title: Effect of adjuvant chemotherapy on recurrence-free survival varies by neo-adjuvant treatment in patients with stage III rectal cancer.
abstract: BACKGROUND
  Adjuvant chemotherapy still is a controversial therapy for rectal cancer patients. The aim of this study was to analyze the effect of adjuvant chemotherapy on recurrence-free survival (RFS) for patients with stage III rectal cancer treated in clinical practice, taking into account which neo-adjuvant treatment patients received.
  
  
  METHODS
  Patients from regions in the Netherlands diagnosed between 1996 and 2013 with pathological stage III rectal cancer who received short-course radiotherapy, chemoradiation or no neo-adjuvant treatment and who underwent surgery were included. After stratification by neo-adjuvant treatment, 5-year RFS according to adjuvant chemotherapy receipt was calculated using Kaplan-Meier curves. Cox regression was used to discriminate the independent effect of adjuvant chemotherapy on the risk of recurrence/death.
  
  
  RESULTS
  The study population consisted of 829 patients, of whom 537 (65%) patients received short-course radiotherapy, 128 (15%) patients received chemoradiation and 164 (20%) patients received no neo-adjuvant treatment. Adjuvant chemotherapy was administered to 152 (18%) patients. Adjuvant chemotherapy was associated with improved 5-year RFS for patients who received short-course radiotherapy (61% vs. 46%, p = 0.005) and for patients who did not receive any neo-adjuvant treatment (70% vs. 28%, p < 0.0001). In multivariable analyses, adjuvant chemotherapy was associated with a reduced risk of recurrence/death for patients treated with short-course radiotherapy (HR 0.65, 95% CI 0.46-0.93) and for patients without neo-adjuvant treatment (HR 0.35, 95% CI 0.18-0.71), but not for patients treated with chemoradiation (HR 1.11, 95% CI 0.51-2.41).
  
  
  CONCLUSIONS
  Among patients with stage III rectal cancer, the effect of adjuvant chemotherapy on RFS seems to vary by neo-adjuvant treatment.
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Eindhoven, The Netherlands; Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. Electronic address: f.vanerning@iknl.nl.
authors.forename: F N
authors.initials: FN
authors.lastname: van Erning
authors.affiliation: Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: H J T
authors.initials: HJ
authors.lastname: Rutten
authors.affiliation: Department of Radiotherapy, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: van den Berg
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Eindhoven, The Netherlands; Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
authors.forename: V E P P
authors.initials: VE
authors.lastname: Lemmens
authors.affiliation: Department of Internal Medicine, Admiraal de Ruyter Hospital, Goes/Vlissingen, The Netherlands.
authors.forename: H K
authors.initials: HK
authors.lastname: van Halteren
mesh_terms: D000368:Aged; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
keywords: Adjuvant chemotherapy; Chemoradiation; Rectal cancer; Recurrence-free survival; Short-course radiotherapy