Establishment And Validation Of A Nomogram For Non-Functional Colorectal Neuroendocrine Tumors

OBJECTIVE: To analyze the survival factors affecting patients with non-functioning colorectal neuroendocrine tumors and to develop and evaluate a line graph model for predicting their risk.METHODS: To retrospectively analyze the clinicopathological data and survival data of a total of 100 patients who were seen and treated at THE FIRST AFFILIATED HOSPITAL OF DALIAN MEDICAL UNIVERSITY between October 2012 and October 2022 and had clinical presentation of non-functional colorectal neuroendocrine tumors,including age,gender,tumor size,TNM stage,WHO stage,tumor primary site,immunohistochemical CgA results,treatment modality and follow-up,etc.Single-factor and multi-factor Cox regression analyses were performed on all factors affecting patients’ prognosis.Based on the independent risk factors affecting patients’ survival obtained from the multi-factor COX regression analysis,a line graph model for predicting survival risk was established by R language,and the accuracy of the model was evaluated and validated.RESULTS: A total of 100 patients with non-functional colorectal neuroendocrine tumors were included in this study,of whom 28(28%)had a tumor primary site in the colon and 72(72%)in the rectum,with a median age of 34 years and a male-to-female ratio of 51:49.The 5-year survival rate of patients was 76.50%(95% CI 0.6866 to0.8434).Univariate analysis showed statistically significant differences in age(p=0.001),tumor size(p=0.007),T-stage(p<0.001),N-stage(p<0.001),M-stage(p=0.035),WHO-stage(p=0.008)and CgA(p<0.001),a total of seven variables,as univariate factors affecting the prognosis of patient survival;CgA staining positive patients had a median survival time of 47 months,which was significantly better than that of negative patients(median survival time of 31 months).According to WHO staging,patients with G1 and G2-3 stages with concomitant CgA-negative patients had poorer survival(p<0.001 and p=0.036).In patients with T1 and T2-4 stages,survival was poorer in patients with concomitant CgA-negative patients as well(p=0.002 and 0.006).In this study,the median survival was 46.5 months in patients aged ≤60 years and 42.5 months in patients aged >60 years.In patients aged ≤60 years,the difference between CgA expression and patient prognosis was not statistically significant(p=0.089);whereas in the age >60 years group,survival was better in CgA-positive patients than in negative patients.survival was better in patients aged ≤60 years in WHO staging G1 and G2-3(p=0.001 and p=0.20).In T1 staging,survival was better in patients aged ≤60 years(p=0.002);while the age difference was not statistically significant in T2-4 staging(p=0.223).Using a median tumor diameter of 10 mm as a cut-off,patients were divided into two groups,in which CgA-positive patients had significantly better survival than negative patients(p<0.001 and p=0.008).Survival rates were better when patients were≤60 years old with tumor diameters less than 10 mm(p=0.001);when tumor diameters exceeded 10 mm,the difference in survival rates due to age differences was not statistically significant(p=0.100).Among patients with tumor diameter ≤10 mm,67patients with T1 stage and 16 patients with T2-4 stage showed better survival rate for patients with T1 stage(p<0.001);tumor diameter >10 mm,11 patients with T1 stage and 6 patients with T2 stage,again with better survival rate for patients with T1 stage(p=0.025).Multifactorial Cox regression analysis showed that three age(HR=5.091,95%CI 1.549~16.731,p=0.007),CgA(HR=0.153,95% CI 0.053~0.445,p=0.001),T stage(HR=3.599,95% CI 1.738~7.454,p=0.001)variables were independent risk factors affecting the prognosis of patients with non-functional colorectal NEN.The concordance index(C-index)was 0.861(95% CI 0.767~0.955)and 0.923(95% CI0.845~1.001)for the column plot modeling and validation groups,respectively;the AUCs for 5-year specific survival rates were 0.850 and 0.956 for the two groups,respectively.calibration curves showed good agreement between the patient survival rates predicted by the model and the actual patient survival rates The ROC curve results showed that the prediction accuracy of the columnar plot model was better than that of the conventional TNM staging(AUC of 0.896 versus 0.753).CONCLUSIONS: Patients aged ≤60 years with immunohistochemical CgA-positive and T1-staged non-functional colorectal NEN have better prognosis,and the column line graph model constructed based on patient age,immunohistochemical CgA and T-stage for patients with non-functional rectal neuroendocrine tumors has good predictive ability and can provide some reference for clinical prediction of patient prognosis.