Preoperative short-term radiotherapy for primary resectable rectal cancer:
Accelerated once daily (5x5Gy)
versus
accelerated hyperfractionated twice daily (12x2,5Gy b.i.d.)
(ONCE-TWICE trial)
A phase II single-blinded multi-institutional randomised study

The standard management of primary resectable rectal cancer in the Netherlands
and other European countries is preoperative short-term radiotherapy (5 x 5 Gy
= 25 Gy within one week) followed by curative surgery.
However, in spite of extensive testing of this regimen in large scale
randomised phase III studies, discussion remains about possible and, more
recently, demonstrated long term impairment of bowel-function due to this
radiotherapy regimen.
Furthermore, an effective but little toxic radiotherapy regimen in order to
improve local control may be needed in the foreseeable future, so that
full-dose preoperative chemotherapy can be administered after short-term
preoperative radiotherapy in high-risk tumours instead of the concomitant
preoperative long-term radiochemotherapy regimens presently used.

The objective of this prospective randomised trial is to test the hypothesis
that hyperfractionated short course preoperative radiotherapy (12 x 2.5 Gy
twice daily) leads to less radiation-induced bowel toxicity compared to the
standard fractionation schedule of 5 x 5 Gy.

Prospective randomised single-blinded multi-institutional phase II study.

Arm A: 5 x 5 Gy preoperative pelvic radiotherapy (standard)
Arm B: 12 x 2,5 Gy preoperative pelvic radiotherapy (experimental arm)
Comment: On the basis of the most accepted radiobiological modelling (the
linear-quadratic model), the two arms are equivalent with respect to
tumour-effects (intended prevention of local recurrence), but the experimental
arm is less toxic for normal tissue.

All available evidence taken together, the experimental arm is likely to be
less toxic than the standard treatment. The purpose of this study is to see
whether this is also clinically relevant.