This retrospective observational cohort study was approved by the Research Ethics Committee of Chongqing Medical University and followed the 1983 revision of the 1975 Helsinki Declaration. Because of the retrospective design of this study, the requirement of informed consent is exempted. From June 1, 2021 to June 1, 2022, unresectable HCC patients who visited our center were included in this study. HCC was diagnosed according to the European Association for liver Research (EuropeanAssociationfortheStudyoftheLiver,EASL) criteria. The inclusion criteria are as follows: (A) it is classified as stage A or B or C of HCC (BCLC) in Barcelona; (B) after evaluation by two experienced hepatobiliary surgeons (with more than 15 years of experience in hepatectomy), the tumor cannot undergo radical resection due to lack of surgical margin; or the estimated residual liver volume (FLV) after resection is less than 30%, and the residual liver volume of cirrhosis HCC is less than 40%; (C) it is classified as Child-PughA or B grade. Excluded if any of the following criteria are met; (A) previous history of HCC treatment; (B) distant metastasis; (C) severe underlying heart, lung or kidney disease; (D) second primary malignant tumor. All patients signed the informed consent form before treatment, and voluntarily chose TACE-HAIC combined with tislelizumab and lenvatinib program or HAIC combined with tislelizumab and lenvatinib program.
Treatment process
TACE-HAIC combined tislelizumab and lenvatinib
Fluorouracil 750mg (trade name) + oxaliplatin 150mg + pirarubicin 30mg was mixed in 9mL water-soluble contrast medium and 1mL aseptic injection water, and the mixture was fully mixed with 10ml lipiodol to make an emulsion, then the catheter was inserted into the feeding artery of HCC by Seldinger method, and the emulsion was injected into the artery through the catheter, embolized with lipiodol and microspheres as needed, indwelling catheter and sheath for perfusion. Perfusion chemotherapy drugs including oxaliplatin 85mg/m2, 2h perfusion completed;calcium folinate 400mg/m2, 2h perfusion completed༛5-fluorouracil 400mg/m2 was injected intravenously, 5-fluorouracil 400mg/m2 was injected, and then 5-fluorouracil 2400mg/m2 was continuously perfused for 46 hours (mFOLFOX regimen). Then, according to the condition of the patients, tislelizumab 200mg was infused once a month, and lenvatinib was taken orally with 2 tablets of 60KG (4mg) or 3 tablets of 60KG (6mg) once a day. The treatment was repeated every 4 weeks.
HAIC combined with combined tislelizumab and lenvatinib
Under the guidance of fluoroscopy, the catheter was inserted into the main feeding artery of HCC by Seldinger method. and the catheter was fixed, and the other end was connected to the arterial infusion pump. Perfusion chemotherapy drugs including oxaliplatin 85mg/m2, 2h perfusion completed;calcium folinate 400mg/m2, 2h perfusion completed༛5-fluorouracil 400mg/m2 was injected intravenously, 5-fluorouracil 400mg/m2 was injected, and then 5-fluorouracil 2400mg/m2 was continuously perfused for 46 hours (mFOLFOX regimen). Then, according to the condition of the patients, tislelizumab 200mg was infused once a month, and lenvatinib was taken orally with 2 tablets of 60KG (4mg) or 3 tablets of 60KG (6mg) once a day. The treatment was repeated every 4 weeks.
When the disease progresses, unbearable adverse reactions occur, and the patient is suitable for other treatments, the research treatment is terminated.
Follow-up and evaluation
Blood routine, hepatitis B pathogen, liver function, serum alpha-fetoprotein (AFP) level, tumor size, number and location, BCLC stage, CHILD grade and treatment regimen were detected before each course of treatment. Enhanced computed tomography (computedtomography,CT) was performed every 6 weeks. Blood tests, including liver function tests and serum alpha-fetoprotein (alpha-fetoprotein, AFP) levels, were performed during each treatment. For patients whose tumors were reduced to resectable size, the resectability of unresectable HCC was evaluated by 2 experienced hepatobiliary surgeons with more than 15 years of experience in hepatectomy. According to the solid tumor response Assessment criteria (RECIST), tumor response is evaluated by radiologists who are blind to treatment. Disease control rate (DCR) is defined as complete remission rate (CR) + partial remission rate (PR) + stable phase (SD). Objective remission rate (ORR) is defined as the ratio of CR + PR.
Statistical analysis
To compare the differences between groups of baseline variables, Student's t test was used to measure variables satisfying normal distribution, and rank sum test was used if they were not satisfied. Chi-square test, corrected chi-square test, Fisher test and rank sum test were used to count variables or rank variables. PFS was estimated by Kaplan-Meier method. All P values are bilateral, and P values less than 0.05 are considered significant. Statistical Package for Social Sciences version 26.0 (SPSS Inc., Chicago, IL, USA) was used for all statistical processing.