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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_307"
                     title="Good Results in Poor-Risk Rectal Cancer (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/HematologyOncology/ColonCancer/tb/18169?impressionId=1265749513673"
                     
      &lt;p&gt;Patients with high-risk rectal cancer had high response and three-year survival rates on a regimen of preoperative chemotherapy, followed by standard chemoradiation and then surgical resection, according to results of a multicenter study.&lt;/p&gt;
&lt;p&gt;Three-fourths of patients had objective responses to neoadjuvant chemotherapy, increasing to 89% after chemoradiation, researchers reported online in &lt;em&gt;The Lancet Oncology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Additionally, 97% of patients who underwent surgery had microscopically clear surgical margins. At three years, 83% of patients remained alive, including almost 70% who were progression free.&lt;/p&gt;
&lt;p&gt;&quot;Intensification of systemic therapy with neoadjuvant combination chemotherapy before standard treatment is feasible in poor-risk, potentially operable rectal cancer, with acceptable safety and promising long-term outcomes,&quot; David Cunningham, MD, of the Royal Marsden Hospital in Sutton, England, and co-authors concluded.&lt;/p&gt;
&lt;p&gt;&quot;Future development of this multidisciplinary treatment strategy in randomized trials is warranted.&quot;&lt;/p&gt;
&lt;p&gt;Although surgery remains the primary and potentially curative therapy for localized rectal cancer, local recurrence rates as high as 40% have been reported with conventional resection.&lt;/p&gt;
&lt;p&gt;The introduction of standardized surgery and total mesorectal excision reduced local recurrence rates to less than 10%, which has been associated with improved survival, the authors noted.&lt;/p&gt;
&lt;p&gt;Preoperative radiotherapy and then chemoradiation further reduced the risk of local recurrence, but did not improve overall survival compared with surgery alone.&lt;/p&gt;
&lt;p&gt;Combination chemotherapy has led to higher response rates and progression-free survival compared with monotherapy for patients with advanced rectal cancer, the authors continued. Adjuvant chemotherapy containing oxaliplatin (Eloxatin) also has improved outcomes in resected colon cancer.&lt;/p&gt;
&lt;p&gt;Given that oxaliplatin-fluoropyrimidine combinations have become a preferred standard, investigators designed a clinical trial of high-risk rectal cancer to investigate preoperative treatment with oxaliplatin and capecitabine (Xeloda).&lt;/p&gt;
&lt;p&gt;A previous report involving the first 77 patients enrolled in the trial showed substantial tumor regression, rapid improvement in symptoms, and a high rate of clear surgical margins (&lt;em&gt;J Clin Oncol&lt;/em&gt; 2006; 24: 668-74).&lt;/p&gt;
&lt;p&gt;Nine treatment-related cardiac events occurred in eight of the 77 patients, prompting a protocol amendment to exclude patients with a recent history of clinically significant cardiac problems.&lt;/p&gt;
&lt;p&gt;The updated results comprised 105 patients, and only one cardiac event occurred after the change in eligibility criteria, the authors wrote.&lt;/p&gt;
&lt;p&gt;All of the patients had MRI-defined, poor-risk but nonmetastatic rectal cancer. Patients received four cycles of neoadjuvant chemotherapy over 12 weeks, followed by chemoradiotherapy consisting of a total radiation dose of 54 Gy administered over six weeks, plus daily capecitabine.&lt;/p&gt;
&lt;p&gt;After total mesorectal excision, patients received 12 weeks of adjuvant capecitabine.&lt;/p&gt;
&lt;p&gt;The primary endpoint was pathologic complete response, and median follow-up was 55 months.&lt;/p&gt;
&lt;p&gt;Radiologically confirmed response rates were 74% after neoadjuvant chemotherapy and 89% after chemoradiation. Of 97 patients who had surgery, 93 had microscopically clear margins, and 21 of 105 patients had pathologic complete responses.&lt;/p&gt;
&lt;p&gt;Three-year progression-free and overall survival were 68% and 83%, respectively. Among patients who had surgery, three-year, relapse-free survival was 74%.&lt;/p&gt;
&lt;p&gt;&quot;Our findings show the feasibility of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision, which accord with the initial results of this study,&quot; the authors declared.&lt;/p&gt;
&lt;p&gt;&quot;High radiological response rates to preoperative treatment were recorded, and the number of pathological complete responses surpassed the prespecified number needed to meet the primary objective of this trial.&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 England&apos;s National Health Service and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Cunningham and co-author Niall Tebbutt disclosed relationships with Roche and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Co-author Ian Chau disclosed relationships with Roche and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Co-author Yu Jo Chua disclosed relationships with Roche and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Co-author Gina Brown disclosed a relationship with sanofi-aventis.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_259"
                     title="ASCO GI: Gene Therapy Shows Promise in Esophageal Cancer (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18122?impressionId=1265749513673"
                     
      &lt;p&gt;ORLANDO  --  Injecting the gene encoding for tumor necrosis factor-alpha (TNF-alpha) directly into tumors led to pathologic complete responses in a third of patients and a median survival of four years in a small study of patients with locally advanced esophageal cancer.&lt;/p&gt;
&lt;p&gt;The gene-therapy strategy led to nodal conversion and downstaging in a majority of patients, most of whom underwent surgical resection following chemoradiation and the intratumoral injections of TNF.&lt;/p&gt;
&lt;p&gt;Patients who received the three lowest doses of TNF in the dose-finding study had a five-year median survival of 56%.&lt;/p&gt;
&lt;p&gt;&quot;This represents an encouraging increase in survival relative to historical controls,&quot; Kenneth J. Chang, MD, of the University of California Irvine, reported here at the Gastrointestinal Cancers Symposium. &quot;These results warrant further evaluation.&quot;&lt;/p&gt;
&lt;p&gt;However, another investigator in the multicenter study cautioned that the trial was stopped because of treatment-related deaths that have not been fully explained, and that the regimen is complicated and time-consuming.&lt;/p&gt;
&lt;p&gt;The primary objective of the study was to assess the safety, feasibility, and tolerability of weekly intratumoral injections of TNFerade, a second-generation replication-deficient adenovector, carrying the transgene encoding human TNF-alpha, regulated by the radiation-inducible promotor Egr-1.&lt;/p&gt;
&lt;p&gt;Upon its release inside a tumor, the gene therapy stimulates TNF production to help destroy the tumor. The therapy was developed for use with radiation and conventional chemotherapy.&lt;/p&gt;
&lt;p&gt;The gene therapy has received FDA fast-track status for evaluation as treatment for pancreatic cancer.&lt;/p&gt;
&lt;p&gt;Chang reported results from a dose-finding study involving 24 patients with locally advanced esophageal cancer. All were surgical candidates before enrollment. Each patient received five weekly injections of TNF concurrent with 5-FU, cisplatin, and external-beam radiation therapy. The TNF doses evaluated ranged from 4 x 10&lt;sup&gt;8&lt;/sup&gt; to 4 x 10&lt;sup&gt;11&lt;/sup&gt; PU.&lt;/p&gt;
&lt;p&gt;Staging results showed that all but one of the patients had T3 disease, and 18 had nodal involvement (N1).&lt;/p&gt;
&lt;p&gt;The preoperative therapy was administered over 5.5 weeks. Following a recovery period of five to 11 weeks, patients were to undergo surgical resection, which ultimately was performed in 19 of the 24 study participants.&lt;/p&gt;
&lt;p&gt;Of the 19 patients who underwent resection, six (32%) had pathologic complete responses. Chang reported that nine of 16 evaluable patients converted from N1 to N0 status following preoperative therapy, and 11 of 20 were downstaged from T3 to T2-T0.&lt;/p&gt;
&lt;p&gt;Median overall survival for the patients was 47.7 months. The 56% five-year survival applied to patients in the first three dosing levels. Patients who received the highest dose have not been followed long enough to determine five-year survival.&lt;/p&gt;
&lt;p&gt;During the discussion that followed the presentation, Jaffer Ajani, MD, of M.D. Anderson Cancer Center in Houston, cited concerns about the treatment-related deaths and complexity of the regimen.&lt;/p&gt;
&lt;p&gt;&quot;This is a very big production; it&apos;s not simple to do,&quot; said Ajani. &quot;You have to have a gastroenterologist available to inject every week.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Your numbers are very small, and the pathological CR rate is no different than any other reported in even larger trials,&quot; he added. &quot;And then the subgroups with survival, I&apos;m not sure how meaningful that is because your numbers are so small.&quot;&lt;/p&gt;
&lt;p&gt;Responding to the concern about treatment-related deaths, Chang said none of the deaths was related to the TNF injections.&lt;/p&gt;
&lt;p&gt;With regard to the survival data, he acknowledged the small size of the study and said, &quot;It is what it is.&quot;&lt;/p&gt;
&lt;p&gt;&quot;It appears, as an adjunct, to be safe, and given the preliminary data, I think it is encouraging enough to go on to a larger trial,&quot; said Chang. &quot;That is basically what we are saying. We have something interesting that warrants further study.&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 GenVec.&lt;/p&gt;&lt;p&gt;One or more investigators disclosed relationships with GenVec.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_242"
                     title="Ultrasound Aids Early Ovarian Cancer Detection (CME/CE)"
                     score="0"
                     href="http://www.medpagetoday.com/Radiology/DiagnosticRadiology/tb/18096?impressionId=1265749513673"
                     
      &lt;p&gt;Serum biomarkers identified through proteomic analysis, coupled with contrast-enhanced ultrasound, ultimately may provide a means for early diagnosis of ovarian cancer, researchers say.&lt;/p&gt;
&lt;p&gt;&quot;Exciting preliminary data have shown that specific combinations of peptides from molecules, such as &lt;em&gt;BRCA2&lt;/em&gt;, exist in the serum of epithelial ovarian cancer patients,&quot; Sonia Dutta, MD, of Mount Sinai School of Medicine in New York, and colleagues reported in the February&lt;em&gt; American Journal of Roentgenology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;This discovery suggests that &quot;highly discriminatory proteins&quot; may serve as biomarkers for early epithelial cell ovarian cancer, although the findings must be further validated, the authors wrote.&lt;/p&gt;
&lt;p&gt;Despite advances in surgery and chemotherapy, survival from advanced stage ovarian cancer is only 30%, and the authors cite a &quot;dire need&quot; for a validated screening method to detect the disease early.&lt;/p&gt;
&lt;p&gt;Unsuccessful efforts find a biomarker for this deadly malignancy have focused primarily on a single cancer-specific marker, which the authors concede is a &quot;mission impossible.&quot;&lt;/p&gt;
&lt;p&gt;Impediments to the identification of cancer-specific markers include the molecular heterogeneity that characterizes different tumors, the sharing of pathophysiologic events among cancer and other diseases, and low marker production and concentration.&lt;/p&gt;
&lt;p&gt;To overcome these difficulties, a new approach known as proteomics is being used to analyze the entire protein complement of a cell.&lt;/p&gt;
&lt;p&gt;The rationale for this analytical technique lies in a significantly greater understanding of the tumor microenvironment. It is now known that tumor cells participate in complex interactions with surrounding structures and other cell populations.&lt;/p&gt;
&lt;p&gt;&quot;This biochemical cross-talk is hypothesized to generate a cascade of specific and sensitive biomarkers elaborated directly from the tumor cell population, indirectly from the interacting non-tumor cells or extracellular molecules, or a specific product of the microecology,&quot; they explained.&lt;/p&gt;
&lt;p&gt;In fact, the most specific cancer markers may turn out to be molecules that normally are not malignant but that have been modified by that tumor microenvironment  --  clipped, cleaved, phosphorylated, or glycosylated  --  and carry a detailed picture of the local pathophysiology.&lt;/p&gt;
&lt;p&gt;Previous techniques used in the hunt for markers, such as two-dimensional gel electrophoresis, were unable to detect these altered or clipped molecules, which occupy the low molecular weight range of the proteome.&lt;/p&gt;
&lt;p&gt;Mass spectrometry, which is most sensitive in the low molecular weight range, is now a tool used to explore these modified protein molecules and has already revealed a vast number of previously unknown biomarkers.&lt;/p&gt;
&lt;p&gt;The next steps, the researchers explained, will be to develop capture reagents that can measure the markers and, using reverse-phase protein array, to further characterize proteins of interest.&lt;/p&gt;
&lt;p&gt;But any diagnostic information gained through proteomic analysis must be verified by some imaging technique. Conventional ultrasound has proven inadequate, but pulse-inversion harmonic ultrasound currently appears to differentiate malignant from benign lesions.&lt;/p&gt;
&lt;p&gt;For example, although the time to peak enhancement with contrast-enhanced ultrasound is similar in benign and malignant masses, a small study found that malignant lesions have: &lt;ul&gt; &lt;li&gt;Greater peak enhancement (23.3 versus 12.3 dB, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Longer half wash-out time (139.9 versus 46.3 seconds, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Greater area under the enhancement curve (2,012.9 versus 523.9 seconds, &lt;em&gt;P&lt;/em&gt;=0.07)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The authors noted that these enhancement kinetics data were from just 17 patients and are therefore limited, but stated that the technique &quot;shows great promise.&quot;&lt;/p&gt;
&lt;p&gt;In addition, the diagnostic capacity of ultrasound can be further increased by the use of intravenous contrast agents, which may help visualize the early microvascular changes typical of malignancy.&lt;/p&gt;
&lt;p&gt;The researchers predicted that, by using a combination of clinically relevant biomarkers identified through proteomic analyses plus contrast-enhanced ultrasound, &quot;we will likely be able to shift from an era of diagnosing advanced-stage ovarian cancer to that of early-stage disease and, most important, save the lives of many women.&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;No disclosures were provided.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_109"
                     title="ASCO-GI: Neoadjuvant Chemoradiation Improves Esophageal Cancer Survival"
                     score="-0.005"
                     href="