Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free ...survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were the key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for the administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for the BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended for obtaining a curative response in patients with a low tumor burden. This article reviews the therapeutic response, management of adverse events, post-progression treatment after Lenvatinib, and treatment strategy for BCLC intermediate stage HCC.
Transarterial chemoembolization (TACE) has been standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, all intermediate-stage HCC patients did not benefit from TACE ...treatment because intermediate-stage HCC encompasses a wide variety of HCCs. Owing to remarkable progress in systemic therapy, including molecular-targeted therapy for advanced-stage HCC, the standard treatment of HCC has recently shifted to systemic therapy. However, it remains controversial as to which treatment should be initially performed for intermediate-stage HCC. In addition, although curative treatment can be considered when the tumor shrinks, the timing of conversion therapy remains uncertain. This review summarizes the advances of HCC treatment and discusses treatment strategies for intermediate-stage HCC.
Image-guided percutaneous ablation is considered best in the treatment of early-stage hepatocellular carcinoma (HCC). Ablation is potentially curative, minimally invasive, and easily repeatable for ...recurrence. Ethanol injection used to be the standard in ablation. However, radiofrequency ablation has recently been the most prevailing ablation method for HCC. Many investigators have reported that radiofrequency ablation is superior to ethanol injection, from the viewpoints of treatment response, local tumor curativity, and overall survival. New-generation microwave ablation can create a larger ablation volume in a shorter time period. Further comparison studies are, however, mandatory between radiofrequency ablation and microwave ablation, especially in terms of complications and long-term survival. Irreversible electroporation, which is a non-thermal ablation method that delivers short electric pulses to induce cell death due to apoptosis, requires further studies, especially in terms of long-term outcomes. It is considerably difficult to compare outcomes in ablation with those in surgical resection. However, radiofrequency ablation seems to be a satisfactory alternative to resection for HCC 3 cm or smaller in Child-Pugh class A or B cirrhosis. Furthermore, radiofrequency ablation may be a first-line treatment in HCC 2 cm or smaller in Child-Pugh class A or B cirrhosis. Various innovations would further improve outcomes in ablation. Training programs may be effective in providing an excellent opportunity to understand basic concepts and learn cardinal skills for successful ablation. Sophisticated ablation would be more than an adequate alternative of surgery for small- and possibly middle-sized HCC.
This paper investigates a constrained distributed online optimization problem over strongly connected communication networks, where a local cost function of each agent varies in time due to ...environmental factors. We propose a distributed online projected subgradient method over unbalanced directed networks. The performance of the proposed method is evaluated by a regret which is defined by the error between the cumulative cost over time and the cost of the optimal strategy in hindsight. We show that a logarithmic regret bound can be achieved for strongly convex cost functions. We also demonstrate the validity of the proposed method through a numerical example on distributed estimation over a diffusion field.
This paper considers a stochastic systems modelling and stabilization of the rigid body motion of a spacecraft with stochastic disturbances. To rigorously deal with dynamics disturbed by a stochastic ...process, the rigid body motion is described by a stochastic differential equation on
. This enables us to quantitatively evaluate the uncertainty using stochastic calculus. We present a stochastic stabilizing controller and a stability theorem, which claim that the error of the rigid body motion with respect to a given desired motion is exponentially ultimately bounded in the mean square sense. The resultant stochastic model has no equilibrium point due to persistent noise effect. This makes stability analysis more difficult than the conventional stochastic stability concepts. However, the present stability theorem guarantees that the error exponentially converges to the vicinity of the target state and then remains bounded even under persistent noise. Finally, numerical simulations validate the proposed method.
Transcatheter arterial chemoembolization (TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma (HCC) in the intermediate stage according to the Barcelona Clinic Liver ...Cancer (BCLC) guidelines. Recently, balloon-occluded TACE (B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion (LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of B-TACE.
In this paper, we revisit primal–dual dynamics for convex optimization and present a generalization of the dynamics based on the concept of passivity. We hypothesize that supplying a stable zero to ...one of the integrators in the dynamics allows one to eliminate the assumption of strict convexity on the cost function. Then, we prove this hypothesis based on the passivity paradigm together with the invariance principle for Carathéodory systems. Additionally, we show that the presented algorithm is also a generalization of existing augmented Lagrangian-based primal–dual dynamics and discuss the benefit of the presented generalization in terms of noise reduction and convergence speed. Finally, the presented algorithm is demonstrated through simulation of lighting control in a building.
The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential ...HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC.
Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety.
For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0-18.8) in the HAIC group and 15.2 months (95% CI, 8.2-19.7) in the sorafenib group (hazard ratio HR, 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7-5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3-6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group.
Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution.
UMIN ID 000006147 , registration data: August 11, 2011.
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