title: Dose-effect relationship in chemoradiotherapy for locally advanced rectal cancer: a randomized trial comparing two radiation doses.
abstract: OBJECTIVE
  Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation.
  
  
  METHODS
  The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of ≤5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; arm B). Concomitant chemotherapy, uftoral 300 mg/m2 and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0).
  
  
  RESULTS
  The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04).
  
  
  CONCLUSIONS
  This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.
authors.affiliation: Danish Colorectal Cancer Group South, Vejle Hospital, Vejle, Denmark. anders.jakobsen@slb.regionsyddanmark.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
authors.forename: John
authors.initials: J
authors.lastname: Ploen
authors.forename: Té
authors.initials: T
authors.lastname: Vuong
authors.forename: Ane
authors.initials: A
authors.lastname: Appelt
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.forename: Soren R
authors.initials: SR
authors.lastname: Rafaelsen
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D001918:Brachytherapy / Q000379:methods*; D003718:Denmark; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011792:Quebec; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D012074:Remission Induction; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D005472:Fluorouracil