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28.10.2014

New treatments for lung cancer, can tinnitus be proven - How to DIY

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Paradigm shift seems an inadequate, though often-used, description of what has happened in lung cancer therapy in the past decade. While the future of lung cancer treatment as outlined by the authors is promising, the present holds considerable challenges for clinicians and researchers. Signs of non-small cell lung cancer include a cough that doesn't go away and shortness of breath. Tests that examine the lungs are used to detect (find), diagnose, and stage non-small cell lung cancer. A thin membrane called the pleura covers the outside of each lung and lines the inside wall of the chest cavity. The pleural cavity normally contains a small amount of fluid that helps the lungs move smoothly in the chest when you breathe. There are two main types of lung cancer: non-small cell lung cancer and small cell lung cancer. Other less common types of non-small cell lung cancer are: pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. Tests and procedures to detect, diagnose, and stage non-small cell lung cancer are often done at the same time. Physical exam and history : An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. Sputum cytology : A procedure in which a pathologist views a sample of sputum (mucus coughed up from the lungs) under a microscope, to check for cancer cells.
Fine-needle aspiration (FNA) biopsy of the lung: The removal of tissue or fluid from the lung using a thin needle.
Bronchoscopy : A procedure to look inside the trachea and large airways in the lung for abnormal areas. Thoracoscopy : A surgical procedure to look at the organs inside the chest to check for abnormal areas. Thoracentesis : The removal of fluid from the space between the lining of the chest and the lung, using a needle. Light and electron microscopy : A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.
Immunohistochemistry : A test that uses antibodies to check for certain antigens in a sample of tissue. Whether the cancer has mutations (changes) in certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) gene. Washington: Scientists have identified a potential new drug target for treating lung cancer. In a new study by University of Kentucky Markey Cancer Center researchers have suggested that targeting a key enzyme and its associated metabolic programming may lead to novel drug development to treat the disease. Teresa Fan, one of the lead researchers of the study, said that they now knew much more about metabolic reprogramming of cancerous tissues in human patients, particularly that the activation of pyruvate carboxylase is important to lung cancer cell growth and survival. Expand your knowledge with our comprehensive e-learning module on angiogenesis in gastric cancer.
Investment in lung cancer is clearly disproportionate to the money spent on investigating its causes and that invested in potential therapeutic interventions. Meanwhile, lung cancer is the second most common cancer in the UK, with nearly 40,000 new cases diagnosed a year, according to the most recently available statistics. New prescribing strategies based, for example, on the identification of genetic mutations in individual patients and differentiating between squamous and non-squamous histology, may help to make better use of new targeted therapies in the future—and even more cost-effective use of well-established cytotoxic chemotherapy regimens. These were among the issues that emerged during Oncology Outcomes—Taking Control of Tomorrow, a meeting of oncologists and other health-care professionals with an interest in prescribing and service provision for lung cancer patients, held at the Royal College of Physicians in London on 5 November 2010. For the future, Dame Gill said that priority should be given to greater public awareness of the burden of lung cancer, more effective diagnosis, access to optimum treatments and top-quality specialist follow-up of patients. Dr Jesme Fox (Medical Director, Roy Castle Lung Cancer Foundation) drew attention to the fact that one of the main reasons for ambivalent attitudes towards lung cancer is that in countries such as the UK, where fewer people are now smoking, there is little sympathy for sufferers with a disease that is mainly caused by cigarette smoking. Turning to the anticipated squeeze on NHS budgets, Dr Fox said there would be no escaping painful decisions on how best to make savings in order to fund service developments in lung cancer.
She outlined the RCLCF’s key campaigning priorities, including better research into early detection, efforts to reduce the stigma and negativity associated with lung cancer, access for all patients to lung cancer clinical nurse specialists, ensuring high-quality data collection through the National Lung Cancer Audit, speedier referral to a hospital-based specialist for investigation of suspicious symptoms, and greater equity throughout the UK in terms of early diagnosis, treatment and care. Professor Nick James (School of Cancer Sciences, University of Birmingham) reported that half of all drugs in clinical trials are for cancer indications. The problem, however, was that new cancer drugs were usually only licensed (initially, at least) in end-stage disease—and that although they might improve survival, there was a high price to pay for any clinical benefit.


He pointed out that NICE has no budget for implementing its recommendations, and that during November 2010 doubts were raised about its role in terms of funding the prescribing of new drugs. Professor James added that although NHS spending on cancer drugs multiplied sixfold between 1998 and 2007, and that approvals for new cancer drugs are expected to continue, it was clear that future budget restrictions would soon put a brake on this rate of increase. Professor Nicholas Thatcher (Christie Hospital NHS Trust, Manchester) outlined current thinking in terms of first-line therapy for in advanced non-small cell lung cancer (NSCLC).
Attention was now turning, said Professor Thatcher to first-line clinical trials with conventional therapy in combination with one or more of the new targeted therapies. Dr Marianne Nicolson (Aberdeen Royal Infirmary, Scotland, UK) argued the case for greater use of personalised therapeutic interventions and more discriminating patient selection, with the emphasis on maintenance and second-line treatment for patients with advanced NSCLC. She reported that during the 2000s, clinical trials involving cytotoxic drugs such as gemcitabine, paclitaxel and docetaxel had all been studied extensively, but had not found favour as candidates for maintenance therapy in routine clinical practice—probably because although significantly longer PFS had been documented, there were only modest improvements in overall survival (OS) as well as increased adverse events and impaired QoL. Finally, Dr Nicolson reported data to suggest that delaying treatment with a chemotherapeutic agent such as docetaxel not only achieves no significant clinical benefit in terms of OS, it also increases the risk of the patient not being fit enough for maintenance therapy [9]. With targeted drugs, there is no worthwhile improvement for induction followed by maintenance (although erlotinib improves survival post-stable disease following induction chemotherapy. Dr Sanjay Popat (Royal Marsden Hospital, London) and Dr Riyaz Shah (Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust) outlined recent developments that may well have a bearing on future prescribing and strategy for patients with lung cancer. However, as Dr Shah made clear, the future for UK practice in terms of delivery of lung cancer care is likely to become increasingly complex.
Nearly 70% argued that more campaigning is needed so that lung cancer gets a fairer share of the current cancer research funding pot. 86% were of the view that people should be encouraged to insure against the need for co-payment with the NHS for access to cancer services. Two-thirds of responders said that it would not be possible to deliver the complexity of lung cancer care required in the future at every district general hospital. Oncology Outcomes was attended by 30 health-care professionals and key opinion leaders in the field of lung cancer. The BATTLE trial[1] has demonstrated the feasibility of obtaining larger patient specimens, and the authors’ diagnostic and treatment algorithm (and any sensible algorithm one can imagine) hinges on obtaining a diagnostic biopsy with adequate tissue for biomarker testing. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer.
A history of the patient’s health habits, including smoking, and past jobs, illnesses, and treatments will also be taken. UK's Center for Environmental and Systems Biochemistry (CESB) researchers measured the in situ activity of the two enzymes in patients with early stage lung cancer.
Ultimately, figuring out how to target PC may help researchers develop new, more effective therapeutic strategies to improve upon current lung cancer treatments, which are limited and harmful. Meanwhile, lung cancer research should focus on screening patients to identify those most likely to benefit from specific therapeutic options, predictors of success, pulmonary rehabilitation, radiotherapy and better imaging techniques. New therapeutic options, specialist training, as well as specific and effective diagnostic tests should be high on the agenda.
Dr Fox reported that her own organisation is the only national lung cancer charity registered in the UK—in sharp contrast to the prolific charitable provision enjoyed by other cancers. Lung cancer is a devastating disease, characterised by late diagnosis, few curative treatment options and poor survival rates. Rapid growth of cancer drug sales was a feature of the late 2000s, resulting in a global market worth $48 billion in 2008.
For the immediate future, the goal would be to improve cure and life prolongation rates in cancer. An educational grant was provided by Boehringer-Ingelheim Ltd in order to facilitate arrangements for the meeting and the writing of this report. Carrizosa and colleagues lead us on a comprehensive tour of the molecular targets and therapies that have shaped this new framework for evaluating and treating patients with lung cancer. Nevertheless, our ability to obtain sufficient tissue to make treatment decisions lags behind our understanding of the importance of selecting therapy based on molecular markers. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non–small-cell lung cancer. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non–small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group study BR.21.


Oxygen is inhaled into the lungs and passes through the thin membranes of the alveoli and into the bloodstream (see inset). When they infused the patients with a glucose tagged with stable heavy atoms immediately prior to surgical removal of tumor tissue, they found that PC was selectively activated - in other words, PC expression may play an important role in the development of lung cancer. Indeed, only 51% of lung cancer patients currently receive any kind of active treatment. By engaging with patients, lung cancer specialists and other health-care professionals can make a more effective contribution towards reversing these trends’.
She reported the outcomes of a number of trials such as AVAIL (AVAstin in Lung) [5], FLEX (First-Line Erbitux in Lung Cancer) [6], ESCAPE (Evaluation of Sorafenib, Carboplatin And Paclitaxel Efficacy in NSCLC) and WJTOG 0203 [7] where agents such as bevacizumab, cetuximab, sorafenib and gefitinib, respectively, been had been added to conventional chemotherapy in the maintenance setting—all with little evidence of clinical benefit in terms of survival.
However, Boehringer-Ingelheim Ltd had no input into the data chosen and the report was reviewed for factual accuracy only. Evaluation of patients with a suspected diagnosis of advanced lung cancer has long focused on acquiring tissue in the most rapid and safe manner possible, often resulting in small cytologic specimens. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.EnlargeBronchoscopy.
They discuss acquired resistance to EGFR- and ALK-directed therapies, with an eye towards future platforms for combating resistance. Even in the controlled setting of clinical trials with tissue acquisition as a goal, obtaining sufficient tissue for molecular studies remains a challenge, with recovery rates of viable tumor samples typically less than 50% across multiple clinical trials.[2-7] In a typical outpatient setting, care may be fragmented and biopsies performed without the input of a medical oncologist. A bronchoscope is inserted through the mouth, trachea, and major bronchi into the lung, to look for abnormal areas. They outline other recent developments in lung cancer treatment, including an overview of potential KRAS-directed therapies and a discussion of developments in immunotherapy.
The authors also provide a clear and useful algorithm for personalized lung cancer treatment (see Figure 4 in their article).
This change will require, at a minimum, education of colleagues across multiple disciplines and earlier involvement of the medical oncologist in the care of a patient with suspected lung cancer. A chest x-ray is done after the procedure to make sure no air is leaking from the lung into the chest.EnlargeFine-Needle Aspiration Biopsy of the Lung. Carrizosa and colleagues, if successful, will ultimately result in the division of lung cancer patients into smaller and more descriptive subsets.
In this future, each of these subsets is akin to a rare malignancy, and the hope of an immediately available personalized treatment option for each patient remains distant without a rapid increase in the accrual of patients to clinical trials. A biopsy needle is inserted through the chest wall and into the area of abnormal lung tissue. Participation of adult cancer patients in clinical trials is dismal at 2% to 4%,[8] with even lower participation rates for minorities and the elderly (who comprise most of our lung cancer patients).
A small piece of tissue is removed through the needle and checked under the microscope for signs of cancer.
We would advocate for an algorithm where “refer for clinical trial participation” appears first at each decision point.
The Lung Cancer Mutation Consortium study, a touchstone for those advocating molecular testing, would not have been possible without large-scale participation of patients and the cooperation of multiple institutions from the very outset of the therapeutic decision-making process. The success story of crizotinib (Xalkori) for patients with ALK translocations also illustrates how rapid identification and accrual of patients to molecularly targeted clinical trials leads to better access to appropriate therapy for patients, not just for patients participating in the clinical trial but also for those who subsequently benefited from the relatively rapid approval of this agent by the US Food and Drug Administration (FDA). Identification of molecular drivers and the development of targeted therapies for small-cell lung cancer (SCLC) lag far behind NSCLC. While different disease biology may account for some of this discrepancy, the same challenges we face in achieving progress in NSCLC are, at least in part, to blame for the lack of progress in SCLC. Similarly, if we are to provide new options for the large numbers of NSCLC patients with no actionable mutation, we must focus on identifying new mutations through tissue acquisition. In the meantime, these patients are ideal candidates for the large number of available immunotherapy trials. Achieving the goal of personalized lung cancer therapy will require abandoning or adapting long-held practices.



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