title: High-dose preoperative radiation for cancer of the rectum: impact of radiation dose on patterns of failure and survival.
abstract: OBJECTIVE
  A variety of dose-time schedules are currently used for preoperative radiation therapy of rectal cancer. An analysis of patients treated with high-dose preoperative radiation therapy was undertaken to determine the influence of radiation dose on the patterns of failure, survival, and complications.
  
  
  METHODS
  Two hundred seventy-five patients with localized rectal cancer were treated with high-dose preoperative radiation therapy. One hundred fifty-six patients received 45 Gy, +/- 10% (low-dose group). Since 1985, 119 patients with clinically unfavorable cancers (fixed, low-lying, or deeply ulcerated) were given a higher dose, 55 Gy, +/- 10%, using a shrinking field technique (high-dose group). All patients underwent curative resection. Median follow-up was 66 months in the low-dose group and 28 months in the high-dose group. Patterns of failure, survival, and complications were analyzed as a function of radiation dose.
  
  
  RESULTS
  Fourteen percent (38/275) of the total group developed a local recurrence; 20% (31/156) in the low-dose group as compared with 6% (7/119) in the high-dose group. The actuarial local recurrence rate at 5 years was 20% for the low-dose group and 8% for the high-dose group, and approached statistical significance with p = .057. For tethered/fixed tumors the actuarial local recurrence rates at 5 years were 28% and 9%, respectively, with p = .05. Similarly, for low-lying tumors (less than 6 cm from the anorectal junction) the rates were 24% and 9%, respectively, with p = .04. The actuarial rate of distant metastasis was 28% in the low-dose group and 20% in the high-dose group and was not significantly different. Overall actuarial 5-year survival for the total group of patients was 66%. No significant difference in survival was observed between the two groups, despite the higher proportion of unfavorable cancers in the high-dose group. The incidence of complications was 2%, equally distributed between the two groups.
  
  
  CONCLUSIONS
  High-dose preoperative radiation therapy for rectal cancer results in excellent local control rates. However, in clinically unfavorable cancers a higher dose (55 Gy) of preoperative radiation can be given safely with significantly improved local control. Careful clinical staging is helpful in selectively treating patients with unfavorable tumors to a higher preoperative radiation dose and thus optimizing their outcome.
authors.affiliation: Department of Radiation Oncology and Nuclear Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107.
authors.forename: N R
authors.initials: NR
authors.lastname: Ahmad
authors.forename: G
authors.initials: G
authors.lastname: Marks
authors.forename: M
authors.initials: M
authors.lastname: Mohiuddin
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000532:radiotherapy* / Q000601:surgery; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate