title: Gender affects acute organ toxicity during radiochemotherapy for rectal cancer: long-term results of the German CAO/ARO/AIO-94 phase III trial.
abstract: BACKGROUND
  The CAO/ARO/AIO-94 phase-III-trial demonstrated a significant improvement of preoperative chemoradiotherapy (CRT) versus postoperative CRT on local control for UICC stage II/III rectal cancer patients, but no effect on long-term survival. In this add-on evaluation, we investigated the association of gender and age with acute toxicity and outcome.
  
  
  METHODS
  According to actual treatment analyses, 654 of 799 patients had received pre- (n=406) or postoperative CRT (n=248); in 145 patients postoperative CRT was not applied. Gender, age and clinicopathological parameters were correlated with CRT-associated acute toxicity and survival.
  
  
  RESULTS
  The 10-year survival was higher in women than in men, with 72.4% versus 65.6% for time to recurrence (p=0.088) and 62.7% versus 58.4% for overall-survival (OS) (p=0.066), as expected. For patients receiving CRT, women showed higher hematologic (p<0.001) and acute organ toxicity (p<0.001) in the entire cohort as well as in subgroup analyses according to pre- (p=0.016) and postoperative CRT (p<0.001). Lowest OS was seen in patients without acute toxicity (p=0.0271). Multivariate analyses for OS showed that acute organ toxicity (p=0.034) was beneficial while age (p<0.001) was associated with worse OS.
  
  
  CONCLUSIONS
  Female gender is significantly associated with CRT-induced acute toxicity in rectal cancer. Acute toxicity during CRT may be associated with improved long-term outcome.
authors.affiliation: Department of Radiotherapy, University Medical Center Göttingen, Germany.
authors.forename: Hendrik Andreas
authors.initials: HA
authors.lastname: Wolff
authors.forename: Lena-Christin
authors.initials: LC
authors.lastname: Conradi
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.forename: Andreas
authors.initials: A
authors.lastname: Leha
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.forename: Susanne
authors.initials: S
authors.lastname: Merkel
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Raab
authors.forename: Jörg
authors.initials: J
authors.lastname: Tschmelitsch
authors.forename: Clemens Friedrich
authors.initials: CF
authors.lastname: Hess
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.forename: Christian
authors.initials: C
authors.lastname: Wittekind
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012004:Rectal Neoplasms / Q000401:mortality / Q000628:therapy*; D012737:Sex Factors; D013997:Time Factors
keywords: Gender; Multimodal treatment; Radiochemotherapy; Rectal cancer; Treatment associated toxicity