title: Time to adjuvant chemotherapy and survival outcomes among patients with stage 2 to 3 rectal cancer treated with preoperative chemoradiation.
abstract: BACKGROUND
  Previous studies have evaluated the impact of time to adjuvant chemotherapy (AC) on survival in early-stage colon cancer. However, the optimal time to adjuvant chemotherapy (TTAC) in rectal cancer remains unclear. The objective of this study was to identify an optimal TTAC and determine its prognostic effect in stage 2 to 3 rectal cancer.
  
  
  METHODS
  Patients with stage 2 to 3 rectal cancer treated with preoperative chemoradiation and postoperative AC between 1999 and 2008 were included. Predetermined time points of 4, 6, 8, and 12 weeks from date of surgery were analyzed. Cut-point analysis was then used to determine an optimal TTAC, and overall survival at the identified cut-point was evaluated.
  
  
  RESULTS
  A total of 328 eligible patients were identified with a median age of 61 years (range 22-85 years), 70% male, and 75% stage 3 disease. The median TTAC was 7.0 weeks. Initiation of AC at 6 weeks from date of surgery was associated with a significant survival benefit (hazard ratio 0.52, 95% confidence interval 0.31-0.90, P = .017), while no significant association was seen at 4, 8 or 12 weeks (P > .05). The cut-point analysis identified an optimal TTAC of 5.6 weeks association with improved survival compared to those with a TTAC greater than 5.6 weeks (hazard ratio 0.42, 95% confidence interval 0.22-0.82, P = .0087). This cut-point was also found to be a significant prognostic factor in multivariable analysis (P = .04) adjusted for Eastern Cooperative Oncology Group performance status, age, gender, stage, margin status, and grade.
  
  
  CONCLUSIONS
  This study suggests that initiation of AC within an earlier time frame is associated with improved overall survival.
authors.affiliation: Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Gillian
authors.initials: G
authors.lastname: Gresham
authors.affiliation: Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Winson Y
authors.initials: WY
authors.lastname: Cheung
authors.affiliation: Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Speers
authors.affiliation: Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Ryan
authors.initials: R
authors.lastname: Woods
authors.affiliation: Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada. Electronic address: hkennecke@bccancer.bc.ca.
authors.forename: Hagen
authors.initials: H
authors.lastname: Kennecke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000379:methods*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
keywords: Chemoradiotherapy; Early-stage rectal cancer; Time to initiation of adjuvant chemotherapy