Three drugs vs two drugs first-line chemotherapy regimen in advanced gastric cancer patients: a retrospective analysis.

The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival) and OS (overall survival) in advanced gastric cancer patients in the clinical practice. Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis.

Neoadjuvant multimodal treatment of pancreatic ductal adenocarcinoma.

Treatment of pancreatic ductal adenocarcinoma (PDAC) is increasingly multidisciplinary, with neoadjuvant strategies (chemotherapy, radiation, and surgery) administered in patients with resectable, borderline resectable, or locally advanced disease. The rational supporting this management is the achievement of both higher margin-negative resections and conversion rates into potentially resectable disease and in vivo assessment of novel therapeutics. International guidelines suggest an initial staging of the disease followed by a multidisciplinary approach, even considering the lack of a treatment approach to be considered as standard in this setting.

Emerging Immunotargets in Metastatic Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is one of the most immunoresponsive human cancers. High-dose IL-2 and Interferon-α were once the principle therapies for metastatic RCC, however they had harsh-tolerance profiles and limited response rates. In the last decade, targeted therapies have supplanted cytokine therapy due to higher response rates and more favorable toxicity profiles.

Randomized Trial of Low-Dose Morphine Versus Weak Opioids in Moderate Cancer Pain.

Purpose: The WHO guidelines on cancer pain management recommend a sequential three-step analgesic ladder. However, conclusive data are lacking as to whether moderate pain should be treated with either step II weak opioids or low-dose step III strong opioids.

Patients And Methods: In a multicenter, 28-day, open-label randomized controlled study, adults with moderate cancer pain were assigned to receive either a weak opioid or low-dose morphine.

Gastrointestinal neuroendocrine tumors: Searching the optimal treatment strategy--A literature review.

Neuroendocrine tumors of the gastro-entero-pancreatic system (GEP-NETs) are a heterogeneous group of neoplasms, with different malignant potential and behavior. Many treatment options are available. Surgery should be considered for localized tumors and in some selected cases of metastatic disease.

Out-of-pocket costs for cancer survivors between 5 and 10 years from diagnosis: an Italian population-based study.

Purpose: To illustrate the out-of-pocket (OOP) costs incurred by a population-based group of patients from 5 to 10 years since their cancer diagnosis in a country with a nationwide public health system.

Methods: Interviews on OOP costs to a sample of 5-10 year prevalent cases randomly extracted from four population-based cancer registries (CRs), two in the north and two in the south of Italy. The patients' general practitioners (GPs) gave assurance about the patient's physical and psychological condition for the interview.

Effects of metformin on clinical outcome in diabetic patients with advanced HCC receiving sorafenib.

Background And Objective: Several studies have reported an association between type 2 diabetes mellitus and hepatocellular carcinoma (HCC). Data from several retrospective studies and meta-analyses have highlighted a reduction of about 50% in the risk of developing HCC in cirrhotic patients treated with metformin for diabetes. The aim of this study was to evaluate the different outcomes of patients who received or did not receive metformin during treatment with sorafenib.

Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal?

Background: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline mutations in MisMatch Repair (MMR) genes, particularly in MLH1, MSH2 and MSH6. Patients with LS seem to have a more favourable prognosis than those with sporadic CRC, although the prognostic impact of different mutation types is unknown. Aim of our study is to compare survival outcomes of different types of MMR mutations in patients with LS-related CRC.

New findings on thymic epithelial tumors: Something is changing.

Thymic epithelial tumors (TETs) are uncommon neoplasms with a wide range of anatomical, clinical, histological and molecular malignant entities. To date the management of TETs within clinical practice is based on a multimodal therapeutic strategy including surgery, chemotherapy and radiotherapy with a multidisciplinary approach and prognostic evaluation is mainly based on Masaoka staging and World Health Organization classification. Therefore novel strategies are needed, especially for refractory and/or recurrent TETs and for thymic carcinomas that present a poor prognosis.

Computational analysis of the mutations in BAP1, PBRM1 and SETD2 genes reveals the impaired molecular processes in renal cell carcinoma.

Clear cell Renal Cell Carcinoma (ccRCC) is due to loss of von Hippel-Lindau (VHL) gene and at least one out of three chromatin regulating genes BRCA1-associated protein-1 (BAP1), Polybromo-1 (PBRM1) and Set domain-containing 2 (SETD2). More than 350, 700 and 500 mutations are known respectively for BAP1, PBRM1 and SETD2 genes. Each variation damages these genes with different severity levels.

Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis.

Background: Several clinical trials have reported that therapies targeting programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while tumor response has been related to PD-L1 expression.

Objective: To investigate the prognostic role of PD-L1 expression in patients affected by renal cell carcinoma (RCC).

Methods: MEDLINE/PubMed, the Cochrane Library, and ASCO University were searched for studies investigating the prognostic role of PD-L1 expression in RCC.

The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib.

Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib.

A phase I, dose-escalation study of volasertib combined with nintedanib in advanced solid tumors.

Background: Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinases. This study determined the maximum tolerated dose (MTD) and pharmacokinetics of volasertib combined with nintedanib, a potent and orally bioavailable triple angiokinase inhibitor, in patients with advanced solid tumors.

Patients And Methods: This open-label, dose-escalation trial recruited patients with advanced metastatic solid tumors following failure of conventional treatment (NCT01022853; Study 1230.

Prognostic clinical factors in pretreated colorectal cancer patients receiving regorafenib: implications for clinical management.

Background: We assessed the impact on survival of angiogenesis and inflammation-related factors, particularly LDH serum levels, platelet, neutrophil and lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR), in metastatic colorectal cancer patients receiving regorafenib monotherapy.

Methods: LDH serum levels, neutrophil, lymphocyte and platelet counts were collected at the start of regorafenib monotherapy. Cut-off values were calculated by ROC curve analysis.

MicroRNA in pancreatic adenocarcinoma: predictive/prognostic biomarkers or therapeutic targets?

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, short overall survival and few chemotherapeutic choices. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of around 22 nucleotides involved in the pathogenic mechanisms of carcinogenesis and metastasis. They have been studied in many tumors in order to identify potential diagnostic, prognostic or therapeutic targets.

Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy.

We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G).

Panitumumab for the treatment of metastatic colorectal cancer: a review.

In recent years, the treatment of metastatic colorectal cancer (mCRC) has evolved significantly with the increase of new therapeutic options, leading to an improved median survival for these patients. In particular, the identification of molecular targets in tumor cells has led to the introduction of biological drugs for the treatment of mCRC. Panitumumab is a fully human monoclonal antibody that binds the EGF receptor of tumor cells and inhibits downstream cell signaling with antitumor effect on inhibition of tumor growth.

Metabolic alterations in renal cell carcinoma.

Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies.

BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: molecular diagnostics and possible targets for personalized therapies.

Several novel recurrent mutations of histone modifying and chromatin remodeling genes have been identified in renal cell carcinoma. These mutations cause loss of function of several genes located in close proximity to VHL and include PBRM1, BAP1 and SETD2. PBRM1 encodes for BAF180, a component of the SWI/SNF chromatin remodeling complex, and is inactivated in, on average, 36% of clear cell renal cell carcinoma (ccRCC).

KRAS mutation status is associated with specific pattern of genes expression in pancreatic adenocarcinoma.

Aims: To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations.

Materials & Methods: Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients' survival.

Inside the 2015 ASCO Genitourinary Cancers Symposium.

The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, Rosen Shingle Creek, Orlando, FL, USA, 26-28 February 2015 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium was held in Orlando (FL, USA), from 26 to 28 February 2015. This meeting was focused on 'Integrating Biology into patient-centric care' and represented an attractive opportunity for oncology professionals with a special interest in the diagnosis and treatment of genitourinary tumors. The identification and validation of biomarkers for tumor response had been the focus of several researchers at the symposium, together with the development of novel targeted agents.

HER family receptor expression and prognosis in pancreatic cancer.

Background: HER family receptors play a key role in tumor progression in several malignancies, such as colorectal, lung or breast cancer. The aims of this study were to investigate expression of HER-1, HER-2 and HER-3 in pancreatic cancer (PC) samples and evaluate the association between HER-family receptor expression and patients' clinical outcomes.

Methods: Tissue samples from 91 PC patients were subjected to immunohistochemical staining to assess the expression of HER-1, HER-2 and HER-3.

Patient and caregiver needs in oncology. An Italian survey.

Aims And Background: Cancer is a disease that has far-reaching consequences for patients and their families. The present study targets unmet caregiver needs so that better support can be provided and planned for.

Methods: The first phase of the study was to conduct a survey designed to explore basic needs (medical and nursing information, psychological support, social welfare).

Sorafenib induces cathepsin B-mediated apoptosis of bladder cancer cells by regulating the Akt/PTEN pathway. The Akt inhibitor, perifosine, enhances the sorafenib-induced cytotoxicity against bladder cancer cells.

Sorafenib, a tyrosine kinase inhibitor, has been demonstrated to exert anti-tumor effects. However, the molecular mechanisms underlying its effects on bladder cancer remain unknown. Here, we evaluated the mechanisms responsible for the sorafenib-induced anti-tumor effects on 5637 and T24 bladder cancer cells.