Combination of transcatheter arterial chemoembolization and interrupted dosing sorafenib improves patient survival in early–intermediate stage hepatocellular carcinoma

Lee, Teng‐Yu; Chen, Lin; Chen, Chiung Yu; Wang, Tsang En; Lo, Gin Ho; Chang, Chi-Sen; Chao, Yee

doi:10.1097/md.0000000000007655

Cited by 17 publications

(13 citation statements)

References 31 publications

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“…Lee et al investigated TACE and interrupted dosing of sorafenib compared to TACE alone for early or intermediate-stage HCC. 32 They showed that local response rates were significantly better in the combination group. OS was also significantly longer in those receiving the combined treatment than in those receiving TACE alone over the 2 years of follow-up.…”

Section: Key Pointmentioning

confidence: 99%

Role of locoregional therapies in the wake of systemic therapy

Palmer

Malagari

Kulik

2020

Journal of Hepatology

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Multiple systemic agents have recently been approved in the first-and second-line setting for hepatocellular carcinoma (HCC), increasing the therapeutic options for patients and treating physicians. The randomised controlled trials that led to these approvals were predominantly conducted in a population comprised of patients with advanced HCC. However, these trials also included a subset of patients who had progressed after locoregional therapies (LRTs), mostly transarterial chemoembolisation. With a greater number of systemic agents available, the role of LRTs has become a topic of debate, specifically regarding when to transition to systemic therapy in unresectable HCC and the potential opportunities for combining locoregional and systemic therapies. Trials of immuno-oncology agents (notably T cell checkpoint inhibitors) are ongoing in the advanced disease setting and these agents also present opportunities for combination therapies, both with other systemic agents and with LRTs in earlier stage disease. This article will review strategies to guide patient selection for LRT as well as the development of locoregional-systemic combinations based on scientific rationale and the challenges of clinical trial design in this setting.

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Section: Key Pointmentioning

confidence: 99%

Role of locoregional therapies in the wake of systemic therapy

Palmer

Malagari

Kulik

2020

Journal of Hepatology

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“…Several studies have demonstrated that radiofrequency ablation and transarterial chemoembolization are effective treatments for recurrence after hepatectomy and for patients with hepatocellular carcinoma with venular invasion. 28 – 30 A study involving an orthotopic mouse model found that sorafenib prevented the recurrence and metastasis of liver tumours. 31 Another study revealed a positive effect with sorafenib adjuvant chemotherapy after surgery in patients with liver cancer with microvascular invasion.…”

Section: Discussionmentioning

confidence: 99%

Sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) and microvascular infiltration: a systematic review and meta-analysis

Tong

2020

J Int Med Res

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Objective Microvascular invasion is shown to be an independent risk factor for liver cancer recurrence. Timely treatment may reduce the recurrence rate and prolong total survival time. The aim of this study was to investigate the effectiveness of sorafenib in treating patients with hepatocellular carcinoma (HCC) and microvascular invasion Methods A comprehensive literature search was conducted in PubMed, EMBASE, MEDLINE, web of science and Cochrane Library databases for articles published up to December 2019. Two researchers independently reviewed and cross-checked independent reports with sufficient information. A meta-analysis was conducted to assess the impact of sorafenib on mortality in patients with HCC and microvascular involvement. Results Four studies were included in the qualitative and quantitative analyses, comprising 955 cancer events and 505 cancer deaths. Meta-analyses showed that sorafenib treatment was associated with an improved survival rate versus no sorafenib treatment in patients with HCC and microvascular invasion (relative risk 1.369, 95% confidence interval 1.193, 1.570). Conclusions Sorafenib treatment may improve survival in patients with HCC and microvascular invasion. However, due to the potential for residual confounding, the results should be interpreted with caution.

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“…Data was collected from patients with hepatic carcinoma who were treated with TACE therapy (oxaliplatin 130 mg/m 2 ) at the Department of Hepatobiliary Surgery between January 2014 and June 2017 in North China University of Science and Technology Affiliated Hospital (Tangshan, China). Inclusion criteria were as follows: Based Specification for Diagnosis and Treatment of Primary Liver Cancer (20); liver function A-B level (Child-Pugh Classification) (21,22); Barcelona Clinical Liver Cancer Staging System (BCLC) B stage (23); patients with no surgical history and other therapy treatments, and patients with no other primary tumor. The exclusion criteria were as follows: Patients suffering from other severe diseases, including heart and renal dysfunction, diffuse liver cancer, coagulation disorders, and patients infected with hepatitis C. Patients were sorted into HBV-associated liver cancer and non-HBV-associated liver cancer groups depending on whether they were positive for hepatitis B surface antigen, hepatitis B e-antigen (HBeAg) and hepatitis B core antibody.…”

Section: Methodsmentioning

confidence: 99%

Exosomes derived from HBV‑associated liver cancer promote chemoresistance by upregulating chaperone‑mediated autophagy

Liu

Guo

et al. 2018

Oncol Lett

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Liver cancer, which is the second leading cause of tumor-associated mortality, is of great concern worldwide due to its resistance to chemotherapeutic drugs. Transcatheter arterial chemoembolization (TACE) has previously been used as a treatment for unresectable liver tumors in China; however, the response to TACE treatment differs between patients. It has been reported that hepatitis B virus (HBV)-as sociated tumors are less sensitive to TACE treatment compared with non-HBV-associated liver cancer. Previous studies have demonstrated that exosomes serve a crucial role in hepatic carcinoma chemoresistance. We therefore hypothesized that HBV may modulate chemosensitivity via exosomes. The aim of the present study was to investigate how exosomes affect chemoresistance by assessing their role in chaperone-mediated autophagy (CMA)-dependent chemoresistance in HBV-associated liver cancer. Iconography data from HBV-positive and HBV-negative patients with hepatic carcinoma receiving TACE treatment were assessed, and it was revealed that the tumor volume was decreased in the patients with non-HBV-associated liver cancer compared with that in the patients with HBV-associated tumors following TACE therapy. Furthermore, it was revealed that exosomes from HBV-infected liver cancer cells were able to downregulate cell apoptosis when treated with oxaliplatin compared with exosomes from normal HepG2 cells. Furthermore, the results demonstrated that HBV-associated exosomes modulate cell death via activating the CMA pathway, and its key molecule, lysosome-associated membrane protein (Lamp2a), was also upregulated. Lamp2a-knockdown was also found to reverse anti-apoptotic effects in liver cancer. Taken together, the results of the present study suggest that chemoresistance in patients with HBV-associated hepatic tumors may be mediated by exosomes, and thus may provide a basis for the development of novel treatment strategies for chemoresistant liver cancer.

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Combination of transcatheter arterial chemoembolization and interrupted dosing sorafenib improves patient survival in early–intermediate stage hepatocellular carcinoma

Abstract: Supplemental Digital Content is available in the text

Cited by 17 publications

References 31 publications

Role of locoregional therapies in the wake of systemic therapy

Role of locoregional therapies in the wake of systemic therapy

Sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) and microvascular infiltration: a systematic review and meta-analysis

Exosomes derived from HBV‑associated liver cancer promote chemoresistance by upregulating chaperone‑mediated autophagy

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