Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer. Efficacy in combination with hormonal therapy

Background: Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT.Methods: Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not.Results: Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev.Conclusion: Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents

Targeting angiogenesis in advanced non-small-cell lung cancer: are biomarkers needed?

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Inflammatory markers as prognostic factors of survival in patients affected by hepatocellular carcinoma undergoing transarterial chemoembolization

Transarterial chemoembolization (TACE) is a good choice for hepatocellular carcinoma (HCC) treatment when surgery and liver transplantation are not feasible. Few studies reported the value of prognostic factors influencing survival after chemoembolization. In this study, we evaluated whether preoperative inflammatory factors such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio affected our patient survival when affected by hepatocellular carcinoma. Methods. We retrospectively evaluated a total of 72 patients with hepatocellular carcinoma that underwent TACE. We enrolled patients with different etiopathogeneses of hepatitis and histologically proven HCC not suitable for surgery. The overall study population was dichotomized in two groups according to the median NLR value and was analyzed also according to other prognostic factors. Results. The global median overall survival (OS) was 28 months. The OS in patients with high NLR was statistically significantly shorter than that in patients with low NLR. The following pretreatment variables were significantly associated with the OS in univariate analyses: age, Child-Pugh score, BCLC stage, INR, and NLR. Pretreated high NLR was an independently unfavorable factor for OS. Conclusion. NLR could be considered a good prognostic factor of survival useful to stratify patients that could benefit from TACE treatment

COX-2 targeting in cancer: a new beginning?

Cyclo-oxygenase-2 (COX-2), the inducible enzyme catalyzing the rate-limiting step in the conversion of arachidonic acid into eicosanoids, is overexpressed in a wide variety of malignancies and associates with poor prognostic features [1]. Consequently, selective COX-2 inhibitors have been explored as therapeutic or chemopreventive agents in different settings; however, initial enthusiasm was tempered by reports of substantial gastrointestinal toxicity as well as of increased cardiovascular risk, mostly coming from postmarketing use as anti-inflammatory drugs and Cancer Research Campaign (UK) chemoprevention trials and eventually resulting in the withdrawal of rofecoxib from the market [2]

Osimertinib in patients with advanced epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: Rationale, evidence and place in therapy

The identification of epidermal growth factor receptor (EGFR) mutations represented a fundamental step forward in the treatment of advanced non-small cell lung cancer (NSCLC) as they define a subset of patients who benefit from the administration of specifically designed targeted therapies. The inhibition of mutant EGFR through EGFR-tyrosine kinase inhibitors (TKIs), either reversible, first-generation gefitinib and erlotinib, or irreversible, second-generation afatinib, has dramatically improved the prognosis of patients harboring this specific genetic alteration, leading to unexpected clinical benefit. Unfortunately, virtually all patients who initially respond to treatment develop acquired resistance to EGFR-TKIs within 9-14 months. The EGFR T790M secondary mutation has emerged as a cause of treatment failure in approximately 60% of resistant cases. To date, several compounds designed with the aim to overcome T790M-mediated resistance are under clinical investigation. The aim of this review is to discuss emerging data regarding the third-generation EGFR-TKI, osimertinib, for the treatment of EGFR T790M mutant advanced NSCLC

Do institutional arrangements make a difference to transport policy and implementation? Lessons for Britain

This paper describes local government decision-making in transport in three areas of the UK, London, West Yorkshire and Edinburgh, in which major changes in local government decision-making structures have taken place over the last decade, and between which arrangements are now very different. The research discusses whether institutional change has had a beneficial or adverse effect, and whether any of the current structures provides a more effective framework for policy development and implementation. The results show that although the sites share a broadly common set of objectives there are differences in devolved responsibilities and in the extent to which various policy options are within the control of the bodies charged with transport policy delivery. The existence of several tiers of government, coupled with the many interactions required between these public sector bodies and the predominantly private sector public transport operators appears to create extra transactional barriers and impedes the implementation of the most effective measures for cutting congestion. There is, however, a compelling argument for the presence of an overarching tier of government to organise travel over a spatial scale compatible with that of major commuter patterns. The extent to which such arrangements currently appear to work is a function of the range of powers and the funding levels afforded to the co-ordinating organisation

Youth chances: integrated report

This document provides an overview of the key findings from this five-year ground-breaking research project about the experiences of lesbian, gay, bisexual, trans and questioning (LGBTQ) 16-25year olds in England funded by the Big Lottery Fund and conducted by METRO Charity in collaboration with Ergo Consulting and the University of Greenwich. Methods: The project surveyed 7,126 young people aged 16-25. Of these 6,514 were LGBTQ young people. 612 were heterosexual non-trans young people and 956 were trans young people. 29 commissioners of services for young people and 52 relevant service providers across England were also surveyed. Findings: Show high levels of discrimination, abuse and mental health issues that young LGBTQ people face which indicate a need for more to be done to improve the lives of LGBTQ young people. Sections of the report are: 1. Being different Over half of LGBQ respondents (53%) knew they were LGBQ by the age of 13. Over half of trans respondents (58%) knew they were trans by the same age. When coming out as LGBQ or trans, over four fifths of LGBQ respondents (81%) and nearly two thirds of trans respondents (62%) told a friend first. Over a quarter of LGBQ young people (29%) have not told their mother, nearly a half (45%) have not told their father, and 5% have not told anybody. Approximately half of trans respondents have not told parents or siblings that they are trans and 28% have not told anybody. Young people tell us that they most want emotional support to help them when they are coming out but most are not getting it. The second most important thing to them is to meet other LGBTQ people and again over half of them did not get this opportunity. 2. Participation LGBTQ young people are twice as likely not to feel accepted in the area where they currently live, compared to heterosexual non-trans young people. 59% of LGBTQ young people that would be interested in joining a religious organisation have stopped or reduced their involvement owing to their sexuality or gender identity. Over a third of LGBTQ young people (34%) are not able to be open about their sexuality or gender identity at a sports club they are involved in. 3. Staying safe 73% of the LGBTQ sample agreed that discrimination against LGB people is still common and 90% of the LGBTQ sample agreed that discrimination against trans people is still common. About three quarters of LGBTQ young people (74%) have experienced name calling, nearly a half (45%) have experienced harassment or threats and intimidation and almost a quarter (23%) have experienced physical assault. 88% of LGBTQ young people do not report incidents to the police and when cases are reported only 10% lead to a conviction. 29% of LGBTQ respondents reported domestic or familial abuse, compared to 25% of the heterosexual non trans group. Over a third (36%) of LGBTQ respondents cited their sexuality or gender identity as at least a contributing factor in the abuse. Almost one in five (18%) LGBTQ young people have experienced some form of sexual abuse, compared with one in ten (11%) of non-trans heterosexuals in our sample. Most LGBTQ respondents who have experienced sexual abuse (79%) have not received any help or support. Nearly one in ten LGBTQ young people report that they have had to leave home for reasons relating to their sexuality or gender identity. 4. Enjoying and achieving Nearly half of LGBTQ young people (49%) reported that their time at school was affected by discrimination or fear of discrimination. Consequences reported included missing lessons, achieving lower grades, feeling isolated and left out and having to move schools are all reported. 61% reported name calling because they were LGBTQ or people thought they were. This figure includes the experiences of heterosexual non-trans respondents: it is an issue for all young people. About one in five LGBTQ young people experience physical attack at school on account of their sexual identity or gender identity. The majority do not report this and only a small proportion of those who do experience resolution. For some reporting the abuse means that it gets worse. Around two thirds of LGBTQ young people say they learn a lot about relationships and safer sex between a man and a woman, compared to less than 5% who say they learn a lot about same sex relationships and safer sex. 89% of LGBTQ young people report learning nothing about bisexuality issues and 94% report learning nothing about transgender issues. Only 25% of LGBTQ young people report that they learned anything at school about safer sex for a male couple