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Papel de los factores inflamatorios sistémicos en los tumores neuroendocrinos gastroenteropancreáticos (TNE-GEP) tratados con péptidos marcados con radionúclidos (PRRT): de la biología a la teragnosis
Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis
E. Abou-Jokh Casasa, N. Martínez-Lagob, M.C. Mallón Araujoa,
Autor para correspondencia
maramallon@gmail.com

Autor para correspondencia.
, J.M. Cabezas Agrícolac, Z. Nogareda Seoaned, A. Cousillas Castiñeirae, A. Ruibal Morellf, V. Pubul Núñeza
a Department of Nuclear Medicine, Santiago de Compostela University Hospital, España
b Department of Oncology, Complexo Hospitalario Universitario A Coruña, España
c Department of Endocrinology, Santiago de Compostela University Hospital, España
d Department of Nuclear Medicine, Lucus Augusti University Hospital, España
e Department of Oncology, Complejo Hospitalario de Pontevedra, España
f Professor Emeritus ad honorem USC, Santiago de Compostela University Hospital, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La terapia de p&#233;ptidos marcados con radion&#250;clidos &#40;PRRT&#41; es una estrategia dirigida que utiliza p&#233;ptidos radiomarcados como vectores de una diana biol&#243;gica&#44; dise&#241;ada para administrar niveles de radiaci&#243;n citot&#243;xica a las c&#233;lulas cancerosas que sobreexpresan receptores espec&#237;ficos&#46; El estudio NETTER-1 fue el primer ensayo cl&#237;nico aleatorizado&#44; controlado&#44; de fase III con pacientes diagnosticados con tumores neuroendocrinos gastroenteropancre&#225;ticos &#40;TNE-GEP&#41; G1-G2 tratados con PRRT&#44; que examin&#243; la eficacia y seguridad del &#91;<span class="elsevierStyleSup">177</span>Lu&#93;Lu-Dotatate en pacientes con TNE del intestino medio&#46; Demostr&#243; que la PRRT fue altamente efectiva para controlar la progresi&#243;n de la enfermedad en comparaci&#243;n con los an&#225;logos de somatostatina en dosis altas&#44; donde a&#250;n no se hab&#237;a alcanzado la mediana de supervivencia libre de progresi&#243;n &#40;PFS&#44; del ingl&#233;s <span class="elsevierStyleItalic">progression free survival</span>&#41; en el grupo que recibi&#243; &#91;<span class="elsevierStyleSup">177</span>Lu&#93;Lu-Dotatate&#46; Al mismo tiempo&#44; fue de 8&#44;4 meses en el grupo control&#44; lo que se interpret&#243; como un riesgo un 79&#37; menor de progresi&#243;n de la enfermedad o muerte con la PRRT<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Hay algunos factores pron&#243;sticos ampliamente estudiados en pacientes con TNE tratados con PRRT&#44; como el grado tumoral&#44; el Ki 67&#37;&#44; la cirug&#237;a del tumor primario y las met&#225;stasis&#44; y la presencia de enfermedad &#243;sea<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2&#44;3</span></a>&#46; A pesar de esto&#44; es esencial investigar otros factores pron&#243;sticos que podr&#237;an definir los resultados cl&#237;nicos en pacientes con TNE cuya heterogeneidad y diferencia con otros c&#225;nceres m&#225;s comunes son bien conocidas&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">&#218;ltimamente&#44; los biomarcadores sist&#233;micos de inmunoinflamaci&#243;n han atra&#237;do mucha atenci&#243;n ya que la interacci&#243;n entre el sistema inmunitario&#44; la inflamaci&#243;n y el c&#225;ncer ha sido bien establecida y no solo se ha demostrado que afecta la aparici&#243;n&#44; la proliferaci&#243;n&#44; el desarrollo y la met&#225;stasis de los tumores&#44; sino tambi&#233;n su respuesta a diferentes tratamientos<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a>&#46; Est&#225; bien establecido que la inflamaci&#243;n cr&#243;nica conduce a la liberaci&#243;n de citocinas proinflamatorias y otras inmunomoduladoras&#44; creando un microambiente favorable para la progresi&#243;n tumoral y las met&#225;stasis&#46; Adem&#225;s&#44; la inflamaci&#243;n genera estr&#233;s oxidativo&#44; que aumenta la inflamaci&#243;n&#44; por lo que los 2<span class="elsevierStyleHsp" style=""></span>son denominadores comunes en la carcinog&#233;nesis&#46; El estr&#233;s oxidativo induce especies reactivas de ox&#237;geno que causan da&#241;o al ADN y activa v&#237;as de se&#241;alizaci&#243;n que desregulan el ciclo celular y aumentan el riesgo de desarrollo del c&#225;ncer<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Los biomarcadores de inflamaci&#243;n sist&#233;mica son factores pron&#243;sticos independientes en c&#225;nceres colorrectal&#44; g&#225;strico&#44; renal y otros&#46; Adem&#225;s de esos marcadores&#44; los estudios han demostrado que otros componentes hematol&#243;gicos de la respuesta inflamatoria sist&#233;mica y ciertas combinaciones espec&#237;ficas&#44; como el &#237;ndice neutr&#243;filos-linfocitos &#40;NLR&#44; del ingl&#233;s <span class="elsevierStyleItalic">neutrophil to lymphocyte ratio</span>&#41;&#44; el &#237;ndice plaquetas-linfocitos &#40;PLR&#44; del ingl&#233;s <span class="elsevierStyleItalic">platelet to lymphocyte ratio</span>&#41; y otras&#44; pueden servir como factores pron&#243;sticos y est&#225;n asociadas con la supervivencia en pacientes con c&#225;ncer&#46; Sin embargo&#44; la funci&#243;n de esos marcadores basados en la inflamaci&#243;n sigue siendo incierta en los TNE-GEP avanzados o metast&#225;sicos&#44; especialmente en los tratados con PRRT<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Teniendo en cuenta que la recurrencia y las met&#225;stasis son causas significativas de muerte y mal pron&#243;stico para las neoplasias malignas m&#250;ltiples<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a>&#44; se necesitan nuevos factores pron&#243;sticos para predecir el resultado cl&#237;nico&#46; Por lo tanto&#44; este estudio tiene como objetivo establecer si diferentes &#237;ndices inflamatorios pueden predecir el resultado cl&#237;nico en pacientes diagnosticados con GEP o TNE de origen desconocido tratados con PRRT&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se trata de un estudio observacional&#44; longitudinal y retrospectivo en el que se buscaron &#237;ndices base pron&#243;sticos de inflamaci&#243;n en pacientes diagnosticados con GEP avanzado o TNE de origen desconocido que expresaran receptores de somatostatina tratados con PRRT&#46; La informaci&#243;n relacionada con esta cohorte de pacientes fue recolectada a trav&#233;s de la historia cl&#237;nica&#46; Estos datos se trataron de forma confidencial y encriptada para su an&#225;lisis&#44; y se obtuvo el consentimiento por escrito de todos los pacientes&#46; Adem&#225;s&#44; el comit&#233; de &#201;tica M&#233;dica aprob&#243; nuestro estudio en nuestro hospital universitario&#46; Todos los participantes del estudio dieron su consentimiento informado por escrito para almacenar su informaci&#243;n en la base de datos del hospital y su uso para futuras investigaciones en el momento de la determinaci&#243;n del seguimiento&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Cuarenta pacientes fueron incluidos en el estudio&#44; correspondientes a casos diagnosticados de GEP o TNE de origen desconocido que expresan receptores de somatostatina y recibieron tratamiento con &#91;<span class="elsevierStyleSup">177</span>Lu&#93;Lu-Dotatate en el Servicio de Medicina Nuclear desde mayo del 2016 hasta diciembre del 2020&#46; Los pacientes fueron hospitalizados para la administraci&#243;n de cada ciclo&#59; 30<span class="elsevierStyleHsp" style=""></span>min antes de la perfusi&#243;n de PRRT&#44; se administr&#243; por v&#237;a oral una c&#225;psula que conten&#237;a 300<span class="elsevierStyleHsp" style=""></span>mg de netupitant y 0&#44;5<span class="elsevierStyleHsp" style=""></span>mg de palonosetr&#243;n &#40;Akynzeo&#174;&#41;&#46;A continuaci&#243;n&#44; se inici&#243; una infusi&#243;n de amino&#225;cidos &#40;2&#44;5&#37; de arginina y 2&#44;5&#37; de lisina&#44; 1 l&#41; 30<span class="elsevierStyleHsp" style=""></span>min antes de la administraci&#243;n del radiof&#225;rmaco&#44; con una duraci&#243;n de 4-6<span class="elsevierStyleHsp" style=""></span>h&#46; El radiof&#225;rmaco se coadministr&#243; utilizando un sistema de bomba dual&#46; Todas las dosis del ciclo fueron de 7&#44;4 GBq &#40;200 mCi&#41; de &#91;<span class="elsevierStyleSup">177</span>Lu&#93;Lu-Dotatate&#44; inyectadas durante 30<span class="elsevierStyleHsp" style=""></span>min&#44; completando 4<span class="elsevierStyleHsp" style=""></span>ciclos de tratamiento&#46; El intervalo previsto entre los ciclos de tratamiento fue de 6 a 10 semanas&#46; El seguimiento incluy&#243; una tomograf&#237;a computarizada &#40;TC&#41; o una resonancia magn&#233;tica realizada entre 3 y 6 meses despu&#233;s del &#250;ltimo tratamiento y despu&#233;s de eso cada 6 meses&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Se registraron los siguientes valores recogidos del an&#225;lisis de sangre basal previo al tratamiento y despu&#233;s de la segunda dosis de PRRT&#58; leucocitos&#44; neutr&#243;filos&#44; linfocitos&#44; monocitos&#44; plaquetas y alb&#250;mina&#46; Con estos par&#225;metros anal&#237;ticos&#44; calculamos el NLR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de neutr&#243;filos&#47;recuento de linfocitos&#44; &#237;ndice de monocitos-linfocitos&#44; MLR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de monocitos&#47;recuento de linfocitos&#44; PLR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de plaquetas&#47;recuento de linfocitos&#44; el &#237;ndice alb&#250;mina-linfocitos &#40;ALR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>niveles de alb&#250;mina&#47;recuento de linfocitos y la derivada del &#237;ndice de neutr&#243;filos-linfocitos &#40;dNLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de neutr&#243;filos&#47;&#40;recuento de leucocitos<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>recuento de neutr&#243;filos&#41;&#44; tanto en el an&#225;lisis basal como despu&#233;s de la segunda dosis de tratamiento&#46; Se calcul&#243; una puntuaci&#243;n de inflamaci&#243;n sist&#233;mica &#40;SIS&#41; para cada paciente sumando el n&#250;mero de factores de riesgo&#44; con un punto asignado a cada factor de riesgo&#46; Al mismo tiempo&#44; se calcul&#243; la media de cada &#237;ndice&#44; utiliz&#225;ndola como punto de corte para determinar si estos aumentaban o disminu&#237;an&#44; para probar los factores pron&#243;sticos&#46; Adem&#225;s&#44; el comportamiento de cada &#237;ndice desde el an&#225;lisis basal hasta el obtenido despu&#233;s de la segunda dosis fue estudiado&#44; clasific&#225;ndolos en 4<span class="elsevierStyleHsp" style=""></span>categor&#237;as&#58; permanecer altos&#44; permanecer bajos&#44; aumentar o disminuir&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Los an&#225;lisis estad&#237;sticos se realizaron utilizando el paquete estad&#237;stico IBM SPSS&#174; versi&#243;n 23&#46;0 con los datos obtenidos&#46; La PFS se calcul&#243; desde la fecha de inicio del tratamiento con PRRT hasta la progresi&#243;n de la enfermedad o la muerte por cualquier causa&#46; La supervivencia global se calcul&#243; desde la fecha de inicio del tratamiento con PRRT hasta la muerte por cualquier motivo&#46; El an&#225;lisis primario se realiz&#243; mediante el m&#233;todo de Kaplan-Meier para calcular la mediana de PFS y OS y los intervalos de confianza &#40;IC&#41; del 95&#37;&#46; Las diferencias entre las curvas de supervivencia se compararon mediante la prueba de rango logar&#237;tmico con un nivel de significaci&#243;n bilateral de 0&#44;05&#46; Se utiliz&#243; la prueba de chi cuadrado para comparar variables cl&#237;nicas y demogr&#225;ficas&#46; Se utiliz&#243; la regresi&#243;n de Cox para evaluar la asociaci&#243;n con variables independientes&#46; Adem&#225;s&#44; las variables independientes como la tasa de respuesta objetiva &#40;ORR&#44; del ingl&#233;s <span class="elsevierStyleItalic">objective response ratio&#41;</span> se expresan como respuesta completa &#40;RC&#41; &#43; respuesta parcial &#40;RP&#41;&#44; y la tasa de control de la enfermedad &#40;DCR&#44; del ingl&#233;s <span class="elsevierStyleItalic">disease control ratio&#41;</span> se define como RC &#43; RP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>enfermedad estable &#40;EE&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resultados</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Caracter&#237;sticas de los pacientes</span><p id="par0050" class="elsevierStylePara elsevierViewall">Cuarenta pacientes diagnosticados de TNE-GEP avanzado o de origen desconocido tratados entre mayo del 2016 y diciembre del 2020 se inscribieron en este estudio&#46; La mediana de edad fue de 63 a&#241;os &#40;rango&#58; 41-85 a&#241;os&#41; y 22 eran hombres &#40;55&#37;&#41;&#46; Las caracter&#237;sticas cl&#237;nicas y patol&#243;gicas se resumen en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#46; De la poblaci&#243;n estudiada&#44; el 62&#44;5&#37; eran tumores gastrointestinales y el 28&#44;2&#37; eran TNE pancre&#225;ticos&#44; el 95&#37; eran de grado 1-2&#44; el 92&#37; de los pacientes ten&#237;an met&#225;stasis&#44; el 55&#37; se sometieron a resecci&#243;n tumoral primaria y el 20&#37; para su met&#225;stasis&#46; Los tratamientos previos incluyeron un 82&#44;5&#37; de an&#225;logos de somatostatina&#44; un 65&#37; de everolim&#250;s&#44; un 27&#44;5&#37; de sunitinib y un 15&#37; de quimioterapia&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Desde el inicio del tratamiento con &#91;<span class="elsevierStyleSup">177</span>Lu&#93;Lu-Dotatate &#40;PRRT&#41;&#44; la mediana de PFS fue de 21&#44;7 meses &#40;IC del 95&#37;&#58; 10&#44;7-32&#44;8 meses&#41; y la OS fue de 32&#44;1 meses &#40;IC del 95&#37;&#58; 19&#44;6&#8211;44&#44;7 meses&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Quince pacientes que completaron 4<span class="elsevierStyleHsp" style=""></span>ciclos de tratamiento fallecieron durante el seguimiento &#40;37&#44;5&#37;&#41;&#46; La DCR con PRRT en toda la poblaci&#243;n de pacientes con TNE-GEP fue del 81&#37;&#44; principalmente debido a una alta tasa de enfermedad estable &#40;52&#44;5&#37;&#41; ya que se observ&#243; RP en 5 pacientes y uno ten&#237;a RC &#40;de los 33 pacientes con TC post-PRRT&#41;&#46; Adem&#225;s&#44; la ORR fue del 18&#37;&#44; principalmente debido a las RP en 5 pacientes&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">El grado tumoral &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; el Ki 67&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#44; los antecedentes de cirug&#237;a del tumor primario &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41; y la resecci&#243;n de las met&#225;stasis &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; fueron factores predictivos de PFS&#46; Un grado tumoral alto y un Ki 67&#37; elevado fueron factores predictores negativos mientras que el antecedente de cirug&#237;a del tumor primario y de sus met&#225;stasis se asociaron con una PFS prolongada &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">PFS y OS y marcadores de inflamaci&#243;n sist&#233;mica</span><p id="par0065" class="elsevierStylePara elsevierViewall">En el an&#225;lisis basal&#44; los valores de corte para determinar los &#237;ndices normales o patol&#243;gicos fueron los siguientes&#58; para el NLR 2&#44;61&#44; para el MLR 0&#44;31&#44; para el PLR 110&#44;14&#44; para el ALR 2&#44;39 y finalmente para el dNLR 1&#44;71&#46; En el an&#225;lisis realizado despu&#233;s del segundo ciclo de PRRT&#44; los puntos de corte fueron para NLR2 2&#44;3&#44; para MLR2 0&#44;3&#44; para PLR2 131&#44;61&#44; ALR2 4&#44;16 y dNLR2 1&#44;48&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">En el an&#225;lisis basal&#44; la PFS fue estad&#237;sticamente significativa m&#225;s corta&#44; en pacientes con NLR elevada &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; ALR &#40;0&#44;03&#41; y dNLR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> y <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#41;&#46; Los &#237;ndices basales MLR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;06&#41;&#44; PLR &#40;0&#44;29&#41; y ALR &#40;0&#44;06&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#44; as&#237; como todos los &#237;ndices analizados despu&#233;s del segundo ciclo de PRRT &#40;NLR2&#44; MLR2&#44; PLR2&#44; ALR2 y dNLR2&#59; <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#44; no fueron predictores estad&#237;sticamente significativos de PFS&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; la OS se asoci&#243; negativamente a un NLR elevado &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; PLR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41; y dNLR en el an&#225;lisis basal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; Los &#237;ndices basales MLR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;07&#41; y ALR &#40;0&#44;06&#41;&#44; as&#237; como todos los dem&#225;s &#237;ndices analizados despu&#233;s del segundo tratamiento &#40;NLR2&#44; MLR2&#44; PLR2&#44; ALR2 y dNLR2&#41; no fueron predictores estad&#237;sticamente significativos de OS&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Con respecto a la PFS y el comportamiento de los &#237;ndices inflamatorios entre el an&#225;lisis basal y despu&#233;s del segundo ciclo de tratamiento &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#44; se pueden intuir los siguientes hallazgos&#58; NLR basal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;008&#41;&#44; un MLR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41; y un dNLR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; los &#237;ndices que permanecen bajos o disminuyen con respecto al an&#225;lisis realizado despu&#233;s del segundo ciclo fueron estad&#237;sticamente significativos asociados con SLP prolongada&#46; Por otro lado&#44; no se encontraron diferencias estad&#237;sticamente significativas con respecto a PLR y ALR&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; los &#237;ndices basales NLR y dNLR que permanecen bajos o disminuyen con respecto al an&#225;lisis realizado despu&#233;s del segundo ciclo se asociaron estad&#237;sticamente significativamente con una mejor OS &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01 y 0&#44;003&#41;&#46; No se encontraron diferencias estad&#237;sticamente significativas con respecto a MLR&#44; PLR y ALR&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discusi&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">El estudio piloto de Black et al&#46; abri&#243; una nueva y fascinante rama de investigaci&#243;n en el campo de los TNE&#44; que estudia diferentes &#237;ndices de inflamaci&#243;n sist&#233;mica para predecir los resultados cl&#237;nicos de los pacientes diagnosticados con TNE tratados con PRRT<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Siguiendo esta l&#237;nea de investigaci&#243;n&#44; este estudio determin&#243; que los &#237;ndices inflamatorios sist&#233;micos son tan importantes como otros factores pron&#243;sticos estudiados &#40;como el grado tumoral&#44; el Ki 67&#37;&#41; en pacientes diagnosticados con TNE que recibieron PRRT&#46; En este estudio&#44; una elevaci&#243;n en los &#237;ndices de NLR&#44; ALR y dNLR en el an&#225;lisis basal previo al tratamiento se asoci&#243; con una PFS m&#225;s corta que los pacientes con an&#225;lisis normal&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">La identificaci&#243;n de estos factores pron&#243;sticos es relevante en la pr&#225;ctica cl&#237;nica&#44; especialmente en los TNE donde el curso de la enfermedad var&#237;a desde una presentaci&#243;n excesivamente agresiva &#40;supervivencia de aproximadamente 6<span class="elsevierStyleHsp" style=""></span>meses&#41; hasta un proceso indolente &#40;supervivencia de aproximadamente 20 a&#241;os&#41;&#44; pudiendo guiar el tratamiento cl&#237;nico<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a>&#46; Sin embargo&#44; pocos estudios han evaluado la eficacia del uso de marcadores inflamatorios sistem&#225;ticos combinados en pacientes con TNE-GEP en el curso del tratamiento con radioligandos&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En un intento por mejorar la estratificaci&#243;n del paciente para el tratamiento y predecir la supervivencia&#44; se han estudiado muchos marcadores inflamatorios y ciertas combinaciones espec&#237;ficas&#44; como la prote&#237;na C reactiva &#40;PCR&#41;&#44; el NLR&#44; el PLR y el MLR en relaci&#243;n con un mal pron&#243;stico de varios c&#225;nceres&#44; ya que est&#225;n involucrados en el desarrollo&#46; progresi&#243;n&#44; respuesta al tratamiento y pron&#243;stico<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6&#44;8&#44;9</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Los marcadores de la respuesta inflamatoria en fase aguda&#44; particularmente la PCR y la alb&#250;mina&#44; son marcadores de inflamaci&#243;n sensibles y confiables en pacientes con c&#225;ncer&#46; Sin embargo&#44; estos par&#225;metros no se incluyeron en este estudio porque sus concentraciones no se realizaron a cabo como parte de la evaluaci&#243;n antes y durante la PRRT&#59; escenario como el previsto en el estudio de Walsh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Uno de los marcadores m&#225;s estudiados hasta la fecha es el &#237;ndice NLR&#44; considerado en una amplia variedad de art&#237;culos como el marcador m&#225;s &#250;til para predecir la OS y la PFS en pacientes con c&#225;ncer<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a>&#44; donde los &#237;ndices altos de NLR se asociaron con una peor PFS y OS en los pacientes&#46; Adem&#225;s&#44; Alman et al&#46; demostraron que los &#237;ndices NLR y PLR podr&#237;an servir como factores predictivos de supervivencia en pacientes con TNE-GEP<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Zhang et al&#46; concluyeron que las tasas elevadas de NLR se asociaron con una peor PFS y OS en pacientes con c&#225;ncer de recto localmente avanzado&#46; Adem&#225;s&#44; el NLR se identific&#243; como el marcador de inflamaci&#243;n sist&#233;mica m&#225;s efectivo para la inflamaci&#243;n sist&#233;mica y el valor predictivo se confirm&#243; mediante el an&#225;lisis ROC dependiente del tiempo<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">En un estudio&#44; que incluy&#243; datos sobre 2&#46;715 pacientes&#44; se investig&#243; el valor predictivo del NLR en el c&#225;ncer gastroesof&#225;gico operable&#46; La mayor&#237;a de los estudios informaron que el NLR fue un predictor independiente de supervivencia en el c&#225;ncer gastroesof&#225;gico operable<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a>&#46; En otro estudio que incluy&#243; datos sobre 445 pacientes&#44; investigando el valor predictivo del NLR en el c&#225;ncer de p&#225;ncreas&#44; 2<span class="elsevierStyleHsp" style=""></span>estudios informaron que el NLR era un predictor de OS&#59; sin embargo&#44; este no fue el caso para la supervivencia libre de enfermedad<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; Zou et al&#46; demostraron que el NLR y el PLR podr&#237;an servir como factores predictivos de supervivencia en los TNE-GEP de manera confiable&#46; Sin embargo&#44; ese estudio se centr&#243; principalmente en el papel del NLR y el PLR en los TNE-GEP<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Otro enfoque estudiado por Yang et al&#46; fue el c&#225;lculo de un &#237;ndice inmunoinflamatorio sist&#233;mico &#40;SII&#41;&#44; basado en los recuentos de linfocitos&#44; neutr&#243;filos y plaquetas&#44; que se ha sugerido recientemente que se asocia con un mal resultado en el carcinoma hepatocelular&#44; el carcinoma de c&#233;lulas escamosas&#44; el c&#225;ncer de es&#243;fago&#44; el c&#225;ncer de pulm&#243;n de c&#233;lulas peque&#241;as y otros&#46; Seg&#250;n el resultado de su metaan&#225;lisis&#44; un SII alto se asoci&#243; con un peor resultado de la OS&#44; tiempo hasta la recurrencia&#44; la PFS&#44; la supervivencia c&#225;ncer espec&#237;fica y supervivencia libre de reca&#237;das<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; nuestros resultados muestran un papel exacto para NLR y dNLR en la predicci&#243;n del pron&#243;stico para los pacientes con TNE-GEP tratados con PRRT&#46; Sin embargo&#44; la limitaci&#243;n en este estudio es la peque&#241;a cohorte de pacientes&#46; Por lo tanto&#44; se debe realizar una validaci&#243;n adicional para confirmar estos hallazgos antes de la integraci&#243;n en la pr&#225;ctica cl&#237;nica&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Colaboradores del grupo de trabajo</span><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Anido Herranz&#44; Urbano&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">Bar&#243;n&#44; Francisco&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital Universitario de A Coru&#241;a&#59; <span class="elsevierStyleItalic">Beiras Sarasquete&#44; Carolina&#44;</span> Servicio de Cirug&#237;a&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">Bernardez&#44; Beatriz&#44;</span> Servicio de Farmacolog&#237;a&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">Cameselle Teijeiro&#44; Jose Manuel&#44;</span> Servicio de Anatom&#237;a Patol&#243;gica&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">Castro Alvari&#241;o&#44; Javier&#44;</span> Servicio de Oncolog&#237;a&#44; Universidad de Ferrol&#59; <span class="elsevierStyleItalic">Concha L&#243;pez&#44; &#193;ngel&#44;</span> Servicio de Anatom&#237;a Patol&#243;gica&#44; Hospital Universitario de A Coru&#241;a&#59; <span class="elsevierStyleItalic">Costa Rivas&#44; Marinha&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital de Povisa&#59; <span class="elsevierStyleItalic">Couto Vorner&#44; Ignacio&#44;</span> Servicio de Gastroenterolog&#237;a&#44; Hospital Universitario de A Coru&#241;a&#59; <span class="elsevierStyleItalic">Carral Maseda&#44; Alberto&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital Universitario de Lugo&#59; <span class="elsevierStyleItalic">Jos&#233; Mar&#237;a De Mat&#237;as Leralta&#44;</span> Servicio de Endocrinolog&#237;a&#44; Hospital Universitario de Lugo&#59; <span class="elsevierStyleItalic">De la Iglesia Garc&#237;a&#44; Daniel&#44;</span> Servicio de Gastroenterolog&#237;a&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">Fernandez Calvo&#44; Ovidio&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital Universitario de Lugo&#59; <span class="elsevierStyleItalic">Fern&#225;ndez Catalina&#44; Pablo&#44;</span> Servicio de Endocrinolog&#237;a&#44; Hospital Universitario de Pontevedra&#59; <span class="elsevierStyleItalic">Francisco Gonz&#225;lez&#44; Mar&#237;a&#44;</span> Servicio de Gastroenterolog&#237;a&#44; Hospital Universitario de Ourense&#59; <span class="elsevierStyleItalic">Frojan Parga&#44; Mar&#237;a Purificaci&#243;n&#44;</span> Servicio de Cirug&#237;a&#44; Hospital Universitario de Ourense&#59; <span class="elsevierStyleItalic">Gutierrez&#44; Ceferino&#44;</span> Servicio de Medicina Nuclear&#44; Hospital de Povisa&#59; <span class="elsevierStyleItalic">Isidro San Juan&#44; Mar&#237;a Luisa&#44;</span> Servicio de Endocrinolog&#237;a&#44; Hospital Universitario&#59; <span class="elsevierStyleItalic">Martinez de Llano&#44; Sofia Rodriguez&#44;</span> Servicio de Medicina Nuclear&#44; Hospital Universitario de A Coru&#241;a&#59; <span class="elsevierStyleItalic">Mato Mato&#44; Jose Antonio&#44;</span> Servicio de Endocrinolog&#237;a&#44; Hospital Universitario&#59; <span class="elsevierStyleItalic">Mu&#241;iz Garcia&#44; Gloria&#44;</span> Servicio de Medicina Nuclear&#44; Hospital Universitario de Ourense&#59; <span class="elsevierStyleItalic">Pardo Roja&#44; Purificaci&#243;n&#44;</span> Servicio de Radiolog&#237;a&#44; Hospital Universitario de Ourense&#59; <span class="elsevierStyleItalic">Penin Corderi&#44; Mar&#237;a del Carmen&#44;</span> Servicio de Anatom&#237;a Patol&#243;gica&#44; Hospital Universitario&#59; <span class="elsevierStyleItalic">Pell&#243;n&#44; Mar&#237;a Luz&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital de Ferrol&#59; <span class="elsevierStyleItalic">P&#233;rez Fontan&#44; Javier&#44;</span> Servicio de Radiolog&#237;a&#44; Hospital Universitario de A Coru&#241;a&#59; <span class="elsevierStyleItalic">Prieto Tenrreiro&#44; Alma Mar&#237;a&#44;</span> Servicio de Endocrinolog&#237;a&#44; Hospital de Ferrol&#59; <span class="elsevierStyleItalic">Pu&#241;al Rodr&#237;guez&#44; Jos&#233; Antonio&#44;</span> Servicio de Cirug&#237;a&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">Quind&#243;s Varela&#44; Maria&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital Universitario de A Coru&#241;a&#59; <span class="elsevierStyleItalic">Rodriguez Fonseca&#44; Omar&#44;</span> Servicio de Medicina Nuclear&#44; Hospital Universitario de Lugo&#59; <span class="elsevierStyleItalic">Tom&#233;&#44; Santiago&#44;</span> Servicio de Medicina Interna&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">Varela Ferreiro&#44; Silvia&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital Universitario Santiago de Compostela&#59; <span class="elsevierStyleItalic">V&#225;zquez Est&#233;vez&#44; Sergio&#44;</span> Servicio de Oncolog&#237;a&#44; Hospital Universitario de Lugo&#59; <span class="elsevierStyleItalic">Veiga Barreiro&#44; Jesus Alberto&#44;</span> Servicio de Anatom&#237;a Patolog&#237;a&#44; Hospital de Ferrol&#59; <span class="elsevierStyleItalic">Vieira Leite de Lima&#44; Cecilia&#44;</span> Servicio de Radiolog&#237;a&#44; Hospital Universitario Santiago de Compostela&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Contribuciones de los autores</span><p id="par0150" class="elsevierStylePara elsevierViewall">EAJC y NML han escrito el manuscrito&#44; recogido los datos y realizado algunos an&#225;lisis estad&#237;sticos&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">MCMA proces&#243; los datos y realiz&#243; los an&#225;lisis estad&#237;sticos&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">ZNS&#44; ACC y JMC contribuyeron al diagn&#243;stico y seguimiento de los pacientes&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">VPN y ARM supervisaron la recolecci&#243;n de datos y el dise&#241;o del estudio&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Financiaci&#243;n</span><p id="par0170" class="elsevierStylePara elsevierViewall">Esta investigaci&#243;n no recibi&#243; ninguna subvenci&#243;n espec&#237;fica de ninguna agencia de financiaci&#243;n en los sectores p&#250;blico o comercial&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicto de intereses</span><p id="par0175" class="elsevierStylePara elsevierViewall">Declaramos que ninguno de los autores tiene ning&#250;n conflicto de intereses que revelar&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los &#237;ndices inflamatorios sist&#233;micos se han validado como indicadores de inflamaci&#243;n sist&#233;mica como marcadores predictivos de mal pron&#243;stico para diversas enfermedades oncol&#243;gicas&#46; Sin embargo&#44; se desconoce el impacto pron&#243;stico de los marcadores de inflamaci&#243;n sist&#233;mica en pacientes con tumores neuroendocrinos gastroenteropancre&#225;ticos &#40;TNE-GEP&#41; tratados con p&#233;ptidos marcados con radion&#250;clidos &#40;PRRT&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Realizamos un estudio observacional&#44; retrospectivo&#44; multic&#233;ntrico de 40 pacientes con TNEs-GEP y TNE de origen desconocido tratados con PRRT entre el 2016 y el 2020&#46; Los marcadores inflamatorios sist&#233;micos se calcularon de la siguiente manera&#58; relaci&#243;n neutr&#243;filos a linfocitos &#40;NLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de neutr&#243;filos&#47;recuento de linfocitos&#44; relaci&#243;n de monocitos a linfocitos &#40;MLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de monocitos&#47;recuento de linfocitos&#44; relaci&#243;n de plaquetas a linfocitos &#40;PLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de plaquetas&#47;recuento de linfocitos&#44; relaci&#243;n de alb&#250;mina a linfocitos &#40;ALR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>niveles de alb&#250;mina&#47;recuento de linfocitos y relaci&#243;n derivada de neutr&#243;filos a linfocitos &#40;dNLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>recuento de neutr&#243;filos&#47;&#40;recuento de leucocitos &#8211; recuento de neutr&#243;filos&#41;&#46; Se utilizaron datos anal&#237;ticos basales pretratamiento y despu&#233;s de la segunda dosis para el c&#225;lculo de los distintos &#237;ndices&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La mediana de edad fue de 63 a&#241;os &#40;rango 41-85&#41;&#44; el 55&#37; eran hombres&#46; Los valores de corte de referencia para NLR fueron 2&#44;61&#44; para MLR 0&#44;31&#44; para PLR 110&#44;14&#44; para ALR 2&#44;39 y para dNLR 1&#44;71&#46; Los valores de corte despu&#233;s de la segunda dosis fueron&#44; para NLR 2&#44;3&#44; para MLR 0&#44;3&#44; para PLR 131&#44;61&#44; ALR 4&#44;16 y dNLR 1&#44;48&#46; La mediana de la sobrevivencia libre de progresi&#243;n &#40;SLP&#41; fue de 21&#44;7 meses &#40;IC del 95&#37;&#58; 10&#44;7-32&#44;8 m&#41; y la supervivencia global &#40;SG&#41; fue de 32&#44;1 meses &#40;IC del 95&#37;&#58; 19&#44;6-44&#44;7 m&#41;&#44; la SLP fue m&#225;s corta en pacientes con NLR elevado &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; ALR &#40;0&#44;03&#41; y dNLR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; en el an&#225;lisis basal&#46; La tasa de control de enfermedad &#40;DCR&#41; fue del 81&#37; y la tasa de respuesta objetiva &#40;ORR&#41; del 18&#37;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En los TNE-GEP o de origen desconocido tratados con PRRT hemos identificado el impacto predictivo y pron&#243;stico de los factores inflamatorios sist&#233;micos en la anal&#237;tica basal pretratamiento&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Aim</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes&#46; However&#44; the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors &#40;GEP-NETs&#41; treated with peptide receptor radionuclide therapy &#40;PRRT&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted an observational&#44; retrospective&#44; multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020&#46; The systemic inflammatory markers were calculated as follows&#58; neutrophil to lymphocyte ratio &#40;NLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>neutrophil count&#47;lymphocyte count&#44; monocyte to lymphocyte ratio &#40;MLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>monocyte count&#47;lymphocyte count&#44; platelet to lymphocyte ratio &#40;PLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>platelet count&#47;lymphocyte count&#44; albumin to lymphocyte ratio &#40;ALR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>albumin levels&#47;lymphocyte count and derived Neutrophil to Lymphocyte ratio &#40;dNLR&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>neutrophil count&#47;&#40;leucocytes count &#8211; neutrophils count&#41;&#46; Baseline analysis and after the second dose were used for the calculation of different ratios&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The median age was 63 years &#40;range 41&#8211;85&#41;&#44; 55&#37; were male&#46; The baseline cut-off values for NLR were 2&#46;61&#44; for MLR 0&#46;31&#44; for PLR 110&#46;14&#44; for ALR 2&#46;39 and for dNLR 1&#46;71&#46; The cut-off values after the 2&#176; dose were&#44; for NLR 2&#46;3&#44; for MLR 0&#46;3&#44; for PLR 131&#46;61&#44; ALR 4&#46;16&#44; and dNLR 1&#46;48&#46; Median progression-free survival &#40;PFS&#41; was 21&#46;7 months &#40;95&#37; CI 10&#46;7&#8211;32&#46;8 months&#41; and overall survival &#40;OS&#41; was 32&#46;1 months &#40;95&#37; CI 19&#46;6&#8211;44&#46;7 months&#41;&#44; PFS was shorter in patients with elevated NLR <span class="elsevierStyleItalic">&#40;P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; ALR &#40;0&#46;03&#41;&#44; and dNLR <span class="elsevierStyleItalic">&#40;P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; in baseline analysis&#46; DCR was 81&#37; and ORR 18&#37;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In GEP or unknown origin NETs treated with PRRT&#44; we have identified the predictive and prognostic impact of baseline systemic inflammatory factors&#46;</p></span>"
        "secciones" => array:4 [
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Curvas de Kaplan-Meier para PFS &#40;A&#41; y OS &#40;B&#41; de toda la cohorte del estudio&#46; La mediana de PFS desde el inicio del tratamiento fue de 21&#44;7 meses &#40;IC del 95&#37;&#58; 10&#44;7-32&#44;8 meses&#41; y la mediana de OS fue de 32&#44;1 meses &#40;IC del 95&#37;&#58; 19&#44;6&#46;44&#44;7 meses&#41;&#46;</p>"
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        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Representaci&#243;n gr&#225;fica de la supervivencia global &#40;OS&#41; a partir del diagn&#243;stico de TNE &#40;meses&#41; e &#237;ndices inflamatorios en el an&#225;lisis basal&#46; A&#41; &#205;ndice neutr&#243;filos&#47;linfocitos &#40;NLR&#41;&#46; B&#41; &#205;ndice plaquetas&#47;linfocitos &#40;PLR&#41;&#46; C&#41; &#205;ndice derivada neutr&#243;filos&#47;linfocitos &#40;dNLR&#41;&#46; D&#41; &#205;ndice linfocitos&#47;monocitos &#40;LMR&#41;&#46; E&#41; &#205;ndice alb&#250;mina&#47;linfocitos &#40;ALR&#41;&#46; F&#41; &#205;ndice inflamatorio sist&#233;mico &#40;SIS&#41;&#46;</p>"
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                  \t\t\t\t">16 &#40;40&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">TNE gastrointestinal</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25 &#40;62&#44;5&#37;&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Duodeno&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;52&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&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">37 &#40;92&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \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">21 &#40;52&#44;5&#37;&#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
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">6 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;004</span></td><td class="td" title="\n
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                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NR&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">NR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;8&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;4&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Localizaci&#243;n del tumor</span></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"><span class="elsevierStyleHsp" style=""></span>Gastrointestinal&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">28&#44;0&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;355</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">NR&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;145</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"><span class="elsevierStyleHsp" style=""></span>Pancre&#225;tico&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">21&#44;5&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;1&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"><span class="elsevierStyleHsp" style=""></span>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">16&#44;8&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">NR&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TNE</span> funcionales</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"><span class="elsevierStyleHsp" style=""></span>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">27&#44;2&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;621 &#40;0&#44;3-1&#44;5&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;272</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">32&#44;1&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;520 &#40;0&#44;2-1&#44;4&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;171</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"><span class="elsevierStyleHsp" style=""></span>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">15&#44;8&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">20&#44;1&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Grado tumoral</span></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"><span class="elsevierStyleHsp" style=""></span>G1&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">28&#44;0&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span></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">32&#44;1&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span></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"><span class="elsevierStyleHsp" style=""></span>G2&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">19&#44;8&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">NR&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"><span class="elsevierStyleHsp" style=""></span>G3&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&#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">2&#44;3&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Ki 67&#37;</span></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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8804; 2&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&#44;2&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;001</span></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">32&#44;1&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;171</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"><span class="elsevierStyleHsp" style=""></span>3-20&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">21&#44;5&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">28&#44;3&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"><span class="elsevierStyleHsp" style=""></span>20-55&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">5&#44;2&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">5&#44;2&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Cirug&#237;a del tumor primario</span></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"><span class="elsevierStyleHsp" style=""></span>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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;301 &#40;0&#44;1-0&#44;7&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;006</span></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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;252 &#40;0&#44;1-0&#44;7&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;005</span></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"><span class="elsevierStyleHsp" style=""></span>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">16&#44;8&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&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                0 => """
                  <table border="0" frame="\n
                  \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">Par&#225;metro&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">Mediana de PFS&#44; meses&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">HR &#40;IC del 95&#37;&#41;&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">Valor de p&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">Mediana de OS&#44; meses&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">HR &#40;IC del 95&#37;&#41;&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">Valor de p&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">NLR</span></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"><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#44;61&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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;266 &#40;0&#44;1-0&#44;7&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;04</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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;160 &#40;0&#44;1-0&#44;6&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;001</span></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"><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2&#44;61&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&#44;8&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&#44;7&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">LMR</span></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"><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3&#44;09&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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;330 &#40;0&#44;1-0&#44;9&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;039</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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;340 &#40;0&#44;1-1&#44;2&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;08</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"><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3&#44;09&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&#44;5&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;1&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PLR</span></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"><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>110&#44;14&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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;404 &#40;0&#44;1-1&#44;0&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;044</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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;693 &#40;0&#44;3-1&#44;8&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;456</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"><span class="elsevierStyleHsp" style=""></span>&#8805; 110&#44;14&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&#44;0&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;1&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ALR</span></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"><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#44;39&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&#44;2&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;353 &#40;0&#44;1-0&#44;9&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;016</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">39&#44;2&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;418 &#40;0&#44;2-1&#44;1&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;070</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"><span class="elsevierStyleHsp" style=""></span>&#8805; 2&#44;39&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&#44;8&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">20&#44;01&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">dNLR</span></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"><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#44;71&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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;353 &#40;0&#44;1-0&#44;9&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001</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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;155 &#40;0&#44;1-0&#44;5&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;001</span></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"><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#44;71&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&#44;8&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&#44;7&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Grupos</span><span class="elsevierStyleItalic">SIS</span></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"><span class="elsevierStyleHsp" style=""></span>0-2&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">NR&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>131&#44;61&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">NR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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Información del artículo
ISSN: 2253654X
Idioma original: Español
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