Multimodal approaches to the treatment of hepatocellular carcinoma

Abstract

The prevalence of hepatocellular carcinoma in Europe and the US is increasing and is currently the leading cause of death in patients with cirrhosis. Surveillance programs for patients with cirrhosis aim to detect tumors at an early stage, when the greatest therapeutic benefits can be achieved. Curative treatments for early-stage tumors include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib can improve survival for patients with intermediate and advanced tumors, respectively. In clinical practice, combination therapies are often used, despite limited evidence to support this approach from randomized controlled trials. Combination therapy with radiofrequency ablation (RFA) plus percutaneous ethanol injection can, however, improve survival for selected patients compared with RFA alone. Combined treatment with TACE and RFA also improves patients' survival compared with TACE or RFA monotherapy. TACE performed before or after surgical resection, however, is not beneficial. Prevention of tumor progression in patients awaiting liver transplantation requires nonsurgical treatments; however, the real advantages of the available treatment modalities are yet to be defined. The role of sorafenib administration in combination with TACE after the use of potentially curative treatments, for the treatment of intermediate hepatocellular carcinoma, or in selective settings after liver transplantation, requires further study.

Sorafenib and hepatic arterial infusion chemotherapy for unresectable advanced hepatocellular carcinoma: A comparative study

“…Many HCC cases are in an advanced stage or unresectable at the time of diagnosis. Moreover, although unresectable advanced HCC can be treated with hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy, the therapeutic effects are limited (1)(2)(3) and the prognosis of advanced cases of HCC is poor.…”

Concurrent and subsequent radiofrequency ablation combined with hepatectomy for hepatocellular carcinomas

“…In fact, most patients with HCCs received multimodal approaches to treatment that included hepatectomy, TACE, RFA, ethanol ablation, microwave ablation, radiation therapy, or systemic chemotherapy, either in sequence or combination [35,67] . Aggressive combination treatment by concurrent RFA and hepatic resection may enhance the chance of curative treatments for patients with multifocal tumors that are traditionally considered unresectable.…”

“…Either tumor recurrence at the other parts of the liver or extrahepatic metastasis is very common where multifocal HCCs are treated. Although small recurrent tumors in the liver could possibly be ablated, novel adjuvant therapies such as sorafenib may be needed [33][34][35] . Despite the theoretical appeal of combining hepatectomy with RFA, safety can be a concern because both resection and intraoperative RFA are procedures that may potentially cause morbidity [22,23] .…”

Can we develop effective combination antiangiogenic therapy for patients with hepatocellular carcinoma?

“…Sorafenib combined with transarterial chemoembolization (TACE) is currently under clinical investigation [28, 29]. It is theorized that one of the reasons for the high local recurrence rate after TACE is because of increased expression of vascular growth factors and HIF-1 α [30, 31].…”