Prediction Of C-TACE Response And Prognosis In Intermediate-stage Hepatocellular Carcinoma Based On Quantitative CT Parameters

Background: Hepatocellular carcinoma(HCC)is one of the top three cancers with the number of deaths from malignant tumors worldwide.Due to the hidden onset of HCC,more than half of the patients are already in the advanced state when the disease is diagnosed,and more than 10-15% of HCC patients are classified as intermediate stage(stage B)[according to Barcelona Clinic Liver Cancer(BCLC)definition].Domestic and foreign guidelines recommend conventional transarterial chemoembolization(C-TACE)as the current standard treatment for patients with midterm HCC.However,C-TACE treatment also has some shortcomings.In the past,it has been reported in the literature that C-TACE treatment has a high local recurrence rate and low reproducibility(multiple surgical operations and embolization lead to occlusion of the blood supply artery of the lesion).C-TACE is the most prominent problem faced by C-TACE in clinical practice,such as multiple defects such as blood vessel variation or incomplete treatment of tumor lesions with multiple blood supply,resulting in a high local tumor recurrence rate.It has been reported that only 15-55% of patients can achieve objective remission.The huge difference in therapeutic effects of C-TACE between different patients may be attributed to the fact that mid-stage HCC includes a highly heterogeneous patient population,including tumor burden,liver function,tumor blood supply,whether the tumor boundary is clear and There are many potential factors such as tumor blood vessel variation.Therefore,it is necessary to explore the corresponding predictive indicators to help clinicians to screen out the patient groups who benefit from C-TACE treatment as much as possible before the first C-TACE treatment for patients with mid-term HCC,and to provide patients with personalized and precise treatment strategies.The long-term survival benefit of patients has important clinical significance.The principle of C-TACE is mainly to inject chemoembolizers through the tumor supply artery,which not only effectively blocks the tumor blood supply,but also acts as a local chemotherapy to promote tumor tissue necrosis to achieve the purpose of treatment.Therefore,whether the arterial blood supply of tumor lesions is abundant or not may play a key role in determining the efficacy of C-TACE treatment.In clinical practice,giving patients a detailed treatment plan or evaluating the therapeutic effect of C-TACE is usually based on CT enhanced scanning.Studies have confirmed that the average CT attenuation value(Hounsfield unit,HU)based on enhanced CT images can reflect the abundance of blood supply in the delineated area to a certain extent.Therefore,it is worth exploring whether the quantitative parameters based on enhanced CT scan of the liver can be used to predict the response and prognosis of the first CTACE treatment in patients with mid-term HCC.Methods: We retrospectively included 192 patients with Intermediate HCC with Child-Pugh A or B liver function who received C-TACE as the first-line treatment in the Department of Interventional Therapy of Guangdong Provincial People’s Hospital from 2010 to mid-2019(a total of 468 intrahepatic lesions were included as Target lesion).Before the patient received C-TACE treatment,the upper abdomen enhanced CT scan was used to outline the area of interest of the target lesion on the largest diameter level of the lesion,and the average CT attenuation value in the plain,arterial and portal phases was measured.Use formulas to calculate the CT quantitative parameters of the target lesion: arterial enhancement ratio(AER)and arterial portal venous enhancement ratio(APR).AER reflects the ratio of the percentage of enhancement of arterial phase between the target lesion and normal liver parenchyma,and APR is the ratio of the percentage of enhancement between the arterial phase and the portal phase of the target lesion.According to m RECIST criteria to evaluate the treatment response of target lesions and patients,the treatment response of patients and target lesions included in the study are divided into two categories: response group [defined as complete response(CR)+ partial response(PR)] and non-responsive group [defined as stable disease(SD)+ progressive disease(PD)].And use receiver-operating characteristic curves(ROC)to analyze the ability of these two CT quantitative parameters to predict treatment response and patient survival benefit.Results: 192 patients and 468 target lesions eligible for admission were included in the final analysis.The mean longest diameters of the target lesions in the response group and non-response group were 5.9 cm and 6.2 cm,respectively,and the difference was not statistically significant(P = 0.642).There was no significant difference in clinical baseline characteristics between patients in the response group and the non-response group.After the first C-TACE treatment,a total of 57(29.7%)patients and 123(26.3%)target lesions were evaluated as CR,and another 18(9.4%)patients and 79(16.9%)target lesions were evaluated as PR.The objective response rate(ORR)and disease control rate(DCR)were 39.1% and 69.8%,respectively.As of October 2019,the median follow-up time was 22.0 months(range: 5.1-51.9 months).The median progression-free survival(PFS)of patients in the response group and non-response group was 6.8 months [95% confidence interval(CI): 5.7–7.9 months] and 2.5 months,respectively Months(95% CI: 2.2–2.6 months).The PFS of responding patients was significantly longer than that of non-responding patients(P <0.001).The median overall survival(OS)of the response group and the non-response group were 29.4 months(95% CI: 26.4-31.3 months)and 18.3 months(95% CI: 15.7-20.9 months),respectively.The OS of the response group was significantly longer than that of the non-response group(P <0.001).In target lesions and patient response to treatment,the average AER and APR values of the responding group were significantly higher than those of the nonresponsive group [target lesions(AER: 3.93 vs.2.16;APR: 2.36 vs.2.11,both P <0.001);Overall patient response(AER: 3.57 vs.2.47;APR: 2.38 vs.2.11,both P <0.001)].Statistical analysis,the predictive power of CT quantitative parameters for the response state(CR+PR),at the target lesion level,the AUC of AER and APR were 0.87 and 0.63,respectively,P <0.001;the overall response of the patient,the AUCs of AER,APR were 0.81 and 0.65,respectively,P <0.001.AER has better predictive performance than APR in target lesions and patient response to treatment(AUC: 0.87 vs.0.63,0.81 vs.0.65,all P<0.001).Conclusions: Based on the quantitative CT parameters(AER and APR)of the multi-phase enhanced CT scan before C-TACE,it can predict the treatment response of mid-term HCC patients to C-TACE.We provide this method,which can help clinicians to screen out the best interim HCC patient population eligible for C-TACE treatment at a lower cost to a certain extent.