Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: A systematic review and meta‐analysis

Abstract

Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades, there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors, such as macrovascular invasion and extrahepatic spread (EHS). We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics, including patients with both Child-Pugh (CP) scores of A and B. A comprehensive search of several databases from each database inception to February 15, 2016 any language was conducted. We included 14 studies (three randomized controlled studies [RCTs] and 11 observational studies). We included studies that compared sorafenib, transarterial bland embolization/transarterial chemoembolization, yttrium-90/ radiation therapy, ablation (or combination), and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in overall survival (OS) for patients with advanced HCC and metastatic vascular invasion (MVI) and/or EHS and CP A liver disease (hazard ratio, 0.66 [95% confidence interval, 0.51-0.87]; I 2 5 0%). Several observational studies evaluated locoregional therapies alone or in combination with other treatments and were limited by very-low-quality of evidence. This was true for both patients with EHS and MVI. Conclusion: In patients with advanced HCC and CP A liver function, sorafenib is the only treatment that has been shown to improve OS in randomized studies. High-quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease, are lacking. (HEPATOLOGY 2018;67:422-435) T he optimal management of hepatocellular carcinoma (HCC) requires a multidisciplinary approach that brings together expertise in liver surgery, hepatology, interventional radiology, and medical oncology. Current recommendations for screening aim to identify smaller tumors that can be treated with curative intent with surgical resection, radiofrequency ablation (RFA), and/or liver transplant. (1) However, a large number of patients present with disease beyond criteria that would be considered for curative approaches.Historically there has been a large unmet need for systemic treatments in HCC. Only in 2008 were data with the multikinase inhibitor, sorafenib, shown to

Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Predictor of Sorafenib Benefit in Patients with Hepatocellular Carcinoma

“…Over the past 10 years, sorafenib remains the most widely systemic drug for advanced HCC . However, the response to sorafenib seems to be moderate, as shown in the SHARP and AP trials .…”

“…Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is the second‐leading cause of cancer death globally, with increasing incidence and mortality rates . Sorafenib is the most recommended first‐line systemic therapy for advanced HCC worldwide . However, its therapeutic efficacy in HCC is far from satisfactory .…”

Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

“…Presently, sorafenib and bevacizumab are the most widely used targeted therapies in liver cancer treatment [14,15]. Sorafenib, a multikinase inhibitor that blocks the activation of kinases associated with the regulation of tumor growth and angiogenesis, has been recognized as the most effective targeted drug against liver cancer [16]; however, it only prolongs patient survival by approximately 3 months [17,18]. Additionally, most drugs that target liver cancer can cause severe side effects that inevitably have a profound negative impact on the patient's quality of life [19].…”

Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

“…Numerous studies have revealed that vascular invasion is an independent risk factor for the prognosis of HCC patients who underwent surgical treatment [22][23][24]. The presence of vascular invasion of the portal or hepatic veins is associated with a high risk of tumour recurrence and is regarded as a prerequisite for systemic tumour dissemination [25,26]. Our study revealed that TRIM4 expression levels in HCC tissues were negatively associated with vascular invasion and the absence of a tumour capsule, indicating that TRIM4 may be a potential prognostic marker for HCC.…”