Randomized trial of preoperative radiotherapy with a simultaneous integrated boost compared to chemoradiotherapy for cT3-4 rectal cancer.

Background and objectives:

The addition of concomitant chemotherapy to preoperative radiotherapy is widely accepted as the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control, but has no impact on survival or the incidence of distant metastases. Besides, it is associated with considerable toxicity. As an alternative strategy, we explored preoperative helical tomotherapy with a simultaneous integrated boost (SIB) in a phase II study (n = 108 patients). This strategy displayed a promising response rate and local control with a favourable toxicity profile. In the present study, we compare this treatment to standard chemoradiotherapy in a randomized non-inferiority trial. The endpoints are metabolic response, local control, histological downgrading, number of R0 resections, acute and late toxicity, progression-free & overall survival and quality of life.

Inclusion criteria:

1) Histopathologically confirmed rectal adenocarcinoma
2) T3 or T4 disease on MRI or endoluminal ultrasound
3) Patients with unresectable metastatic disease, ECOG performance status > 3 and patients not deemed fit for radiotherapy, capecitabine or surgery are excluded.

Study plan:

Preoperative radiotherapy:
Arm 1: radiotherapy (23 x 2 Gy, helical tomotherapy or VMAT) + capecitabine 825mg/m2 p.o. twice daily, excluding weekends
Arm 2: radiotherapy (23 x 2 Gy, helical tomotherapy or VMAT) + simultaneous integrated boost up to 55.2 Gy on the primary tumor
Adjuvant chemotherapy: Capecitabine 1000mg/m2 p.o twice daily from the evening of day 1 to the morning of day 15, every 3 weeks, 6 cycles (begin 6-8 weeks after surgery)