Contact x-ray brachytherapy (Papillon) in addition to chemoradiotherapy to improve organ preservation in early cT2-T3 rectal adenocarcinoma: The 3-year results of OPERA randomized trial (NCT02505750).

Abstract

3512 Background: The OPERA trial was testing the hypothesis that Contact x-ray brachytherapy (CXB) 50 kV boost will increase the rectal preservation rate in early T2-T3ab rectal adenocarcinoma. We present the 3 years clinical results. Methods: Inclusion criteria were: Age > 18 years, PS: 0-1, adenocarcinoma, distal - middle rectum, cT2-T3ab cN0-N1 < 8mm staged using MRI, M0. Stratification: T < vs ≥ 3 cm diameter. Control arm (A) was chemoradiotherapy (CRT) 45Gy/ 5 weeks with concurrent chemotherapy (Capecitabine 825 mg / m2) and external beam radiotherapy boost (9Gy/ 5 fr/ 1 week). Experimental arm used the same CRT (Cape 45) but the boost used CXB (90 Gy/ 3 fr/ 4 weeks). CXB was given first (B1) for tumor < 3 cm and after cap 45 (B2) for tumor ≥ 3 cm. Response assessment was made at week 14 after treatment start using palpation, endoscopy and MRI. A new assessment could be made at week 20 and 24 with a second MRI.TME was recommended in case of Partial response, Watch& Wait in case of clinical complete response (cCR). Bowel function measurement used LARS score. Main end- point was: Rate of organ preservation at 3 years. The hypothesis (in 2014) was 20% arm A vs 40% arm B (HR:0.53). Results: Between 5-2015 and 6-2020, 144 patients were included (France 96, UK 44, Switzerland 4). The analysis was made in 01-2022 with a median Follow-up time of 34 months. Treatment compliance was good in ≥ 90% of patients. Table gives main patients characteristics and clinical outcome. At three years the OP rate (Kaplan Meier estimate) was respectively arm A vs B: 60% vs 81% (HR 0.34 [95% CI 0.19 – 0.73]; p= 0.005). At three years OP for group A1 and B1 were: 65% vs 97% (HR 0.081 [95% CI 0.01-0.64]; p= 0.02). Conclusions: A CXB boost, when combined with chemoradiotherapy, increases the rate of organ preservation in early rectal adenocarcinoma. Starting with CXB in T < 3 cm appears as an attractive option. A B A1 (T < 3cm) B1 (T < 3cm) N° patient 71 73 30 32 Median age 68 69 69 70 Gender M/F 45/26 43/30 18/12 18/14 T2/T3 45/26 47/26 25/5 29/3 Distal/middle 53/18 53/20 21/9 27/5 cCR (W 14-24) 61% 90% p < 0.001 70% 94% p = 0.027 TME 26 12 8 1 Death 2 2 1 0 LARS < 30 80% 83% 87% 86%.