Phase II trial of preoperative chemoradiation with a hyperfractionated radiation boost in locally advanced rectal cancer.
OBJECTIVE
The purpose of this phase II study was to prospectively determine the efficacy of preoperative chemoradiation with a hyperfractionated (Hfx) RT boost to 61.8 Gy in locally advanced rectal cancer.


METHODS
Eligibility stipulated that the primary lesion had to be either T4; or T3 and >4 cm or 40% of the bowel circumference. Radiation (RT) consisted of 45 Gy to the pelvis (1.8 Gy per fraction) followed by 1.2 Gy twice daily (to the gross tumor volume) to a total RT dose of 61.8 Gy. There was 5-FU infused at 1 g/m2/24 hours for 4 days during the 1st and 6th weeks of RT (concurrent with the Hfx boost). Surgical resection was planned 4 to 6 weeks later. Adjuvant chemotherapy (bolus 5-FU/leucovorin) was scheduled for 4 cycles at 28-day intervals.


RESULTS
There were 22 patients, ages 22 to 81 years (median, 64) enrolled in the study. Of the 20 patients evaluable for response, 10 (50%) had evidence of clinical downstaging and 5 patients (25%) had > or =90% fibrosis in the resected specimen. With a median f/u of 40 months (7-158), the 4 years actuarial rate for all patients (n = 22) of OS was 64%, of DFS 62%, and of LC 84%. 3/21 patients (14%) had positive margins, all of whom developed a local failure (P < 0.001).


CONCLUSIONS
This regimen of high dose preoperative chemoRT with a Hfx RT boost (to 61.8 Gy) in patients with bulky, locally advanced rectal cancer results in clinical downstaging in half of the patients with significant fibrosis in the operative specimen.
Movsas
Benjamin
B
Henry Ford Health System, Radiation Oncology, Detroit, MI 48202, USA. bmovsas1@hfhs.org
Diratzouian
Hasmik
H
Hanlon
Alexandra
A
Cooper
Harry
H
Freedman
Gary
G
Konski
Andre
A
Sigurdson
Elin
E
Hoffman
John
J
Meropol
Neal J
NJ
Weiner
Louis M
LM
Coia
Lawrence
L
Lanciano
Rachelle
R
Stein
Joanne
J
Kister
Debra
D
Eisenberg
Burton
B
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011882:Radiotherapy, High-Energy; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil