title: Optimal Timing to Surgery after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.
abstract: BACKGROUND
  Neoadjuvant chemoradiotherapy (nCRT) has demonstrated proven benefit in tumor regression and improved long-term local control for patients with locally advanced rectal cancer. However, precise analysis of the optimal waiting time that maximizes oncologic benefits of nCRT has not been established.
  
  
  METHODS
  The 2006-2012 National Cancer Data Base was queried for patients with stage II and III rectal adenocarcinoma who underwent nCRT followed by surgical resection. Time to surgery was defined as the difference between last date of radiotherapy and date of surgery. Primary study endpoints included resection margin positivity and pathologic downstaging. Multivariable regression modeling with restricted cubic splines was used to evaluate the adjusted association between time to surgery and our study endpoints, and to establish an optimal time threshold for surgery.
  
  
  RESULTS
  A total of 11,760 patients were included. Median time to surgery was 53 days (interquartile range [IQR] 43 to 63 days). After adjusting for patient demographic, clinical, tumor, and treatment characteristics, our model determined an inflection point at 56 days after end of radiotherapy associated with the highest likelihood of complete resection and pathologic downstaging. With adjustment, the risk of margin positivity was increased in those who underwent surgery after 56 days from end of radiotherapy (odds ratio [OR] 1.40, 95% CI 1.21 to 1.61, p < 0.001). The likelihood of downstaging was increasing up to 56 days after radiotherapy (≥56 days vs <56 days, OR 1.2, 95% CI 1.02 to 1.23, p = 0.01).
  
  
  CONCLUSIONS
  This study objectively determined the optimal time for surgery after completion of nCRT for rectal cancer based on completeness of resection and tumor downstaging. Eight weeks appears to be the critical threshold for optimal tumor response.
authors.affiliation: Department of Surgery, Duke University, Durham, NC. Electronic address: zhifei.sun@duke.edu.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Surgery, Duke University, Durham, NC.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Adam
authors.affiliation: Department of Surgery, Duke University, Durham, NC.
authors.forename: Jina
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Surgery, Duke University, Durham, NC.
authors.forename: Mithun
authors.initials: M
authors.lastname: Shenoi
authors.affiliation: Department of Surgery, Duke University, Durham, NC.
authors.forename: John
authors.initials: J
authors.lastname: Migaly
authors.affiliation: Department of Surgery, Duke University, Durham, NC.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Mantyh
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D061665:Time-to-Treatment; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology