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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="0.013"
                     href="http://www.medpagetoday.com/HematologyOncology/LungCancer/tb/18396?impressionId=1265765712168"
                     
      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_341"
                     title="Doctor&apos;s Orders: Brain&apos;s Wiring Makes Change Hard"
                     score="0.008"
                     href="http://www.medpagetoday.com/Psychiatry/Addictions/tb/18207?impressionId=1265765712168"
                     
      &lt;p&gt;Doctor&apos;s Orders&lt;em&gt; is a feature in the collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;. In this monthly segment we explore medical issues of interest to physicians and their patients alike. This month, we look at addiction and addictive behaviors, and what neuroimaging studies have revealed about why it&apos;s so hard to break bad habits. &lt;/em&gt;&lt;/p&gt;&lt;hr&gt;

&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;

&lt;p&gt;By the end of January, many New Year&apos;s resolutions have been tossed out with the leftover holiday cookies. That&apos;s because change is hard  --  and neuroscientists are learning why.&lt;br&gt;
&lt;br&gt;Advances in neuroimaging have enabled researchers to peer inside the brains of addicts and patients with addictive behaviors. They can see in real-time what gets patients hooked: how the brain&apos;s reward system  --  based largely on the neurotransmitter dopamine  --  thirsts for more, while inhibitory control centers experience a system failure.&lt;br&gt;
&lt;br&gt;The pattern is similar across all kinds of behaviors  --  from cocaine and tobacco addiction to overeating. That&apos;s why changing your mind may be the first step toward breaking a habit, but altering the brain&apos;s neural machinery is the real challenge.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Hijacked Pathways&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Drug-taking and other addictive behaviors &quot;hijack&quot; the brain&apos;s reward system, says Petros Levounis, MD, director of the Addiction Institute of New York at St. Luke&apos;s and Roosevelt Hospitals in Manhattan.&lt;/p&gt;
&lt;p&gt;In normal patients, dopamine plays a major role in motivation and reward, surging before and during a pleasurable activity  --  say, eating or sex  --  to make patients want to repeat a behavior that&apos;s crucial to the survival of the species.&lt;/p&gt;
&lt;p&gt;Dopaminergic pathways connect the limbic system, responsible for emotion, with the hippocampus, etching rewarding behaviors into the brain by creating strong, salient memories.&lt;/p&gt;
&lt;p&gt;The problem arises when the memory and the craving to recapture it takes over a person&apos;s life.&lt;/p&gt;
&lt;p&gt;&quot;Imagine what a strong hold these hijacked reward pathways take on our brains and our whole existence when they&apos;re so closely connected, geographically and anatomically speaking, with our memories and our emotions,&quot; Levounis says.&lt;/p&gt;
&lt;p&gt;As the dopamine surge repeats and repeats, it gains speed, but the brakes begin to fail: Normal function in the brain&apos;s frontal lobes, responsible for inhibitory control and executive functioning (read: willpower), tends to decrease in addicts.&lt;/p&gt;
&lt;p&gt;&quot;Ultimately,&quot; Levounis says, &quot;the war on drugs is a war between the hijacked reward pathways that push the person to want to use, and the frontal lobes, which try to keep the beast at bay. That is the essence of addiction.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Similar Patterns&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;These neural pathways have been well studied in the brains of hardcore addicts. Now, researchers say they see similar pathways involved in other bad behaviors.&lt;/p&gt;
&lt;p&gt;Gene-Jack Wang, MD, of Brookhaven National Laboratory on New York&apos;s Long Island, has conducted several brain imaging studies of obese patients using PET-CT scans.&lt;/p&gt;
&lt;p&gt;The scans have revealed similarities in brain activity  --  or a lack thereof  --  between patients addicted to cocaine or alcohol, and those &quot;addicted&quot; to eating. Normally, the PET scan lights up when a contrast of radioactive glucose is metabolized, revealing an area of red activity in the center of the brain.&lt;/p&gt;
&lt;p&gt;But in both drug-addicted and obese patients, the scans show very little red activity, because there aren&apos;t enough receptors to which the radioactive glucose can bind. Wang says the decreased availability of dopamine receptors is the brain&apos;s way of coping with a constant dopamine overload.&lt;/p&gt;
&lt;p&gt;&quot;If a person constantly has an excess of dopamine, the brain will down-regulate,&quot; Wang says, explaining the principle commonly referred to as tolerance. &quot;Once the system is down-regulated, we have to do more in order to get the same amount of feeling in our normal state.&quot;&lt;/p&gt;
&lt;p&gt;Thus, obese patients &quot;will want to eat more in order to compensate for their down-regulated system.&quot;&lt;/p&gt;
&lt;p&gt;In other experiments, Wang and his colleagues have also found that a higher body mass index (BMI) correlated with lower prefrontal cortex function  --  the area associated with inhibitory control.&lt;/p&gt;
&lt;p&gt;&quot;If they&apos;re obese,&quot; Wang said, &quot;they have a problem controlling their eating behaviors.&quot;&lt;/p&gt;
&lt;p&gt;Those studies also revealed that a higher BMI was linked to a decrease in memory and executive functioning.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Out of Control&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Ed Susman was 293 pounds when he decided to join a clinical trial for an investigational weight-loss drug and chronicle his year-long experience for &lt;em&gt;MedPage Today&lt;/em&gt;. (See &lt;a href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; mce_href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; target=&quot;_blank&quot;&gt;Journalist Participant to Present Insider View of Weight-Loss Trial&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Eating, to him, was a &quot;compulsion&quot;  --  as was biting his nails, a habit he picked up at age 4.&lt;/p&gt;
&lt;p&gt;Over the course of the trial, not only did Susman lose 52 pounds, he also stopped his nail-biting.&lt;/p&gt;
&lt;p&gt;He doesn&apos;t yet know if he was in the drug arm of the trial, but he strongly suspects he wasn&apos;t experiencing a placebo effect.&lt;/p&gt;
&lt;p&gt;&quot;I believe I was on the drug because it controlled a compulsion that I had had for 50 years,&quot; Susman says of the nail-biting. &quot;This stopped it cold.&quot;&lt;/p&gt;
&lt;p&gt;Unfortunately, he says, the same didn&apos;t happen with his eating habits, but he&apos;s gained back only 10 of those 52 pounds in the year since his participation in the trial ended.&lt;/p&gt;
&lt;p&gt;The still-investigational drug is lorcaserin  --  a combination of benzazepine and hydrochloride, two neurological agents. Susman says it is &quot;supposed to improve your willpower, your ability to overcome compulsions.&quot;&lt;/p&gt;
&lt;p&gt;Lorcaserin is a selective 5-HT&lt;sub&gt;2C&lt;/sub&gt; receptor agonist, working through the serotonin system, which regulates appetite, mood, and motor behavior.&lt;/p&gt;
&lt;p&gt;Two other investigational obesity drugs target the dopamine reward system  --  Contrave, which is a combination of bupropion and naltrexone, and Qnexa, which combines phentermine and topiramate.&lt;/p&gt;
&lt;p&gt;&quot;Some medications that have used similar dopamine modulation, until now, have failed,&quot; Wang said. &quot;These two companies are using the command of the modulation of the dopamine system with other neurological systems, such as the opiate or norepinephrine system. According to the trials, they&apos;ve been very effective.&quot;&lt;/p&gt;
&lt;p&gt;Wang called the new medications &quot;a bright light for the treatment of obesity.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Kicking the Habit&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Basically, the idea of medications that act on the dopamine system is &quot;to cool down those reward pathways,&quot; Levounis says. There are two strategies for doing so: an agonist strategy, or an antagonist strategy.&lt;/p&gt;
&lt;p&gt;The agonist strategy is &quot;feeding the beast, providing activity in the cell so that the cravings go down,&quot; Levounis said. Classic examples are nicotine patches, or methadone for opioid dependence.&lt;/p&gt;
&lt;p&gt;On the other hand, the antagonist strategy is to block the receptors. Naltrexone, for example, will block opioid receptors so that the drug addict won&apos;t feel anything if he or she attempts to get high.&lt;/p&gt;
&lt;p&gt;&quot;After a while, you say, &apos;This is not worth my time, my money, my trouble,&apos; so you stop using,&quot; Levounis explains.&lt;/p&gt;
&lt;p&gt;These have been the two main strategies in addiction pharmacotherapy, but there&apos;s now a &quot;third avenue&quot;  --  the partial agonist approach.&lt;/p&gt;
&lt;p&gt;The partial agonist is one molecule that blocks most receptors while still providing just a little bit of an &quot;oomph&quot; to calm cravings. That&apos;s how varenicline (Chantix) helps smokers quit, and how buprenorphine gets junkies off heroin or other opioids.&lt;/p&gt;
&lt;p&gt;But what about inhibitory control? What if medications could ramp up will power?&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s an area of active research,&quot; Levounis says. &quot;There are some medications proposed, but nothing to write home about.&quot;&lt;/p&gt;
&lt;p&gt;He said treatment is typically twofold. For addicts, psychiatrists will try to &quot;cool down&quot; the reward pathways, often with medication. Then, they target the diminished frontal lobes.&lt;/p&gt;
&lt;p&gt;&quot;We try to beef up the frontal lobes as much as we can, and we do that with psychotherapy,&quot; Levounis said.&lt;/p&gt;
&lt;p&gt;Researchers agree that psychotherapy is key to regaining self-control, and it&apos;s the predominant treatment used in patients with addictive behaviors.&lt;/p&gt;
&lt;p&gt;Mark Smaller, PhD, a psychoanalyst in private practice in Chicago, said psychotherapy often reveals an underlying cause for an addiction or compulsive behavior. Usually, it&apos;s anxiety or depression.&lt;/p&gt;
&lt;p&gt;Acknowledging those problems may help change behaviors. Once they&apos;re realized, a patient can start working against them, with the help of the brain&apos;s own neuroplasticity. Essentially, neurons can disconnect and reconnect, or loosen their connections and tighten them, which often manifests in noticeable change.&lt;/p&gt;
&lt;p&gt;&quot;[Psychological] insights can actually begin to change brain chemistry and diffuse compulsions,&quot; he said. &quot;If you address those issues, you can have a positive impact on your life that can change the chemistry of your brain.&quot;&lt;/p&gt;
&lt;p&gt;Smaller said it &quot;creates a new psychological  --  if not neurological  --  structure that can help regulate behavior.&quot;&lt;/p&gt;
&lt;p&gt;Although research on neuroplasticity is relatively young, the concept of &quot;rewiring&quot; the brain is not new.&lt;/p&gt;
&lt;p&gt;In fact, too often, the electrician metaphor has been employed as an excuse for indulging, an explanation for a New Year&apos;s resolution deferred: &quot;I can&apos;t stop eating chocolate, I&apos;m just not wired that way.&quot;&lt;/p&gt;

&lt;hr&gt;
&lt;p&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; alt=&quot;&quot;&gt;&lt;em&gt; is a collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;.&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="-0.001"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265765712168"
                     
      &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="-0.001"
                     href="http://www.medpagetoday.com/HematologyOncology/LungCancer/tb/18105?impressionId=1265765712168"
                     
      &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="20100101_19_174"
                     title="AACR-IASLC: MicroRNA Linked to SCLC Response (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/MeetingCoverage/AACR-IASLC/tb/18008?impressionId=1265765712168"
                     
      &lt;p&gt;CORONADO, Calif.  --  Tiny genetic segments may give a big tip-off to platinum chemoresistance in patients with small cell lung cancer, researchers said.&lt;/p&gt;
&lt;p&gt;Three microRNAs were linked to de novo chemoresistance in a small study led by Glen J. Weiss, MD, of Scottsdale Healthcare and the Translational Genomics Research Institute (TGen), both in Scottsdale, Ariz.&lt;/p&gt;
&lt;p&gt;He presented the results here at the Joint Conference on Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.&lt;/p&gt;
&lt;p&gt;Further validation would be needed before denying any patient chemotherapy based on the findings, cautioned Tyler Jacks, PhD, of the Massachusetts Institute of Technology and president of the AACR.&lt;/p&gt;
&lt;p&gt;However, &quot;biomarkers of this sort will be useful in diagnosing patients and applying relevant therapies  --  in this instance perhaps applying novel therapies, given the belief that the conventional therapies will be of no value to these individuals,&quot; he said as discussant on the study at a press conference.&lt;/p&gt;
&lt;p&gt;Weiss agreed.&lt;/p&gt;
&lt;p&gt;&quot;This is early stage,&quot; he said in an interview. &quot;But hopefully down the road it will have implications for treating patients with small cell [lung cancer].&quot;&lt;/p&gt;
&lt;p&gt;Non-small cell lung cancer has been a success story for personalized treatment.&lt;/p&gt;
&lt;p&gt;It was revolutionized by discovery of epidermal growth factor receptor (EGFR) mutations as both a prognostic factor and treatment target for the EGFR tyrosine kinase inhibitors.&lt;/p&gt;
&lt;p&gt;But for small cell lung cancer, the standard treatment is platinum-based chemotherapy with only two real options in first-line treatment, the researchers said.&lt;/p&gt;
&lt;p&gt;Worse, 15% to 30% of small cell tumors are intrinsically resistant to platinum chemotherapy and never respond.&lt;/p&gt;
&lt;p&gt;&quot;[Small cell] lung cancer patients haven&apos;t had a real advance in 15 years or more for chemotherapy,&quot; Weiss told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;What we&apos;re trying to do is identify the group that doesn&apos;t respond to standard therapy so that we can identify new treatments for them up front instead of treating everyone the same.&quot;&lt;/p&gt;
&lt;p&gt;Among the genetic possibilities for these efforts, microRNA  --  RNA molecules of around 20 nucleotides in length  --  are a good option, Weiss explained.&lt;/p&gt;
&lt;p&gt;They regulate gene expression like messenger RNA but are smaller and more stable across a variety of fluid and tissue types, he said.&lt;/p&gt;
&lt;p&gt;In the study, the researchers analyzed diagnostic tumor samples from 34 patients with small cell lung cancer.&lt;/p&gt;
&lt;p&gt;Among them, 19% had de novo chemoresistance marked by progressive disease. Most had had a partial or complete response to chemotherapy (61.9% and 9.5%, respectively).&lt;/p&gt;
&lt;p&gt;After extraction of total RNA, microRNA profiling revealed 16 top candidates for association with progressive disease.&lt;/p&gt;
&lt;p&gt;The 28 samples with sufficient RNA for further testing showed three microRNAs linked to chemoresistance that were validated by quantitative real-time PCR: &lt;ul&gt; &lt;li&gt;miR-92a-2* with a &lt;em&gt;P&lt;/em&gt;-value of 0.010&lt;/li&gt; &lt;li&gt;miR-147 with a &lt;em&gt;P&lt;/em&gt;-value of 0.018&lt;/li&gt; &lt;li&gt;miR-574-5p with a &lt;em&gt;P&lt;/em&gt;-value of 0.039&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Many of the patients had comorbidities at baseline, including 47.1% with hypertension and 32% with emphysema or chronic obstructive pulmonary disease. But these did not predict chemotherapy response.&lt;/p&gt;
&lt;p&gt;The next step is to validate the biomarkers in an independent cohort of small cell lung cancer patients, the researchers concluded.&lt;/p&gt;
&lt;p&gt;Then studies will need to determine what does work in these chemoresistant patients, Weiss said.&lt;/p&gt;
&lt;p&gt;&quot;We&apos;ve learned that if we&apos;re going to make the next hurdle and if we&apos;re going to better treat this disease, we need more personalized care,&quot; agreed Roy Herbst, MD, PhD, of M.D. Anderson Cancer Center in Houston.&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 the American Cancer Society-Sylvia Chase Pilot Grant, IBIS Foundation of Arizona, and the TGen Foundation.&lt;/p&gt;&lt;p&gt;Weiss reported recieving lab support from TGen Foundation and Scottsdale Healthcare Foundation as well as being party to provisional patents related to microRNAs in lung cancer.&lt;/p&gt;&lt;p&gt;Jacks provided no information on conflicts of interest.&lt;/p&gt;&lt;p&gt;Herbst has reported financial relationships with Genentech, Lilly, Amgen, and AstraZeneca. &lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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