title: Determining the Optimal Timing for Initiation of Adjuvant Chemotherapy After Resection for Stage II and III Colon Cancer.
abstract: BACKGROUND
  Several reports suggest that the efficacy of adjuvant chemotherapy on survival diminishes over time for colon cancer; however, precise timing of its loss of benefit has not been established.
  
  
  OBJECTIVE
  This study aimed to determine the relationship between time to adjuvant chemotherapy and survival and to identify a threshold for increased risk of mortality.
  
  
  METHODS
  This was a retrospective study. Multivariable Cox proportional hazard modeling with restricted cubic splines was used to evaluate the adjusted association between time to adjuvant chemotherapy and overall survival and to establish an optimal threshold for the initiation of therapy.
  
  
  METHODS
  Data were collected from the National Cancer Data Base.
  
  
  METHODS
  Adults who received adjuvant chemotherapy following resection of stage II to III colon cancers were selected.
  
  
  METHODS
  The primary outcome measured was overall survival.
  
  
  RESULTS
  A total of 7794 patients were included. After adjusting for clinical, tumor, and treatment characteristics, our model determined a critical threshold of chemotherapy initiation at 44 days from surgery, after which there was an increase in the overall mortality. At a median follow-up of 61 months, the risk of mortality was increased in those who received adjuvant chemotherapy after 44 days from surgery (adjusted HR, 1.14; 95% CI, 1.05-1.24; p = 0.002), but not in those who received chemotherapy before 44 days from surgery (p = 0.11). Each additional week of delay was associated with a 7% decrease in survival (HR, 1.07; 95% CI, 1.04-1.10; p < 0.001).
  
  
  CONCLUSIONS
  This study was limited by selection bias and the inability to compare specific chemotherapy regimens.
  
  
  CONCLUSIONS
  This study objectively determines the optimal timing of adjuvant chemotherapy for patients with resected colon cancer. Delay beyond 6 weeks is associated with compromised survival. These findings emphasize the importance of the timely initiation of therapy, and suggest that efforts to enhance recovery following surgery have the potential to improve survival by decreasing delay to adjuvant chemotherapy.
authors.affiliation: Department of Surgery, Duke University, Durham, North Carolina.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Sun
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Adam
authors.forename: Jina
authors.initials: J
authors.lastname: Kim
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Nussbaum
authors.forename: Ehsan
authors.initials: E
authors.lastname: Benrashid
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Mantyh
authors.forename: John
authors.initials: J
authors.lastname: Migaly
mesh_terms: D000368:Aged; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D003082:Colectomy / Q000379:methods; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D011184:Postoperative Period; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome