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    <recommendedItem id="20100101_19_452"
                     title="Study Backs Late Cardiotoxicity of Childhood Cancer Treatment (CME/CE)"
                     score="0.015"
                     href="http://www.medpagetoday.com/HematologyOncology/OtherCancers/tb/18384?impressionId=1265773408135"
                     
      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_202"
                     title="Survival Rates Vary with Congenital Anomalies (CME/CE)"
                     score="-0.002"
                     href="http://www.medpagetoday.com/Pediatrics/GeneralPediatrics/tb/18035?impressionId=1265773408135"
                     
      &lt;p&gt;Survival among children with congenital anomalies has increased in recent decades, but still varies notably depending on the condition, a British study found.&lt;/p&gt;
&lt;p&gt;Overall 20-year survival was 85.5% (95% CI 84.8 to 86.3) among children born with at least one congenital anomaly, Peter W.G. Tennant, MsC, of Newcastle University, and colleagues reported online in &lt;em&gt;Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;For specific conditions, the 20-year survival rates were as follows: &lt;ul&gt; &lt;li&gt;Orofacial clefts, 97.6% (95% CI 95.9 to 98.6)&lt;/li&gt; &lt;li&gt;Urinary system, 93.2% (95% CI 91.6 to 94.5)&lt;/li&gt; &lt;li&gt;Cardiovascular system, 89.5% (95% CI 88.4 to 90.6)&lt;/li&gt; &lt;li&gt;Digestive system, 83.2% (95% CI 79.8 to 86)&lt;/li&gt; &lt;li&gt;Chromosomal anomalies, 79.1% (95% CI 76.6 to 81.3)&lt;/li&gt; &lt;li&gt;Nervous system, 66.2% (95% CI 61.5 to 70.5)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Congenital anomalies are recognized as a major cause of perinatal and infant mortality, but little is known about longer-term survival with conditions other than Down syndrome or spina bifida.&lt;/p&gt;
&lt;p&gt;So Tennant and colleagues analyzed data from the Northern Congenital Abnormality Survey, which is a population-based register for the north of England.&lt;/p&gt;
&lt;p&gt;Their study included 13,758 cases of congenital anomaly reported to the registry between January 1985 and December 2003, representing a prevalence of 20.8 per 1,000 births.&lt;/p&gt;
&lt;p&gt;Among these, 0.9% were late miscarriages, 16.3% were terminations after prenatal diagnosis, 3.1% were stillbirths, and 79.7% were live births.&lt;/p&gt;
&lt;p&gt;Of the 10,850 liveborn cases for whom survival status was known, 1,465 (13.5%) died during the course of the study.&lt;/p&gt;
&lt;p&gt;Year of birth was a highly significant predictor of survival, (HR 0.92, 95% CI 0.92 to 0.93, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), which likely relates to important medical and surgical advances such as surfactant therapy and corticosteroid use for respiratory distress syndrome, as well as intrapartum treatment for chorioamnionitis.&lt;/p&gt;
&lt;p&gt;The rate of termination for fetal anomaly increased over time, rising from 12.4% (95% CI 9.8 to 15.5) in 1985 to 18.3% (95% CI 15.6 to 21.2) in 2003.&lt;/p&gt;
&lt;p&gt;The investigators further analyzed survival among specific subtypes of anomalies and found rates of 20-year survival exceeding 95% for the following: &lt;ul&gt; &lt;li&gt;Ventricular septal defects, 98.3% (95% CI 96.6 to 99.1)&lt;/li&gt; &lt;li&gt;Pulmonary valve stenosis, 98.1% (95% CI 96.1 to 99.1)&lt;/li&gt; &lt;li&gt;Cleft lip and palate, 97.7% (95% CI 94.6 to 99.1)&lt;/li&gt; &lt;li&gt;Atrial septal defects, 96.3% (95% CI 93.3 to 98)&lt;/li&gt; &lt;li&gt;Cleft palate, 96.3% (95% CI 92.8 to 98.1)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;In contrast, subtypes with less than 50% one-year survival included arhinencephaly/holoprosencephaly, common arterial trunk, and hypoplastic left heart.&lt;/p&gt;
&lt;p&gt;Previous studies have found ten-year survival rates ranging from 76.5% to 88.6% for Down syndrome, 80.9% for all phenotypes of spina bifida, and 64% for spina bifida with hydrocephalus.&lt;/p&gt;
&lt;p&gt;In this study, the ten-year survival for Down syndrome was 83.9%, which probably reflects differences in care over time and by location, as well as surgical management and changing rates of terminations.&lt;/p&gt;
&lt;p&gt;The ten-year survival for spina bifida without hydrocephalus was 86.7% but fell to 53.3% with hydrocephalus, and 20-year survival remained 36.7% lower in those having hydrocephalus (95% CI 24 to 40, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;Previous estimates of survival among children with cardiovascular anomalies ranged from 74.7% to 76.9% at five years, which are substantially lower than the 91.1% reported in the present study.&lt;/p&gt;
&lt;p&gt;As with Down syndrome, this may represent advances in care, but also may reflect the fact that the investigators stratified cases according to the presence of multiple anomalies.&lt;/p&gt;
&lt;p&gt;&quot;This effect is inconsequential for primary anomalies with a high mortality rate, such as hypoplastic left heart syndrome, since the effect of the primary anomaly is likely to overwhelm the effect of any additional anomalies. However, as the severity of the primary anomaly decreases, the confounding effect of any additional anomalies is likely to increase,&quot; they explained.&lt;/p&gt;
&lt;p&gt;For example, the 20-year survival of 98.3% for ventricular septal defect would have fallen to 91.7% if multiple anomalies had not been classified separately.&lt;/p&gt;
&lt;p&gt;The biggest limitation of the study was that only 10% of patients were born twenty years before the matching date of the study (Jan. 28, 2008) so that 20-year survival rates were only estimates for most of the anomaly subtypes.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, David H. Stone, MD, of the University of Glasgow, called for more research and funding for congenital anomalies.&lt;/p&gt;
&lt;p&gt;&quot;Birth-defect registries have had a chequered history since their initial proliferation after the thalidomide disaster,&quot; he wrote.&lt;/p&gt;
&lt;p&gt;They are a crucial source of data, but face an endless struggle for funding, with the result that good quality data on etiology, prevalence, and outcomes are sparse.&lt;/p&gt;
&lt;p&gt;&quot;The publication of today&apos;s findings from the north of England should provide a much-needed boost to the cause of congenital anomaly surveillance,&quot; Stone 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;Funding for the study was provided by BDF Newlife.&lt;/p&gt;&lt;p&gt;All investigators and the editorialist declared no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
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                     title="Mutations Predict Poor Outcome in Neuroblastoma"
                     score="-0.005"
                     href="