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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_465"
                     title="Genetic Pathways Play Role in NSCLC Survival (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HematologyOncology/LungCancer/tb/18396?impressionId=1265778096326"
                     
      Researchers say they&apos;ve found genetic characteristics associated with age and sex differences observed in recurrence-free survival among non-small cell lung cancer patients.&lt;br&gt;
&lt;br&gt;Older patients at higher risk for recurrence had increased activation of wound-healing and invasiveness pathways, while high-risk women had increased activation of invasiveness and &lt;em&gt;STAT3&lt;/em&gt; pathways, Anil Potti, MD, of Duke University, and colleagues reported in the Feb. 10 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;High-risk men had increased activation of the &lt;em&gt;STAT3&lt;/em&gt;, tumor necrosis factor, &lt;em&gt;EGFR&lt;/em&gt;, and wound-healing pathways, Potti the researchers found.&lt;br&gt;
&lt;br&gt;&quot;This analysis represents one of the first large-scale attempts to comprehensively characterize the biology of early-stage [non-small cell lung cancer] at a molecular pathway level and demonstrates a clear distinction in gene expression profiles within relevant age and sex categories,&quot; they wrote.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;There&apos;s lots of evidence that clinical and pathologic factors are clinically relevant, the researchers noted, but little is known about the underlying biological differences in lung tumor gene expression among patients with different characteristics, including age and gender.&lt;/p&gt;
&lt;p&gt;So Potti and colleagues conducted a retrospective analysis of 787 patients with predominantly early stage non-small cell lung cancer at Duke University from July 2008 to June 2009.&lt;/p&gt;
&lt;p&gt;They stratified their results by risk of recurrence, age, and gender.&lt;/p&gt;
&lt;p&gt;They found that high-risk patients under 70 had greater activation of the &lt;em&gt;Src&lt;/em&gt; and tumor necrosis factor pathways than low-risk patients (25% versus 6%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001; and 76% versus 42%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, respectively).&lt;/p&gt;
&lt;p&gt;In patients 70 and older, those at high risk for recurrence had greater activation of the wound-healing and invasiveness pathways than low-risk patients (40% versus 24%, &lt;em&gt;P&lt;/em&gt;=0.02; and 64% versus 20%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, respectively).&lt;/p&gt;
&lt;p&gt;&quot;Although this is a novel finding, biologically this is not entirely unexpected,&quot; the researchers wrote in reference to the data in older patients. &quot;The invasiveness and wound-healing gene signatures likely identify tumors at high risk of metastasis, along with the wound-healing signature identifying activation of angiogenesis pathways.&quot;&lt;/p&gt;
&lt;p&gt;Their findings also corroborated previous evidence that biology and clinical course of the disease are sex-specific, as the analysis found that women had significantly better progression-free survival than men (&lt;em&gt;P&lt;/em&gt;=0.008).&lt;/p&gt;
&lt;p&gt;In general, men had a higher probability of activation of these pathways than women:&lt;ul&gt;&lt;li&gt;Chromosomal instability (&lt;em&gt;P&lt;/em&gt;=0.001)&lt;/li&gt;&lt;li&gt;Epigenetic stem cell (&lt;em&gt;P&lt;/em&gt;=0.03)&lt;/li&gt;&lt;li&gt;Invasiveness (&lt;em&gt;P&lt;/em&gt;=0.005)&lt;/li&gt;&lt;li&gt;&lt;em&gt;Myc&lt;/em&gt; (&lt;em&gt;P&lt;/em&gt;=0.02)&lt;/li&gt;&lt;li&gt;Wound-healing (&lt;em&gt;P&lt;/em&gt;=0.004)&lt;/li&gt;&lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Women, meanwhile, had a higher probability of activation of the &lt;em&gt;E2F1&lt;/em&gt; pathway (&lt;em&gt;P&lt;/em&gt;=0.04).&lt;/p&gt;
&lt;p&gt;When stratified by risk, high-risk women had increased activation of the invasiveness and &lt;em&gt;STAT3&lt;/em&gt; pathways compared with low-risk women (99% versus 2%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001; and 72% versus 35%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, respectively).&lt;/p&gt;
&lt;p&gt;Compared with low-risk men, those with high risk had increased activation of the following pathways:&lt;ul&gt;&lt;li&gt;&lt;em&gt;STAT3&lt;/em&gt; (87% versus 18%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt;&lt;li&gt;Tumor necrosis factor (90% versus 46%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) &lt;/li&gt;&lt;li&gt;&lt;em&gt;EGFR&lt;/em&gt; (13% versus 2%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt;&lt;li&gt;Wound-healing pathways (50% versus 22%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt;&lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Multivariate analyses confirmed pathway-based subphenotypes in women (HR 2.02, 95% CI 1.34 to 3.03, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and in patients under 70 (HR 1.83, 95% CI 1.24 to 2.71, &lt;em&gt;P&lt;/em&gt;=0.003).&lt;/p&gt;
&lt;p&gt;&quot;While differences in clinical outcomes and the biology of [non-small cell lung cancer] based on age and sex have been previously noted, we were able to describe the molecular networks contributing to these differences,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;They said the findings are &quot;apt for therapeutic interventions when planning clinical trials with drugs that target specific pathway-related abnormalities or tumor biology.&quot;&lt;/p&gt;
&lt;p&gt;&quot;With genomic assays now being increasingly practical and clinically applicable, with turnaround times of five to seven days,&quot; they concluded, &quot;we believe our findings, while hypothesis generating and needing further validation, represent a step forward in defining pathway-driven cohorts of [non-small cell lung cancer] that likely explain the age-and sex-specific differences.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by grants from the Emilene Brown Cancer Research Fund, the Harold and Linda Chapman Lung Cancer Fund, the Jimmy V Foundation, the American Cancer Society, and the National Cancer Institute.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_450"
                     title="SSRI and Tamoxifen Increase Mortality Risk (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/18376?impressionId=1265778096326"
                     
      Overlapping use of tamoxifen and the antidepressant paroxetine (Paxil) significantly increases the risk of breast cancer mortality, data from a large cohort of breast cancer patients showed.&lt;br&gt;
&lt;br&gt;The excess breast-cancer mortality risk ranged as high as 91%, depending on the duration of simultaneous use, researchers reported online in &lt;em&gt;BMJ.&lt;/em&gt;&lt;br&gt;
&lt;br&gt;Women taking other antidepressants with tamoxifen, including other selective serotonin reuptake inhibitors (SSRIs), did not have an increased risk of breast cancer death.&lt;br&gt;
&lt;br&gt;&quot;We estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 patients so treated; the risk with more extensive overlap would be greater,&quot; David Juurlink, MD, PhD, of Sunnybrook Health Sciences Center in Toronto, and colleagues concluded.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;The findings add to an accumulation of evidence suggesting that inhibition of the cytochrome P450 2D6 isozyme (CYP2D6) may adversely affect outcomes in breast cancer patients taking tamoxifen. CYP2D6 is the principle catalyst for converting tamoxifen into endoxifen, a metabolite with 100-fold greater affinity for the estrogen receptor.&lt;/p&gt;
&lt;p&gt;Multiple studies have shown that women who have a poor-metabolizer phenotype have lower levels of endoxifen, as do women treated with drugs that inhibit CYP2D6.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, in patients who receive tamoxifen in addition to a CYP2D6 inhibitor, endoxifen concentrations vary inversely with the degree of CYP2D6 inhibition,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Paroxetine is used to treat depression and vasomotor symptoms in breast cancer patients treated with tamoxifen. Paroxetine is not the only SSRI antidepressant used by breast cancer patients, but it is the only SSRI that irreversibly inhibits CYP2D6.&lt;/p&gt;
&lt;p&gt;Whether the metabolic effects of CYP2D6 inhibition translated into adverse breast cancer outcomes had not been determined.&lt;/p&gt;
&lt;p&gt;To examine the issue, Juurlink and colleagues compared prescribing data with clinical records of 24,430 breast cancer patients, ages 66 and older, who initiated tamoxifen therapy from 1993 to 2005. Of those, 7,500 also received an antidepressant.&lt;/p&gt;
&lt;p&gt;Ultimately, the investigators narrowed the study population to 2,430 women who took a single SSRI during tamoxifen therapy. The most commonly prescribed SSRI was paroxetine (25.9%), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15%), fluoxetine (10.4%), and fluvoxamine (7.2%).&lt;/p&gt;
&lt;p&gt;During a mean follow-up of 2.38 years, 1,074 patients died, including 374 breast cancer deaths.&lt;/p&gt;
&lt;p&gt;The analysis showed an increased risk of breast cancer death only among women taking paroxetine.&lt;/p&gt;
&lt;p&gt;The breast cancer mortality risk increased with the duration of concomitant use of paroxetine and tamoxifen. As the duration of therapeutic overlap increased from 25%, to 50%, to 75% of time on tamoxifen, the excess risk of breast cancer death increased from 24%, to 54%, to 91%.&lt;/p&gt;
&lt;p&gt;Investigators repeated the analysis, using death from any cause. Overlapping treatment with tamoxifen and paroxetine led to an increased mortality risk of 13%, 28%, and 46% as the duration of overlap increased from 25% to 75%.&lt;/p&gt;
&lt;p&gt;The results suggest clear implications for use of SSRIs in breast cancer patients on tamoxifen, Frank Andersohn, MD, and Stefan Willich, MD, of Charite University in Berlin, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;&quot;The straightforward answer is to avoid prescribing strong CYP2D6-inhibiting SSRIs (such as paroxetine or fluoxetine) for women with breast cancer who are prescribed tamoxifen, and to consider instead drugs with low potential to inhibit CYP2D6 (such as citalopram or venlafaxine),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;For women who are already taking a potent inhibitor of CYP2D6, doctors should consider switching to a drug that does not inhibit the enzyme, they added. However, any switch should be accomplished gradually, as abrupt discontinuation of an antidepressant confers risk, as well, they noted.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Co-author Kathleen Pritchard disclosed relationships with sanofi-aventis, AstraZeneca, Roche, Pfizer, Ortho-Biotech, YM Biosciences, Novartis, Abraxis, Amgen, GlaxoSmithKline, Bristol Myers Squibb, and Roche&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="-0.002"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265778096326"
                     
      &lt;p&gt;Epidemiologist Lawrence Garfinkel, MA, a legendary researcher for the American Cancer Society whose work helped establish a link between cancer and smoking and other activities, died of cardiovascular disease Thursday in Seattle, Washington at 88.&lt;/p&gt;
&lt;p&gt;&quot;The American Cancer Society today mourns the loss of one of its most important historical figures,&quot; said John R. Seffrin, PhD, the society&apos;s chief executive officer.&lt;/p&gt;
&lt;p&gt;&quot;Larry Garfinkel joined the American Cancer Society as a young scientist in 1947, and for more than four decades played an instrumental role in expanding knowledge of and reducing death from smoking.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel&apos;s 1982 Cancer Prevention Study-II (CPS-II) is the largest contemporary study of tobacco and mortality, with 1.2 million participants and 77,000 data-compiling volunteers across 50 states, the District of Columbia, and Puerto Rico.&lt;/p&gt;
&lt;p&gt;CPS-II uncovered the effects of lifestyle factors, such as obesity, alcohol consumption, medications, genetic elements, that affect cancer and other chronic diseases, the analysis of which still reveals important clues about cancer today.&lt;/p&gt;
&lt;p&gt;The study also found lung cancer mortality rates in women increased five-fold from data collected in the original Cancer Prevention Study, while cancer rates among non-smoking women remained the same. This information provided strong evidence that lung cancer was almost exclusively a disease found in smokers.&lt;/p&gt;
&lt;p&gt;Garfinkel was born on January 11, 1922 in Manhattan&apos;s Lower East Side and was raised in the South Bronx.&lt;/p&gt;
&lt;p&gt;He served in the army during World War II, where he was seriously injured in northern France in August, 1944.&lt;/p&gt;
&lt;p&gt;Ultimately, Garfinkel graduated from the City College of New York and received a Masters Degree from Columbia University. He also received several honorary doctorates.&lt;/p&gt;
&lt;p&gt;Garfinkel began work for the ACS in 1947.&lt;/p&gt;
&lt;p&gt;He assisted E. Cuyler Hammond, MD, and Daniel Horn, MD, in the first ACS prospective mortality study of 187,783 males in the late 1940&apos;s by coordinating much of the field work, including training thousands of ACS volunteers in data collection techniques.&lt;/p&gt;
&lt;p&gt;Garfinkel acted as the co-principal investigator of the larger Cancer Prevention Study I (CPS-I) in 1959. The study enrolled 1 million participants across 25 states and required over 68,000 volunteers to collect data.&lt;/p&gt;
&lt;p&gt;In the 1960s, he contributed to more than two dozen major papers on the relation between smoking and health. He was co-author of one of the first reports combining epidemiology with pathology and provided some of the first direct evidence of lung damage related to smoking.&lt;/p&gt;
&lt;p&gt;Garfinkel also contributed to issuance of the landmark 1964 Surgeon General&apos;s report on smoking and health.&lt;/p&gt;
&lt;p&gt;He was appointed director of ACS research in 1979 after Hammond&apos;s retirement.&lt;/p&gt;
&lt;p&gt;Garfinkel retired from the ACS in 1989. Over the course of his career, he had contributed to more than 100 journal articles.&lt;/p&gt;
&lt;p&gt;Richard D. Klausner, MD, then-director of the National Cancer Institute, said at the time: &quot;Few individuals have contributed as much to our present-day knowledge about the disease consequences of smoking.&lt;/p&gt;
&lt;p&gt;&quot;His remarkable achievement is an important reminder what a tremendous impact an individual can make, and inspires all of us to continue the fight against cancer.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel continued to volunteer with the ACS after his retirement and taught biostatistics at the New York University Dental School.&lt;/p&gt;
&lt;p&gt;He is survived by his brothers, Harold and Melvin; his sons, Martin and Herb; a daughter-in-law, Margaret Cary, and two grandchildren.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_248"
                     title="Continued Smoking Worsens Lung Cancer Prognosis (CME/CE)"
                     score="-0.002"
                     href="http://www.medpagetoday.com/HematologyOncology/LungCancer/tb/18105?impressionId=1265778096326"
                     
      &lt;p&gt;It&apos;s never too late to stop smoking, even for smokers already diagnosed with lung cancer, a new analysis shows.&lt;/p&gt;
&lt;p&gt;A systematic review of published trials of smokers diagnosed with early stage lung cancer disclosed that patients who stopped smoking when diagnosed were about twice as likely to survive for five years as those who continued to smoke after diagnosis, wrote Amanda Parsons, PhD, a research fellow at the University of Birmingham in England, and colleagues in a paper published online Jan. 22 by &lt;em&gt;BMJ.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Continuing smoking was associated with a significantly increased risk of all cause mortality (hazard ratio 2.94, 95% CI, 1.15 to 7.54) as well as increased risk of cancer recurrence (HR 1.86, 95% CI 1.01 to 3.41), they wrote.&lt;/p&gt;
&lt;p&gt;The authors extrapolated the benefit of smoking cessation from both the recurrence and mortality data, since none of the studies contained specific information on the &quot;effect of quitting smoking on cancer specific mortality or on development of a second primary tumor in non-small cell lung cancer.&quot;&lt;/p&gt;
&lt;p&gt;They used life table-modeling to come up with the estimate that 33% of smokers diagnosed with early stage NSCLC at age 65 would survive for five years if they continued to smoke, versus an estimated 70% among those who quit smoking after diagnosis.&lt;/p&gt;
&lt;p&gt;&quot;This review has found evidence that after lung cancer has been diagnosed, reductions in risk of developing a second primary or recurrence were associated with quitting within seven years, suggesting that, even at this stage the prognostic outlook can be improved by smoking cessation,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Whether this observation can be explained by nicotine or by other components of tobacco smoke is unknown, but regardless of the exact mechanism of harm, the authors wrote, the findings &quot;support the hypothesis that continued smoking affects the behavior of a lung tumor.&quot;&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Tom Treasure, MD, a cardiothoracic surgeon at University College London, and psychiatrist Janet Treasure, PhD, also from University College, wrote that Parsons et al demonstrated that the impact of continued smoking is so large that both patients and &quot;those caring for them should be given this information because the potential benefit is great.&quot;&lt;/p&gt;
&lt;p&gt;There is one significant problem both for patients and doctors, the editorialists noted: &quot;Fewer than one in three patients with lung cancer survive even one year, so the patients likely to benefit are probably healthier to begin with. So, although the information is valuable, it&apos;s application may be limited.&quot;&lt;/p&gt;
&lt;p&gt;Discussing its limitations, the review&apos;s authors noted that it was based on data from 10 observational studies, which raises the &quot;possibility of uncontrolled confounding.&quot;&lt;/p&gt;
&lt;p&gt;Moreover, definitions of smoking &quot;abstinence were generally poor and only five of the 10 studies assigned patients to smoking categories on the basis of smoking status recorded at six months or more after diagnosis.&quot;&lt;/p&gt;
&lt;p&gt;Additionally, they noted, it appears that &quot;smokers with unfavorable prognostic factors were most likely to give up smoking, so that unadjusted estimates underestimated the benefits of quitting.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the UK Center for Tobacco Control Studies, the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research.&lt;/p&gt;&lt;p&gt;Parsons said she has been reimbursed by Pfizer, maker of varenicline (Chantix) and nicotine nasal spray and inhaler products (Nicotrol).&lt;/p&gt;&lt;p&gt;The editorial writers disclosed no competing interests.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_496"
                     title="AASLD: Schizophrenics and Drug Abusers Get Short Shrift in HCV Therapy"
                     score="-0.006"
                     href="