Impact of skeletal muscle volume on patients with BCLC stage-B hepatocellular carcinoma undergoing sorafenib therapy.

AIM: Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post-progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC-B) remains unclear. We conducted sub-analyses of a previous study on BCLC-B and compared our findings with data on HCC with BCLC stage C (BCLC-C). METHODS: We retrospectively enrolled 356 patients with HCC (BCLC-B, n = 78; and BCLC-C, n = 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0 cm2 /m2 for male and 38.0 cm2 /m2 for female participants). RESULTS: Both OS and PPS showed no significant differences in patients with non-MV depletion and those with MV depletion in the BCLC-B group (Median OS [MST] 19.3 vs. 13.5 months [p = 0.348]; median PPS 9.7 vs. 10.8 months [p = 0.578]). In the BCLC-C group, patients with non-MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p = 0.001] and median PPS 7.9 vs. 5.4 months [p = 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC-C group but not in the BCLC-B group. CONCLUSIONS: Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC-B undergoing sorafenib therapy.

Effect of body composition on survival benefit of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: A comparison with sorafenib therapy.

AIM: Sorafenib is used as a first-line treatment for advanced hepatocellular carcinoma (HCC). However, hepatic arterial infusion chemotherapy (HAIC) has also gained acceptance, but only in Japan. We explored the role of body composition as a factor affecting the survival benefit of HAIC compared to sorafenib for the treatment of advanced HCC. METHODS: We conducted a retrospective study using the clinical records of 133 patients with advanced HCC treated either with HAIC or sorafenib. Prior to treatment induction, skeletal muscle index and visceral fat area (VFA) were measured at the third lumbar vertebral and umbilical levels, respectively, using computed tomography. Muscle depletion and high-VFA (H-VFA) were defined using published cut-offs. We analyzed clinical parameters, including body composition as prognostic factors. RESULTS: In the HAIC group, multivariate analysis identified a positive response to HAIC (hazard ratio [HR], 0.438; p = 0.022), and conversion from HAIC to sorafenib (HR, 0.374; p = 0.008) as favorable prognostic factors for survival. In contrast, tumor number < 7 (HR, 0.475; p = 0.008), absence of extra-hepatic spread (HR, 0.511; p = 0.015), absence of muscle depletion (HR, 0.555; p = 0.044), and H-VFA (HR, 0.483; p = 0.015) were studied in the sorafenib group. CONCLUSIONS: Body composition was identified as a prognostic factor for patient survival after treatment with sorafenib, but not for HAIC, and may be used as a biomarker when selecting between HAIC or sorafenib treatment of patients with advanced HCC. Additionally, conversion to sorafenib in patients receiving HAIC could improve survival regardless of response status.

Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis.

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs. METHODS: A total of 50 HCC patients [Child-Pugh A/B, 34/16 patients; maximum tumor size 2.9 cm (mean); tumor number <5/≥5 = 29/21 patients] were administered a mixture of cisplatin and lipiodol, followed by the injection of DSMs. RESULTS: According to the criteria of the Liver Cancer Study Group of Japan, the response [complete response (CR) + partial response (PR)] rate and CR rate were 72 and 38%, respectively [CR, 19 patients; PR, 17; stable disease, 9; progressive disease, 5]. The 1-, 2-, 3-, and 4-year cumulative survival rates were 85, 67, 41, and 35%, respectively, and the median survival time was 32.6 months. Multivariate analysis identified tumor number <5 nodules [odds ratio 10.651, 95% confidence interval (CI) 2.168-52.317; P = 0.004] as an independent predictor of response and des-γ-carboxyprothrombin level <100 mAU/mL [hazard ratio (HR), 0.268, 95% CI 0.091-0.786, P = 0.017] and therapeutic effect CR or PR (HR 0.255, 95% CI 0.099-0.659; P = 0.005) as independent predictors of survival. CONCLUSION: Transcatheter arterial infusion chemotherapy using lipiodol and DSMs might be considered as a potential intervention in HCC patients, especially those with tumors of <5 nodules.

A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: We designed a novel transcatheter arterial infusion chemotherapy (TAI) using iodized oil (lipiodol) and degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) patients. In this study, we investigated the efficacy of TAI using lipiodol and DSM in a prospective randomized trial. METHODS: We randomly divided 45 patients with HCC into 3 groups: TAI using lipiodol (lipiodol group, n = 15), TAI using DSM (DSM group, n = 15), and TAI using lipiodol and DSM (lipiodol + DSM group, n = 15). In the lipiodol group, a mixture of cisplatin and lipiodol was administered. In the DSM group, a mixture of cisplatin and DSM was administered. In the lipiodol + DSM group, a mixture of cisplatin and lipiodol was administered, followed by DSM. RESULTS: The response rates were 40% in the lipiodol group, 53.4% in the DSM group, and 80% in the lipiodol + DSM group, respectively. The response rate tended to improve in the lipiodol + DSM group (lipiodol group vs. lipiodol + DSM group, P = 0.07). The median progression-free survival time was 177 days in the lipiodol group, 287 days in the DSM group, and 377 days in the lipiodol + DSM group. The progression-free survival in the lipiodol + DSM group was significantly better than those in the DSM group (P = 0.020) and the lipiodol group (P = 0.035). There were no serious adverse effects among the 3 groups. CONCLUSIONS: TAI using lipiodol and DSM was superior to TAI using lipiodol only and TAI using DSM only because of improvements in therapeutic effects and progression-free survival.

Pilot study of combination therapy with transcatheter arterial infusion chemotherapy using iodized oil and percutaneous radiofrequency ablation during occlusion of hepatic blood flow for hepatocellular carcinoma.

OBJECTIVE: We have reported that radiofrequency (RF) ablation with balloon occlusion of the hepatic artery (balloon-occluded RF ablation) increases the coagulation area compared with standard RF ablation. In this study, we evaluated the efficacy and safety of combination therapy with transcatheter arterial infusion chemotherapy (TAI) using iodized oil and balloon-occluded RF ablation in patients with hepatocellular carcinoma. PATIENTS AND METHODS: We studied 12 patients with 12 HCC nodules (mean tumor diameter, 27.3 mm). All patients were classified as Child-Pugh Class A. Immediately after TAI using iodized oil, we performed balloon-occluded RF ablation. RESULTS: One treatment session of the combination therapy was done for 10 of 12 nodules (83%). The greatest long-axis and short-axis dimensions of the area coagulated after the combination therapy were 48.8+/- 5.5 mm and 41.9 +/- 4.1 mm, respectively. During follow-up (mean, 33.4 months), there was no local recurrence. The 1, 2, and 3-year survival rates were 100%, 92%, and 83%, respectively. No fatal complications were observed. CONCLUSIONS: The combination therapy is an effective and safe treatment under favorable liver reserve capacity. Using the combination therapy, it is possible to finish one treatment session for patients with HCC nodules measuring less than 3 cm in greatest dimension.