e15603 Background: Neoadjuvant chemoradiotherapy (nCRT) not only could bring tumor downsizing and downstaging but also could achieve clinical complete response (cCR) or pathological complete response (pCR). Although immunotherapy benefits MSI-H/dMMR rectal cancer patients, little response is observed in MSS/pMMR patients. Several clinical trials including VOLTAGE trial demonstrated that a combination of PD-1 inhibitor and nCRT could result in a promising pathological response even in MSS/pMMR patients. But the elucidation regarding organ preservation after treatment is lacking. Watch and Wait (W&W) is an effective strategy in rectal cancer patients showing cCR after nCRT to preserve organs. This study was designed to explore the efficacy, safety, and organ preservation rate of a combination of nCRT and PD-1 inhibitor(sintilimab) in MSS/pMMR patients with ultra-low rectal cancers. Methods: This was a single-arm, phase II trial. Patients with ultra-low rectal cancer that was confirmed as MSS/pMMR T1-3aN0-1M0 and received 50 Gy (25×2 Gy) chemoradiotherapy and 2 cycles of sintilimab, followed by 6 cycles of capecitabine or CAPOX regimen plus 2 cycles of sintilimab as consolidation therapy. Patients with cCR were managed using the W&W strategy, patients with ncCR were given local excision. The primary outcome was cCR rate and secondary outcomes were anal preservation rate, organ preservation rate, tumor regression grade (TRG), and safety profile. Results: From 2021 January to 2021 December, a total of 23 patients were enrolled. The median age was 55 y (range; 38 to 75). Male patients were 61%. cT2 was 56.5% (13/23), cT3 was 43.5% (10/23), cN0 was 69.6% (16/23), and cN1 was 30.4% (7/23). All patients completed 50Gy chemoradiotherapy. Nineteen patients received 4 cycles of sintilimab treatment, 3 patients received 3 cycles of sintilimab, and 1 patient received 1 cycle of sintilimab. cCR was 43.5% (10/23), ncCR was 26.1% (6/23), and cPR was 30.4% (7/23). The anal preservation rate was not assessed in 1 patient due to cerebral ischemic stroke. The anal preservation rate was 95.5% (21/22), rectal preservation rate was 59.1% (13/22). Ten patients underwent surgery. Among them, two patients achieved pCR, and the major pathologic response rate (TRG0-1) was 60.0% (6/10). The overall CR(cCR+pCR) rate was 52.2% (12/23). Grade 3/4 treatment-related adverse events occurred in 17.4% (4/23) of patients. No unexpected adverse events or deaths were observed. Conclusions: Given the favorable tolerability and encouraging cCR rate, nCRT plus sintilimab could be a feasible and safe option for patients with pMMR/MSS, ultra-low rectal cancer who have a strong desire to preserve the anus. Based on these results, a prospective, randomized, controlled, multicenter, phase III study is currently in progress (NCT05215379). Clinical trial information: ChiCTR2100042785.

Background. The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. Method. Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. Results. X-tile plots identified 3 (P<0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P<0.001, P=0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P<0.001). Conclusion. More TD count (TD count≥4) was significantly associated with poor disease-specific survival in CRC patients.

BackgroundMost prognostic signatures for colorectal cancer (CRC) are developed to predict overall survival (OS). Gene signatures predicting recurrence-free survival (RFS) are rarely reported, and postoperative recurrence results in a poor outcome. Thus, we aim to construct a robust, individualized gene signature that can predict both OS and RFS of CRC patients.MethodsPrognostic genes that were significantly associated with both OS and RFS in GSE39582 and TCGA cohorts were screened via univariate Cox regression analysis and Venn diagram. These genes were then submitted to least absolute shrinkage and selection operator (LASSO) regression analysis and followed by multivariate Cox regression analysis to obtain an optimal gene signature. Kaplan–Meier (K–M), calibration curves and receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of this signature. A nomogram integrating prognostic factors was constructed to predict 1-, 3-, and 5-year survival probabilities. Function annotation and pathway enrichment analyses were used to elucidate the biological implications of this model.ResultsA total of 186 genes significantly associated with both OS and RFS were identified. Based on these genes, LASSO and multivariate Cox regression analyses determined an 8-gene signature that contained ATOH1, CACNB1, CEBPA, EPPHB2, HIST1H2BJ, INHBB, LYPD6, and ZBED3. Signature high-risk cases had worse OS in the GSE39582 training cohort (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.42 to 1.67) and the TCGA validation cohort (HR = 1.39, 95% CI = 1.24 to 1.56) and worse RFS in both cohorts (GSE39582: HR = 1.49, 95% CI = 1.35 to 1.64; TCGA: HR = 1.39, 95% CI = 1.25 to 1.56). The area under the curves (AUCs) of this model in the training and validation cohorts were all around 0.7, which were higher or no less than several previous models, suggesting that this signature could improve OS and RFS prediction of CRC patients. The risk score was related to multiple oncological pathways. CACNB1, HIST1H2BJ, and INHBB were significantly upregulated in CRC tissues.ConclusionA credible OS and RFS prediction signature with multi-cohort and cross-platform compatibility was constructed in CRC. This signature might facilitate personalized treatment and improve the survival of CRC patients.

Background: Anastomotic leakage (AL) is one of the commonest and most serious complications after rectal cancer surgery. The previous analyses on predictors for AL included small-scale patients, and their prediction models performed unsatisfactorily.Methods: Clinical data of 5,220 patients who underwent anterior resection for rectal cancer were scrutinized to create a prediction model via random forest classifier. Additionally, data of 836 patients served as the test dataset. Patients diagnosed with AL within 6 months' follow-up were recorded. A total of 20 candidate factors were included. Receiver operating characteristic (ROC) curve was conducted to determine the clinical efficacy of our model, and compare the predictive performance of different models.Results: The incidence of AL was 6.2% (326/5,220). A multivariate logistic regression analysis and the random forest classifier indicated that sex, distance of tumor from the anal verge, bowel stenosis or obstruction, preoperative hemoglobin, surgeon volume, diabetes, neoadjuvant chemoradiotherapy, and surgical approach were significantly associated with AL. After propensity score matching, the temporary stoma was not identified as a protective factor for AL (P=0.58). Contrastingly, the first year of performing laparoscopic surgery was a predictor (P=0.009). We created a predictive random forest classifier based on the above predictors that demonstrated satisfactory prediction efficacy. The area under the curve (AUC) showed that the random forest had higher efficiency (AUC =0.87) than the nomogram (AUC =0.724).Conclusions: Our findings suggest that eight factors may affect the incidence of AL. Our random forest classifier is an innovative and practical model to effectively predict AL, and could provide rational advice on whether to perform a temporary stoma, which might reduce the rate of stoma and avoid the ensuing complications.

Background: Simultaneous resection for patients with synchronous colorectal cancer liver metastases (CRLM) remains an optimal option for the sake of curability. However, few studies so far focus on outcome of this subgroup of patients (who receive simultaneous resection for CRLM). Substantial heterogeneity exists among such patients and more precise categorization is needed preoperatively to identify those who may benefit more from surgery. In this study, we formulated this internally validated scoring system as an option.Methods: Clinicopathological and follow-up data of 234 eligible CRLM patients undergoing simultaneous resection from January 2010 to March 2019 in our center were included for analysis. Patients were randomized to either a training or validation cohort. We performed multivariable Cox regression analysis to determine preoperative factors with prognostic significance using data in training cohort, and a nomogram scoring system was thus established. Time-dependent receiver operating characteristic (ROC) curve and calibration plot were adopted to evaluate the predictive power of our risk model. Results:In the multivariable Cox regression analysis, five factors including presence of node-positive primary defined by enhanced CT/MR, preoperative CEA level, primary tumor location, tumor grade and number of liver metastases were identified as independent prognostic indicators of overall survival (OS) and adopted to formulate the nomogram. In the training cohort, calibration plot graphically showed good fitness between estimated and actual 1-and 3-year OS. Time-dependent ROC curve by Kaplan-Meier method showed that our nomogram model was superior to widely used Fong's score in prediction of 1-and 3-year OS (AUC 0.702 vs. 0.591 and 0.848 vs. 0.801 for 1-and 3-year prediction in validation cohort, respectively). Kaplan-Meier curves for patients stratified by the assessment of nomogram showed great discriminability (P<0.001). Conclusions:In this retrospective analysis we identified several preoperative factors affecting survival of synchronous CRLM patients undergoing simultaneous resection. We also constructed and validated a risk model which showed high accuracy in predicting 1-and 3-year survival after surgery. Our risk model is expected to serve as a predictive tool for CRLM patients receiving simultaneous resection and assist physicians to make treatment decision.