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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%.

131 Background: We previously reported the benefit of Contact X-ray Brachytherapy boost (CXB) in achieving a higher clinical complete response (cCR) following partial response to external beam chemoradiotherapy (EBCRT). We now update our report on the organ preservation rate and long-term durability of the cCR in this cohort. Methods: Outcome data for rectal cancer patients referred to our institution from 2003 to 2012 were retrieved from an institutional database after an audit approval. These patients were referred after initial local multidisciplinary team discussion. All patients had EBCRT 45Gy/25/5 weeks with capecitabine 825mg/m2 (Mon-Fri). Those who respond well but has a small residual tumour were offered CXB boost of 90Gy in 3 fractions over 4-6 weeks as they were not suitable or unwilling to undergo completion surgery. Following treatment, patients had close 3 monthly follow-ups with DRE, endoscopy, and MRI in the first 2 years, then 6 monthly up to 5 years. Results: Of 345 consecutive patients with rectal cancer referred to us, 83 patients who responded well to EBCRT but with small suspicious residual disease (≤3 cm) were offered CXB boost. Median age was 72 years (range 36–87) and 58 (69.9%) were males. Initial MRI tumor stages were cT2 (n = 28), cT3 (n = 55) and 54.2% were node positive. The median follow up of surviving patients was 6.4 years (range 2-11 years). cCR was achieved after CXB boost in 53/83 (64%). After achieving cCR, 8/53 (15%) developed local regrowth. However, all patients successfully underwent curative surgery with R(0) resection rate of 24/30 (80%) and only 21/83 (25%) had stoma. Organ preservation was achieved in 62/83 (75%). 12/53 (14%) patients developed metastatic disease. At the end of the study period, 64/83(77%) were cancer free. Conclusions: Our long-term data suggests dose escalation with CXB boost following EBCRT can achieved high organ preservation rate with excellent long-term durable cCR. This approach can provide an alternative treatment option for elderly or comorbid patient patients who are not suitable for surgery. This can also be an option for some patients who wish to avoid surgery upfront after initial diagnosis. Those who needed surgery later for treatment failure can be salvage successfully. A phase 3 European randomised trial OPERA (Organ Preservation in Early Rectal Adenocarcinoma) was set up to evaluate this concept further.