title: Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer.
abstract: BACKGROUND
  To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer.
  
  
  METHODS
  Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months).
  
  
  RESULTS
  Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003).
  
  
  CONCLUSIONS
  The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.
authors.affiliation: Department of Radiation Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Janjan
authors.forename: C N
authors.initials: CN
authors.lastname: Crane
authors.forename: B W
authors.initials: BW
authors.lastname: Feig
authors.forename: K
authors.initials: K
authors.lastname: Cleary
authors.forename: R
authors.initials: R
authors.lastname: Dubrow
authors.forename: S A
authors.initials: SA
authors.lastname: Curley
authors.forename: L M
authors.initials: LM
authors.lastname: Ellis
authors.forename: J
authors.initials: J
authors.lastname: Vauthey
authors.forename: R
authors.initials: R
authors.lastname: Lenzi
authors.forename: P
authors.initials: P
authors.lastname: Lynch
authors.forename: R
authors.initials: R
authors.lastname: Wolff
authors.forename: T
authors.initials: T
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Pazdur
authors.forename: J
authors.initials: J
authors.lastname: Abbruzzese
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
authors.forename: P
authors.initials: P
authors.lastname: Allen
authors.forename: B
authors.initials: B
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Skibber
mesh_terms: D000328:Adult; D000368:Aged; D001003:Anal Canal / Q000601:surgery; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil