title: Can histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival?
abstract: OBJECTIVE
  This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT).
  
  
  METHODS
  A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6-12 weeks later by surgical excision. The CRM rate and incidence, site, and pattern of local and systemic recurrences were recorded. The median follow-up was 25 months.
  
  
  RESULTS
  The overall median survival was 37 months, with a 5-year overall survival rate of 34%. Of the 150 patients, 122 underwent curative resection; 12% had a complete pathologic response, and downstaging to pT1-T2 occurred in an additional 16%. A negative CRM (R0) was achieved in 65% overall (98 of 150). Local recurrence occurred in 10% of those with R0 resection and 62% of those with R1-R2 resections. Distant metastases occurred in 29% of those with R0 resections and 75% of those with R1-R2 resections. The 3-year disease-free and 3-year overall survival rate was 9% and 25% and 52% and 64%, respectively, for patients with and without a histologically positive CRM.
  
  
  CONCLUSIONS
  After 5-fluorouracil-based CRT, a positive CRM predicted for a high risk of subsequent local recurrence and a 3-year disease-free survival rate of only 9%. For this reason, the CRM should be considered a major prognostic factor and should be validated in future trials as an early alternative clinical endpoint.
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, United Kingdom. mawdsley@gci.ac.uk
authors.forename: Suzannah
authors.initials: S
authors.lastname: Mawdsley
authors.forename: Rob
authors.initials: R
authors.lastname: Glynne-Jones
authors.forename: Juliet
authors.initials: J
authors.lastname: Grainger
authors.forename: Paul
authors.initials: P
authors.lastname: Richman
authors.forename: Andreas
authors.initials: A
authors.lastname: Makris
authors.forename: Mark
authors.initials: M
authors.lastname: Harrison
authors.forename: Richard
authors.initials: R
authors.lastname: Ashford
authors.forename: Richard A
authors.initials: RA
authors.lastname: Harrison
authors.forename: Melanie
authors.initials: M
authors.lastname: Osborne
authors.forename: Jeremy I
authors.initials: JI
authors.lastname: Livingstone
authors.forename: Peter
authors.initials: P
authors.lastname: MacDonald
authors.forename: Ian C
authors.initials: IC
authors.lastname: Mitchell
authors.forename: John
authors.initials: J
authors.lastname: Meyrick-Thomas
authors.forename: John M A
authors.initials: JM
authors.lastname: Northover
authors.forename: Alastair
authors.initials: A
authors.lastname: Windsor
authors.forename: Richard
authors.initials: R
authors.lastname: Novell
authors.forename: Marina
authors.initials: M
authors.lastname: Wallace
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D016685:Mitomycin; D002955:Leucovorin; D005472:Fluorouracil