The Evolving Systemic Treatment for Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the common and fatal malignancies, which remains a global health challenge, with an estimated incidence of more than 1 million cases by 2025. The current major progress has improved the management of patients with advanced disease. Systemic treatments with multitarget agents, antiangiogenics alone or in combination with an immune checkpoint inhibitor (ICI), have been approved following positive results from phase III clinical studies. Several ongoing trials are currently exploring novel combinations and are expected to further change the HCC treatment landscape. In this review, we present all approved targeted agents for advanced HCC with an emphasis on their clinical efficacy and discuss the exciting results of the combination of targeted therapy and ICI. Finally, we also summarize the advances in clinical research for HCC

Multidisciplinary Approach to a Patient with Acinar Cell Carcinoma, a Rare Pancreatic Malignancy

Acinar cell carcinoma (ACC) of the pancreas is a relatively rare malignant neoplasm that constitutes about 1% of all pancreatic exocrine tumors. The disease is generally managed similarly as pancreatic ductal adenocarcinoma (PDAC), with surgical resection for localized disease and systemic chemotherapy in the metastatic setting. Here, we present a case of a 69-year-old patient with ACC of the pancreatic head treated with a multidisciplinary approach

Research progress on KRAS mutations in colorectal cancer

The RAS gene family, responsible for signal transduction within the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways, is frequently involved in carcinogenesis, and alterations in its member genes can be detected, with variable frequency, in a wide variety of solid and hematological cancers. These alterations may behave as prognostic-predictive biomarkers and driver mutations, making them an interesting therapeutic target. Since their discovery, many strategies have been pursued to act on their signaling pathways. Indeed, in clinical practice, KRAS, the most prominent member of the RAS gene family, represents an especially elusive target in most malignancies; pathway inhibition is carried out upstream, on the EGFR receptor, or downstream, most frequently on the BRAF/MEK/ERK cascade. Recently, clinically relevant direct RAS inhibition has been successfully achieved with the development of potent and selective covalent inhibitors of KRAS c.34G>T (p.G12C). These latest-generation drugs represent both a new and interesting tool in the therapeutic armamentarium and a symbolic end to the myth of KRAS undruggability. However, their clinical relevance and appropriate place in treatment strategies remain to be determined

Benefits and Complications Following First-Line Treatment with Atezolizumab plus Bevacizumab in a Patient with HCC: a Case Report

Until recently, sorafenib was the only systemic treatment available for patients with advanced hepatocellular carcinoma (HCC) since its approval in 2007. In the IMbrave150 trial, atezolizumab plus bevacizumab, as first-line therapy, demonstrated improvement in overall survival (OS) and progression-free survival (PFS) in patients with unresectable HCC compared with sorafenib. Based on these results, this combination is recommended as a standard of care for treatment-naïve patients with advanced HCC and Child-Pugh A cirrhosis. Earlier, we presented a review of systemic treatments for advanced HCC.^1^ Here, we reported the case of a 61-year-old patient with excellent response to the treatment with atezolizumab plus bevacizumab, despite a serious complication

Neo-Adjuvant Treatment in Primary Resectable Pancreatic Cancer: A Systematic Review and PRISMA-Compliant Updated Metanalysis of Oncological Outcomes

Background: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. Methods: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. Results: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72–0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56–0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32–0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23–2.36) were also found in patients treated with NAT, despite high heterogeneity. Conclusions: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required