title: Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival.
abstract: OBJECTIVE
  Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS).
  
  
  METHODS
  A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m2/day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection.
  
  
  RESULTS
  Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03).
  
  
  CONCLUSIONS
  All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. kirsty.wiltshire@lycos.com
authors.forename: Kirsty L
authors.initials: KL
authors.lastname: Wiltshire
authors.forename: Iain G
authors.initials: IG
authors.lastname: Ward
authors.forename: Carol
authors.initials: C
authors.lastname: Swallow
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Bernard
authors.initials: B
authors.lastname: Cummings
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Pamela
authors.initials: P
authors.lastname: Catton
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: Chong S
authors.initials: CS
authors.lastname: Wong
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wong
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
authors.forename: Malcolm
authors.initials: M
authors.lastname: Moore
authors.forename: James
authors.initials: J
authors.lastname: Brierley
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011183:Postoperative Complications / Q000209:etiology; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil