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Chemotherapeutic Nanoparticle-Based Liposomes Enhance the Efficiency of Mild Microwave Ablation in Hepatocellular Carcinoma Therapy.

ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer, and the 5-year overall survival (OS) rate for HCC remains unsatisfying worldwide. Microwave ablation (MWA) is a minimally invasive therapy that has made progress in treating HCC. However, HCC recurrence remains problematic. Therefore, combination therapy may offer better outcomes and enhance MWA efficiency through improved tumor control. We have developed doxorubicin-loaded liposomes (DNPs) as an efficient nanoplatform to enhance MWA of hepatocellular carcinoma even at the mild ablation condition. In this study, we demonstrated that the uptake of DNPs by HCC cells was increased 1.5-fold compared with that of free DOX. Enhanced synergism was observed in the combination of DNPs and MWA, which induced nearly 80% cell death. The combination of mild MWA and DNPs enhanced the ablation efficiency of HCC with significant inhibition of liver tumors and accounted for the longest survival rate among all groups. A much higher accumulation of the DNPs was observed in the transitional zone than in the ablation zone. No apparent systemic toxicity was observed for any of the treatments after 14 days. The present work demonstrates that DNPs combined with MWA could be a promising nanoparticle-based therapeutic approach for the treatment of hepatocellular carcinoma and shows potential for future clinical applications.

SUBMITTER: Wu S

PROVIDER: S-EPMC7054279 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Chemotherapeutic Nanoparticle-Based Liposomes Enhance the Efficiency of Mild Microwave Ablation in Hepatocellular Carcinoma Therapy.

Wu Songsong S Zhang Dongyun D Yu Jie J Dou Jianping J Li Xin X Mu Mengjuan M Liang Ping P

Frontiers in pharmacology 20200226

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer, and the 5-year overall survival (OS) rate for HCC remains unsatisfying worldwide. Microwave ablation (MWA) is a minimally invasive therapy that has made progress in treating HCC. However, HCC recurrence remains problematic. Therefore, combination therapy may offer better outcomes and enhance MWA efficiency through improved tumor control. We have developed doxorubicin-loaded liposomes (DNPs) as an efficient nanoplatfo ...[more]

PMID: 32174827

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Project description:BackgroundHigh early recurrence (ER) of hepatocellular carcinoma (HCC) after microwave ablation (MWA) represents a sign of aggressive behavior and severely worsens prognosis. The aim of this study was to estimate the outcome of HCC following MWA and develop a response algorithmic strategy based on multiparametric MRI and clinical variables.MethodsIn this retrospective study, we reviewed the records of 339 patients (mean age, 62 ± 12 years; 106 men) treated with percutaneous MWA for HCC between January 2014 and December 2017 that were evaluated by multiparametric MRI. These patients were randomly split into a development and an internal validation group (3:1). Logistic regression analysis was used to screen imaging features. Multivariate Cox regression analysis was then performed to determine predictors of ER (within 2 years) of MWA. The response algorithmic strategy to predict ER was developed and validated using these data sets. ER rates were also evaluated by Kaplan-Meier analysis.ResultsBased on logistic regression analyses, we established an image response algorithm integrating ill-defined margins, lack of capsule enhancement, pre-ablative ADC, ΔADC, and EADC to calculate recurrence scores and define the risk of ER. In a multivariate Cox regression model, the independent risk factors of ER (p < 0.05) were minimal ablative margin (MAM) (HR 0.57; 95% CI 0.35 - 0.95; p < 0.001), the recurrence score (HR: 9.25; 95% CI 4.25 - 16.56; p = 0.021), and tumor size (HR 6.21; 95% CI 1.25 - 10.82; p = 0.014). Combining MAM and tumor size, the recurrence score calculated by the response algorithmic strategy provided predictive accuracy of 93.5%, with sensitivity of 92.3% and specificity of 83.1%. Kaplan-Meier estimates of the rates of ER in the low-risk and high-risk groups were 6.8% (95% CI 4.0 - 9.6) and 30.5% (95% CI 23.6 - 37.4), respectively.ConclusionA response algorithmic strategy based on multiparametric MRI and clinical variables was useful for predicting the ER of HCC after MWA.

Project description:ObjectivesWe aimed to compare the therapeutic outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) as first-line therapies in patients with small single perivascular hepatocellular carcinoma (HCC).MethodsA total of 144 eligible patients with small (≤ 3 cm) single perivascular (proximity to hepatic and portal veins) HCC who underwent RFA (N = 70) or MWA (N = 74) as first-line treatment were included. The overall survival (OS), disease-free survival (DFS), and local tumor progression (LTP) rates between the two ablation modalities were compared. The inverse probability of treatment weighting (IPTW) method was used to reduce selection bias. Subgroup analysis was performed according to the type of hepatic vessels.ResultsAfter a median follow-up time of 38.2 months, there were no significant differences in OS (5-year OS: RFA 77.7% vs. MWA 74.6%; p = 0.600) and DFS (5-year DFS: RFA 24.7% vs. MWA 40.4%; p = 0.570). However, a significantly higher LTP rate was observed in the RFA group than the MWA group (5-year LTP: RFA 24.3% vs. MWA 8.4%; p = 0.030). IPTW-adjusted analyses revealed similar results. The treatment modality (RFA vs. MWA: HR 7.861, 95% CI 1.642-37.635, p = 0.010) was an independent prognostic factor for LTP. We observed a significant interaction effect of ablation modality and type of peritumoral vessel on LTP (p = 0.034). For patients with periportal HCC, the LTP rate was significantly higher in the RFA group than in the MWA group (p = 0.045). However, this difference was not observed in patients with perivenous HCC (p = 0.116).ConclusionsIn patients with a small single periportal HCC, MWA exhibited better tumor control than RFA.Key points• Microwave ablation exhibited better local tumor control than radiofrequency ablation for small single periportal hepatocellular carcinoma. • There was a significant interaction between the treatment effect of ablation modality and type of peritumoral vessel on local tumor progression. • The type of peritumoral vessel is vital in choosing ablation modalities for hepatocellular carcinoma.

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Chemotherapeutic Nanoparticle-Based Liposomes Enhance the Efficiency of Mild Microwave Ablation in Hepatocellular Carcinoma Therapy.

Publications

Chemotherapeutic Nanoparticle-Based Liposomes Enhance the Efficiency of Mild Microwave Ablation in Hepatocellular Carcinoma Therapy.

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