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    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265750068129"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors concluded.&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 authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_214"
                     title="Analysis Affirms Cervical Cancer Standard (CME/CE)"
                     score="-0.002"
                     href="http://www.medpagetoday.com/Oncology/OtherCancers/tb/18060?impressionId=1265750068129"
                     
      &lt;p&gt;Chemoradiotherapy for unresected cervical cancer significantly improves survival, regardless of the type of chemotherapy used, a systematic review of individual patient data suggests.&lt;/p&gt;
&lt;p&gt;As compared with radiotherapy alone, chemotherapy given with the radiation improved five-year survival by almost 20%, and patients benefited whether they received platinum- or nonplatinum-based chemotherapy, British investigators reported in the first 2010 issue of the &lt;em&gt;Cochrane Database of Systematic Reviews.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;A course of chemotherapy after completion of chemoradiotherapy resulted in a trend toward further improvement in survival, a finding that requires validation, Claire L. Vale, PhD, of the Medical Research Council Clinical Trials Unit in London, and colleagues reported.&lt;/p&gt;
&lt;p&gt;&quot;This meta-analysis provides an unconfounded estimate of the effect of chemoradiotherapy compared with radiotherapy,&quot; the authors wrote. &quot;Adding chemotherapy to radiotherapy offers a modest, but significant additional benefit on all outcomes and for all stages of disease. There is also the potential to use both platinum and nonplatinum regimens.&quot;&lt;/p&gt;
&lt;p&gt;Since 1999, chemoradiotherapy has been standard of care for women with cervical cancer. The standard was widely adopted after favorable reports from five clinical trials, followed by a &lt;a href=&quot;http://www.nih.gov/news/pr/feb99/nci-22.htm&quot; mce_href=&quot;http://www.nih.gov/news/pr/feb99/nci-22.htm&quot; target=&quot;_blank&quot;&gt;clinical alert from the National Cancer Institute&lt;/a&gt;, recommending that &quot;concomitant chemotherapy should be considered instead of radiotherapy alone in women with cervical cancer.&quot;&lt;/p&gt;
&lt;p&gt;However, interpretation of the benefits was complicated by differences in control-arm therapies, heterogeneity in trial results, and inconsistency in outcome definitions.&lt;/p&gt;
&lt;p&gt;&quot;[We] concluded that an individual patient data meta-analysis would be required to obtain time-to-event analyses of local and distant recurrence, more reliable estimates of effect in patient subgroups, and a better attribution of relative toxicities,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Use of individual patient data allowed more precise evaluation of differences in treatment effects by trial or patient characteristics, they continued. Moreover, they sought updated follow-up for each patient in each trial, which permitted assessment of outcomes over the long term.&lt;/p&gt;
&lt;p&gt;The review was limited to randomized comparisons of concomitant chemoradiotherapy versus radiotherapy alone for patients with locally advanced, previously untreated cervical cancer. The investigators reviewed published and unpublished studies. The primary outcome was overall survival from the time of randomization.&lt;/p&gt;
&lt;p&gt;The primary analysis comprised 15 clinical trials, 3,452 patients, and 1,138 deaths. Eleven trials used platinum-based chemotherapy, three used nonplatinum regimens (5FU, mitomycin, or the combination), and one trial randomized patients to chemoradiotherapy with either 5FU or cisplatin.&lt;/p&gt;
&lt;p&gt;In 13 trials that compared chemoradiotherapy with the same radiotherapy regimen, the addition of chemotherapy led to an absolute improvement in five-year survival of 6% (66% versus 60%), which translated into a 19% reduction in the hazard ratio (HR 0.81, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;The two remaining trials compared chemoradiotherapy followed by more chemotherapy versus radiotherapy alone. Those two trials demonstrated a 54% reduction in the mortality hazard (HR 0.46, 95% CI 0.32 to 0.66, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and an absolute survival benefit of 19% at five years (79% versus 60%).&lt;/p&gt;
&lt;p&gt;Patients treated with platinum-based chemotherapy had a 17% reduction in the mortality hazard (&lt;em&gt;P&lt;/em&gt;=0.017), and nonplatinum chemotherapy resulted in a 23% reduction in the hazard (&lt;em&gt;P&lt;/em&gt;=0.009).&lt;/p&gt;
&lt;p&gt;Chemoradiotherapy also reduced the incidence of local and distant recurrence and progression and improved disease-free survival.&lt;/p&gt;
&lt;p&gt;A trend toward improved survival by tumor stage was observed, but the results were not uniform across patient subgroups.&lt;/p&gt;
&lt;p&gt;The dose of radiotherapy or chemotherapy did not affect the magnitude of the benefit.&lt;/p&gt;
&lt;p&gt;Hematologic and gastrointestinal toxicity occurred more often with chemoradiotherapy, but data were insufficient to permit analysis of long-term toxicity.&lt;/p&gt;
&lt;p&gt;&quot;These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of nonplatinum based chemoradiotherapy,&quot; the authors wrote in conclusion.&lt;/p&gt;
&lt;p&gt;&quot;Furthermore,&quot; they wrote, &quot;although these results suggest an additional benefit from adjuvant chemotherapy this requires testing in randomized clinical trials.&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 authors had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_196"
                     title="Adjuvant Therapy Improves Survival in Pancreatic Cancer (CME/CE)"
                     score="-0.003"
                     href="http://www.medpagetoday.com/Oncology/OtherCancers/tb/18039?impressionId=1265750068129"
                     
      &lt;p&gt;Adjuvant chemoradiotherapy significantly improves survival of patients with resectable pancreatic cancer, according to medical records of almost 3,000 patients.&lt;/p&gt;
&lt;p&gt;Chemoradiotherapy extended median survival by more than 30% compared with surgical resection only, researchers reported in the January &lt;em&gt;Archives of Surgery&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&lt;em&gt; &lt;/em&gt;In a multivariate analysis, adjuvant chemoradiotherapy proved to be one of only three predictors of improved survival, the other two being treatment at high-volume and academic centers.&lt;/p&gt;
&lt;p&gt;&quot;This analysis provides strong evidence in a real-world setting that postoperative chemoradiotherapy and possibly adjuvant radiotherapy alone improve clinical outcome in patients with pancreatic cancer,&quot; Relin Yang, MD, of the University of Miami, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;We further substantiate that this benefit is independent of the improved clinical outcomes obtained at high-volume centers and teaching facilities,&quot; they added.&lt;/p&gt;
&lt;p&gt;&quot;Nonetheless, this benefit remains modest, underscoring that further investigation is needed to establish a better adjuvant regimen after complete resection of pancreatic cancer.&quot;&lt;/p&gt;
&lt;p&gt;Complete surgical resection remains the only curative option for patients with early-stage pancreatic adenocarcinoma. Fewer than 25% of patients have cancer amenable to resection. For that small subset of patients, the role of adjuvant therapy remains controversial, the authors wrote.&lt;/p&gt;
&lt;p&gt;To address the issue, Yang and colleagues analyzed data from a population-based cancer registry. They augmented the data&apos;s predictive potential with information related to patient demographics, comorbidities, treatment, and type of facility.&lt;/p&gt;
&lt;p&gt;The authors identified 2,877 patients whose pancreatic adenocarcinoma was diagnosed and treated surgically with curative intent from 1998 to 2002. About 60% of the patients were older than 65. Some 90% were white (86.7% non-Hispanic), and 90% had no history of alcohol abuse.&lt;/p&gt;
&lt;p&gt;The authors reported that 51.9% of patients received neither chemotherapy nor chemoradiotherapy. About 25% received chemoradiotherapy, and another 10% received chemotherapy alone. Most patients were treated at low-volume centers (57.6%) and nonteaching facilities (72.8%).&lt;/p&gt;
&lt;p&gt;Median overall survival was 15 months, and 90-day postsurgical survival was 88.8%. Patients younger than 40 had the best survival (25.7 months versus 13.4 months for patients older than 65, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Race, ethnicity, and abstention from alcohol and tobacco did not significantly influence survival. Survival decreased as a patient&apos;s poverty level increased. Localized disease, well-differentiated tumors, and smaller tumor size were associated with significantly better survival (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Patients treated with surgery only had a significantly lower (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) median overall survival of 12.6 months compared with patients who received chemotherapy or radiation preoperatively (19.9 months) or postoperatively (17.0 months).&lt;/p&gt;
&lt;p&gt;Median survival was 18.2 months among patients treated at high-volume centers versus 13.1 months at low-volume centers (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001). Treatment at a teaching facility was associated with a median survival of 19.8 months compared with 13.6 months for nonteaching facilities (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Multivariate analysis correcting for comorbidities showed that postoperative chemoradiotherapy significantly reduced the mortality hazard ratio (HR 0.69, &lt;em&gt;P&lt;/em&gt;=0.04). The reduced hazard exceeded the benefit associated with treatment at a high-volume center (HR 0.85, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) or at a teaching facility (HR 0.84, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and was independent of facility type.&lt;/p&gt;
&lt;p&gt;The authors confirmed findings from other studies showing a beneficial effect of treatment in high-volume and teaching facilities, and a benefit for all patients who receive adjuvant chemoradiotherapy, Nita Ahuja, MD, of Johns Hopkins, wrote in a commentary.&lt;/p&gt;
&lt;p&gt;However, the study had several prominent weaknesses: missing information on cancer stage in more than 50% of patients, unknown margin status, and no information on the type or duration of adjuvant therapy.&lt;/p&gt;
&lt;p&gt;The study also did not address another major controversy involving adjuvant therapy for pancreatic cancer.&lt;/p&gt;
&lt;p&gt;&quot;At the end of the day, the present study will do little to quell the debate over the relative benefits of adjuvant chemoradiotherapy compared with chemotherapy alone after surgical resection of pancreatic cancer,&quot; Ahuja wrote.&lt;/p&gt;
&lt;p&gt;North Americans have a bias toward adjuvant chemoradiotherapy, supported primarily by data from a single small randomized clinical trial and several retrospective studies, Ahuja continued. European clinicians favor adjuvant chemotherapy based on one large clinical trial showing a benefit for chemotherapy and another showing no survival advantage for chemoradiotherapy.&lt;/p&gt;
&lt;p&gt;&quot;The present study will do little to change the minds of either camp,&quot; Ahuja concluded.&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;Neither Yang and co-authors nor Ahuja had any disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_2_214"
                     title="Vitamin D Benefits from Sun Exposure Outshine Cancer Risk"
                     score="-0.005"
                     href="