Transarterial Chemoembolization Combined with Lenvatinib plus PD-1 Inhibitor for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study

Purpose To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE-L-P) versus TACE combined with lenvatinib (TACE-L) for patients with advanced hepatocellular carcinoma (HCC).Methods Data of advanced HCC patients treated with TACE-L-P or TACE-L from January 2019 to December 2020 were retrospectively analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were determined.Results A total of 81 patients were included in this study (41 received TACE-L-P and 40 received TACE-L). The patients in TACE-L-P group had prolonged OS (median, 16.9 vs. 12.1 months, p=0.009), longer PFS (median, 7.3 vs. 4.0 months, p=0.002) and higher objective response rate (56.1% vs. 32.5%, p=0.033) and disease control rate (85.4% vs. 62.5%, p=0.019) than those in TACE-L group. Multivariate analyses revealed that the treatment option of TACE-L, main portal vein invasion and extrahepatic metastasis were the independent risk factors for OS, while TACE-L and extrahepatic metastasis were the independent risk factors for PFS. In subgroup analyses, a superior survival benefit was achieved with TACE-L-P in patients with extrahepatic metastasis or tumor number >3 but not in those with main portal vein invasion. The incidence and severity of AEs in TACE-L-P group were comparable to those in TACE-L group (any grade, 92.7% vs. 95.0%, p=1.000; grade 3, 36.6% vs. 32.5%, p=0.699).Conclusion TACE-L-P significantly improved survival over TACE-L with an acceptable safety profile in advanced HCC patients, especially those with extrahepatic metastasis or tumor number >3 but without main portal vein invasion.

Successful Conversion Surgery for Massive Hepatocellular Carcinoma with Tumor Thrombus in Main Portal Vein after Treatment with Lenvatinib Combined with Toripalimab: A Case Report

Background:Advanced hepatocellular carcinoma (HCC) with Portal vein invasion has an extremely dismal prognosis. We report a rare case of advanced HCC with portal vein tumor thrombus (PVTT). First, Lenvatinib(Len) combined with Toripalimab(Tor) was treated. The patient was successfully treated with radical surgical resection after the tumor thrombus shrank. Postoperative pathology showed complete response (CR).Case presentation:A 52-year-old male patient had a massive liver cancer in his right liver, and the tumor thrombus grew to the main portal vein. He passed 4 cycles of Len combined with Tor, the tumor shrank rapidly, the level of tumor markers dropped rapidly, The tumor thrombus was successfully confined from the main portal vein to the right branch of the portal vein. Therefore, the patient underwent a right hepatectomy and successfully removed a complete PVTT. Histopathological results showed that the primary tumor and tumor thrombus were only infiltrated by inflammatory cells, and there were no viable tumor cells.Conclusions:Len combined with Tor can be used as a preoperative neoadjuvant regimen for the treatment of advanced HCC with massive macrovascular invasion.

Development of a Prognostic Scoring System for Hepatocellular Carcinoma Patients With Main Portal Vein Tumor Thrombus Undergoing Conventional Transarterial Chemoembolization: An Analysis of 173 Patients

BackgroundPatients with hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (mPVTT) have poor prognosis. Promising systemic therapies, such as target therapies, have limited benefits. The purpose of this study is to retrospectively evaluate the benefits of conventional TACE (c-TACE) and to establish a prognostic stratification of HCC patients with mPVTT.MethodsThis is a single center retrospective study conducted over 5 years (duration of performing c-TACE), on consecutive HCC patients with mPVTT receiving c-TACE. Univariable and multivariable analysis were used to explore factors independently associated with overall survival (OS). Based on Cox-regression analysis, prognostic models were developed and internally validated by bootstrap methods. Discrimination and performance were measured by Akaike information criterion, concordance index, and likelihood ratio test.ResultsA total of 173 patients were included. Median OS was 6.0 months (95%CI: 3.92~8.08). The independent variables correlated with survival were largest tumor diameter, tumor number, mPVTT extension, and AFP. In the final model, patients were assigned 2 points if largest tumor diameter ≥8 cm, or tumor number ≥2, 1point if main trunk was complete obstructed, or AFP ≥400 ng/ml. By summing up these points, patients were divided into three risk groups according to the score at the 15rd and 85th percentiles, in which median OS were 18, 7, and 3.5months, respectively (p<0.001). The model shown optimal discrimination, performance, and calibration.Conclusionsc-TACE could provide survival benefits in HCC patients with mPVTT and the proposed prognostic stratification may help to identify good candidates for the treatment, and those for whom c-TACE may be futile.

Efficacy and Safety of Lenvatinib for Advanced Hepatocellular Carcinoma Patients Beyond REFLECT Study Indications in a Real-World Setting in China

Background/purpose: Lenvatinib was found to be non-inferior to sorafenib in a Phase 3 REFLECT trial on advanced hepatocellular carcinoma. However, patients with a liver tumor volume of greater than 50% of total liver volume or with main portal vein tumor thrombus, which often occurs in clinical practice, were excluded from the REFLECT trial. This study aimed to examine the safety and efficacy of lenvatinib on patients beyond REFLECT study indications in a real-world setting.Method: This was a retrospective, single-center observational study focused on unresectable hepatocellular carcinoma (u-HCC) patients with the tumor accounting for more than 50% of the liver volume or with main portal vein tumor thrombus. From June 2018 to February 2019, 21 u-HCC patients with above characteristics were enrolled. The therapeutic effects were determined using the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) in the 12th week. Grades of adverse events followed with the Common Terminology Criteria for Adverse Events version (CTCAE) 4.0. The median Progression-Free Survival (PFS) and median Over Survival (OS) were determined at the 12th month.Results: The median observation period was 11.5 months. Fatigue, leukopenia and dysphoria were the most frequent adverse events. Leukopenia, hand-foot skin reaction and decreased appetite were the most frequent adverse events, and were higher than Grade 2. 7 of the patients had elevated Child-Pugh scores, 3 of whom increased from Child-Pugh A to B. All of the adverse events could be controlled by appropriate dose reduction, interruption and symptomatic treatment. No liver function failure occurred. The probability of tumor marker (AFP or PIVKA-II) decline was 100% and 60% at one month and three months after administration respectively. In the m-RECIST evaluation in the 12th week, 0, 7, 7 and 7 patients achieved complete response, partial response, stable disease and progressive disease respectively. The objective response rate was 33.3%. The median PFS and OS was 5.3 and 11.2 , respectively. 1 year survival rate was 42.9%.Conclusion: Lenvatinib treatment can be accomplished with safety and a good response for patients beyond REFLECT study indications in a real-world setting.

Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Tertiary Care Center Experience

Background Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) occurring in 30 to 40% of cases. The presence of PVTT in HCC is regarded as an advanced disease that confers poor prognosis and survival. Transarterial chemoembolization (TACE) has traditionally been considered to be contraindicated in cases of PVTT, due to the risk of hepatic infarction, and further deteriorate liver function. We evaluated safety, technical efficacy, and outcomes of TACE in HCC with PVTT. Methods From search results of the hospital database, out of 652 patients who underwent TACE for HCC, 73 patients of HCC with PVTT were retrospectively evaluated. Post-TACE tumor response by computed tomography (CT)/magnetic resonance imaging (MRI) imaging as per modified response evaluation criteria in solid tumors (mRECIST) criteria, if any occurrence of acute hepatic failure was assessed. Prognostic factors influencing survival were also determined. Results In our study population, the mean age of the patients was 58 years. The 12- and 24-month survival rates were 59 and 14%, respectively, with an overall median survival of 12.3 months. A total of 58.9% patients had branch portal vein tumor thrombus and 41.1% had tumor thrombus in the main portal vein. We did not encounter any mortality or acute liver failure following TACE in a 30-day period. Both univariate and multivariate analysis revealed Child–Pugh score (p = 0.01) and the extent of tumoral thrombus (p 0.004) as a significant prognostic factor. Patients with branch PVTT, no ascites, and Child–Pugh A had better survival than those having main portal vein tumor thrombus, ascites, and Child–Pugh B. Conclusion Our study concluded that TACE can achieve good disease control and improved survival in HCC with portal vein invasion despite being considered as a relative contraindication. Technical expertise, selection of patients, such as superselective catheterization and preserved liver function, are the key factors for a safe therapeutic procedure. Child–Pugh score and extent of portal vein invasion were the significant prognostic factors determining survival.

No Association of Homocysteine, Anticardiolipin Antibody, and Anti-β2 Glycoprotein I Antibody With Portal Venous System Thrombosis in Liver Cirrhosis

Portal venous system thrombosis (PVST), a common complication of liver cirrhosis, is closely associated with thrombophilia. To explore the association of homocysteine (Hcy), anticardiolipin antibody (aCL), and anti-β2 glycoprotein I antibody (aβ2GPI), which are possible thrombophilic factors, with PVST in liver cirrhosis. Overall, 654 non-malignant patients (219 with and 435 without liver cirrhosis) admitted between January 2016 and June 2020 were retrospectively evaluated. Presence of PVST, degree of main portal vein (MPV) thrombosis, and clinically significant PVST were identified. Hcy level, hyperhomocysteinemia (HHcy), aCL positivity, and aβ2GPI positivity were compared according to the presence of liver cirrhosis and PVST. Positive aβ2GPI was significantly more frequent in patients with liver cirrhosis than those without, but Hcy level and proportions of HHcy and positive aCL were not significantly different between them. PVST could be evaluated in 136 cirrhotic patients. Hcy level [10.57 μmol/L (2.71-56.82) versus 9.97 μmol/L (2.05-53.44); P = 0.796] and proportions of HHcy [4/44 (9.1%) versus 13/81 (16.0%); P = 0.413] and positive aCL [1/23 (4.3%) versus 10/52 (19.2%); P = 0.185] and aβ2GPI [9/23 (39.1%) versus 21/52 (40.4%); P = 0.919] were not significantly different between cirrhotic patients with and without PVST. There was still no significant association of Hcy level, HHcy, aCL, or aβ2GPI with PVST based on Child-Pugh classification, MPV thrombosis >50%, and clinically significant PVST. Hcy, aCL, and aβ2GPI may not be associated with PVST in liver cirrhosis, suggesting that routine screening for Hcy, aCL, and aβ2GPI should be unnecessary in such patients.