title: Long-term results of a randomized trial in locally advanced rectal cancer: no benefit from adding a brachytherapy boost.
abstract: OBJECTIVE
  Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer.
  
  
  METHODS
  Between March 2005 and November 2008, 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic complete response (pCR) at the time of surgery; secondary endpoints included overall survival (OS), progression-free survival (PFS), and freedom from locoregional failure.
  
  
  RESULTS
  Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. In all, 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up time of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, hazard ratio [HR] = 1.24, P=.34) and PFS (63.9% vs 52.0%, HR=1.22, P=.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, P=.06) in the standard and in the brachytherapy arms, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration.
  
  
  CONCLUSIONS
  Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery.
authors.affiliation: Department of Oncology, Vejle Hospital, Vejle, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. Electronic address: ane.lindegaard.appelt@rsyd.dk.
authors.forename: Ane L
authors.initials: AL
authors.lastname: Appelt
authors.affiliation: Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Vogelius
authors.affiliation: Danish Colorectal Cancer Group South, Vejle Hospital, Vejle, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Pløen
authors.affiliation: Danish Colorectal Cancer Group South, Vejle Hospital, Vejle, Denmark.
authors.forename: Søren R
authors.initials: SR
authors.lastname: Rafaelsen
authors.affiliation: Danish Colorectal Cancer Group South, Vejle Hospital, Vejle, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.affiliation: Danish Colorectal Cancer Group South, Vejle Hospital, Vejle, Denmark.
authors.forename: Birgitte M
authors.initials: BM
authors.lastname: Havelund
authors.affiliation: Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Danish Colorectal Cancer Group South, Vejle Hospital, Vejle, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001918:Brachytherapy; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D003718:Denmark; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D020266:Radiotherapy, Conformal; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
chemical_list: D005641:Tegafur; D014498:Uracil; D002955:Leucovorin