Analysis Of Prognostic Factors And Establishment Of A Multi-dimensional Prediction Model For Colorectal Cancer Patients With Synchronous Liver Metastasis

PART I The distinction of clinicopathological characteristics,surgical strategy and prognosis in colorectal cancer patients with synchronous liver metastasis in China and the U.S.based on CNCC cohort and SEER databaseBackground and purpose:The incremental improvements in survival for CRC patients with liver metastasis,surgical treatment strategy may provide indirect evidence of the improvements in outcomes.Population-based studies are lacking in China and the U.S.According to two large national databases,the aims of this study are to perform a systematic analysis of colorectal cancer patients with synchronous liver metastasis(SCRLM)between China and the U.S.pertaining to the clinicopathological characteristics,surgical treatment and survival.Furthermore,we will assess the dynamic time trends of surgical treatment and survival for colorectal cancer patients with synchronous liver metastasis in the two nations.Materials and Methods:Data of SCRLM were registered in the SEER registry and the Chinese National Cancer Center(CNCC)cohort from 2010 to 2017.Outcomes included patient and tumor characteristics,surgical treatment strategy and survival between China and the U.S.over the last decade were demonstrated.Results:A total of 7,072 colorectal cancer patients with synchronous liver metastasis from the SEER database and 1,286 patients from the CNCC cohort were identified in the two countries from 2010 through 2017.The median age of U.S patients was significantly higher than that patients in the Chinese and the proportion of patients older than 60 years was also higher.The U.S.has a higher proportion of patients whose primary disease located in the right colon(40.6%vs 25%)and a lower proportion of patients in the rectum(19.8%vs 34.5%)compared with China.The proportion of patients underwent surgery and hepatic resection in China was higher than that in the U.S.,while the proportion of patients underwent resection of primary CRC in the U.S.was higher than China.The proportion of patients underwent resection of primary CRC were reducing over time both in the U.S.and China,while the 3-year CSS were increasing.Although the 3-year CSS was 26.70%in U.S.,while 3-year CSS was 34.33%in china,there was no difference in the 3-year CSS between China and U.S.after propensity score matching.Conclusion:In last decade,the cancer specific survival(CSS)has been increasing in China and U.S.based on SEER database and CNCC cohort.There was no difference in the 3-year CSS between China and U.S.after propensity score matching,although differences in clinicopathological characteristics and treatment strategies.PART ? Analysis of prognostic factors and establishment of prediction model for colorectal cancer patients with synchronous unresectable liver metastasisBackground and purpose:The prognostic factors for unresectable SCRLM included the number of organs involved in metastasis,patterns of metastatic spread,primary tumor location,molecular markers and molecular subtype.There was no prediction model for the patients with unresectable liver metastases.This study aims to establish the nomogram for unresectable SCRLM.Materials and Methods:Colorectal cancer patients with synchronous unresectable liver metastasis diagnosed from 2010 to 2017,SEER database as the development cohort and the CNCC cohort as validation cohort.The Kaplan-Meier method and log-rank test was used to estimated the CSS and compare in subgroup respectively.Prognostic factors were identified from proportional hazards model,and the nomogram was developed to predict the 1-year and 3-year CSS.The C-index and time-dependent receiver operating characteristic(ROC)was used to test the discriminative ability.Calibration curves were used to validate the power of the nomogram.On this basis,a novel prediction model was established by combining the multi-dimensional clinical data of the CNCC cohort.Results:The SEER database included 5255 patients as the development cohort,and the CNCC cohort included 657 patients as the validation cohort.A study based on the SEER database found that age,primary tumor location,tumor differentiation,extrahepatic metastasis,resection of the primary tumor,and CEA level were independent factors affecting the prognosis of patients with synchronous unresectable liver metastasis.This nomogram shows a good agreement between the actual survival rate and the predicted survival rate between the calibration curves of 1-year and 3-year CSS.The 1-year and 3-year AUC were 0.728 and 0.745,respectively.The calibration curve and ROC curve of the external validation cohort also show that the nomogram can better predict the survival outcome.The study based on the CNCC cohort also found that RAS/BRAF-status,primary tumor resection,extrahepatic metastasis,AJCC T stage,CEA,CA199,and albumin levels,liver metastases received local treatment and targeted drug therapy were independent factors affecting the prognosis of patients with asymptomatic unresectable liver metastases.The novel nomogram C-index was 0.772.The 1-year and 3-year AUC are 0.886 and 0.853 respectively.Conclusion:The prediction models based on the SEER database and CNCC cohort improved the accuracy to evaluate prognosis of colorectal cancer patients with synchronous unresectable liver metastasis.The model based on the CNCC cohort has stronger predictive ability,but may still require external validations from other medical centers cohorts or from a prospective study.