We demonstrated that MVI classification can stratify HCC patients by different patterns of recurrence and risk of survival after curative resection.

Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression‐free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child‐Pugh class, baseline serum des‐gamma‐carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long‐term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.

Abstract. Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The aim of this study was to evaluate whether there are differences in the clinical characteristics and survival between patients with advanced HCC with extrahepatic metastasis who received and those who did not receive previous treatment. Between April, 1998 and April, 2012, a total of 419 HCC patients with extrahepatic metastasis (81 previously untreated and 338 previously treated) were enrolled in this study. The differences in the clinical characteristics, including metastatic sites, were compared between the two groups. In addition, the prognostic predictors among all the patients and among the 81 previously untreated patients were analyzed. The distribution of the major metastatic sites was similar in the two groups; the most frequent site of extrahepatic metastasis was the lungs, followed by the bones, lymph nodes and adrenal glands. The median survival time (MST) among the 419 patients was 6.8 months. The 1-, 2-, 3-and 5-year survival rates were 31.6, 15.3, 9.5 and 2.3%, respectively. No significant differences in survival were observed between patients who received and those who did not receive previous treatment. The multivariate analysis revealed that the Child-Pugh classification, white blood cell count, neutrophil-lymphocyte ratio (NLR) and primary tumor stage were independent predictors of survival for all the patients and for the 81 previously untreated patients. Differences in the clinical characteristics of patients with advanced HCC with extrahepatic metastasis were identified between patients who received and those who did not receive previous treatment. Furthermore, intrahepatic tumor status, Child-Pugh classification, white blood cell count and NLR were demonstrated to be independent predictors of survival in HCC patients with extrahepatic metastasis. IntroductionHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Recent advances in imaging technology and implementation of surveillance programs for high-risk patients have led to increased detection of early-stage HCC, making curative therapies possible in some patients (1,2). However, the long-term survival of HCC patients remains unsatisfactory, due to the high frequency of intra-and extrahepatic recurrence (3,4). In particular, the development of advanced HCC with extrahepatic metastasis hinders the use of curative therapies, such as surgical resection or radiofrequency ablation, therefore contributing to poor survival. Prior to the approval of sorafenib, several systemic chemotherapeutic regimens had been evaluated for patients with advanced HCC, although no effective therapeutic protocols were identified (5,6). Two randomized placebo-controlled trials demonstrated a survival benefit associated with sorafenib for patients with advanced HCC, including those with extrahepatic metastasis (7,8). As a result, sorafenib is currently considered to be the standard treatment for advanced HCC in the United States, Europe, Japan ...

Data-mining analysis revealed that serum albumin level is an independent risk factor and the most distinguishable factor associated with the incidence of NBNC-HCC. Furthermore, we created an NBNC-HCC profile consisting of albumin and GGT levels, the APRI and the Brinkman index. This profile could be used in the screening strategy for NBNC-HCC.

Abstract. Although sorafenib and hepatic arterial infusion chemotherapy (HAIC) have been proven to improve prognosis in hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MVI), the most appropriate approach remains unclear. The present multicenter, non-randomized, prospective cohort study aimed to compare the efficacy and safety of HAIC and sorafenib in patients with advanced HCC and MVI, without extra-hepatic spread (EHS) and Child-Pugh class A disease. The present study was performed between April 2008 and March 2014, and 64 HCC patients with MVI, without EHS and Child-Pugh class A disease were registered. Of these patients, 44 were treated with HAIC and 20 with sorafenib. HAIC involved cisplatin (50 mg fine powder in 5-10 ml lipiodol) and a continuous infusion of 5-fluorouracil (FU) (1,500 mg/5 days), which is referred to as new 5-FU and cisplatin therapy (NFP). The primary outcome was progression-free survival, and the secondary outcome was overall survival (OS). Clinical factors influencing OS and the therapeutic effect were identified using univariate and multivariate analyses. There were no differences in clinical factors between the two groups. The median progression-free survival was 5.1 and 9.5 months in the sorafenib and NFP groups, respectively (P=0.001). The complete response (CR) or partial response (PR) rates were 10 and 71% in the sorafenib and NFP groups, respectively (P<0.001). The median OS in the sorafenib and NFP groups was 13.2 and 30.4 months, respectively (P=0.013). Multivariate analysis revealed that the independent predictors of survival were Child-Pugh score (5, P=0.022, 95% CI,, grade of portal vein invasion (brunch, P=0.009, 95% CI, 0.220-0.752), and therapeutic effect (CR or PR, P<0.001, 95% CI, 0.220-0.752), and the independent predictor of therapeutic effect was therapeutic regimen (NFP, P<0.001, 95% CI,. NFP should be the first choice for patients with advanced HCC and MVI, without EHS and Child-Pugh A disease.