The impact of nutritional status on pancreatic cancer therapy.

INTRODUCTION: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive disease with poor outcomes. One of the reasons for the dismal prognosis resides in its impressive ability to alter the nutritional status of patients who develop malnutrition, cachexia, anorexia, and sarcopenia in most cases. The ideal way to measure such changes in PDAC patients, in order to readily identify them and avoid complications or discontinuations of treatment is a relatively unexplored area. In addition, most PDAC patients experience pancreatic exocrine insufficiency (PEI) that contributes to the complex puzzle of malnutrition and that can be treated with Pancreatic Enzyme Replacement Therapy (PERT). AREAS COVERED: We review current knowledge on the impact of nutritional status on both surgical and medical treatments for PDAC, reporting available data on the causes of malnutrition, characteristics, and advantages of different tools to investigate nutritional status and possible strategies to improve patient outcomes. EXPERT OPINION: All PDAC patients should receive a careful nutritional assessment at diagnosis, and this should be repeated alongside their treatment path. Screening tools and biochemical variables or scores are associated with prognosis, but bioimpedance vector analysis (BIVA) and radiological assessment of body composition seem more accurate in predicting clinical outcomes and postoperative complications.

Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma.

BACKGROUND: Inflammation is a long-established hallmark of liver fibrosis and carcinogenesis. Eosinophils are emerging as crucial components of the inflammatory process influencing cancer development. The role of blood eosinophils in patients with hepatocellular carcinoma receiving systemic treatment is an unexplored field. OBJECTIVE: The objective of this study was to analyse the prognostic role of the baseline eosinophil count in patients with sorafenib-treated hepatocellular carcinoma. PATIENTS AND METHODS: A training cohort of 92 patients with advanced- or intermediate-stage sorafenib-treated hepatocellular carcinoma and two validation cohorts of 65 and 180 patients were analysed. Overall survival and progression-free survival in relation to baseline eosinophil counts were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed. RESULTS: A negative prognostic impact of low baseline eosinophil counts (< 50*109/L) was demonstrated in all cohorts (training cohort: hazard ratio = 50.1, 95% confidence interval 11.6-216.5, p < 0.0001 for low vs high eosinophil counts; first validation cohort: hazard ratio = 4.55, 95% confidence interval 1.24-16.65, p = 0.022; second validation cohort: hazard ratio = 3.21, 95% confidence interval 1.83-5.64, p < 0.0001). Moreover, low eosinophil counts had a negative prognostic role in patients progressing on or intolerant to sorafenib who received second-line regorafenib, but not capecitabine or best supportive care. CONCLUSIONS: Our analysis identified baseline blood eosinophil counts as a new prognostic factor in patients with sorafenib-treated hepatocellular carcinoma. Concerning second-line therapies, eosinophil counts were associated with survival outcomes only in regorafenib-treated patients, suggesting a possible predictive role in this setting.

Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib.

Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline.

Lenvatinib as a therapy for unresectable hepatocellular carcinoma.

INTRODUCTION: Since 2007 Sorafenib has represented the only approved drug for first-line treatment of advanced hepatocellular carcinoma (HCC). Lenvatinib, an orally active inhibitor of multiple receptor tyrosine kinases (VEGFR 1-3, FGFR 1-4, PDGFRa, RET and KIT), showed preclinical and clinical activity in the treatment of solid tumors, including HCC. Areas covered: In this review, we summarize the current therapeutic paradigm for the systemic treatment of advanced HCC, focusing on Lenvatinib pre-clinical and clinical development. Keywords 'Lenvatinib', ' Target therapy', 'REFLECT trial', 'Hepatocellular carcinoma', 'HCC', 'Sorafenib' were used for literature search on PubMed. Expert commentary: In Phase-III multicentric REFLECT trial Lenvatinib demonstrated a non-inferior overall survival (OS) compared to Sorafenib in the first-line treatment of advanced HCC, with a manageable toxicity profile, becoming a valid alternative option in the therapeutic repertoire of this disease. Nevertheless, the potential role of Lenvatinib in real-life clinical practice has still to be defined, especially in the light of the positive results that have been achieved with other new therapeutic agents (e.g. immunotherapy).