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Brescia, Italy

Zaniboni A.,Fondazione Poliambulanza | Formica V.,University of Rome Tor Vergata
Cancer Chemotherapy and Pharmacology

Background: Since 2013, informative trials exploring the optimal use of available biologic agents in the first-line setting of metastatic colorectal cancer (mCRC) have been presented. These trials have opened a stimulating debate on the biological effect that first-line therapies may have on subsequent lines of treatment even long after the first-line progression. Materials and methods: We reviewed available preclinical and clinical data on the effect of different sequences of the biological drugs approved for use in mCRC patients. The importance of molecular selection of patients based on RAS mutational status and toxicity and quality-of-life issues were also analyzed. Results: Convincing evidence exists on the optimal therapeutic effect obtained by using anti-EGFR agents in first-line treatment before anti-VEGF agents. On the contrary, up-front anti-VEGF agents’ use seems to determine biological changes that increase the risk of acquired resistance to subsequent EGFR inhibitors. This hypothesis is confirmed by the scarce evidence of EGFR inhibitor activity in second-line treatment. Such a therapeutic optimum is subject to a fine molecular selection based on RAS mutational status. Conclusion: There is accumulating evidence suggesting that, after precise and well-established molecular selection, anti-EGFR agents deliver their maximum efficacy in mCRC patients when given early in the treatment strategy. Their toxicity profile seems manageable under the supervision of experienced physicians. Large randomized trials prospectively confirming the impact of different sequencing strategies are eagerly awaited. © 2016 Springer-Verlag Berlin Heidelberg Source

Ruskone-Fourmestraux A.,Hopital St. Antoine | Fischbach W.,University of Wurzburg | Aleman B.M.P.,Netherlands Cancer Institute | Boot H.,Netherlands Cancer Institute | And 6 more authors.

This consensus report of the EGILS (European Gastro-Intestinal Lymphoma Study) group includes recommendations on the management of gastric extranodal marginal zone B-cell lymphoma of MALT. They are based on data from the literature and on intensive discussions and votings of the experts during their annual meetings. Source

The desmoid tumor is a rare tumor with an incidence of 2-4 cases per million people each year, and represents 0.03% of all cancers. The tumor is composed of fibrous tissue that produces masses of well-differentiated hard elastic consistency. According to their site of onset, the desmoid tumors are classified in abdominal, intra-abdominal, and extra-abdominal. The abdominal cases develop inside the abdominal muscles of the abdominal wall upright, especially in women in their 2nd - 4th decade of life, particularly in those who have been pregnant. METHODS: A 66-year-old patient underwent nephrectomy in 2006 for the detection of a massive tumor in the right kidney (EI: pT1bNx). The patient came to our observation for the radiological tracking (CT) of a solid lesion of 4 cm below the right arch, 2 years after surgery. For this reason it was decided to refer the patient to a series of percutaneous biopsies. The report describes a histologic lesion of fibromatosis. After one year a new CT exam showed a significant increase of the size of the lesion, with a diameter of 11.6 x 7.9 cm, and abdominal involvement to ascending colon. Given the discrepancy between the CT data and the histological report, it was decided to refer the patient to a lombotomic exploration and the subsequent removal of the lesion, which appeared of hard, elastic consistency and well capsulated. The final histology test confirmed the fibromatosis lesion. CONCLUSIONS: The desmoid tumor is a rare tumor characterized by the proliferation of fibrotic tissue. The tumor is composed of well-differentiated fibrous tissue and has a hard-elastic consistency. Regarding the development of dermoid tumors, several risk factors were identified, including extra-abdominal fibromatosis, genetic factors, endocrine factors. Other causes may arise from trauma or abdominal injury in surgical outcomes of appendectomy, laparotomy and other surgical scars (scar fibromatosis) or genetic predisposing factors. The surgical resection of dermoid tumors should be the therapy of choice, complete and radical, to cover the possible excision of a wide margin of surrounding structures concerned, and those arrangements should ensure a low rate of relapse. However, in cases of inoperable cancer due to extension, anti-estrogen therapy may have an important therapeutic and well-tolerated effect, besides being relatively non-toxic, even at high doses. A close follow-up is indicated, however, and warmly recommended. Source

Agency: Cordis | Branch: H2020 | Program: IA | Phase: EE-06-2015 | Award Amount: 5.14M | Year: 2016

The aim of the DR-BOB project is to demonstrate the economic and environmental benefits of demand response in blocks of buildings for the different key actors required to bring it to market. To achieve its aim the DR-BOB project will: Integrate existing technologies to form the DR-BOB Demand Response Energy Management solution for blocks-of-buildings with a potential ROI of 5 years or less. Demonstrate the DR-BOB integrated solution at 4 sites operating under different energy market and climatic conditions in the UK, France, Italy and Romania with blocks-of-buildings covering a total of 274,665 m2, a total of 47,600 occupants over a period of at least 12 months. Realise up to 11% saving in energy demand, up to 35% saving in electricity demand and a 30% reduction in the difference between peak power demand and minimum night time demand for building owners and facilities managers at the demonstration. Provide and validate a method of assessing at least 3 levels of technology readiness (1-no capability, 2-some capability, 3-full capability) related to the technologies required for consumers facilities managers, buildings and the local energy infrastructure to participate in the Demand Response Energy Management solution at any given site. Identify revenue sources with at least a 5% profit margin to underpin business models for each of the different types of stakeholders required to bring demand response in the blocks-of-buildings to market in different local and national contexts. Engage with at least 2,000 companies involved in the supply chain for demand response in blocks of buildings across the EU to disseminate the projects goals and findings.

Loupakis F.,University of Pisa | Cremolini C.,University of Pisa | Masi G.,University of Pisa | Lonardi S.,University of Pisa | And 16 more authors.
New England Journal of Medicine

BACKGROUND A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects.METHODS We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival.RESULTS The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62 to 0.90; P = 0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P = 0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P = 0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group.CONCLUSIONS FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; ClinicalTrials.gov number, NCT00719797.). Copyright © 2014 Massachusetts Medical Society. All rights reserved. Source

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