Role of locoregional therapies in the wake of systemic therapy

Palmer, Daniel H.; Malagari, Katerina; Kulik, Laura

doi:10.1016/j.jhep.2019.09.023

Cited by 65 publications

(48 citation statements)

References 76 publications

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“…Lenvatinib plus pembrolizumab has recently become a potent systemic combination therapy for unresectable HCC ( 6 ). In clinical practice, locoregional-systemic combinations are widely applied due to the overall control of tumor conditions ( 13 ). The result of a randomized clinical trial conducted by Ming Shi et al demonstrated that a combination of sorafenib plus HAIC using FOLFOX agents extends overall survival by 87.5% or 6.24 months compared to sorafenib alone in HCC patients with portal vein invasion ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma

et al. 2021

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BackgroundLenvatinib combined with programmed cell death protein-1 (PD-1) inhibitors has resulted in good survival outcomes in the treatment of unresectable hepatocellular carcinoma (HCC). Hepatic artery infusion chemotherapy (HAIC) has also attracted attention due to its high response rates and favorable survival for advanced HCC patients. The present study aimed to compare the efficacy of HAIC combined with PD-1 inhibitors plus lenvatinib (HPL) and PD-1 inhibitors plus lenvatinib (PL) in patients with advanced HCC.MethodsBetween July 2018 and December 2019, patients diagnosed with advanced HCC who initially received HPL or PL treatment were reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.ResultsIn total, 70 patients met the criteria and were included in the present study, and they were divided into the HPL group (n = 45) and PL group (n = 25). The overall response rate (40.0 vs. 16.0%, respectively; p = 0.038) and disease control rate (77.6 vs. 44.0%, respectively; p < 0.001) were higher in the HPL group than in the PL group. The median overall survival was 15.9 months in the HPL group and 8.6 months in the PL group (p = 0.0015; HR = 0.6; 95% CI 0.43–0.83). The median progression-free survival was 8.8 months in the HPL group and 5.4 months in the PL group (p = 0.0320; HR = 0.74; 95% CI 0.55–0.98).ConclusionCompared to PL, HPL was associated with a significantly better treatment response and survival benefits for patients with advanced HCC.

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Section: Discussionmentioning

confidence: 99%

Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma

et al. 2021

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“…Locoregional therapies, including transarterial chemoembolization (TACE) and ablations, are proposed to postpone disease progression ( Palmer et al, 2020 ). Therapy that combines TACE and RFA has been recommended and has proven to be an effective selection for intermediate and advanced HCC (Z. W. Peng et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

A Radiomics Signature-Based Nomogram to Predict the Progression-Free Survival of Patients With Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization Plus Radiofrequency Ablation

Fang

Lai

Zhu

et al. 2021

Front. Mol. Biosci.

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Objective: The study aims to establish an magnetic resonance imaging radiomics signature-based nomogram for predicting the progression-free survival of intermediate and advanced hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) plus radiofrequency ablationMaterials and Methods: A total of 113 intermediate and advanced HCC patients treated with TACE and RFA were eligible for this study. Patients were classified into a training cohort (n = 78 cases) and a validation cohort (n = 35 cases). Radiomics features were extracted from contrast-enhanced T1W images by analysis kit software. Dimension reduction was conducted to select optimal features using the least absolute shrinkage and selection operator (LASSO). A rad-score was calculated and used to classify the patients into high-risk and low-risk groups and further integrated into multivariate Cox analysis. Two prediction models based on radiomics signature combined with or without clinical factors and a clinical model based on clinical factors were developed. A nomogram comcined radiomics signature and clinical factors were established and the concordance index (C-index) was used for measuring discrimination ability of the model, calibration curve was used for measuring calibration ability, and decision curve and clinical impact curve are used for measuring clinical utility.Results: Eight radiomics features were selected by LASSO, and the cut-off of the Rad-score was 1.62. The C-index of the radiomics signature for PFS was 0.646 (95%: 0.582–0.71) in the training cohort and 0.669 (95% CI:0.572–0.766) in validation cohort. The median PFS of the low-risk group [30.4 (95% CI: 19.41–41.38)] months was higher than that of the high-risk group [8.1 (95% CI: 4.41–11.79)] months in the training cohort (log rank test, z = 16.58, p < 0.001) and was verified in the validation cohort. Multivariate Cox analysis showed that BCLC stage [hazard ratio (HR): 2.52, 95% CI: 1.42–4.47, p = 0.002], AFP level (HR: 2.01, 95% CI: 1.01–3.99 p = 0.046), time interval (HR: 0.48, 95% CI: 0.26–0.87, p = 0.016) and radiomics signature (HR 2.98, 95% CI: 1.60–5.51, p = 0.001) were independent prognostic factors of PFS in the training cohort. The C-index of the combined model in the training cohort was higher than that of clinical model for PFS prediction [0.722 (95% CI: 0.657–0.786) vs. 0.669 (95% CI: 0.657–0.786), p＜0.001]. Similarly, The C-index of the combined model in the validation cohort, was higher than that of clinical model [0.821 (95% CI: 0.726–0.915) vs. 0.76 (95% CI: 0.667–0.851), p = 0.004]. The calibration curve, decision curve and clinical impact curve showed that the nomogram can be used to accurately predict the PFS of patients.Conclusion: The radiomics signature was a prognostic risk factor, and a nomogram combined radiomics and clinical factors acts as a new strategy for predicted the PFS of intermediate and advanced HCC treated with TACE plus RFA.

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“…Since HCCs are solely supplied by the hepatic artery, transarterial treatments have proven to be extremely effective in delivering targeted embolic therapies to tumors while preserving and minimizing exposure to the surrounding liver parenchyma, especially when performed in an extremely selective manner (Breedis and Young, 1954;Kerbel, 2008;Pillai et al, 2020). TACE is the most widely used therapeutic intervention for patients with intermediate-stage HCC (Palmer et al, 2020). There are four types of embolization used for HCC treatment in clinic: bland embolization, conventional TACE, drug-eluting bead chemoembolization (DEB-TACE), and TARE (Kritzinger et al, 2013;Kloeckner et al, 2020).…”

Section: Transarterial Chemoembolizationmentioning

confidence: 99%

Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development

Wang

et al. 2021

Front. Mol. Biosci.

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Despite the application of antiviral drugs and improved surveillance tools, the number of patients diagnosed with hepatocellular carcinoma (HCC) at an advanced stage and with a dismal prognosis is still on the rise. Systemic treatment with multiple multitargeted tyrosine kinase inhibitors (TKIs), such as sorafenib, has been a widely utilized approach for a decade. In addition, the use of a combination of TKIs with other types of compounds, including immune checkpoint inhibitors (ICIs) and antiangiogenic inhibitors, has shown efficacy in treating advanced HCC. However, the presence of intolerable adverse events, low disease response and control rates, and relative short overall survival of such combinatory therapies makes novel or optimized therapies for advance HCC urgently needed. Locoregional therapy (transarterial chemoembolization, and thermal ablation) can destroy primary tumors and decrease tumor burden and is widely used for HCC management. This type of treatment modality can result in local hypoxia and increased vascular permeability, inducing immunogenic effects by releasing tumor antigens from dying cancer cells and producing damage-associated molecular patterns that facilitate antiangiogenic therapy and antitumor immunity. The combination of systemic and locoregional therapies may further produce synergistic effects without overlapping toxicity that can improve prognoses for advanced HCC. In preliminary studies, several combinations of therapeutic modes exhibited promising levels of safety, feasibility, and antitumor effects in a clinical setting and have, thus, garnered much attention. This review aims to provide a comprehensive, up-to-date overview of the underlying mechanisms of combined systemic and locoregional therapies in the treatment of advanced HCC, commenting on both their current status and future direction.

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Role of locoregional therapies in the wake of systemic therapy

Cited by 65 publications

References 76 publications

Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma

Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma

A Radiomics Signature-Based Nomogram to Predict the Progression-Free Survival of Patients With Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization Plus Radiofrequency Ablation

Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development

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