title: Neoadjuvant chemoradiation versus hyperfractionated accelerated radiotherapy in locally advanced rectal cancer.
abstract: BACKGROUND
  Neoadjuvant therapy is increasingly used in resectable locally advanced rectal cancer. The exact role of the addition of chemotherapy is not established. We compared neoadjuvant therapy using chemoradiation (CRT) or hyperfractionated accelerated radiotherapy (HART).
  
  
  METHODS
  Clinical, pathological, and survival data were obtained from patients with resectable stage II or III rectal cancer within 7 cm from the anal verge. A group of 50 patients was treated with a preoperative dose of 41.6 Gy of radiotherapy (RT) in two daily fractions of 1.6 Gy over 13 days immediately followed by surgery (HART). A second group of 96 patients received 45 Gy of conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 5-fluorouracil-based chemotherapy followed by surgery within 4 to 6 weeks (CRT). Both groups were compared in terms of morbidity, pathological downstaging, local recurrence, and survival.
  
  
  RESULTS
  Both groups were comparable in terms of preoperative clinicopathological variables. The mean distance from the anal verge was 5.8 cm (HART) versus 4.9 cm (CRT). Sphincter preservation was possible in 74% (HART) versus 83.5% (CRT) of patients (P = .013). The clinical anastomotic leak rate was 2% (HART) versus 2.2% (CRT). Pathological complete response was observed in 4% (HART) versus 18% (CRT) of the resected specimens (P = .002). A pelvic recurrence developed in 6% (HART) versus 4.4% (CRT) of patients (P = .98). Overall 5-year survival was 58% (HART) versus 66% (CRT) (P = .19); disease-free 5-year survival was 51% (HART) versus 62% (CRT) (P = .037).
  
  
  CONCLUSIONS
  Compared with preoperative HART followed by immediate surgery, preoperative CRT followed by a 6-week waiting period enhances pathological response and increases sphincter preservation rate. This could be explained by the addition of chemotherapy or the longer interval between neoadjuvant therapy and surgery. No statistically significant difference was observed in local control or overall survival.
authors.affiliation: Department of Surgical Oncology, University Hospital, De Pintelaan 185, B-9000, Ghent, Belgium. Wim.ceelen@ugent.be
authors.forename: Wim
authors.initials: W
authors.lastname: Ceelen
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.forename: Piet
authors.initials: P
authors.lastname: Pattyn
authors.forename: Marc
authors.initials: M
authors.lastname: van Eijkeren
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gillardin
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
authors.forename: Peter
authors.initials: P
authors.lastname: Smeets
authors.forename: Nancy
authors.initials: N
authors.lastname: Van Damme
authors.forename: Els
authors.initials: E
authors.lastname: Monsaert
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012189:Retrospective Studies