title: Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma.
abstract: OBJECTIVE
  An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity.
  
  
  METHODS
  Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45-54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28-56 days) and Group B (10-week to 14-week interval; 67-97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student's t-test were calculated.
  
  
  RESULTS
  Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant.
  
  
  CONCLUSIONS
  Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Jefferson Medical College, Philadelphia, PA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Stein
authors.forename: Najjia N
authors.initials: NN
authors.lastname: Mahmoud
authors.forename: Pramila Rani
authors.initials: PR
authors.lastname: Anné
authors.forename: Deborah G
authors.initials: DG
authors.lastname: Rose
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Isenberg
authors.forename: Scott D
authors.initials: SD
authors.lastname: Goldstein
authors.forename: Edith
authors.initials: E
authors.lastname: Mitchell
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fry
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin