Construction Of Prediction Model And Optimization Of Treatment Strategy For Lateral Lymph Node Metastasis In Rectal Cancer

PART Ⅰ:MRI-guided risk factor exploration and prediction model construction for lateral lymph node metastasis after neoadjuvant chemoradiotherapy of rectal cancerBackground Lateral lymph node(LLN)metastasis is a common metastatic site in patients with middle-low rectal cancer.Neoadjuvant chemoradiotherapy(nCRT)combined with selective lateral lymph node dissection(LLND)is currently effective treatments for LLN metastasis.However,the diagnostic criteria for LLN metastasis after nCRT are still lacking,and the indications for selective LLND are unclear.Therefore,a large number of patients receive negative pathological dissection,resulting in unnecessary surgical trauma.Aim Based on clinicopathological and imaging features,the diagnostic criteria for LLN metastasis after nCRT of rectal cancer were explored and the corresponding prediction model was constructed and verified.Methods A combination of retrospective and prospective research methods was used to collect and analyze the clinicopathological data of patients enrolled in the multi-center registry database of LLN metastasis in rectal cancer from January 2012 to December 2019.Multivariate logistic regression analysis was used to investigate the risk factors associated with LLN metastasis after nCRT.R(3.6.0 for windows)software was used to establish a nomogram prediction model for the risk factors included in the multivariate logistic regression model,draw receiver operating characteristic(ROC)curves of the training set and the validation set,and evaluate the diagnostic performance of the prediction model by calculating the area under the curve(AUC)and correction curve,respectively.Results A total of 160 patients were included in this study,which were divided into training set and validation set according to the ratio of 7:3 for the construction and validation of predictive models.When 7mm after nCRT is used as the LLN short-diameter cut-off value,LLN metastasis after nCRT can be well predicted.The results of multivariate regression analysis showed that LLN short diameter≥7 mm(P<0.001),malignant features(P=0.005),clinical N1/N2 stage(P=0.007)and poor differentiation(P=0.007)were independent risk factors for LLN metastasis after nCRT.Using LLN short diameter,malignant features,clinical T stage,clinical N stage differentiation,a total of 5 clinicopathological and imaging features,nomogram prediction model were constructed to predict LLN metastasis after nCRT.The AUC values of prediction model in the training and validation sets are 0.836 and 0.827,respectively.The slope of the calibration curve of the model is close to 1 in both the training and validation sets.In addition,the LLN region was refined for subgroup analysis.The results showed that 4 mm and 7 mm after nCRT were used as LLN short-diameter cut-off values,respectively,which could better predict internal iliac and obturator lymph node metastasis after nCRT.Conclusion In this study,a prediction model for LLN metastasis after nCRT in rectal cancer was constructed,which could effectively assess the risk of LLN metastasis after nCRT in rectal cancer,and had good predictive efficiency.In the era of precision medicine,it is very necessary to refine LLN region and accurately diagnose and predict LLN metastasis for different regions.In the future,large-scale prospective studies are still needed to further confirm the conclusions.PART Ⅱ:Exploration and Optimization of treatment strategies for lateral lymph node metastasis in rectal cancerBackground Lateral lymph node dissection(LLND)is of great value in the treatment of rectal cancer patients with lateral lymph node(LLN)metastasis.However,there are still many controversial issues in the diagnosis and treatment of LLN metastasis in rectal cancer.Aim To explore and optimize treatment strategies for LLN metastasis in rectal cancer based on the safety,prognostic significance,postoperative recurrence pattern,and other related fields of LLND.Methods A combination of retrospective and prospective research methods was used to collect and analyze the clinicopathological data of patients enrolled in the multi-center registry database from January 2012 to December 2019.According to different research objectives,statistical methods such as propensity score matching,multivariate logistic regression analysis,and multivariate COX regression analysis were used to statistically analyze the data.Oncology treatment effectiveness and prognosis were evaluated by local recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),diseases-free survival(DFS),and overall survival(OS).Results The incidence of grade 2-5 postoperative complications after LLND was 15.2%,and the incidence of grade 3-5 complications was 8.0%.Operation time≥260 minutes was an independent risk factor for the occurrence of both grade 2-5(OR,3.03;95%CI,1.57-5.85;P=0.001)and grade 3-5 serious complications(OR,2.67;95%CI,1.06-6.73;P=0.037)after LLND;Laparoscopic LLND had short-term advantages such as shorter operation time(300 vs 255 min,P<0.001),less intraoperative blood loss(300 vs 50 ml,P<0.001),lower grade 2-5 complication rate(24.0%vs 12.0%,P=0.027),faster recovery to liquid diet(3.0 vs 4.1 days,P<0.001),and higher number of LLN dissection(9 vs 7,P=0.025).In addition,laparoscopic LLND achieved 3-year OS(78.4%vs 84.6%,P=0.581)and DFS(74.8%vs 74.2%,P=0.745)similar to open LLND;The 3-year OS(60.0%vs 84.8%,P=0.007)and DFS(41.0%vs 68.9%,P=0.002)were significantly worse in the pathologically positive LLN group than those in the pathologically negative LLN group.However,the 3-year LRFS(77.8%vs 84.2%,P=0.344)in the pathologically positive LLN group was similar to that in the pathologically negative LLN group.In addition,the postoperative recurrence pattern of pathologically positive LLN patients was mainly distant metastasis,among which the lung and liver were the most common target organs for postoperative metastasis;The 3-year OS(70.2%vs 14.6%,P<0.001)and DFS(52.6%vs 10.6%,P<0.001)in patients with internal iliac and obturator iliac metastasis were significantly better than those with external iliac and common iliac metastasis,and the prognosis of the former was similar to that of patients with N2b stage.In subgroup analysis of patients with internal iliac and obturator metastases,3-year DFS(58.7%vs 27.0%,P=0.032)and 3-year DMFS(65.2%vs 28.6%,P=0.040)with internal iliac metastases was significantly better than that of patients with obturator metastases;3-year OS(78.6%vs 47.2%,P=0.007)and DFS(65.7%vs 24.9%,P=0.011)in patients with LLN metastasis without mesenteric lymph nodes metastasis were significantly better than those with both mesenteric lymph nodes and LLN metastasis.Conclusion This study discusses and analyzes the controversial issues in the diagnosis and treatment process of LLN metastasis for rectal cancer focusing on four aspects:safety of LLND and risk factors for complications,application of laparoscopic technology in LLND,prognostic value of therapeutic LLND and postoperative recurrence pattern,prognostic characteristics and survival analysis of patients with LLN metastasis.Combined with the above results,the treatment strategy for LLN metastasis of rectal cancer was optimized.