A Prognostic Nomogram For Progression-free Survival Of Primary Liver Cancer After Transarterial Chemoembolization (TACE)

Background: According to the Global Cancer Statistics published in 2018,primary liver cancer ranks sixth in the incidence of common malignant tumors worldwide and is also one of the most common causing death of patients,which seriously threatens human life.The current treatments applied to primary liver cancer mainly include surgical resection,liver transplantation,transarterial chemoembolization,radiofrequency ablation,immune-targeted therapy and so on.Due to the insidious onset of liver cancer and the lack of obvious early symptoms,many patients have already entered the middle or advanced stage of the disease when they are diagnosed,thus lose the opportunity of surgery.With the appearance of minimally invasive concept and the development of technology,transarterial chemoembolization(TACE)has gradually become one of the most common methods for non-surgical treatment of liver cancer.For patients with liver cancer treated with TACE,the correct and accurate assessment of prognosis is the key to guide the subsequent treatment.Since the Barcelona Clinic Liver Cancer(BCLC)staging system was proposed in 1999,various new biomarkers and scoring systems have emerged internationally,but they have not been well applied to the prognositic assessment of survival of patients with liver cancer due to various limitations.With the rise of R language in recent years,nomogram has become an excellent prediction tool with its unique advantages over traditional staging systems as well as evaluation criteria.Most of the currently reported nomograms for predicting the prognosis of liver cancer include only baseline data of patients(general condition,biochemical indicators,tumor characteristics,etc.),and less consideration has been given to the dynamic changes of indicators throughout the course of the disease.Objection: In this study,we conducted a retrospective analysis of patients with liver cancer treated with TACE to identify relevant risk factors and constructed a predictive model of nomogram that better fit the change of patients’ disease,so as to assess the survival prognosis of patients treated with TACE and thus guide the subsequent treatments.Methods: A total of 346 patients with primary liver cancer who underwent TACE as initial treatment at the Department of Infection,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2018 to January 2021 were retrospectively included,of which 208 patients were allocated to the derivation cohort randomly.And progression free survival(PFS)was used as the follow-up time endpoint according to the modified Response Evaluation Criteria in Solid Tumors(mRECIST).Univariate analysis by Kaplan-Meier analysis and multivariate analysis by COX regression model screened out the indicators associated with short-term prognosis,and R language was used to construct a nomogram.The remaining 138 patients were allocated to the validation cohort randomly to validate the nomogram model.And the nomogram was compared with the classical BCLC staging system.Results:After univariate and multivariate analyses of the derivation cohort,the predictors affecting the PFS in patients with liver cancer undergoing TACE were: 1.baseline indicators: age(HR=2.104,95% CI=1.327-3.076,P=0.013),ALBI grade(2grade vs 1grade,HR=1.977,95% CI=1.215-3.712,P=0.029;3grade vs 1grade,HR=2.011,95% CI=1.664-2.871,P=0.000),portal vein tumor thrombus(HR=2.541,95% CI=1.662-3.491,P=0.000);2.indicators of 1 month follow-up after initial TACE treatment : NLR(HR=1.675,95% CI= 1.475-2.396,P=0.032),the change of AFP*(1 vs 0,HR=2.065,95%CI=1.568-3.715,P=0.015;2 vs 0,HR=2.224,95% CI=1.456-3.585,P=0.005),the change of DCP*(1 vs 0,HR=3.343,95% CI=1.79-5.95,P=0.000;2 vs 0,HR=3.669,95%CI=2.471-5.877,P=0.000)(Note: * 0 indicates a decrease of ≥20% in follow-up results compared with baseline;2 indicates an increase of ≥20%;1 indicates a change between 0and 2);3.the numbers of TACE in 6months(HR=0.387,95% CI=0.134-0.521,P=0.007).These independent predictors were used to construct a prognostic nomogram for PFS after TACE in patients with liver cancer.In derivation cohort,calibration curve of the nomogram showed a high agreement between the predicted and the actual PFS probability of patients with the C-index=0.712,which outperformed the BCLC staging system(Cindex=0.688).This result was confirmed in the validation cohort,the C-index of which was0.734,better than BCLC staging system(C-index=0.663).Conclusion: The nomogram constructed in this study not only included pre-treatment baseline data of patients with liver cancer,but also incorporated some post-treatment follow-up indicators,which had significant dynamic advantages compared with previously reported models.After validation,the model was proved to have good predictive efficacy and outperformed BCLC staging system.Although the results need to be further validated by more samples and other center cohorts due to the limitations of sample size and being a single-center study.Nevertheless,this study demonstrated that the nomogram constructed from the above indicators had clinical significance and could be used as a complementary assessment to predict the survival and prognosis of patients with liver cancer treated with TACE.