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TPS210 Background: Neoadjuvant chemoradiotherapy (NACRT) could bring tumor downstaging and pathological response (pCR), and also survival benefit for locally advanced rectal cancer (LARC) patients. Several single arm prospective clinical trials have investigated combination effect of immunotherapy (PD-1 or PD-L1 antibody) and NACRT in LARC patients, such as the VOLTAGE clinical trial. A randomized trial is needed to confirm the benefit of immunotherapy in this setting and explore predictive biomarkers. This is a clinical trial with two cohorts according the MMR/MSI status (clinicalTrials.gov, NCT04304209). Methods: In this study, LARC patients with pMMR/MSS/MSI-L tumor will enter cohort B and be randomized into two arms. Main inclusion criteria include: cT3-4N0M0 or cTxN+M0 rectal adenocarcinoma, pMMR/MSS/MSI-L confirmed by immunohistochemistry or gene test, aged 18-75y; ECOG performance 0-1; no previous anti-tumor treatment for rectal adenocarcinoma. Main exclusion criteria include: active autoimmune diseases or a history of autoimmune diseases, and inadequate main organ functions. Patients in the experimental arm will receive four cycles of neoadjuvant PD1 antibody Sintilimab, Capeox chemotherapy and concurrent radiotherapy, followed by curative surgery or watch and wait, then four cycles of adjuvant Capeox chemotherapy. Patients in the control arm will receive four cycles of neoadjuvant Capeox chemotherapy and concurrent radiotherapy, followed by curative surgery or watch and wait, then four cycles of adjuvant Capeox chemotherapy Primary outcome measure is pCR rate. Secondary outcome measures include acute toxicity, tumor regression grade, R0 resection rate, local recurrence, distant metastasis. Sample size for this cohort is 134. Whole exome sequencing, RNA sequencing and immunohistochemistry of the rectal primary tumor are planned for biomarker searching and synergy effect mechanism investigation. The first patient has been enrolled in June, 2020. Clinical trial information: NCT04304209.

113 Background: Preoperative chemoradiotherapy followed by total mesorectal excision (TME) surgery has been widely adopted as the standard treatment for stage II-III rectal cancers. However, the role of adjuvant chemotherapy in pathological T3N0M0 (pT3N0M0) patients remains controversial. A reliable prognostic model is needed to discriminate the high-risk patients from the low-risk patients, and optimize adjuvant chemotherapy treatment decisions by predicting the likelihood of adjuvant chemotherapy benefit for the target population. Methods: We gathered and analyzed 276 patients in Sun Yat-Sen University Cancer Center from March 2005 to December 2011. All patients underwent total mesorectal excision, without preoperative therapy, and were pathologically proven pT3N0M0 rectal cancer. LASSO regression model was used for variable selection and risk factor prediction. Multivariable cox regression was used to develop the predicting model. Optimum cut-off values were determined using X-Tile plot analysis. The 10-fold cross validation was adopted to validate the model. The performance of the nomogram was evaluated with its calibration, discrimination and clinical usefulness. Results: A total of 188 patients (68.1%) had adjuvant chemotherapy and no patients had adjuvant radiotherapy. Age, carbohydrate antigen 19-9 [CA199], monocyte percentage [MONO%], lymph node dissection numbers [LNDs] and nerve invasion were identified as significantly associated variables that could be combined for an accurate prediction risk of CSS for pT3N0M0 patients. The model adjusted for CSS showed good discrimination with a C-index of 0.723 (95% CI = 0.652 to 0.794). The calibration curves showed that the nomogram adjusted for CSS was able to predict 3-, 5-, and 10-year CSS accurately. The corresponding predicted probability was used to stratify high and low-risk patients. Adjuvant chemotherapy improved survival rate in the low-risk patients (HR = 0.338, 95% CI: 0.135 to 0.848, P = 0.021), while it did not exhibit a significant benefit in the high-risk patients. Conclusions: The nomogram effectively predicts CSS in patients with pT3N0M0 rectal cancer, which can be conveniently used in clinical practice. Adjuvant chemotherapy may improve overall survival in the low-risk patients. But the benefit of adjuvant chemotherapy was not seen in the high-risk patients.

e15602 Background: Immunotherapy has shown satisfactory effect for dMMR/MSI-H colorectal cancer patients. Whether Pd-1 antibody would bring benefit for dMMR/MSI-H locally advanced rectal cancer (LARC) patients in neoadjuvant setting is worthy of investigation. This is a clinical trial with two cohorts according the MMR/MSI status(clinicalTrials.gov, NCT04304209). Methods: LARC patients with dMMR or MSI-H tumor will enter Cohort A and receive neoadjuvant Pd1 antibody sintilimab for four cycles and subsequent surgery or watch and wait, followed by adjuvant four cycles of Pd1 antibody sintilimab with or without chemotherapy. Main inclusion criteria include: cT3-4N0M0 or cTxN+M0 rectal adenocarcinoma, dMMR/MSI-H confirmed by immunohistochemistry (IHC) or gene test, aged 18-75y; ECOG performance 0-1; no previous anti-tumor treatment for rectal adenocarcinoma. Primary outcome is pathologic complete response (pCR) rate. We use a Simon two-stage optimum design to test the null hypothesis of a 15% pCR rate, the historical response rate to standard neoadjuvant chemoradiotherapy (NACRT), against the desired alternative of 30% pCR rate. This had a one-sided type I error of 5% and a power of 80%. In the first stage of this design, 19 patients will be accrued. If 3 or fewer pCR was observed, the study was to be terminated and declared negative. If the trial goes on to the second stage, a total of 55 patients will be studied. The study was deemed to have met its primary endpoint if confirmed pCR were observed in 13 or more patients. Considering 10% dropout rate, a total of 61 patients will be enrolled. Whole exome sequencing, bulk RNA sequencing, single cell RNA sequencing and IHC of the rectal primary tumor are planned. The study started in October, 2019. Results: Eight patients have been enrolled and six have response evaluation results. Four patients achieved clinical complete response (cCR) after 4 cycles of neoadjuvant Pd1 antibody sintilimab treatment and three of them enter watch and wait strategy and finished the adjuvant 4 cycles of Pd1 antibody sintilimab treatment. The 4th patient was diagnosed as lynch syndrome, but molecular test was not feasible for the tumors located at the sigmoid and hepatic flexure because of ileus. He received subtotal colectomy and tumors at the sigmoid and hepatic flexure also achieved pCR. The 5th patient has partial response after 4 and 8 cycles of sintilimab treatment, and then received Dixon surgery and pathology showed major reponse (5% cancer cell left only in the mucosal layer, ypTis). The 6th patient has partial response after 4 and 8 cycles of sintilimab treatment, and sintilimab was still continued concerning intact bladder conservation. No grade 3 toxicity was noted yet. Conclusions: Pd1 antibody sintilimab achieved 4CR (pCR+cCR) in 6 dMMR/MSI-H LARC patients with limited toxicities. Pd1 antibody is quite effective and may be an alternative for these patients. Clinical trial information: NCT04304209.