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<span class="elsevierStyleSmallCaps">iii</span>B y <span class="elsevierStyleSmallCaps">iii</span>C&#44; respectivamente&#46; Si bien el brazo control difer&#237;a &#40;ipilimumab a dosis altas para el CheckMate&#160;238 y placebo para el Keynote&#160;054&#41;&#44; ambos f&#225;rmacos &#40;nivolumab y pembrolizumab&#41; demostraron un beneficio en la supervivencia libre de reca&#237;da &#40;SVLR&#41;&#58; 50&#37; para nivolumab y 39&#37; con ipilimumab a los 5 a&#241;os y 59&#44;8&#37; para pembrolizumab frente al 41&#44;4&#37; en el grupo placebo a 5 a&#241;os&#46; Actualmente&#44; la SVLR&#44; siguiendo la clasificaci&#243;n de la AJCC en su 8&#46;<span class="elsevierStyleSup">a</span> edici&#243;n&#44; con nivolumab a 5 a&#241;os es del 66&#37; y del 49&#37; con ipilimumab en estadios <span class="elsevierStyleSmallCaps">iii</span>B&#44; del 44&#37; vs&#46; 39&#37; para estadios <span class="elsevierStyleSmallCaps">iii</span>C y del 28&#37; vs&#46; 0&#37; para los <span class="elsevierStyleSmallCaps">iii</span>D<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a>&#46; La supervivencia libre de met&#225;stasis a distancia para pembrolizumab a 3&#44;5 a&#241;os es del 80&#44;8&#37; en estadio <span class="elsevierStyleSmallCaps">iii</span>A vs&#46; 70&#44;8&#37; con placebo&#44; del 68&#44;1&#37; vs&#46; 51&#37; en estadios <span class="elsevierStyleSmallCaps">iii</span>B y del 55&#44;8&#37; vs&#46; 39&#44;2&#37; en estadios <span class="elsevierStyleSmallCaps">iii</span>C &#40;AJCC 7&#46;<span class="elsevierStyleSup">a</span> edici&#243;n&#41;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Los efectos secundarios de grado 3-4 relacionados con el tratamiento aparecieron en el 14&#44;4&#37; de los pacientes con nivolumab y en el 14&#44;5&#37; con pembrolizumab&#44; con una tasa de abandono del 7&#44;7&#37; y del 14&#44;4&#37;&#44; respectivamente<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; La calidad de vida no se alter&#243; con nivolumab ni con pembrolizumab<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#44;8</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Los resultados en la pr&#225;ctica cl&#237;nica habitual pueden ser distintos a los de los ensayos&#46; Los estudios de registro se realizaron utilizando la 7&#46;<span class="elsevierStyleSup">a</span> edici&#243;n de la clasificaci&#243;n de la AJCC y todos los pacientes fueron intervenidos con linfadenectom&#237;a tras la positividad de la biopsia selectiva del ganglio centinela &#40;BSGC&#41;&#46; Sin embargo&#44; actualmente se utiliza la 8&#46;<span class="elsevierStyleSup">a</span> edici&#243;n de la AJCC<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> y&#44; tras los resultados de los estudios MLST&#160;II y DeCOG<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">10&#44;11</span></a>&#44; hay un uso m&#237;nimo de la linfadenectom&#237;a&#44; por lo que es &#250;til obtener datos del uso de adyuvancia en pacientes con melanoma en la pr&#225;ctica cl&#237;nica&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Estos datos son necesarios para validar los obtenidos en los ensayos&#44; si bien en adyuvancia disponemos de pocos estudios&#46; De Meza <span class="elsevierStyleItalic">et al&#46;</span> han comunicado un an&#225;lisis de pr&#225;ctica cl&#237;nica de 641 pacientes en estadios III o IV en adyuvancia con nivolumab y pembrolizumab tras linfadenectom&#237;a y reclasificaci&#243;n a la 8&#46;<span class="elsevierStyleSup">a</span> edici&#243;n de la AJCC&#46; A un a&#241;o&#44; la SVLR fue del 70&#44;6&#37;&#44; y la toxicidad de grado 3 o mayor apareci&#243; en el 18&#37; de los pacientes<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a>&#46; En otro estudio de Hofmann <span class="elsevierStyleItalic">et al&#46;</span>&#44; de 30 pacientes tratados con nivolumab&#44; observaron el 40&#37; de recurrencias&#44; la mitad durante la adyuvancia&#44; con el 16&#44;7&#37; de toxicidad de grado 3-4<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a>&#46; El grupo alem&#225;n comunic&#243; los resultados de un an&#225;lisis retrospectivo de 100 pacientes que recib&#237;an inmunoterapia con una SVLR estimada a un a&#241;o del 64&#44;8&#37;&#44; con una toxicidad de grado 3 o mayor del 16&#37; y una suspensi&#243;n por efectos adversos del 22&#37;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a>&#46; M&#225;s recientemente&#44; se comunicaron los resultados de una gran cohorte de Alemania&#44; Austria y Suiza&#44; con 1&#46;198 pacientes tratados con anti-PD1 y anti-BRAF&#47;anti-MEK&#46; La SVLR a un a&#241;o fue del 74&#44;1&#37; con un 12&#44;3&#37; de los pacientes que interrumpieron el tratamiento debido a los efectos adversos<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a>&#46; Asimismo&#44; han sido comunicados los datos de una cohorte italiana de acceso expandido&#44; con una SVLR y supervivencia global a un a&#241;o del 76&#44;6&#37; y del 93&#44;8&#37;&#44; respectivamente<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Con el estudio CADIM &#40;Caracterizaci&#243;n de la ADyuvancia con Inmunoterapia en pacientes con Melanoma&#41; se pretende analizar las caracter&#237;sticas de los pacientes con melanoma tratados en adyuvancia con inmunoterapia en la Comunidad Aut&#243;noma de la Regi&#243;n de Murcia fuera de ensayo cl&#237;nico&#46; Se presentan los datos finales actualizados de los 81 pacientes tratados en el Hospital Cl&#237;nico Universitario Virgen de la Arrixaca &#40;HCUVA&#41; de la ciudad de Murcia y en el Complejo Hospitalario de Cartagena &#40;CHC&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Plan de estudio y esquema de tratamiento</span><p id="par0030" class="elsevierStylePara elsevierViewall">Desde febrero de 2018 hasta diciembre de 2022&#44; 81 pacientes con melanoma resecado en estadio III o IV recibieron&#44; fuera de ensayo cl&#237;nico&#44; nivolumab &#40;3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg iv cada 2 semanas&#41; o pembrolizumab &#40;3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg iv cada 3 semanas&#41; hasta completar un a&#241;o como pr&#225;ctica cl&#237;nica habitual&#44; incluyendo las suspensiones precoces a causa de la recurrencia de la enfermedad&#44; toxicidad inaceptable o retirada del consentimiento&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Todos los pacientes firmaban el consentimiento informado habitual usado en los centros donde se ha realizado el estudio&#46; El estudio fue aprobado por el Comit&#233; de &#201;tica de Investigaci&#243;n Cl&#237;nica del Hospital Virgen de la Arrixaca&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Fueron criterios de inclusi&#243;n&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Edad &#8805;18 a&#241;os&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Melanoma en estadios III &#40;con afectaci&#243;n ganglionar igual o mayor de 1<span class="elsevierStyleHsp" style=""></span>mm&#41; o IV de la 8&#46;<span class="elsevierStyleSup">a</span> edici&#243;n de la AJCC resecados&#46; Los melanomas de mucosas se estadificaron utilizando la propuesta de Cui <span class="elsevierStyleItalic">et al&#46;</span> basada en la 8&#46;<span class="elsevierStyleSup">a</span> edici&#243;n de la AJCC<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Se incluyen melanomas acrales&#44; de mucosas y de primario desconocido&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#41;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Inicio de adyuvancia &#8804; 12 semanas de la &#250;ltima cirug&#237;a&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">e&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Los pacientes no han recibido previamente otros tratamientos &#40;sist&#233;micos&#44; radioterapia&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">f&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall">El estado libre de enfermedad se documenta antes del inicio de la adyuvancia&#44; a trav&#233;s de la exploraci&#243;n f&#237;sica y las t&#233;cnicas de imagen utilizadas en la pr&#225;ctica cl&#237;nica habitual&#46; El seguimiento se realiza con las mismas t&#233;cnicas cada 3-4 meses&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">g&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">ECOG&#160;&#8804;&#160;2&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">h&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Pruebas de laboratorios normales antes del inicio &#40;2 semanas&#41; del tratamiento&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">i&#41;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Ausencia de met&#225;stasis cerebrales&#46;</p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">Se excluyeron del estudio los pacientes con&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">a&#41;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Otros tumores activos al menos 3 a&#241;os antes de iniciar el tratamiento adyuvante&#44; salvo c&#225;ncer de piel &#40;no melanoma&#41; o carcinomas <span class="elsevierStyleItalic">in situ</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">b&#41;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Enfermedades autoinmunes conocidas y activas&#44; salvo aquellos que requirieran reposici&#243;n hormonal o alteraciones cut&#225;neas sin necesidad de tratamiento sist&#233;mico&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">c&#41;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Melanoma ocular&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lisis estad&#237;stico</span><p id="par0110" class="elsevierStylePara elsevierViewall">El an&#225;lisis estad&#237;stico se realiz&#243; utilizando el programa <span class="elsevierStyleItalic">Statistical Package for the Social Sciences</span> versi&#243;n 20&#46; Se hizo un an&#225;lisis descriptivo de los datos&#46; Las variables categ&#243;ricas se describieron como valores absolutos y porcentajes y las cuantitativas como medianas e intervalos&#46; Los tiempos de supervivencias se calcularon utilizando el m&#233;todo de Kaplan-Meier&#46; La SVLR se calcul&#243; desde la fecha de inicio del primer ciclo hasta la fecha de la reca&#237;da&#44; ya fuera locorregional o a distancia&#44; o de muerte &#40;relacionada o no con el melanoma&#41; o hasta la de censura del &#250;ltimo seguimiento&#46; La supervivencia global se calcul&#243; desde la fecha de inicio del tratamiento hasta la fecha del fallecimiento o la fecha de censura en el &#250;ltimo seguimiento&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Poblaci&#243;n a estudio</span><p id="par0115" class="elsevierStylePara elsevierViewall">Las caracter&#237;sticas de los pacientes se resumen en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#46; Se incluyeron un total de 81 pacientes&#44; con una mediana de edad de 58 a&#241;os &#40;18-82&#41;&#44; la mayor&#237;a hombres &#40;58&#37;&#41;&#46; El subtipo de melanoma m&#225;s frecuente fue el cut&#225;neo &#40;76&#44;5&#37;&#41;&#44; seguido del de mucosas &#40;12&#44;3&#37;&#41;&#46; Con relaci&#243;n a los estadios&#44; seg&#250;n la clasificaci&#243;n TNM de la AJCC 8&#46;<span class="elsevierStyleSup">a</span> edici&#243;n&#44; el 81&#44;5&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>66&#44; 7 de ellos eran melanoma de mucosas&#41; eran estadios III&#44; la mayor parte de ellos estadio <span class="elsevierStyleSmallCaps">iii</span>C &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#59; 46&#44;9&#37;&#41; y 15 pacientes &#40;18&#44;5&#37;&#41; en estadio IV resecados&#46; De los 10 pacientes con melanoma de mucosas&#44; 7 eran estadio <span class="elsevierStyleSmallCaps">iii</span> y los 3 restantes&#44; estadio <span class="elsevierStyleSmallCaps">iv</span> resecados&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">La mayor&#237;a de los pacientes eran BRAF nativo &#40;40&#44;7&#37;&#41;&#44; el 28&#44;4&#37; eran BRAF mutados&#44; y el 30&#44;9&#37; de los casos&#44; desconocido&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">La BSGC se realiz&#243; en el 79&#37; de los pacientes y el 45&#44;7&#37; de los pacientes fueron intervenidos de linfadenectom&#237;a ganglionar&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Supervivencia libre de reca&#237;da y supervivencia global</span><p id="par0130" class="elsevierStylePara elsevierViewall">Al corte de datos en diciembre de 2022&#44; la mediana de seguimiento era de 22&#44;8 meses&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">La SVLR fue de 45&#44;6 meses &#40;IC&#160;95&#37;&#58; 40&#44;2-51&#44;1&#41; sin haberse alcanzado la mediana&#44; con un porcentaje del 84&#37; de pacientes libres de reca&#237;da a un a&#241;o y del 81&#44;5&#37; a los 2 a&#241;os&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">La SVLR en funci&#243;n de estadio fue de 18&#44;4 meses &#40;IC&#160;95&#37;&#58; 0-40&#44;2&#41;&#44; 19&#44;1 meses &#40;IC&#160;95&#37;&#58; 0-38&#44;6&#41;&#44; 19&#44;9 meses &#40;IC&#160;95&#37;&#58; 10&#44;3-29&#44;4&#41;&#44; 3&#44;6 meses &#40;valor &#250;nico&#41; y 8&#44;3 meses &#40;IC&#160;95&#37;&#58; 0-16&#44;9&#41; para los estadios <span class="elsevierStyleSmallCaps">iiiA&#44; iiiB&#44; iiiC&#44; iiiD</span> y <span class="elsevierStyleSmallCaps">iv&#44;</span> respectivamente&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">La mediana de supervivencia global fue de 49&#44;3 meses &#40;IC&#160;95&#37;&#58; 44&#44;3-54&#44;2&#41; sin alzanzar la mediana&#44; con 12 pacientes fallecidos a la fecha de corte de datos&#46; El 98&#37; segu&#237;a vivo al a&#241;o del inicio del tratamiento y el 91&#44;4&#37; a los 2<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">La mediana de supervivencia global en funci&#243;n de estadio fue de 18&#44;4 meses &#40;IC&#160;95&#37;&#58; 0-40&#44;2&#41;&#44; 25&#44;1 meses &#40;IC&#160;95&#37;&#58; 15&#44;6-34&#44;6&#41;&#44; 23&#44;2 meses &#40;IC&#160;95&#37;&#58; 18&#44;2-28&#44;2&#41;&#44; 38&#44;6 meses &#40;valor &#250;nico&#41; y 16&#44;9 meses &#40;IC&#160;95&#37;&#58; 07&#44;1-24&#44;7&#41; para los estadios <span class="elsevierStyleSmallCaps">iii</span>A&#44; <span class="elsevierStyleSmallCaps">iii</span>B&#44; <span class="elsevierStyleSmallCaps">iii</span>C&#44; <span class="elsevierStyleSmallCaps">iii</span>D y IV&#44; respectivamente&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Se han observado diferencias estad&#237;sticamente significativas a favor de aquellos pacientes que completan la adyuvancia tanto en SVLR&#44; con HR 0&#44;138 &#40;0&#44;040-0&#44;471&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#44; como en supervivencia global con HR 0&#44;189 &#40;0&#44;057-0&#44;624&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41;&#46; No se observaron otras diferencias estad&#237;sticamente significativas en funci&#243;n del resto de las variables&#44; incluyendo el estado mutacional de BRAF&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Causas de finalizaci&#243;n de tratamiento y patrones de recurrencia</span><p id="par0160" class="elsevierStylePara elsevierViewall">El tratamiento lo completaron el 48&#37; de los pacientes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41;&#46; De los pacientes que no acabaron el tratamiento &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>41&#41;&#44; 16 lo estaban recibiendo en el momento de corte de los datos y 27 lo interrumpieron de forma precoz por reca&#237;da &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&#44; toxicidad &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; u otras causas &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">Hasta 16 pacientes presentaron recurrencia de la enfermedad &#40;19&#44;8&#37;&#41;&#44; la mayor&#237;a &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#59; 81&#44;2&#37;&#41; durante la adyuvancia&#46; Las met&#225;stasis se produjeron de forma local &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#59; 50&#37;&#41; y a distancia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#59; 50&#37;&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Seguridad</span><p id="par0170" class="elsevierStylePara elsevierViewall">El 39&#44;5&#37; de los pacientes present&#243; efectos adversos inmunomediados &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; La mayor parte fueron leves&#44; con un 34&#44;5&#37; de toxicidades de grado 1-2&#46; El 12&#44;3&#37; de los pacientes present&#243; toxicidad inmunorrelacionada igual o superior al grado 3&#46; La suspensi&#243;n definitiva del tratamiento por efectos adversos ocurri&#243; en el 13&#44;6&#37; de los casos &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">El efecto adverso grave m&#225;s frecuente fue la toxicidad hep&#225;tica &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#59; 4&#44;9&#37;&#41; seguida de la artropat&#237;a &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#59; 2&#44;4&#37;&#41; con casos aislados &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41; de colitis&#44; uve&#237;tis&#44; encefalitis y tiroiditis&#46; No se registraron casos de neumonitis ni de toxicidad card&#237;aca en nuestra serie&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Ocurrieron 4 fallecimientos durante el tratamiento en pacientes sin recidiva&#44; uno de ellos debido a toxicidad grave inmunomediada &#40;crisis tirot&#243;xica y encefalitis&#41;&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discusi&#243;n</span><p id="par0185" class="elsevierStylePara elsevierViewall">Los resultados del estudio CADIM se han comunicado parcialmente en diversas reuniones y congresos<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a>&#46; En este documento comunicamos los resultados finales de los 81 pacientes tratados en el HCUVA y en el CHC&#46; Consideramos la poblaci&#243;n seleccionada como representativa de la poblaci&#243;n global de nuestra comunidad aut&#243;noma&#44; al englobar estos centros m&#225;s del 90&#37; de la poblaci&#243;n total de los pacientes con melanoma tratados en adyuvancia con inmunoterapia&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Con relaci&#243;n a la poblaci&#243;n analizada&#44; las caracter&#237;sticas de nuestra poblaci&#243;n son similares a las comunicadas en otros estudios de pr&#225;ctica cl&#237;nica&#44; tanto en sexo<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12&#44;13&#44;15&#44;16</span></a>&#44; como en edad<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12&#44;13&#44;16&#44;19&#44;20</span></a>&#46; En esta serie&#44; la presencia de melanoma de primario desconocido es algo menos frecuente &#40;3&#44;7&#37;&#41; que en otros estudios de pr&#225;ctica cl&#237;nica&#44; en los que representa desde el 5&#44;9&#37; hasta el 11&#44;9&#37; de los pacientes<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12&#44;13&#44;16&#44;19</span></a>&#46; La distribuci&#243;n por estadios es similar a la de otros estudios&#59; destaca la proporci&#243;n de pacientes en estadios IV resecados &#40;18&#44;5&#37;&#41;&#44; superior a la de estudios similares<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12-15&#44;19&#44;20</span></a> salvo en el an&#225;lisis del acceso expandido italiano<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a> &#40;23&#44;1&#37;&#41;&#46; Destaca tambi&#233;n el porcentaje de pacientes en tratamiento adyuvante con melanoma de mucosas &#40;12&#44;3&#37;&#41;&#44; superior tambi&#233;n al de otros an&#225;lisis &#40;0&#44;3-2&#44;8&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12&#44;16</span></a>&#46; La mayor&#237;a de los pacientes que componen nuestra serie no presentan mutaci&#243;n en BRAF&#44; lo que coincide con la distribuci&#243;n de la mayor&#237;a de las series de pr&#225;ctica cl&#237;nica<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12&#44;16&#44;19&#44;20</span></a>&#46; La alta proporci&#243;n &#40;30&#44;9&#37;&#41; de pacientes con BRAF desconocido se podr&#237;a explicar porque no se solicita su determinaci&#243;n en situaci&#243;n de adyuvancia&#44; pues no es un dato determinante para la toma de decisiones sobre el tratamiento en situaci&#243;n adyuvante&#44; al no estar financiada la terapia dirigida a esta poblaci&#243;n en Espa&#241;a&#46; Por &#250;ltimo&#44; con relaci&#243;n a las caracter&#237;sticas de los pacientes&#44; en la serie presentada se realiz&#243; BSGC a un porcentaje importante de pacientes &#40;79&#37;&#41;&#44; de manera similar a las series publicadas en la pr&#225;ctica cl&#237;nica &#40;60-65&#44;8&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">14&#44;15&#44;17</span></a>&#59; ocurre lo mismo con el porcentaje de pacientes tratados mediante linfadenectom&#237;a&#58; el 45&#44;7&#37; en nuestra serie frente a otras &#40;del 45&#44;1 al 85&#44;8&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">14&#44;15&#44;17&#44;19</span></a>&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Los resultados obtenidos de SVLR son num&#233;ricamente superiores &#40;84&#37; a un a&#241;o&#41; a los comunicados en la pr&#225;ctica cl&#237;nica&#46; Los datos de la cohorte austriaca son del 64&#44;8&#37;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a>&#44; los de la neerlandesa del 70&#44;6&#37;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> y los de la italiana del 76&#44;6&#37; de SVLR a un a&#241;o&#46; Todos ellos reflejan unas diferencias en supervivencia a favor de nuestro estudio&#44; posiblemente debidas al n&#250;mero limitado de pacientes&#44; pues la distribuci&#243;n por sexo&#44; edad y estadios es similar&#44; si bien la proporci&#243;n de pacientes con melanomas de mucosas&#44; ulcerados o con estadios IV resecados en nuestra serie es mayor&#44; lo que no favorece inicialmente una mayor supervivencia&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">En nuestro estudio&#44; el 49&#44;2&#37; de los pacientes hab&#237;an completado el tratamiento&#44; el 19&#44;8&#37; lo continuaban y el 30&#44;9&#37; hab&#237;an suspendido el tratamiento&#44; la mayor&#237;a por progresi&#243;n &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#59; 16&#37;&#41; y toxicidad &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#59; 13&#44;7&#37;&#41;&#46; Otros an&#225;lisis muestran una amplia variaci&#243;n en los pacientes que completan el tratamiento&#44; entre el 63&#44;2&#37;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a> y el 42&#37;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a>&#44; que dejan el tratamiento precozmente por recidiva &#40;el 18&#44;7 y el 19&#37;&#44; respectivamente&#41; o por toxicidad &#40;el 10&#44;3&#37; y el 32&#37;&#44; respectivamente&#41;&#44; entre otras causas&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">La mayor parte de los pacientes que presentaron reca&#237;da de su enfermedad &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#47;16&#59; 81&#44;3&#37;&#41; lo hicieron intraadyuvancia&#44; porcentaje discretamente m&#225;s elevado que el 76&#37; observado por Owen <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">21</span></a>&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Las distintas supervivencias observadas en los principales ensayos de pr&#225;ctica cl&#237;nica se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#46; Aquellos estudios con un mayor seguimiento<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">16&#44;19&#44;20</span></a> son los que presentan tambi&#233;n una SVLR a 12 meses m&#225;s elevada y cercana a nuestros datos &#40;84&#37; de pacientes libres de reca&#237;da a un a&#241;o&#41;&#46; En nuestro estudio se han identificado diferencias estad&#237;sticamente significativas que favorecen a los pacientes que finalizan la adyuvancia en t&#233;rminos de SLVR y supervivencia global&#44; si bien otros estudios<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> no encuentran diferencias en supervivencia entre los que finalizan y los que abandonan de forma prematura el tratamiento&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">La frecuencia de toxicidades inmunomediadas graves en nuestro estudio ha sido del 12&#44;3&#37;&#44; similar a los estudios de adyuvancia&#44; con el 14&#44;4&#37; en el estudio Checkmate&#160;238 y el 14&#44;7&#37; en el Keynote&#160;054 y a la de otros datos de pr&#225;ctica cl&#237;nica<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">15&#44;16</span></a>&#44; pero inferior a los comunicados en otros estudios<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12&#44;20</span></a>&#44; probablemente debida a una recogida menos estricta de la toxicidad en estudios retrospectivos&#44; como el presentado&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">La suspensi&#243;n del tratamiento por toxicidad fue similar al estudio Keynote&#160;054 &#40;13&#44;6&#37; vs&#46; 13&#37;&#41; e inferior a la mostrada en otros estudios de pr&#225;ctica cl&#237;nica con suspensi&#243;n&#44; entre el 17&#44;9&#37; y el 22&#37;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">12&#44;14</span></a>&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">A pesar de las diferencias con otros ensayos y estudios y las limitaciones de las comparaciones indirectas&#44; consideramos que la prolongada mediana de seguimiento en nuestro estudio y la concordancia en los datos de seguridad validan los resultados obtenidos&#44; por lo que nuestros resultados avalan la actividad cl&#237;nica de la inmunoterapia en pacientes con melanoma en estadios III y IV resecados&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Como debilidades&#44; cabe se&#241;alar el car&#225;cter retrospectivo de nuestro estudio y el limitado n&#250;mero de pacientes&#46; En cualquier caso&#44; la mayor&#237;a de los pacientes completaron el tratamiento&#44; el seguimiento de los pacientes es prolongado y ha sido posible obtener la gran mayor&#237;a de las variables consideradas&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusi&#243;n</span><p id="par0235" class="elsevierStylePara elsevierViewall">Un mayor seguimiento nos permitir&#225; conocer el posible desarrollo de efectos inmunomediados a largo plazo&#44; caracterizar las reca&#237;das en estos pacientes y determinar el potencial impacto en la supervivencia de la finalizaci&#243;n precoz del tratamiento&#46; Iniciativas europeas&#44; como EuMelaReg<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a>&#44; facilitar&#225;n y har&#225;n m&#225;s homog&#233;nea la recogida de datos&#44; lo que aportar&#225; mayor calidad a los estudios de la pr&#225;ctica cl&#237;nica&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Financiaci&#243;n</span><p id="par0240" class="elsevierStylePara elsevierViewall">No se ha precisado financiaci&#243;n para la elaboraci&#243;n de este art&#237;culo&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicto de intereses</span><p id="par0245" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Los ensayos cl&#237;nicos han validado el uso de nivolumab y pembrolizumab en adyuvancia&#44; en t&#233;rminos de supervivencia libre de reca&#237;da&#44; en pacientes con melanoma resecado en estadios III y IV&#46; La evidencia en pacientes en la pr&#225;ctica cl&#237;nica es limitada&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material y m&#233;todo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Para el estudio CADIM &#40;Caracterizaci&#243;n de la ADyuvancia con Inmunoterapia en pacientes con Melanoma&#41; se seleccion&#243; de febrero de 2018 a diciembre de 2022&#44; a 81 pacientes con melanoma en estadios III y IV resecados que recibieron nivolumab o pembrolizumab en adyuvancia&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La distribuci&#243;n por estadios fue del 81&#44;5&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>71&#41; para estadios III&#44; mientras que 15 pacientes &#40;18&#44;5&#37;&#41; presentaban un estadio IV resecado&#46; Entre los estadios III&#44; 38 pacientes eran IIIC &#40;46&#44;9&#37;&#41;&#46; Con una mediana de seguimiento de 22&#44;8 meses&#44; la supervivencia libre de reca&#237;da en la poblaci&#243;n con intenci&#243;n de tratar fue del 84&#37; a un a&#241;o y del 81&#44;5&#37; a 2 a&#241;os&#46; La supervivencia global fue del 99&#37; a un a&#241;o y del 91&#44;4&#37; a 2 a&#241;os&#46; Los efectos adversos relacionados con el tratamiento de grado 3-4 aparecieron en el 12&#44;3&#37; de los pacientes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Este estudio presenta los resultados de pacientes con melanoma en estadios III y IV resecados tratados con anti-PD-1 en adyuvancia&#46; En &#233;l se confirma la eficacia y seguridad observada en ensayos cl&#237;nicos&#46; Contrastar los datos de los ensayos cl&#237;nicos con la evidencia encontrada en pr&#225;ctica cl&#237;nica es necesario para hacer m&#225;s &#250;til&#44; confiable y cercano el uso de estos f&#225;rmacos&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical trials have validated the use of nivolumab and pembrolizumab as adjuvant therapies regarding relapse-free survival in patients with resected stage III and IV melanoma&#46; Evidence in real-world patients is currently limited&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and method</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The CADIM trial &#40;Characterization of adjuvant immunotherapy in melanoma patients&#41; recruited a total of 81 patients with resected stage III and IV melanoma on nivolumab or pembrolizumab as adjuvant therapy from February 2018 through December 2022&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The stage distribution rate was 81&#46;5&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>71&#41; for stage III&#44; while 15 patients &#40;18&#46;5&#37;&#41; had resected stage IV&#46; Among stage III patients&#44; 38 were stage IIIC &#40;46&#46;9&#37;&#41;&#46; With a median follow-up of 22&#46;8 months&#44; the relapse-free survival in the intention-to-treat population was 84&#37; at one year and 81&#46;5&#37; at 2 years&#46; The overall survival rate was 99&#37; at one year and 91&#46;4&#37; at 2 years&#46; Grade 3-4 treatment-related adverse events were reported in 12&#46;3&#37; of the patients&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">This study shows the results of resected stage III and IV melanoma patients on adjuvant therapy with anti-PD-1&#44; and eventually confirmed the safety and efficacy profile described by clinical trials&#46; Comparing clinical trial data with real-world evidence is necessary for a more practical&#44; reliable&#44; and accessible use of these drugs&#46;</p></span>"
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                  \t\t\t\t">IIIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;46&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV resecados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;18&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagn&#243;stico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MES&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;29&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma nodular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;38&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma acral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;8&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma de mucosas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;12&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Origen desconocido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;3&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Otros<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;7&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ulceraci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;45&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;13&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Afectaci&#243;n ganglionar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65 &#40;80&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;13&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Checkmate 238<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Keynote-054<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">6</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Schumann <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">De Meza <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Acierto <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hoffmann <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">453&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">514&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">641&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">611&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Varones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mediana de edad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;18-82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56 &#40;19-83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;19-88&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59 y 63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;16-86&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;28-82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mediana de seguimiento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#44;8 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 meses m&#237;nimo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Datos a 12 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;8 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;3 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SVLR &#40;ITT&#41; a un a&#241;o&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#44;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#44;5-77&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SVLR &#40;ITT&#41; a 2 a&#241;os&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Supervivencia global &#40;ITT&#41; a 1 a&#241;o&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Supervivencia global &#40;ITT&#41; a 2 a&#241;os&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#44;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EAG3-4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Linfadenectom&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">De todo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspensi&#243;n prematura&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t">No comunicado&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">15 &#40;18&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">100 &#40;9&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46 &#40;7&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">141 &#40;23&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5 &#40;4&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">10 &#40;12&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2 &#40;0&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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