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    <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=1265762680380"
                     
      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_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=1265762680380"
                     
      &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=1265762680380"
                     
      &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_19_3592"
                     title="ASTRO: Stereotactic Radiation Halts Spread of Lung CA (CME/CE)"
                     score="-0.006"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASTRO/tb/16865?impressionId=1265762680380"
                     
      &lt;p&gt;CHICAGO  --  Stereotactic body radiation contained early-stage, medically inoperable lung cancer at its site of origin in all but one patient involved in a small clinical trial reported here.&lt;/p&gt;
&lt;p&gt;One of 55 patients had local failure at three years, resulting in a local control rate of 98%, Robert D. Timmerman, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues found.&lt;/p&gt;
&lt;p&gt;Half the patients were alive and cancer free at three years, and overall survival at three years was 56%.&lt;/p&gt;
&lt;p&gt;The findings offer a dramatic contrast to the 30% to 50% successful local control with conventional radiation therapy for lung cancer.&lt;/p&gt;
&lt;p&gt;&quot;This is the first significant change in [the outcome of] these patients in 50 years,&quot; Timmerman said at a press briefing during the American Society of Radiation Oncology meeting.&lt;/p&gt;
&lt;p&gt;&quot;The results of the study confirm that stereotactic body radiation therapy should now be considered standard treatment in early-stage lung cancer patients with coexisting serious medical problems, such as emphysema, heart disease, and stroke,&quot; he added. &quot;It also begs the question of whether stereotactic body radiation therapy should be considered in healthier patients with lung cancer who are treated with surgery.&quot;&lt;/p&gt;
&lt;p&gt;Results of the small Phase II trial preclude the need for Phase III evaluation of stereotactic body radiation in early-stage, inoperable lung cancer, said Stephen Hahn, MD, of the University of Pennsylvania in Philadelphia, moderator of the press briefing.&lt;/p&gt;
&lt;p&gt;&quot;We don&apos;t need to do a Phase III trial, because it would be an ethical dilemma to treat these patients with conventional radiation and not offer them stereotactic radiation,&quot; said Hahn.&lt;/p&gt;
&lt;p&gt;Offering a more tempered reaction, Anthony Zietman, MD, of Harvard and Massachusetts General Hospital, said stereotactic radiation will not supplant conventional radiation therapy for most lung cancers. Stereotactic radiation therapy is best suited for small, peripherally located tumors, he said.&lt;/p&gt;
&lt;p&gt;Stereotactic radiation therapy also will not replace surgery for operable lung cancer, said Timmerman.&lt;/p&gt;
&lt;p&gt;The findings came from a Radiation Therapy Oncology Group trial that enrolled patients from May 2004 to October 2006. Eligible patients had T1 or T2 lung cancer (primary tumor mass &amp;lt; 3 cm more than 2 cm from the central bronchial tree)&lt;strong&gt; &lt;/strong&gt;and medical conditions that disqualified them from surgery. The median age of the patients was 72, and median follow-up was 48 months.&lt;/p&gt;
&lt;p&gt;Radiation therapy consisted of three 20-Gy fractions delivered over the course of one week. Correction for tissue heterogeneity revealed an actual total dose of about 54 Gy.&lt;/p&gt;
&lt;p&gt;Investigators defined local failure as an increase in lesion size of at least 20% on CT and either a confirmatory biopsy or PET imaging that revealed tracer uptake similar to pretreatment levels.&lt;/p&gt;
&lt;p&gt;Analysis of contouring showed that 98% of target lesions and 73% of normal tissue structures were outlined per protocol or with only minor deviations.&lt;/p&gt;
&lt;p&gt;Grade 3-4 adverse events occurred in nine (17%) patients, the most common being pulmonary/upper respiratory and musculoskeletal. No treatment-related deaths occurred.&lt;/p&gt;
&lt;p&gt;Three-year disease-free survival was 48%, and overall survival was 56%. Timmerman said 18% of patients died of metastatic lung cancer.&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;Timmerman disclosed relationships with Elekta Oncology, Varian Medical Systems, and D3 Corporation.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_145"
                     title="Palliative Radiation for Lung Cancer May Do More Than Palliate"
                     score="-0.006"
                     href="