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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The risk of developing a venous thrombotic event is 4 times greater among cancer patients than the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> In fact&#44; around 20&#37; of deep venous thrombosis and pulmonary embolisms are a result of an active cancer &#40;i&#46;e&#46;&#44; cancer diagnosed in the previous year or in active treatment&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Venous thromboembolism &#40;VTE&#41; is the second cause of death among cancer patients&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Moreover&#44; cancer patients receiving anticoagulants due to VTE have a higher risk of recurrence and bleeding than anticoagulated patients without cancer&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Pharmacological thromboprophylaxis is recommended in cancer patients who must be hospitalized due a medical condition&#44; unless contraindicated&#46; Similarly&#44; patients with active cancer who are scheduled to undergo major surgery should receive pharmacological thromboprophylaxis&#46; However&#44; the evidence is much less consistent in cancer outpatients who are receiving chemotherapy&#46; Scientific societies recommend the use of well-validated risk models&#44; such as the Khorana model &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; to identify subgroups of patients with a high risk of thrombotic events&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Thromboprophylaxis with low molecular weight heparin &#40;LMWH&#41; should only be considered in patients with a score of &#8805;3 on the Khorana model or advanced pancreatic cancer&#44; and patients with myeloma receiving thalidomide or lenalidomide may receive aspirin or LMWH&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In patients with VTE and cancer&#44; LMWH during the first 3&#8211;6 months is associated with a significantly lower risk of recurrent thrombosis than warfarin&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> It is still not completely clear whether patients should receive therapeutic doses of LMWH throughout their treatment&#44; so we recommend using the LMWH regimen that has been tested in clinical trials for each product &#40;i&#46;e&#46;&#44; full doses of enoxaparin and tinzaparin&#44; and a 75&#37; dose reduction for dalteparin after the first month&#41;&#46; After this 3&#8211;6 month period of anticoagulation&#44; the decision to continue anticoagulants depends on a number of factors&#44; such as tumor activity&#44; indication for anticancer treatment&#44; patient&#39;s tolerance of anticoagulation&#44; patient preferences&#44; and cost and availability of treatment&#46; No clinical trials have been published on the efficacy and safety of LMWH in cancer patients with VTE beyond the first 6 months of treatment&#46; Chai-Adisaksopha et al&#46; used data from the RIETE registry and propensity score matching to compare the efficacy and safety of vitamin K antagonists with LMWH in cancer patients with VTE after the first 6 months of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Patients receiving LMWH had a similar rate of recurrent deep venous thrombosis &#40;relative risk &#91;RR&#93; 1&#46;41&#59; 95&#37; confidence interval &#91;CI&#93; 0&#46;68&#8211;2&#46;93&#41;&#44; recurrent pulmonary thromboembolism &#40;RR 0&#46;73&#59; 95&#37; CI 0&#46;34&#8211;1&#46;58&#41;&#44; major bleeding &#40;RR 1&#46;15&#59; 95&#37; CI 0&#46;55&#8211;2&#46;40&#41;&#44; and non-major bleeding &#40;RR 0&#46;96&#59; 95&#37; CI 0&#46;51&#8211;1&#46;79&#41; compared with those who received vitamin K antagonists&#44; and a higher mortality rate &#40;RR 1&#46;58&#59; 95&#37; CI 1&#46;13&#8211;2&#46;20&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Given the lack of consistent data to support their efficacy and safety in cancer patients&#44; direct-acting anticoagulants &#40;apixaban&#44; dabigatran&#44; edoxaban&#44; and rivaroxaban&#41; are not indicated in the treatment of VTE in these patients&#46; However&#44; data from the Hokusai VTE Cancer clinical trial<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> have recently been published&#44; comparing edoxaban with dalteparin for up to 12 months in 1050 cancer patients with VTE&#46; The primary efficacy event &#40;a composite of recurrent thrombosis and major bleeding&#41; occurred in 67 patients &#40;12&#46;8&#37;&#41; who received edoxaban and in 71 patients &#40;13&#46;5&#37;&#41; who received dalteparin &#40;hazard ratio for edoxaban of 0&#46;97&#59; 95&#37; CI 0&#46;70&#8211;1&#46;36&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;0056 for non-inferiority&#41;&#46; <span class="elsevierStyleItalic">Caravaggio</span> &#40;<a id="intr0010" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT03045406">NCT03045406</a>&#41; is an open-label randomized clinical trial comparing apixaban vs dalteparin in the first 6 months of treatment of symptomatic or incidental VTE in cancer patients over the age of 18 years&#46; The <span class="elsevierStyleItalic">Select-D</span> study &#40;ISRCTN86712308&#41; is an open-label randomized clinical trial which compares dalteparin vs rivaroxaban in patients with VTE and cancer&#46; Moreover&#44; patients with residual deep venous thrombosis in the sixth month of treatment will be randomized to rivaroxaban or placebo for an additional 6 months&#46; <span class="elsevierStyleItalic">CANVAS</span> &#40;<a id="intr0015" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT02744092">NCT02744092</a>&#41; is an open-label randomized clinical trial that will compare the efficacy and safety of 6 months&#8217; treatment with direct-acting oral anticoagulants vs warfarin in cancer patients with confirmed VTE&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Between 8&#37; and 12&#37; of patients with VTE &#40;presumably idiopathic&#41; are diagnosed with occult cancer in the early follow-up period&#46; In view of the results of several studies that have evaluated the usefulness of exhaustive cancer screening in this group of patients&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> the International Society of Thrombosis and Hemostasis recommends limited screening&#44; including clinical history&#44; physical examination&#44; basic clinical laboratory tests &#40;complete blood count&#44; coagulation&#44; liver function tests&#41;&#44; and chest X-ray&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> Recently&#44; a risk prediction score has been developed for occult cancer in patients with VTE&#46; This scale comprises the following variables&#58; male &#40;1 point&#41;&#44; &#62;70 years &#40;2 points&#41;&#44; chronic lung disease &#40;1 point&#41;&#44; anemia &#40;2 points&#41;&#44; platelets &#8805;350&#215;10<span class="elsevierStyleSup">9</span>&#47;L &#40;1 point&#41;&#44; previous surgery &#40;minus 2 points&#41;&#44; VTE &#40;minus 1 point&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> In an external&#44; retrospective validation of this scale&#44; occult cancer was identified in 13&#46;8&#37; of high-risk patients &#40;i&#46;e&#46;&#44; score&#8805;3&#41; compared to 3&#46;6&#37; of low-risk patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; the treatment of VTE associated with malignant disease is a challenge in daily clinical practice&#46; Well-designed studies are needed to identify patients receiving chemotherapy in an outpatient setting in whom pharmacological thromboprophylaxis has an acceptable risk-benefit balance&#46; In addition&#44; ongoing clinical trials are needed to establish the role of direct-acting anticoagulants in the initial and long-term treatment of VTE associated with cancer&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of Interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">DJ is a member of the Data and Safety Monitoring Board of the Caravaggio clinical trial&#46;</p></span></span>"
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">BMI&#8805;35</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">kg&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span>&nbsp;\t\t\t\t\t\t\n
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Editorial
Venous Thromboembolic Disease and Cancer: A Challenge for Clinicians
Enfermedad tromboembólica venosa y cáncer: un reto para los clínicos
Deisy Barriosa, Luis Jara-Palomaresb, David Jiméneza,
Corresponding author
djimenez.hrc@gmail.com

Corresponding author.
a Servicio de Neumología, Hospital Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
b Servicio de Neumología, Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Sevilla, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The risk of developing a venous thrombotic event is 4 times greater among cancer patients than the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> In fact&#44; around 20&#37; of deep venous thrombosis and pulmonary embolisms are a result of an active cancer &#40;i&#46;e&#46;&#44; cancer diagnosed in the previous year or in active treatment&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Venous thromboembolism &#40;VTE&#41; is the second cause of death among cancer patients&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Moreover&#44; cancer patients receiving anticoagulants due to VTE have a higher risk of recurrence and bleeding than anticoagulated patients without cancer&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Pharmacological thromboprophylaxis is recommended in cancer patients who must be hospitalized due a medical condition&#44; unless contraindicated&#46; Similarly&#44; patients with active cancer who are scheduled to undergo major surgery should receive pharmacological thromboprophylaxis&#46; However&#44; the evidence is much less consistent in cancer outpatients who are receiving chemotherapy&#46; Scientific societies recommend the use of well-validated risk models&#44; such as the Khorana model &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; to identify subgroups of patients with a high risk of thrombotic events&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Thromboprophylaxis with low molecular weight heparin &#40;LMWH&#41; should only be considered in patients with a score of &#8805;3 on the Khorana model or advanced pancreatic cancer&#44; and patients with myeloma receiving thalidomide or lenalidomide may receive aspirin or LMWH&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In patients with VTE and cancer&#44; LMWH during the first 3&#8211;6 months is associated with a significantly lower risk of recurrent thrombosis than warfarin&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> It is still not completely clear whether patients should receive therapeutic doses of LMWH throughout their treatment&#44; so we recommend using the LMWH regimen that has been tested in clinical trials for each product &#40;i&#46;e&#46;&#44; full doses of enoxaparin and tinzaparin&#44; and a 75&#37; dose reduction for dalteparin after the first month&#41;&#46; After this 3&#8211;6 month period of anticoagulation&#44; the decision to continue anticoagulants depends on a number of factors&#44; such as tumor activity&#44; indication for anticancer treatment&#44; patient&#39;s tolerance of anticoagulation&#44; patient preferences&#44; and cost and availability of treatment&#46; No clinical trials have been published on the efficacy and safety of LMWH in cancer patients with VTE beyond the first 6 months of treatment&#46; Chai-Adisaksopha et al&#46; used data from the RIETE registry and propensity score matching to compare the efficacy and safety of vitamin K antagonists with LMWH in cancer patients with VTE after the first 6 months of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Patients receiving LMWH had a similar rate of recurrent deep venous thrombosis &#40;relative risk &#91;RR&#93; 1&#46;41&#59; 95&#37; confidence interval &#91;CI&#93; 0&#46;68&#8211;2&#46;93&#41;&#44; recurrent pulmonary thromboembolism &#40;RR 0&#46;73&#59; 95&#37; CI 0&#46;34&#8211;1&#46;58&#41;&#44; major bleeding &#40;RR 1&#46;15&#59; 95&#37; CI 0&#46;55&#8211;2&#46;40&#41;&#44; and non-major bleeding &#40;RR 0&#46;96&#59; 95&#37; CI 0&#46;51&#8211;1&#46;79&#41; compared with those who received vitamin K antagonists&#44; and a higher mortality rate &#40;RR 1&#46;58&#59; 95&#37; CI 1&#46;13&#8211;2&#46;20&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Given the lack of consistent data to support their efficacy and safety in cancer patients&#44; direct-acting anticoagulants &#40;apixaban&#44; dabigatran&#44; edoxaban&#44; and rivaroxaban&#41; are not indicated in the treatment of VTE in these patients&#46; However&#44; data from the Hokusai VTE Cancer clinical trial<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> have recently been published&#44; comparing edoxaban with dalteparin for up to 12 months in 1050 cancer patients with VTE&#46; The primary efficacy event &#40;a composite of recurrent thrombosis and major bleeding&#41; occurred in 67 patients &#40;12&#46;8&#37;&#41; who received edoxaban and in 71 patients &#40;13&#46;5&#37;&#41; who received dalteparin &#40;hazard ratio for edoxaban of 0&#46;97&#59; 95&#37; CI 0&#46;70&#8211;1&#46;36&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;0056 for non-inferiority&#41;&#46; <span class="elsevierStyleItalic">Caravaggio</span> &#40;<a id="intr0010" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT03045406">NCT03045406</a>&#41; is an open-label randomized clinical trial comparing apixaban vs dalteparin in the first 6 months of treatment of symptomatic or incidental VTE in cancer patients over the age of 18 years&#46; The <span class="elsevierStyleItalic">Select-D</span> study &#40;ISRCTN86712308&#41; is an open-label randomized clinical trial which compares dalteparin vs rivaroxaban in patients with VTE and cancer&#46; Moreover&#44; patients with residual deep venous thrombosis in the sixth month of treatment will be randomized to rivaroxaban or placebo for an additional 6 months&#46; <span class="elsevierStyleItalic">CANVAS</span> &#40;<a id="intr0015" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT02744092">NCT02744092</a>&#41; is an open-label randomized clinical trial that will compare the efficacy and safety of 6 months&#8217; treatment with direct-acting oral anticoagulants vs warfarin in cancer patients with confirmed VTE&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Between 8&#37; and 12&#37; of patients with VTE &#40;presumably idiopathic&#41; are diagnosed with occult cancer in the early follow-up period&#46; In view of the results of several studies that have evaluated the usefulness of exhaustive cancer screening in this group of patients&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> the International Society of Thrombosis and Hemostasis recommends limited screening&#44; including clinical history&#44; physical examination&#44; basic clinical laboratory tests &#40;complete blood count&#44; coagulation&#44; liver function tests&#41;&#44; and chest X-ray&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> Recently&#44; a risk prediction score has been developed for occult cancer in patients with VTE&#46; This scale comprises the following variables&#58; male &#40;1 point&#41;&#44; &#62;70 years &#40;2 points&#41;&#44; chronic lung disease &#40;1 point&#41;&#44; anemia &#40;2 points&#41;&#44; platelets &#8805;350&#215;10<span class="elsevierStyleSup">9</span>&#47;L &#40;1 point&#41;&#44; previous surgery &#40;minus 2 points&#41;&#44; VTE &#40;minus 1 point&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> In an external&#44; retrospective validation of this scale&#44; occult cancer was identified in 13&#46;8&#37; of high-risk patients &#40;i&#46;e&#46;&#44; score&#8805;3&#41; compared to 3&#46;6&#37; of low-risk patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; the treatment of VTE associated with malignant disease is a challenge in daily clinical practice&#46; Well-designed studies are needed to identify patients receiving chemotherapy in an outpatient setting in whom pharmacological thromboprophylaxis has an acceptable risk-benefit balance&#46; In addition&#44; ongoing clinical trials are needed to establish the role of direct-acting anticoagulants in the initial and long-term treatment of VTE associated with cancer&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of Interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">DJ is a member of the Data and Safety Monitoring Board of the Caravaggio clinical trial&#46;</p></span></span>"
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ISSN: 15792129
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