patients with bulky, locally advanced rectal cancer results in clinical downstaging in half of the patients with significant fibrosis in the operative specimen.
authors.affiliation: Henry Ford Health System, Radiation Oncology, Detroit, MI 48202, USA. bmovsas1@hfhs.org
authors.forename: Benjamin
authors.initials: B
authors.lastname: Movsas
authors.forename: Hasmik
authors.initials: H
authors.lastname: Diratzouian
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hanlon
authors.forename: Harry
authors.initials: H
authors.lastname: Cooper
authors.forename: Gary
authors.initials: G
authors.lastname: Freedman
authors.forename: Andre
authors.initials: A
authors.lastname: Konski
authors.forename: Elin
authors.initials: E
authors.lastname: Sigurdson
authors.forename: John
authors.initials: J
authors.lastname: Hoffman
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiner
authors.forename: Lawrence
authors.initials: L
authors.lastname: Coia
authors.forename: Rachelle
authors.initials: R
authors.lastname: Lanciano
authors.forename: Joanne
authors.initials: J
authors.lastname: Stein
authors.forename: Debra
authors.initials: D
authors.lastname: Kister
authors.forename: Burton
authors.initials: B
authors.lastname: Eisenberg
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011882:Radiotherapy, High-Energy; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil