A New Risk Prediction Model for Venous Thromboembolism and Death in Ambulatory Lung Cancer Patients.

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers.

Utility of the Khorana and the new-Vienna CATS prediction scores in cancer patients of the HYPERCAN cohort.

Background: Risk assessment models (RAMs) are relevant approaches to identify cancer outpatients at high risk of venous thromboembolism (VTE). Among the proposed RAMs, the Khorana (KRS) and the new-Vienna CATS risk scores have been externally validated in ambulatory patients with cancer.

Objectives: To test KRS and new-Vienna CATS scores in 6-month VTE prediction and mortality in a large prospective cohort of metastatic cancer outpatients during chemotherapy.

Thrombin Generation and D-Dimer for Prediction of Disease Progression and Mortality in Patients with Metastatic Gastrointestinal Cancer.

Background: the tight and reciprocal interaction between cancer and hemostasis has stimulated investigations on the possible role of hemostatic biomarkers in predicting specific cancer outcomes, such as disease progression (DP) and overall survival (OS). In a prospective cohort of newly diagnosed metastatic gastrointestinal (GI) cancer patients from the HYPERCAN study, we aimed to assess whether the hemostatic biomarker levels measured before starting any anticancer therapy may specifically predict for 6-months DP (6m-DP) and for 1-year OS (1y OS). Methods: plasma samples were collected and tested for thrombin generation (TG) as global hemostatic assay, and for D-dimer, fibrinogen, and prothrombin fragment 1 + 2 as hypercoagulation biomarkers.

Validation of the Role of Thrombin Generation Potential by a Fully Automated System in the Identification of Breast Cancer Patients at High Risk of Disease Recurrence.

 The measurement of thrombin generation (TG) potential by the calibrated automated thrombogram (CAT) assay provides a strong contribution in identifying patients at high risk of early disease recurrence (E-DR). However, CAT assay still needs standardization and clinical validation.  In this study, we aimed to validate the role of TG for E-DR prediction by means of the fully automated ST Genesia system.

Thrombin generation predicts early recurrence in breast cancer patients.

Background: Cancer patients present with a hypercoagulable state often associated with poor disease prognosis.

Objectives: This study aims to evaluate whether thrombin generation (TG), a global coagulation test, may be a useful tool to improve the identification of patients at high risk of early disease recurrence (ie, E-DR within 2 years) after breast cancer surgery.

Patients/methods: A cohort of 522 newly diagnosed patients with surgically resected high-risk breast cancer were enrolled in the ongoing prospective HYPERCAN study.

Syndrome of inappropriate anti-diuretic hormone secretion in cancer patients: results of the first multicenter Italian study.

Background: Hyponatremia in cancer patients is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The aim of this observational multicenter study was to analyze the medical and economic implications of SIADH in this setting.

Methods: This study included 90 oncological patients from 28 Italian institutions that developed SIADH between January 2010 and September 2015.

Thrombotic biomarkers for risk prediction of malignant disease recurrence in patients with early stage breast cancer.

In cancer patients, hypercoagulability is a common finding. It has been associated with an increased risk of venous thromboembolism, but also to tumor proliferation and progression. In this prospective study of a large cohort of breast cancer patients, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: (i) are associated with breast cancer-specific clinico-pathological features; and (ii) can predict for disease recurrence.

Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting.

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months.

A multicenter REtrospective observational study of first-line treatment with PERtuzumab, trastuzumab and taxanes for advanced HER2 positive breast cancer patients. RePer Study.

We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance were 21, 4 and 15 months, respectively.

Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer.

Objective: Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need.

Design: We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC.

The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer.

Neoadjuvant chemoradiation therapy is a commonly used option aimed to make less aggressive surgery approaches and to improve quality of life allowing a high proportion of patients operated with sphincter-sparing surgical techniques in locally advanced rectal cancer (LARC). During the last 5 years a number of studies have tested the efficacy of more intensive chemotherapeutic approaches by combining irinotecan or oxaliplatin with fluoropyrimidines and standard radiation treatments as well as testing combined treatments with targeted agents directed against epidermal growth factor receptor (EGFR) or angiogenesis. Herein, we review the results and critiques of the published studies based on the introduction of novel targeted agents in neoadjuvant therapy of LARC.

Antiangiogenic therapy of colorectal cancer: state of the art, challenges and new approaches.

Advanced colorectal cancer is the first tumor type for which an antiangiogenic agent, namely bevacizumab, has been approved by the Food and Drug Administration for therapy in humans; it has been in use since February 2004. This review paper summarizes and discusses the results obtained with this agent and highlights the main open or controversial issues on antiangiogenic therapy, taking into account that the clinical results obtained are below the expectations, particularly in the adjuvant setting.

Pharmacogenetics in breast cancer: focus on hormone therapy, taxanes, trastuzumab and bevacizumab.

Breast cancer is the most common female cancer, with more than one million new patients diagnosed annually worldwide. The great heterogeneity, in terms of prognosis and outcome, within patients with the same clinical and pathological characteristics may limit the potential for personalized therapy. Most of the cytotoxic agents and new targeted agents have a narrow therapeutic index and the administration of an equal dose may result in a wide range of toxicities as well as to different antitumor efficacy.

Antiangiogenic therapies in breast cancer.

Angiogenesis is a complex, multistep process that is involved in the progression and prognosis of several types of cancer. In particular, it has been demonstrated that angiogenesis plays a central role in the progression of breast cancer. This review evaluates results from clinical trials in which the efficacy of conventional chemotherapeutic agents was compared with that of novel antiangiogenic compounds for the treatment of breast cancer, and provides a summary of trials that were ongoing at the time of publication in the neoadjuvant and adjuvant settings.

Anti-angiogenic and anti-HER therapy.

The recent completion of the human genome sequence provided the basis and the tools to better understand the cellular biological complexity in both healthy and disease conditions, such as human cancer. In recent years, the improvement in biological and molecular knowledge enabled us to identify new targets and innovative drugs, allowing the beginning of new therapeutic strategies based on the so called "target oriented therapies".

Combined therapy with weekly irinotecan, infusional 5-fluorouracil and the selective COX-2 inhibitor rofecoxib is a safe and effective second-line treatment in metastatic colorectal cancer.

The purpose of this study was to determine the tolerability and activity of rofecoxib (Vioxx; Merck & Co., Inc., Whitehouse Station, NJ, http://www.

Safety and activity of the combination of pegylated liposomal doxorubicin and weekly docetaxel in advanced breast cancer.

Background: The present study was designed with the aim of evaluating the tolerability and activity of pegylated liposomial doxorubicin (PLD) in combination with weekly docetaxel as first line treatment of advanced breast cancer.

Patients And Methods: Fifty-seven patients entered the study. PLD was administered at escalating doses starting from 30 mg/m2, on day 1; docetaxel was administered at the fixed dose of 35 mg/m2 on days 2 and 9.

Antiangiogenic strategies, compounds, and early clinical results in breast cancer.

Angiogenesis is a multi-step process leading to the formation of new blood vessels from pre-existing vasculature and it is necessary for primary tumor growth, invasiveness and development of metastasis. Experimental and clinical data demonstrated that breast cancer is an angiogenesis-dependent disease and that the vascular endothelial growth factor (VEGF) family plays a key role it being a highly expressed and selective endothelial cell growth factor. Preclinical studies have shown that the angiogenic switch occurs early in the multistage process of breast cancer development.

Thalidomide prolongs disease stabilization after conventional therapy in patients with recurrent glioblastoma.

Thalidomide shows antiangiogenic activity and it has been successfully employed in various tumors. Considering the poor therapeutic options for glioblastoma and the role of angiogenesis in malignant glioma cells growth, we investigated the therapeutic activity of thalidomide in patients affected by recurrent glioblastoma. Inclusion criteria were: recurrent glioblastoma pretreated with surgery and radiotherapy, age >/=18 years, adequate performance status, hematological, renal, and hepatic functions.

Inhibitors of cyclo-oxygenase 2: a new class of anticancer agents?

Experimental studies have shown that cyclo-oxygenase 2 (COX2) is involved in tumour development and progression. Selective inhibitors of COX2 (coxibs) block tumour growth through many mechanisms, especially by antiangiogenic and proapoptotic effects. In experimental models, coxibs potentiate the activity of cytotoxic agents, hormones, and radiotherapy.

Thalidomide: a new anticancer drug?

Experimental studies have demonstrated that thalidomide (Thal), a drug developed as a sedative, has antitumoural properties. The possible antitumour mechanisms of action involve: inhibition of angiogenesis, cytokine-mediated pathways, modulation of adhesion molecules, inhibition of cyclooxygenase-2 and stimulation of immuno response. Therefore, Thal is under clinical evaluation in oncology.

Prognostic and predictive indicators in operable breast cancer.

Because of its biological heterogeneity and wide spectrum of responsiveness to different treatments, breast cancer is a complex disease of difficult clinical management. Over the past several years, knowledge of the molecular mechanisms regulating normal and aberrant cell growth leading to cancer has been enhanced. These advances have enabled the identification of an increasing number of surrogate biomarkers, which have been correlated with prognosis or used as predictors of response to specific treatments.

[Innovative treatment in oncology].

The improved knowledge of the key molecular mechanisms involved in cell transformation and tumor progression allows to the identification of new therapeutic targets for anticancer therapy. Several molecular-targeting compounds have been developed, capable to selectively interfire with tumorangiogenesis, receptors with tyrosin-chinase activity, specific tumor growth factors. A rationale selection of the patients as well as an appropriate monitoring of pharmacodynamics effects of molecular-targeting compounds need of the availability of surrogate markers, assessable in tumor tissue of circulating blood.