Search results for "Digestive System"
showing 10 items of 1747 documents
Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial
2015
Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculate…
Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
2021
Background Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results Among the 1232 lenvatinib-treated HCC pat…
Pharmacogenomics of cetuximab in metastatic colorectal carcinoma
2014
Cetuximab is a chimeric monoclonal antibody that has revolutionized the treatment of metastatic colorectal cancer. Knowledge of the mechanisms that underlie its effectiveness, as well as the primary and secondary resistance mechanisms, have led to important developments in the understanding of cetuximab biology. In light of knowledge gained from recent trials, the efficacy of cetuximab has been clearly demonstrated to depend upon RAS mutational status, moreover cetuximab should only be used in a subset of patients who may benefit. In this article, we critically review clinical and pharmacogenetic issues of cetuximab, focusing on the cost–effectiveness involved with the use of the drug.
Sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.
2011
Abstract Background Recurrence of hepatocellular carcinoma after orthotopic liver transplantation not amenable to surgical approaches is associated with poor outcome. Aims Retrospective evaluation of the safety and efficacy of sorafenib in patients with post-transplant hepatocellular carcinoma recurrence. Methods Patients with post-transplant hepatocellular carcinoma recurrence were treated with sorafenib. Adverse events were assessed using National Cancer Institute Common Toxicity Criteria of AEs version 3.0, tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours. Results First-line therapy after recurrence was surgery ( n = 6), radiation therapy ( n = 1…
The impact of patient and tumour baseline characteristics on the overall survival of patients with advanced hepatocellular carcinoma treated with sor…
2013
Abstract Background Impact of patient and tumour baseline characteristics on the overall survival is not well characterized in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Aims/methods Univariate/multivariate analyses were conducted to identify retrospectively the impact of baseline characteristics on the survival of 110 patients with advanced HCC treated with sorafenib. Results Median survival of the whole cohort was 6.7 months, median survival in Child-Pugh A, B, C patients was 10.5, 6.1 and 3.0 months and median survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C/D was 6.8/2.6 months. Presence of ascites, presence of macrovascular invas…
Management of cirrhotic patients with hepatocellular carcinoma treated with sorafenib
2011
Sorafenib (Nexavar®, Bayer), a multi-targeted tyrosine kinase inhibitor, was the first systemic agent that demonstrated a significant improvement in the overall survival in patients with advanced hepatocellular carcinoma and well-preserved liver function. This drug is now recommended in patients with advanced hepatocellular carcinoma as first-line therapy and for patients not suitable for locoregional treatment. This brief article, produced by a multidisciplinary panel including specialists in gastroenterology and oncology, provides an overview of the major issues related to systemic treatment of hepatocellular carcinoma with sorafenib, including staging and prognostic strategies, assessmen…
Role of Immunotherapy in the Management of Hepatocellular Carcinoma: Current Standards and Future Directions
2020
The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (HCC) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. In phase II studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval …
Regorafenib Efficacy After Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation:A Retrospective Study
2021
Background and aim Safety of regorafenib in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been recently demonstrated. We aimed to assess the survival benefit of regorafenib compared to best supportive care (BSC) in LT-patients after sorafenib discontinuation. Methods This observational multicenter retrospective study included LT-patients with HCC-recurrence who discontinued first-line sorafenib. Group-1 was constituted by regorafenib-treated patients, while control group was selected among patients treated with best supportive care (BSC) due to unavailability of second-line options at the time of sorafenib discontinuation and who were sorafenib-tolerant prog…
Multidisciplinary strategies to improve treatment outcomes in hepatocellular carcinoma
2013
Hepatocellular carcinoma (HCC) is a complex disease with a poor prognosis. Incidence and mortality rates are increasing in many geographical regions, indicating a need for better management strategies. Among several risk factors for HCC, the most common are cirrhosis because of chronic hepatitis B virus or hepatitis C virus infection and alcohol consumption, obesity, and diabetes. In some patients, combined risk factors present additional challenges to the prevention and treatment of HCC. Screening and surveillance of high-risk populations varies widely by geographic regions, and access to optimal surveillance is critical for early diagnosis. The treatment choice for HCC depends on the canc…
Navigating the new landscape of second‐line treatment in advanced hepatocellular carcinoma
2020
Abstract Sorafenib and lenvatinib are approved for first‐line treatment of patients with advanced hepatocellular carcinoma (HCC), and the efficacy of atezolizumab plus bevacizumab has been demonstrated versus sorafenib. Over time, first‐line treatment frequently fails, and regorafenib, cabozantinib, ramucirumab (for patients with alpha fetoprotein ≥400 ng/mL), nivolumab, pembrolizumab and ipilimumab plus nivolumab are approved for use after sorafenib (but not lenvatinib) treatment in advanced HCC. Given the considerable complexity in the therapeutic landscape, the objective of this review was to summarize the clinical evidence for second‐line agents and provide practical guidance for select…