BackgroundRecent research has shown that selected patients with initially unresectable hepatocellular carcinoma (HCC) are able to achieve conversion to resectable disease through systemic or local therapy. Combination regimens comprised of drugs with different mechanisms of action have shown better outcomes than single-drug or single-approach-based treatments; however, to date, combination regimens investigated as part of conversion therapy strategies have been two drug combinations with reported issues of relatively low surgical conversion and objective response rates. In this study, we investigated the efficacy and safety of triple combination therapy with angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy for surgical conversion of advanced HCC.MethodsThis was a single-center, retrospective, single-arm study of patients with unresectable HCC who received at least one cycle of triple combination therapy with an oral anti-angiogenic drug, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy between August 2019 and August 2020. Endpoints included the overall response rate (ORR), surgical conversion rate, time to response and safety. Treatment response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1.ResultsIn total, 34 patients were included in this study, of whom 25 completed treatment evaluation. The best ORR was 96.0% (24/25); 48.0% (n = 12) had a complete response, 48.0% (n = 12) had a partial response, and 4.0% (n = 1) had stable disease. The median time to response was 50.5 (95% CI, 31.02–64.00) days and the surgical conversion rate was 60% (15/25). Of the 25 patients, 56.0% (n = 14) received surgical resection and 28.0% (n = 7) had a pathologic complete response. Toxic side effects were manageable.ConclusionA triple combination therapy regimen of angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy showed significant therapeutic effect with an extremely high surgical conversion rate in patients with initially unresectable HCC.
The novel technique of virtual hepatectomy is useful for evaluation of the portal territory for anatomical sectionectomy, segmentectomy, and hemihepatectomy.
The aim of this study was to investigate the prognostic significance of blood NLR in patients with intermediate-advanced hepatocellular carcinoma (HCC) who received transcatheter arterial embolization (TAE) combined with Sorafenib. A total of 40 patients with intermediate-advanced HCC from January 1, 2010, through May 31, 2013, treated with concurrent TAE in combination with Sorafenib were admitted to this study in our hospital. Potential prognostic factors, including serum NLR, were analyzed. The pretreatment mean NLR was 3.0; 21 (52.5 %) patients with elevated high NLR (>3.0). The median survival of patients with a high NLR was 14 months (95 % CI 10.1-17.9 months) compared with 26 months (95 % CI 17.4-34.6 months) for patients with a low NLR; a significant difference was found in overall survival (P = 0 0.001). Barcelona Clinical Liver Cancer staging classification and NLR >3.0 were all predictors of poorer over survival. Multivariate analysis showed that high NLR was independent factors associated with worse survival. A high periprocedural NLR independently predicts poor survival in patients with unresectable HCC undergoing TAE combined with Sorafenib.
Purpose: We retrospectively evaluated the efficacy and safety of apatinib as a first-line treatment for advanced hepatocellular carcinoma (HCC) and explored whether drug-related hypertension (HTN) could predict its efficacy. Patients and Methods: This retrospective analysis included patients with advanced HCC who received oral treatment with apatinib. We evaluated the effectiveness by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease control rate (DCR), and assessed the safety of the drug based on the occurrence of adverse events. In order to explore whether apatinib-related HTN can be used as a predictor of therapeutic effect, patients were divided into an HTN group and a non-HTN group and adjusted for propensity score-matched (PSM) to reduce mixed deviation. Subgroup analyses of negative prognostic factors for advanced HCC were also performed, including alpha-fetoprotein (AFP), Child-Pugh Score, macrovascular invasion, and extrahepatic metastasis. Results: A total of 208 patients were analyzed, of which 40.9% (n =85) developed drugrelated HTN. For all patients, the OS was 13.4 months (95% CI, 12.2-14.6), the PFS was 5.7 months (95% CI, 5.1-6.3), and the TTP was 6.9 months (95% CI, 6.0-7.8). The OS of the HTN group and the non-HTN group was 17.4 months (m) and 12.5m (p=0.001), and the PFS was 7.4m and 4.7m (p=0.000), respectively. After PSM, the OS (p=0.001) and PFS (p=0.003) of the HTN group were still significantly better than the non-HTN group. Subgroup analysis suggested that overall survival was significantly longer in patients with HTN when serum AFP ≤400 μg/L or extrahepatic metastases. Moreover, OS in the HTN group increased significantly with or without macrovascular invasion. In addition, through the analysis of two groups of patients with PFS>6m and PFS≤6m, we know that the patients with drug-related HTN may develop resistance later, so they have longer survival time. Conclusion: Apatinib demonstrates compelling anti-cancer activity and acceptable safety in advanced HCC. Apatinib-related HTN can potentially predict prolonged survival in patients with advanced HCC.
BackgroundMolecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC).MethodsA total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders.ResultsThe median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3–4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan–Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients.ConclusionPatients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.
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