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    <recommendedItem id="20100101_19_452"
                     title="Study Backs Late Cardiotoxicity of Childhood Cancer Treatment (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HematologyOncology/OtherCancers/tb/18384?impressionId=1265805429583"
                     
      A childhood cancer survivor&apos;s risk of dying from cardiovascular causes rises with the dose of radiation his heart received during treatment, researchers in France and the U.K. affirmed.&lt;br&gt;
&lt;br&gt;Those whose hearts were exposed had a 60% higher risk of cardiovascular death than the general population, even at a dose of 1 Gy (95% CI 20% to 250%), according to Florent de Vathaire, PhD, of L&apos;Institut National de la Sant&amp;#233; et de la Recherche M&amp;#233;dicale in Paris, and colleagues.&lt;br&gt;
&lt;br&gt;The risk jumped to 12.5-fold for a cumulative radiation dose to the heart of 5 to 14.9 Gy, and to 14.9-fold for a dose of more than 15 Gy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 for trend), the researchers reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The notion that exposing the heart to radiation increases the risk of cardiovascular disease and death is not surprising, according to an accompanying editorial.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;However, this study examined cardiovascular mortality effects of both the dose of radiation and the dose of anthracyclines given to childhood cancer victims in the same cohort.&lt;/p&gt;
&lt;p&gt;That&apos;s something previous studies haven&apos;t done, according to editorialists Steven E. Lipshultz, MD, of the University of Miami and Holtz Children&apos;s Hospital in Miami, and M. Jacob Adams, MD, MPH, of the University of Rochester, N.Y.&lt;/p&gt;
&lt;p&gt;&quot;These are pretty profound findings,&quot; Lipshultz told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;These are the exact concerns we&apos;ve had based on careful subclinical assessments of how the heart in these survivors has been working.&quot;&lt;/p&gt;
&lt;p&gt;His group was one of the first to report that survivors of childhood cancer faced not only acute cardiotoxicity from treatment, but also late cardiac effects.&lt;/p&gt;
&lt;p&gt;As more effective treatment for childhood cancers came into play, the dramatic jump in survival rates  --  from less than 50% in the mid-1970s to 80% today  --  yielded a large enough population of survivors to make chronic issues from treatment apparent, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;&quot;It appears that for some of these survivors we have substituted one fatal disease of childhood  --  cancer  --  for another fatal disease of early adult life,&quot; he said.&lt;/p&gt;
&lt;p&gt;de Vathaire&apos;s group studied a cohort of 4,122 French and British children diagnosed with childhood solid cancer between 1942 and 1986 and who survived at least five years.&lt;/p&gt;
&lt;p&gt;Over an average of 27 years of follow-up, they were at 8.3-fold higher risk of dying from any cause compared with the general populations in France and the U.K. (95% CI 7.6 to 9.0).&lt;/p&gt;
&lt;p&gt;The majority of these excess deaths occurred early after diagnosis, five to nine years afterward in this analysis  --  in which all patients survived to five years.&lt;/p&gt;
&lt;p&gt;Based on just 32 deaths from cardiovascular diseases in the cohort, the childhood cancer survivors experienced five times the cardiovascular mortality (95% CI 3.3 to 6.7) expected from the general population (1.7% cumulative at 35 years versus 0.3%).&lt;/p&gt;
&lt;p&gt;This elevation in risk was similar to that seen in large studies from the U.S. and Nordic countries, suggesting generalizability of the results, Lipshultz said.&lt;/p&gt;
&lt;p&gt;Radiation therapy also conferred a 5.0-fold elevation in risk of cardiovascular disease-related death (95% CI 1.2 to 21.4).&lt;/p&gt;
&lt;p&gt;Like radiation, a higher cumulative dose of anthracycline chemotherapy also increased risk of dying from cardiac diseases, compared with the general population (RR 4.4 for a dose over 360 mg/m&lt;sup&gt;2&lt;/sup&gt;, 95% CI 1.3 to 15.3).&lt;/p&gt;
&lt;p&gt;However, radiotherapy and chemotherapy did not appear to interact for cardiovascular mortality (&lt;em&gt;P&lt;/em&gt;=0.4).&lt;/p&gt;
&lt;p&gt;Notably, the vinca alkaloids were also significantly linked to cardiovascular disease-related death risk among childhood cancer survivors, even after adjustment for sex, treatment period, age at diagnosis, follow-up, and all other treatment modalities (RR 3.6, 95% CI 1.0 to 12.9).&lt;/p&gt;
&lt;p&gt;Currently, guidelines support regular long-term cardiovascular screening for childhood cancer survivors who received anthracycline-based chemotherapy but provide little to no direction for those treated with nonanthracycline chemotherapy or radiation, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;These results suggested all three groups should be getting cardiac follow-up, he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;However, because other research has suggested that these individual treatments affect the heart in different ways, such as diastolic rather than systolic dysfunction with radiotherapy, screening modalities may need to account for this as well, he said.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that cardiovascular disease was probably under-reported as a cause of death in the cohort.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, 15 of the deaths classified as results of cancer as the principal cause had cardiovascular diseases as the immediate cause,&quot; they wrote.&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 Ligue Nationale Contre le Cancer; the Programme Hospitalier de Recherche Clinique; the Agence Fran&amp;#231;aise de S&amp;#233;curit&amp;#233; Sanitaire et Produit de Sant&amp;#233;; Electricit&amp;#233; de France; the Wyeth Foundation for childhood and adolescent health; and a grant from the Foundation of France.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;The editorialists 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_214"
                     title="Analysis Affirms Cervical Cancer Standard (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Oncology/OtherCancers/tb/18060?impressionId=1265805429583"
                     
      &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="-0.006"
                     href="http://www.medpagetoday.com/Oncology/OtherCancers/tb/18039?impressionId=1265805429583"
                     
      &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>
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                     title="Partial Nephrectomy Called Underused for Small Kidney Tumors"
                     score="-0.006"
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