Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial.
OBJECTIVE
To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer.


METHODS
Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively.


RESULTS
All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located < or = 6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis).


CONCLUSIONS
In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a basis for additional investigation regarding RT dose escalation or the addition of concomitant chemotherapy.
Allal
Abdelkarim S
AS
Division of Radiation Oncology, University Hospital of Geneva, 24 Michelli-du-Crest Street, 1211 Geneva 14, Switzerland. Abdelkarim.Allal@hcuge.ch
Bieri
Sabine
S
Bründler
Marie-Anne
MA
Soravia
Claudio
C
Gertsch
Philippe
P
Bernier
Jacques
J
Morel
Philippe
P
Roth
Arnaud D
AD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000532:radiotherapy* / Q000601:surgery