Radioembolization for the treatment of liver tumors general principles.

Radioembolization aims to selectively target radiation to all liver tumors while limiting the dose to normal liver parenchyma. The deposition of yttrium-90 ((90)Y) microspheres delivered through the hepatic artery are preferentially implanted within liver tumors in a 3:1 to 20:1 ratio compared with a normal liver. The principles and mode of action of radioembolization are fundamentally different from the conventional embolization of liver tumors through transarterial embolization or chemoembolization.

Pilot clinical trial of type 1 dendritic cells loaded with autologous tumor lysates combined with GM-CSF, pegylated IFN, and cyclophosphamide for metastatic cancer patients.

Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-α, TNF-α, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh.

Efficacy and safety of sorafenib in combination with mammalian target of rapamycin inhibitors for recurrent hepatocellular carcinoma after liver transplantation.

There is currently no consensus on the most suitable treatment for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation. This open, multicenter, retrospective, uncontrolled cohort study was designed to evaluate the safety and preliminary efficacy of the combined use of a mammalian target of rapamycin (mTOR) inhibitor and sorafenib in this setting. In 31 patients who suffered from HCC recurrence after liver transplantation, the immunosuppressive therapy was changed to mTOR inhibitors, and systemic treatment with sorafenib was initiated.

Radioembolization for hepatocellular carcinoma.

Radioembolization is a form of brachytherapy in which intra-arterially injected (90)Y-loaded microspheres serve as sources for internal radiation purposes. It produces average disease control rates above 80% and is usually very well tolerated. Main complications do not result from the microembolic effect, even in patients with portal vein occlusion, but rather from an excessive irradiation of non-target tissues including the liver.

Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.

Unlabelled: A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.

A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies.

Transarterial therapies for hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is often fatal due to local growth inside the liver and its unique arterial vascularization provides the basis for transarterial therapies. Around 35% of patients are diagnosed at stages in which transarterial therapies are indicated as first-line therapy; many others are treated after recurrence or progression to surgery or percutaneous ablation. However, the scientific evidence supporting the use of transarterial therapy is heterogeneous and certainly weak for several subgroups.

Risk factors of lung, head and neck, esophageal, and kidney and urinary tract carcinomas after liver transplantation: the effect of smoking withdrawal.

Liver transplant recipients have an increased risk of malignancy. Smoking is related to some of the most frequent causes of posttransplant malignancy. The incidence and risk factors for the development of neoplasia related to smoking (head and neck, lung, esophageal, and kidney and urinary tract carcinomas) were studied in 339 liver transplant recipients.

Treatment of murine fulminant hepatitis with genetically engineered endothelial progenitor cells.

Background & Aims: Cell therapy has been used to attenuate liver injury. Here we evaluated whether genetic engineering of either bone marrow-derived mononuclear cells (MNC) or endothelial progenitor cells (EPC) many enhance their hepatoprotective properties.

Methods: Mice with ConA-induced hepatitis or with lethal fulminant hepatitis resulting from administration of an adenovirus encoding CD40L (AdCD40L) received an intra-splenic injection of saline or 2 × 10(6) unmodified MNC or EPC or the same cells transduced ex vivo with an adenovirus expressing luciferase (MNCLUC and EPCLUC) or encoding the hepatoprotective cytokine cardiotrophin-1 (CT-1) (MNCCT-1 and EPCCT-1).

Integrating radioembolization with chemotherapy in the treatment paradigm for unresectable colorectal liver metastases.

Clinical decisions regarding the treatment of metastatic colorectal cancer require consideration of current and evolving modalities to best achieve prolonged patient survival. Clinical trials have established that for first-line treatment of patients with or without extrahepatic metastases, radioembolization augments the response produced by chemotherapy in patients with unresectable liver metastases. This includes progression-free and overall survivals that compare favorably with phase II to III data of current chemotherapy regimens.

Integrating radioembolization into the treatment paradigm for metastatic neuroendocrine tumors in the liver.

Surgical resection of hepatic metastases from neuroendocrine tumors (mNETs) is controversial because the potential survival benefit of this intervention must be balanced against the risk of surgical morbidity and mortality. In patients with unresectable mNETs in the liver, radioembolization has been used to treat tumors from a range of primary sites, including carcinoid and islet cell carcinomas as well as nonfunctional, asymptomatic tumors. Initial clinical studies and retrospective studies on a large cohort of patients indicate that radioembolization is well tolerated and highly effective in achieving a durable hepatic tumor response and ameliorating symptoms.

Prognosis of hepatocellular carcinoma in relation to treatment across BCLC stages.

Background: The Barcelona Clinic Liver Cancer (BCLC) staging system recommends first-line therapy for each tumor stage. We evaluated the effect of compliance with BCLC treatment allocation on the prognosis of patients with hepatocellular carcinoma (HCC).

Methods: We retrospectively analyzed 359 consecutive, newly diagnosed HCC patients treated in our Liver Unit during a 14-year period.

Hepatitis C virus induces the expression of CCL17 and CCL22 chemokines that attract regulatory T cells to the site of infection.

Background & Aims: The mechanisms by which Foxp3+ T regulatory cells (Treg) accumulate in HCV infected livers are not known. Here, we studied the role of chemokines CCL17 and CCL22 in this process.

Methods: Chemokine mRNA levels were determined by qPCR in liver biopsies from 26 HCV chronically infected patients (CHC), 11 patients with treatment-induced sustained virological response (SVR), 16 patients with other liver diseases unrelated to HCV, and 24 normal livers.

Radioembolization in the treatment of unresectable liver tumors: experience across a range of primary cancers.

Radioembolization is a proven treatment to slow disease progression and improve survival in patients with colorectal cancer liver metastases and hepatocellular carcinoma. Accumulating evidence supports its use in metastases from neuroendocrine tumors and breast cancer. Cancers with radiobiologic profiles similar to those of colorectal and breast cancer, including melanoma, lung cancer, and nodular cholangiocarcinoma, are being studied as candidates for radioembolization.

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres.

Purpose: Selective internal radiotherapy (SIRT) with yttrium-90 ((90)Y) resin microspheres can improve the clinical outcomes for selected patients with inoperable liver cancer. This technique involves intra-arterial delivery of β-emitting microspheres into hepatocellular carcinomas or liver metastases while sparing uninvolved structures. Its unique mode of action, including both (90)Y brachytherapy and embolization of neoplastic microvasculature, necessitates activity planning methods specific to SIRT.

Integrating radioembolization ((90)Y microspheres) into current treatment options for liver tumors: introduction to the international working group report.

Liver-directed therapies for unresectable cancers in the liver are evolving with increased efficacy and decreasing toxicity. One of these approaches uses radioactive microspheres delivered to hepatic tumors via the hepatic artery system-radioembolization. Use of this therapy is rapidly increasing worldwide with over 20,000 patients treated thus far.

General selection criteria of patients for radioembolization of liver tumors: an international working group report.

A combined treatment approach that incorporates surgical resection, ablation, chemotherapy, targeted agents, and radiotherapy has augmented the management of liver tumors (both primary and metastatic). The challenge that remains is how to reduce the burden of liver disease and thus enable greater patient eligibility for resection as well as lengthened survival for those who remain unsuitable for surgery. Radioembolization can deliver high doses of radiation preferentially to liver tumors and is a valuable treatment option that should be considered as part of a multimodal treatment approach for the management of patients in whom the liver is the sole or dominant site of disease.

Liver radioembolization using 90Y resin microspheres in elderly patients: tolerance and outcome.

Purpose: Yttrium 90 (90Y) microsphere radioembolization (90Y-RE) is an emerging locoregional treatment for liver cancer. The most common complications of 90Y-RE arise from excessive irradiation of nontarget organs (eg, gastrointestinal tract, lung, and nontumoral liver). Patients with advanced age may have substantial comorbidities that can affect their life expectancy, and tolerance to radiation in elderly patients may be altered.

Gene therapy for liver cancer: clinical experience and future prospects.

In contrast to the large quantity of preclinical evidence for efficacy, few gene therapy agents have reached clinical development for the treatment of primary and secondary liver cancer. This review discusses the published clinical trials that have explored the feasibility, safety and efficacy of gene therapy strategies for the treatment of liver cancer. Strategies include restoration of tumor suppressor genes, genetic prodrug-activating therapy, genetic immunotherapy and oncolytic virotherapy.

Synergistic effects of CTLA-4 blockade with tremelimumab and elimination of regulatory T lymphocytes in vitro and in vivo.

Anti-CTLA-4 monoclonal antibodies (mAb) that block the interaction of CTLA-4 with CD80 and CD86 such as tremelimumab and ipilimumab are currently being tested in the clinic for cancer treatment exploiting their properties to de-repress tumor-specific cellular immunity. Addition of the fully human anti-CTLA-4 (tremelimumab) to cultures of human T cells with allogenic dendritic cells (DCs) did not increase proliferation. Magnetic bead-mediated elimination of CD4(+) CD25(+) regulatory T cells (T(reg)) before setting up those alloreactive cultures also largely failed to increase primary proliferation.

Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization.

Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology. This suggests that not all patients with intermediate-stage HCC will derive similar benefit from TACE, and that some patients may benefit from other treatment options.

A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect.

Clinical development of combination strategies in immunotherapy: are we ready for more than one investigational product in an early clinical trial?

Stimulating the innate and adaptive immunity against cancer necessitates the tricking of a system evolved to fight microbial pathogens and directing its activity towards transformed self-tissue. Efficacious interventions to start and sustain the response will probably require a number of agents to tamper simultaneously or sequentially with several immune mechanisms. Although master switches controlling various functions may exist, the goal of a curative immune response will probably demand the combined actions of several therapeutic components.

Radioembolization for hepatocellular carcinoma: a review of the evidence and treatment recommendations.

Treatment decisions for hepatocellular carcinoma involve the evaluation of multiple factors including tumor size, location, and morphology; comorbidity and/or extrahepatic disease; health status; patient preferences; and the treating physician's expertise and skill. For patients who are not candidates for transplant or resection, and for whom other therapies (radiofrequency ablation, systemic chemotherapies, transarterial embolization or chemoembolization), may have limited efficacy, an urgent need for bridging procedures, to enable surgery or ablation, or meet transplantation criteria, has led to investigations with radioembolization. A number of recent reports have supported the effectiveness of Yttrium-90 ((90)Y) labeled microspheres to treat intermediate and advanced disease in patients with good overall functional status and liver reserve; patients with portal vein involvement and in a limited role to treat unresectable early-stage disease.