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Results Overall 447 patients were included; 300 in the discovery cohort (median follow-up: 4.2 years) and 147 in the validation cohort (median follow-up: 3 years). Between the two cohorts, there were no significant difference in the 3-year DC (88% [95% CI: 84%-91%] vs. 84% [95% CI: 77%-89%], p=0.16) or OS (72% [95% CI: 67%-77%] vs. 69% [95% CI: 61%-77%], p=0.26). The Multivariable analysis identified pN2-3 and histological grade 2-3 (G2-3) as DM predictors. The high-risk group included patients who had both poor predictors (pN2-3 and G2-3), while low-risk group consisted of patients who had one or no poor predictors. In the discovery cohort, the 3-year DC rate was 78% (95% CI: 70%-84%) and 97% (95% CI: 92%-99%) in high- and low-risk groups respectively (p<0.001), with the concordance index (c-index) of 0.72. In the validation cohort, the risk group classification performed similarly (3-year DC: 69% [95% CI: 54%-79%] vs. 95% [95% CI: 87%- 98%], p<0.001) with the c-index value of 0.73. The 3-year OS for the high- vs. low- risk group was 85% (95% CI: 79- 91%) vs. 95% (95% CI: 91%-98%) in the discovery cohort (p<0.001), and 74% (95% CI: 63-86%) and 93% (95% CI: 87%-99%) in the validation cohort (p<0.001). Conclusion The proposed classification allowed for the definition of a high risk group of DM with poor survival. This validated model (G2-3/pN2-3) could be used to identify OSCC patients who may benefit from: 1) more aggressive screening for DM (before initiating the treatment) in order to avoid unnecessary or inappropriate management, 2) experimental systemic treatment intensification to impact development of DM, and 3) a more aggressive post-treatment surveillance schedule for early detection of DM and consideration of experimental ablative treatments for oligometastatic or early systemic treatment for non-oligometastatic disease. OC-0278 NAR score as surrogate for disease-free survival in the CAO/ARO/AIO-04 phase 3 rectal cancer trial E. Fokas 1 , R. Fietkau 2 , A. Hartmann 3 , W. Hohenberger 4 , R. Grützmann 4 , M. Ghadimi 5 , T. Liersch 5 , P. Ströbel 6 , G. Grabenbauer 7 , C. Wittekind 8 , R. Sauer 2 , M. Kaufmann 9 , T. Hothorn 9 , C. Rödel 1 1 University of Frankfurt, Department of Radiotherapy and Oncology, Frankfurt, Germany 2 University of Erlangen-Nürnberg, Department of Radiation Therapy, Erlangen, Germany 3 University of Erlangen-Nürnberg, Institute of Pathology, Erlangen, Germany 4 University of Erlangen-Nürnberg, Department of General and Visceral Surgery, Erlangen, Germany 5 University Medical Center Göttingen, Department of General- Visceral and Pediatric Surgery, Göttingen, Germany 6 University Medical Center Göttingen, Institute of Pathology, Göttingen, Germany 7 DiaCura & Klinikum Coburg, Department of Radiation Oncology and Radiotherapy, Coburg, Germany 8 University of Leipzig, Institute of Pathology, Leipzig, Germany 9 University of Zurich, Epidemiology- Biostatistics and Prevention Institute, Zurich, Switzerland Purpose or Objective We assessed the recently-developed neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with Proffered Papers: CL 6: Lower GI

rectal carcinoma treated in the CAO/ARO/AIO-04 randomized phase 3 trial. Material and Methods The NAR score was available in 1191 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. The NAR score was classified as low (NAR<8), intermediate (NAR=8-16), and high (NAR>16) according to the NSABP R-04 trial dataset that demonstrated better overall survival rates with lower NAR. Cox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1-4) were used to assess individual-level surrogacy of NAR for DFS. Results After a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT significantly improved 3-year DFS (75.9% [95% CI 72.30-79.50] vs 71.3% [95% CI 67.60-74.90]; p=0.034; PC 1) and resulted in a shift towards lower NAR groups (p=0.034, PC 2) compared to fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI, 88.2-95.2), 81.8% (95% CI, 78.4-85.1) and 58.1 (95% CI 52.4-63.9) for low, intermediate and high NAR score, respectively (p<0.001; PC 3). NAR score remained an independent prognostic factor for DFS (low vs high NAR: HR 4.670; 95% CI 3.106-7.020; p<0.001; low vs intermediate NAR: HR 1.971; 95% CI 1.303-2.98; p=0.001) in multivariable analysis. The treatment effect on DFS was captured by NAR (HR = 2.34; 95% CI, 1.125-4.866; p=0.023), satisfying individual-level PC 4. Conclusion This is, to our knowledge, the first study to validate the prognostic role and surrogacy of NAR score for DFS within a large randomized phase 3 trial based on the strict Prentice criteria. Our results corroborate the National Research Group (NRG) Oncology and the National Cancer Institute (NCI) Clinical Trials Network strategy to use NAR score as the primary endpoint in early phase trials. The NAR score constitutes an immediately available and easily usable endpoint that can predict treatment effects on the clinical outcome and help to speed up response- adapted therapeutic decisions. Further large phase 3 trial datasets are required to confirm trial-level surrogacy. OC-0279 a randomized phase II study testing for optimal strategy for patients with high risks rectal cancer T. Vuong 1 , P. Kavan 2 , A.G. Martin 3 , L. Azoulay 4 , D. Donath 5 , C. Lavoie 6 , E. Ferland 7 , N. Nguyen 8 , C.A. Vasilevsky 9 , S. Desgroseilliers 10 , S. Drolet 11 , C. Richard 12 , M. Boutros 13 , G. Batist 14 1 Jewish General Hospital- McGill University, Radiation Oncology Department oncology, Montreal, Canada 2 Jewish General Hospital-McGill University, Medical Oncology Department oncology, Montreal, Canada 3 University of Laval- Quebec, Radiation Oncology, Quebec, Canada 4 Jewish General Hospital. McGill University, Epidemiology and Statistics- Department oncology, Montreal, Canada 5 CHUM- University of Montreal-, Radiation Oncology, Montreal, Canada 6 CHUQ- university of Laval, Radiation Oncology, Quebec, Canada 7 Pierre Boucher Hospital, Medical Oncology, Longueil- Quebec, Canada 8 Charles Lemoyne Hospital, Medical Oncology, Longueil, Canada 9 Jewish General Hospital- McGill University, Colo-rectal surgery Department oncology, Montreal, Canada 10 Pierre Boucher Hospital, General Surgery, Longueil- Quebec, Canada 11 CHUQ- university of Laval, Colo-rectal surgery, Quebec, Canada 12 CHUM- University of Montreal-, Colo-rectal surgery,