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a grande maioria dos trabalhos&#44; incluindo o grupo espanhol<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; s&#243; estudaram os ex&#245;es 19 e 21 &#40;e&#44; neste&#44; s&#243; a <span class="elsevierStyleItalic">muta&#231;&#227;o Leu858Arg</span>&#41;&#46; J&#225; foi referido anteriormente que ocorriam muta&#231;&#245;es nos ex&#245;es 18 e 20 e que algumas tinham valor preditivo de resposta<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; Apontava-se para valores de 5&#37; ex&#227;o 18&#59; 49&#37; ex&#227;o 19&#59; 1&#37; ex&#227;o 20&#59; 45&#37; ex&#227;o 21&#46; O valor preditivo positivo da muta&#231;&#227;o <span class="elsevierStyleItalic">Gly719</span> no ex&#227;o 18 est&#225; bem estabelecido e o valor preditivo negativo das inser&#231;&#245;es do ex&#227;o 20<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; Penzel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; em 1047 casos analisados&#44; encontraram uma taxa de muta&#231;&#227;o de 15&#44;6&#37; &#40;ex&#227;o 18 &#8211; 10&#44;4&#37;&#59; ex&#227;o 19 &#8211; 49&#44;7&#37;&#59; ex&#227;o 20 &#8211; 5&#44;5&#37;&#59; ex&#227;o 21 &#8211; 34&#44;4&#37;&#46;&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">N&#227;o tem sido tamb&#233;m consensual a que grupo de doentes deve ser pedida a muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> e os estudos efetuados t&#234;m exclu&#237;do habitualmente os doentes com tumores epidermoides e grandes fumadores&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ainda sem defini&#231;&#227;o clara sobre qual o valor da bi&#243;psia &#40;em tumor prim&#225;rio vs&#46; met&#225;stases&#41; para o estudo da muta&#231;&#227;o&#44; no entanto&#44; sempre que poss&#237;vel&#44; o primeiro estudo da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> tem sido efetuado no tumor prim&#225;rio e n&#227;o nas met&#225;stases&#46; Tamb&#233;m sem grande tradi&#231;&#227;o entre n&#243;s&#44; efetuar nova pun&#231;&#227;o aos doentes que progridem a efetuaefetuar ITK&#46; Em cerca de 50&#37; dos casos de progress&#227;o ocorre a muta&#231;&#227;o <span class="elsevierStyleItalic">Thr790Met</span> &#40;ex&#227;o 20&#41;&#46; Esta muta&#231;&#227;o confere resist&#234;ncia ao tratamento com ITK&#44; sendo uma muta&#231;&#227;o secund&#225;ria que aparece ap&#243;s tratamento e aquisi&#231;&#227;o de resist&#234;ncia e s&#243; muito raramente uma muta&#231;&#227;o prim&#225;ria &#40;alguns autores defendem que pode j&#225; estar presente em subclones residuais de c&#233;lulas tumorais antes do tratamento com ITK&#41;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As melhores respostas ao tratamento com ITK e muta&#231;&#245;es obt&#234;m-se em doentes com dele&#231;&#245;es no ex&#227;o 19 e na muta&#231;&#227;o <span class="elsevierStyleItalic">Leu858Arg</span> do ex&#227;o 21&#44; embora tendencialmente com resultados um pouco inferiores &#224; dele&#231;&#227;o do ex&#227;o 19&#59; as muta&#231;&#245;es <span class="elsevierStyleItalic">Gly719</span> &#40;ex&#227;o 18&#41; e <span class="elsevierStyleItalic">Leu 861</span> &#40;ex&#227;o 21&#41; est&#227;o associadas a boa resposta&#46; A evid&#234;ncia &#233; cl&#237;nica e experimental <span class="elsevierStyleItalic">&#40;in vitro&#41;</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A Unidade de Pneumologia Oncol&#243;gica &#40;UPO&#41; do Servi&#231;o de Pneumologia do Centro Hospitalar Gaia-Espinho &#40;CHGE&#41; iniciou a pesquisa da muta&#231;&#227;o do gene do <span class="elsevierStyleItalic">EGFR</span> em 2006 em colabora&#231;&#227;o com o IPATIMUP &#40;Instituto de Patologia e Imunologia Molecular da Universidade do Porto&#41; em doentes selecionados e j&#225; com o uso aprovado em Portugal de erlotinib em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linhas&#46; Em 2010&#44; com a aprova&#231;&#227;o do gefitinib em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha passou a efetuar esta sequencia&#231;&#227;o em todos os doentes com CPNPC&#44; independentemente da histologia&#44; estadio&#44; h&#225;bitos tab&#225;gicos ou sexo&#44; e a tratar com gefitinib em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha todos os doentes com muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> positiva<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; Pretendia-se&#44; assim&#44; a recolha de dados epidemiol&#243;gicos de forma prospetiva&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material e m&#233;todos</span><p id="par0070" class="elsevierStylePara elsevierViewall">Apresentamos os resultados de um registo cont&#237;nuo&#44; para pesquisa de muta&#231;&#245;es do <span class="elsevierStyleItalic">EGFR</span> em doentes com CPNPC&#44; realizado no Servi&#231;o de Pneumologia do Centro Hospitalar de 2006 a 2010&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Foram avaliados os resultados obtidos ap&#243;s tratamento em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com ITK em doentes com CPNPC doen&#231;a avan&#231;ada que efetuaefetuaram a pesquisa de muta&#231;&#227;o do EGFR&#46; Os resultados em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha nos doentes mutados n&#227;o s&#227;o alvo de apresenta&#231;&#227;o&#44; dado ainda o pequeno n&#46;&#176; de casos&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">No per&#237;odo entre 2006-2009&#44; os crit&#233;rios de inclus&#227;o para o estudo da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> foram histologia adenocarcinoma&#44; n&#227;o fumadores ou ex-fumadores&#44; independentemente do sexo&#59; no ano de 2010&#44; os crit&#233;rios de inclus&#227;o foram diagn&#243;stico de CPNPC&#44; independentemente do sexo ou do estadio ou h&#225;bitos tab&#225;gicos&#46; Os doentes foram classificados de acordo com h&#225;bitos tab&#225;gicos&#44; em fumadores&#44; ex-fumadores &#40;doentes que deixaram de fumar h&#225; mais de 12 meses&#41; e n&#227;o fumadores&#46; Registo do material dispon&#237;vel para an&#225;lise e demora m&#233;dia de resultado do exame&#44; de acordo com o material enviado&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Nos doentes em estadios avan&#231;ados que efetuaram erlotinib em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha entre 2006 e 2010&#44; os par&#226;metros avaliados inclu&#237;ram idade&#44; sexo&#44; h&#225;bitos tab&#225;gicos&#44; histologia&#44; estadio TNM na apresenta&#231;&#227;o&#44; regimes pr&#233;vios de quimioterapia&#44; estado mutacional do <span class="elsevierStyleItalic">EGFR</span> e sobrevida global de acordo com o estado mutacional&#44; sobrevida mediana global ap&#243;s erlotinib&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Todos os c&#225;lculos estat&#237;sticos foram efetuados com o software <span class="elsevierStyleItalic">SPSS &#40;Statistical Package for the Social Sciences&#41;</span> vers&#227;o 17&#46;0&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Resultados</span><p id="par0095" class="elsevierStylePara elsevierViewall">No per&#237;odo entre 1 de janeiro de 2006 a 31 dezembro de 2010&#44; foi efetuada a sequencia&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> em 374 doentes com CPNPC &#40;248 doentes entre 2006-2009 e 126 doentes em 2010&#41;&#46; No total de doentes analisados&#44; 266 &#40;71&#44;1&#37;&#41; do sexo masculino e 108 &#40;28&#44;9&#37;&#41; do sexo feminino&#46; M&#233;dia de idades de 64&#44;5 &#177; 11&#44;3 anos&#46; Em rela&#231;&#227;o aos h&#225;bitos tab&#225;gicos&#44; 35&#44;8&#37; ex-fumadores&#44; 31&#44;3&#37; n&#227;o fumadores e 32&#44;9&#37; fumadores&#46; O tipo histol&#243;gico predominante &#8211; adenocarcinoma &#40;57&#44;8&#37;&#41;&#44; seguido do carcinoma epidermoide &#8211; 23&#44;5&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">10&#44;1&#37; dos doentes encontravam-se no estadio <span class="elsevierStyleSmallCaps">i</span>&#59; no estadio <span class="elsevierStyleSmallCaps">ii</span>em 2&#44;4&#37; dos casos&#59; estadio IIIA em 5&#44;8&#37; e os estadios IIIB&#47;IV em 81&#44;6&#37; dos casos&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">As muta&#231;&#245;es no gene <span class="elsevierStyleItalic">EGFR</span> foram detetadas em 49 de 374 doentes&#44; correspondendo a uma taxa de muta&#231;&#227;o de 13&#44;1&#37; &#40;a taxa de muta&#231;&#227;o foi de 9&#37; no sexo masculino e 23&#37; no sexo feminino&#41;&#46; No total de doentes mutados&#44; 46&#44;9&#37; eram n&#227;o fumadores e 59&#44;2&#37; correspondiam a adenocarcinoma &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Quando considerados separadamente&#44; a taxa de muta&#231;&#227;o nos doentes selecionados entre 2006 e 2009 foi de 16&#44;3 vs<span class="elsevierStyleItalic">&#46;</span> 10&#44;4&#37; no ano de 2010 em que o estudo da muta&#231;&#227;o come&#231;ou a ser efetuado a todos os doentes com CPNPC&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">A distribui&#231;&#227;o por ex&#245;es foi a seguinte&#58; 10&#44;2&#37; no ex&#227;o 18&#59; 38&#44;8&#37; no ex&#227;o 19&#59; 18&#44;4&#37; no ex&#227;o 20 &#40;6&#44;2&#37; foram de resist&#234;ncia&#41;&#59; 32&#44;7&#37; no ex&#227;o 21&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Os doentes do sexo feminino com muta&#231;&#227;o positiva &#40;n&#160;&#61;&#160;25&#41;&#44; a maioria n&#227;o fumadores &#40;22&#47;88&#44;0&#37;&#41; e com predom&#237;nio do adenocarcinoma &#40;20&#47;80&#44;0&#37;&#41;&#46; Neste subgrupo&#44; 44&#37; das muta&#231;&#245;es ocorreram no ex&#227;o 19&#59; 28&#37; no ex&#227;o 21&#59; 12&#37; no ex&#227;o 18 e 12&#37; no ex&#227;o 20 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Nos homens mutados &#40;n&#160;&#61;&#160;24&#41;&#44; 91&#44;7&#37; eram fumadores ou ex-fumadores e o tipo histol&#243;gico predominante foi o carcinoma epidermoide em 45&#44;8&#37; dos doentes&#46; As muta&#231;&#245;es ocorreram em 37&#44;5&#37; no ex&#227;o 21&#59; 29&#44;2&#37; no ex&#227;o 19&#59; 25&#37; ex&#227;o 20 e 8&#44;3&#37; no ex&#227;o 18 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Os doentes mutados n&#227;o fumadores &#40;23&#41;&#44; s&#227;o na sua maioria do sexo feminino &#40;21&#47;91&#44;3&#37;&#41;&#44; 78&#44;3&#37; adenocarcinomas&#44; 17&#44;4&#37; CPNPC e 4&#44;3&#37; carcinomas epiderm&#243;ides&#46; A muta&#231;&#227;o&#44; na maioria dos n&#227;o fumadores&#44; ocorreu no ex&#227;o 19 &#40;43&#44;5&#37;&#41; e ex&#227;o 21 &#40;34&#44;8&#37;&#41;&#44; seguidos do ex&#227;o 18 &#40;13&#44;0&#37;&#41; e ex&#227;o 20 &#40;4&#44;3&#37;&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">No tempo m&#233;dio de demora at&#233; ao resultado da sequencia&#231;&#227;o<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#44; verificou-se&#44; de acordo com o tipo de material dispon&#237;vel para estudo que&#44; as l&#226;minas demoram em m&#233;dia 20 dias&#59; o bloco de parafina 8&#44;32 dias e os detritos celulares &#40;com produtos a fresco &#8211; EBUS&#44; BAT e outras pun&#231;&#245;es&#44; na presen&#231;a de anatomia patol&#243;gica&#41; 6&#44;5 dias &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Do total de doentes sequenciados&#44; 71 em estadio avan&#231;ado ou metastizado efetuaram tratamento de 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com erlotinib 150<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; at&#233; &#224; morte&#44; progress&#227;o da doen&#231;a ou toxicidade inaceit&#225;vel&#46; Neste subgrupo de doentes&#44; verificou-se predom&#237;nio do sexo feminino &#40;43&#47;60&#44;6&#37;&#41;&#44; n&#227;o fumadores &#40;31&#47;43&#44;7&#37;&#41; e histologia adenocarcinoma &#40;43&#47;60&#44;6&#37;&#41;&#46; A muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> positiva em 20 doentes &#40;19&#44;2&#37;&#41;&#44; 55&#37; homens e 45&#37; mulheres&#44; na maioria n&#227;o fumadores &#40;12&#47;60&#44;0&#37;&#41; e histologia adenocarcinoma &#40;14&#47;70&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Na resposta global ao tratamento com erlotinib&#44; nos doentes com <span class="elsevierStyleItalic">muta&#231;&#227;o do EGFR</span> negativa &#40;n&#160;&#61;&#160;51&#41;&#44; verificou-se 47&#44;9&#37; &#40;24&#41; doen&#231;a progressiva&#44; 45&#44;1&#37; &#40;23&#41; doen&#231;a estacion&#225;ria e 7&#44;8&#37; &#40;4&#41; remiss&#227;o parcial&#46; No subgrupo de doentes tratados com erlotinib com muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> positiva &#40;n &#61;&#160;20&#41;&#44; 35&#44;0&#37; &#40;7&#41; apresentaram doen&#231;a progressiva&#44; 50&#44;0&#37; &#40;10&#41; doen&#231;a estacion&#225;ria e 15&#44;0&#37; &#40;3&#41; remiss&#227;o parcial&#44; ou seja&#44; como era de esperar&#44; melhor controlo da doen&#231;a em doentes com muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> positiva quando comparado com os doentes com muta&#231;&#227;o negativa &#40;65&#44;0 vs&#46; 52&#44;9&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">A sobrevida global dos doentes que efetuaram erlotinib com muta&#231;&#227;o do EGFR positiva vs&#46; doentes n&#227;o mutados foi de 47 e 22 meses &#40;p&#160;&#61;&#160;0&#44;038&#41;&#44; respetivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; A sobrevida m&#233;dia ap&#243;s o tratamento com erlotinib no grupo com muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> positiva tamb&#233;m foi superior neste subgrupo quando comparada com os doentes com muta&#231;&#227;o negativa &#40;14 vs&#46; 6 meses&#44; respetivamente p&#160;&#61;&#160;0&#44;003&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discuss&#227;o</span><p id="par0150" class="elsevierStylePara elsevierViewall">A nossa amostra revelou uma taxa de muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> global &#40;2006-2010&#41; de 13&#44;1&#37;&#46; Uma vez que de 2006 a 2009 houve sele&#231;&#227;o de doentes&#44; a taxa de muta&#231;&#227;o foi de 16&#37; vs&#46; 10&#44;4&#37; no ano de 2010 em que o estudo da muta&#231;&#227;o foi efetuado a todos os doentes com CPNPC independentemente do sexo e estadio&#46; Estes n&#250;meros parecem-nos uma mais-valia para o conhecimento da taxa de muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na popula&#231;&#227;o portuguesa&#59; os estudos de preval&#234;ncia da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> no cancro do pulm&#227;o na Europa revelaram&#44; em doentes n&#227;o selecionados&#44; taxas de muta&#231;&#227;o de 10&#37;&#59; em Espanha&#44; Rosell et al&#46;&#44; obtiveram uma taxa de muta&#231;&#227;o de 16&#44;6&#37;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; num grupo selecionado de doentes com CPNPC em estadios avan&#231;ados<span class="elsevierStyleBold">&#46;</span> A continua&#231;&#227;o deste nosso trabalho &#40;que nos anos de 2011 e 2012 se tem mantido igualmente numa popula&#231;&#227;o n&#227;o selecionada&#41; vai permitir tra&#231;ar com seguran&#231;a o perfil da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na popula&#231;&#227;o portuguesa e poder confirmar estes dados agora apresentados&#44; que mostram a presen&#231;a da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na subpopula&#231;&#227;o de doentes do sexo masculino&#44; carcinomas epidermoides e alguns fumadores&#46; A diferen&#231;a &#233;&#44; contudo&#44; muito significativa na taxa de muta&#231;&#227;o em rela&#231;&#227;o aos 2 sexos&#44; sendo o adenocarcinoma respons&#225;vel pela grande maioria dos casos&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Foi poss&#237;vel efetuar a sequencia&#231;&#227;o do gene do <span class="elsevierStyleItalic">EGFR</span> em variados tipos de amostras diagn&#243;sticas&#46; A sequencia&#231;&#227;o de DNA a partir de detritos celulares &#40;a fresco ou ap&#243;s <span class="elsevierStyleItalic">cell blok</span>&#41; foi mais r&#225;pida comparativamente a l&#226;minas ou bloco de parafina&#44; diferen&#231;a essa estatisticamente significativa e com impacto no in&#237;cio do tratamento&#46; Isto s&#243; foi poss&#237;vel com a colabora&#231;&#227;o estreita entre os v&#225;rios elementos envolvidos no diagn&#243;stico do cancro de pulm&#227;o &#40;pneumologia oncol&#243;gica&#44; broncologia&#44; radiologia de interven&#231;&#227;o e anatomia patol&#243;gica&#41;&#46; Nos tumores perif&#233;ricos&#44; ou sempre que seja poss&#237;vel efetuar pun&#231;&#245;es aspirativas&#44; deve-se dar prioridade ao envio deste material a fresco&#44; com obten&#231;&#227;o mais r&#225;pida dos resultados &#40;6&#44;5 dias ap&#243;s o envio dos produtos&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">O estudo da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> deve ser efetuado por rotina em todos os doentes com o diagn&#243;stico de CPNPC e devem ser criadas as condi&#231;&#245;es ao seu uso em todos os hospitais que tratam cancro do pulm&#227;o&#44; tendo em conta o seu correto tratamento&#44; pela possibilidade de uso dos ITK em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha em doentes mutados&#44; com melhor controlo da doen&#231;a do que com os protocolos de quimioterapia convencional&#46; Todos estes pressupostos assentam na resposta ao tratamento e na sobrevida global no grupo de doentes tratados com ITK<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Os resultados da nossa amostra em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha mostraram significado estat&#237;stico no grupo de doentes com muta&#231;&#227;o positiva para o <span class="elsevierStyleItalic">EGFR</span>&#44; comparativamente aos doentes com muta&#231;&#227;o negativa&#44; apesar de a presen&#231;a da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> n&#227;o ser condi&#231;&#227;o obrigat&#243;ria para o in&#237;cio de tratamento&#46; Ainda n&#227;o temos n&#250;mero suficiente de doentes para apresenta&#231;&#227;o dos resultados de 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha dos doentes mutados tratados com ITK&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflito de interesses</span><p id="par0170" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflito de interesses&#46;</p></span></span>"
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          "titulo" => "Bibliografia"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2012-01-12"
    "fechaAceptado" => "2012-08-30"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec565741"
          "palabras" => array:4 [
            0 => "Carcinoma pulmonar n&#227;o pequenas c&#233;lulas"
            1 => "Recetor do fator de crescimento epid&#233;rmico"
            2 => "Inibidores da tirosina quinase"
            3 => "Sobrevida"
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      ]
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec565742"
          "palabras" => array:4 [
            0 => "Non Small Cell Lung Cancer"
            1 => "Epidermal Growth Factor Receptor"
            2 => "Tyrosine kinase inhibitor"
            3 => "Survival"
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    "resumen" => array:2 [
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        "titulo" => "Resumo"
        "resumen" => "<span><span class="elsevierStyleSectionTitle">Introdu&#231;&#227;o</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Em 2006&#44; a Unidade de Pneumologia Oncol&#243;gica do Servi&#231;o de Pneumologia do Centro Hospitalar de Vila Nova de Gaia&#47;Espinho iniciou a sequencia&#231;&#227;o da muta&#231;&#227;o do <span class="elsevierStyleItalic">recetor do fator de crescimento epid&#233;rmico &#40;EGFR&#41;</span> em doentes com CPNPC selecionados e desde 2010 realiza a sequencia&#231;&#227;o sistematicamente em todos os doentes&#44; independentemente da histologia&#44; h&#225;bitos tab&#225;gicos&#44; idade ou sexo&#46; O objetivo deste trabalho foi caracterizar o grupo de doentes que efetuou a sequencia&#231;&#227;o entre 2006-2010&#44; determinar a frequ&#234;ncia da muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span>&#44; avaliar as sobrevidas globais e ap&#243;s uso de inibidores da tirosina quinase &#40;ITK&#41;&#44; nos doentes que efetuaram esta terap&#234;utica em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com conhecimento do estado da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span>&#46;</p></span> <span><span class="elsevierStyleSectionTitle">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise estat&#237;stica descritiva dos doentes que efetuaram sequencia&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> em 2006-2010 e sobrevida mediana global nos doentes que efetuaefetuaram ITK em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha&#46; Registo do material dispon&#237;vel para an&#225;lise e demora m&#233;dia de resultado do exame&#44; de acordo com o material enviado&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A sequencia&#231;&#227;o foi efetuada em 374 doentes&#44; 71&#44;1&#37; sexo masculino&#44; 67&#44;1&#37; n&#227;o&#47;ex-fumadores&#44; 32&#44;9&#37; fumadores&#59; 57&#44;8&#37; adenocarcinoma e 23&#44;5&#37; carcinoma epidermoide &#40;CE&#41;&#46; A muta&#231;&#227;o foi detetada em 49 doentes &#40;13&#44;1&#37;&#41;&#46; No total dos doentes estudados&#44; a taxa de muta&#231;&#227;o foi de 9&#37; no sexo masculino e 23&#37; no sexo feminino&#46; A sobrevida mediana global ap&#243;s o uso de erlotinib foi de 14 meses para os doentes com muta&#231;&#227;o positiva do <span class="elsevierStyleItalic">EGFR versus</span> 6 meses nos doentes n&#227;o mutados &#40;p&#160;&#61;&#160;0&#44;003&#41;&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Conclus&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O nosso grupo teve uma taxa de muta&#231;&#227;o global de 13&#44;1&#37;&#44; com predom&#237;nio no sexo feminino&#44; n&#227;o fumadores&#44; histologia adenocarcinoma&#46; Em doentes selecionados &#40;2006&#47;2009&#41;&#44; a taxa de muta&#231;&#227;o foi de 16&#37;&#59; nos doentes n&#227;o selecionados &#40;2010&#41; foi de 10&#44;4&#37;&#46; Este estudo tem vindo a permitir um melhor conhecimento da taxa de muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na popula&#231;&#227;o portuguesa&#44; bem como avaliar os resultados das sobrevidas dos doentes ap&#243;s uso de inibidores da tirosina quinase &#40;ITK&#41;&#44; efetuada em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com conhecimento pr&#233;vio do estado da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span>&#44; tendo sido encontradas diferen&#231;as nas sobrevidas nos 2 grupos de doentes &#40;mutados e n&#227;o mutados&#41; com significado estat&#237;stico&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A pesquisa muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> deve ser efetuada em todos os doentes com CPNPC&#44; dando possibilidade a um n&#250;mero consider&#225;vel de doentes de poder efetuar um tratamento de 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com ITK &#40;doentes mutados&#41;&#44; bem como de poder usufruir de outros esquemas de quimioterapia&#44; quando progredirem&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span><span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In 2006&#44; the Vila Nova de Gaia&#47;Espinho Hospital Centre Pulmonary Oncology Unit started performing EGFR &#40;Epidermal Growth Factor Receptor&#41; mutation sequencing in selected patients with NSCLC and systematically in all patients since 2010&#44; regardless of histology&#44; smoking habits&#44; age or sex&#46; The aim of this study was to characterize the group of patients that carried out the sequencing between 2006-2010&#44; to determine EGFR mutation frequency&#44; to evaluate the overall survival and the survival after the use of tyrosine kinase inhibitors &#40;TKI&#41;&#44; in patients who performed this therapy in second and third line&#44; knowing the EGFR mutation status&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Descriptive statistical analysis of patients who did EGFR sequencing in 2006-2010 and of overall survival in patients treated with TKI as 2nd and 3rd line therapy&#46; Record of the material available for analysis and average delay of exam results&#44; according to the material submitted&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The sequencing was performed in 374 patients&#44; 71&#44;1&#37; males&#44; 67&#44;1&#37; non&#47;ex-smokers&#44; 32&#44;9&#37; smokers&#44; 57&#44;8&#37; adenocarcinoma and 23&#44;5&#37; squamous cell carcinoma &#40;SCC&#41;&#46; The mutation was detected in 49 patients &#40;13&#44;1&#37;&#41;&#46; In all studied patients&#44; the mutation rate was 9&#37; in males and 23&#37; in females&#46; Median overall survival after erlotinib use of was 14 months for patients with positive EGFR mutation versus 6 months in not mutated patients &#40;p &#61; 0&#46;003&#41;&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Our group had an overall mutation rate of 13&#46;1&#37; with female&#44; non-smokers&#44; adenocarcinoma histology predominance&#46; In selected patients &#40;2006&#47;2009&#41;&#44; the mutation rate was 16&#37;&#44; in not selected patients &#40;2010&#41; the mutation rate was 10&#46;4&#37;&#46; This study has permitted a better understanding of the EGFR mutation rate in the Portuguese population as welll as an evaluation of the patients survival after the use of of tyrosine kinase inhibitors&#44; in second and third line therapy with previous knowledge of the EGFR mutational status&#46; Statistical significant differences in survival were found in the two patient groups &#40;EGFR mutated and non mutated&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The EGFR mutation research should be performed in all patients with NSCLC&#44; giving the possibility to a considerable number of patients to perform a first line treatment with TKI &#40;EGFR mutated patients&#41; and the advantage of performing other chemotherapy schemes&#44; when progression occurs&#46;</p></span>"
      ]
    ]
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          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A&#46; Curva de sobrevida global dos doentes mutados versus n&#227;o mutados &#40;47 vs&#46; 22 meses&#44; p&#160;&#61;&#160;0&#44;038&#41;&#46;</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">B&#46; Curva de sobrevida ap&#243;s tratamento com erlotinib em doentes mutados e WT &#40;14 vs&#46; 6 meses&#44; p&#160;&#61;&#160;0&#44;003&#41;&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col">Vari&#225;veis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Todos doentes &#40;n&#160;&#61;&#160;374&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Doentes mutados &#40;n&#160;&#61;&#160;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">266&#47;71&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;9&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Feminino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">108&#47;28&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#47;23&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Idade</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M&#233;dia&#177;dp&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&#44;52&#160;&#177;&#160;11&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#160;&#177;&#160;9&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M&#237;nimo&#47;m&#225;ximo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#47;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">H&#225;bitos tab&#225;gicos</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ex-fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">134&#47;35&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#47;30&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123&#47;32&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;22&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117&#47;31&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#47;46&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Tipo histol&#243;gico</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">216&#47;57&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&#47;59&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>epidermoide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&#47;23&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#47;24&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ca grandes c&#233;lulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>bronqu&#237;olo-alveolar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;1&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CPNPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#47;16&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;14&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Ex&#227;o</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;10&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#47;38&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#47;18&#44;4&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#47;32&#44;6&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Caracteriza&#231;&#227;o da amostra e frequ&#234;ncia de muta&#231;&#245;es EGFR&#46; &#40;&#42; 6&#44;2&#37; foram muta&#231;&#245;es de resist&#234;ncia&#41;</p>"
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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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Vari&#225;veis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sexo feminino &#40;n&#160;&#61;&#160;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">H&#225;bitos tab&#225;gicos</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#47;88&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;8&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ex-fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;29&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#47;62&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Tipo histol&#243;gico</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#47;80&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;37&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ca epidermoide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#47;45&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CPNPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;16&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Ex&#227;o mutado</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;8&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#47;44&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;29&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#47;25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;28&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;37&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Caracteriza&#231;&#227;o dos doentes mutados por sexo</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bloco de parafina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#44;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#44;6721&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;0255&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">L&#226;mina de histologia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#44;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#44;0888&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#44;1108&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Detritos celulares&nbsp;\t\t\t\t\t\t\n
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        ]
      ]
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                  <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="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Estudo do</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">EGFR</span></span><span class="elsevierStyleBold">e terap&#234;utica com erlotinib</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#47;39&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;55&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Feminino&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#47;45&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Idade</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68&#160;&#177;&#160;8&#44;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">H&#225;bitos tab&#225;gicos</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ex-fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;33&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#47;22&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;15&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>N&#227;o fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#47;43&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#47;60&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tipo histol&#243;gico</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#47;70&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Outro tipo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#47;39&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;30&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">Resposta ao erlotinib</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">EGFR&#160;&#43;&#160;&#61;&#160;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Remiss&#227;o parcial</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;7&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;15&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Doen&#231;a estacion&#225;ria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#47;45&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#47;50&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Doen&#231;a progressiva</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;47&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;35&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sobrevida global media</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sobrevida ap&#243;s uso erlotinib</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab884896.png"
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        ]
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          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas demogr&#225;ficas e resposta ao tratamento dos doentes com estudo do <span class="elsevierStyleItalic">EGFR</span> que efetuaram terap&#234;utica com erlotinib em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliografia"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:18 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Estudo epidemiol&#243;gico do cancro do pulm&#227;o em Portugal nos anos de 2000&#47;2002"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Parente"
                            1 => "H&#46; Queiroga"
                            2 => "E&#46; Teixeira"
                            3 => "R&#46; Sotto-Mayor"
                            4 => "F&#46; Barata"
                            5 => "A&#46; Sousa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Pneumol"
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                        "volumen" => "13"
                        "paginaInicial" => "255"
                        "paginaFinal" => "265"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17571453"
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              "identificador" => "bib0010"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "3 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non&#8211;small-cell lung cancer to gefitinib"
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "R&#46; Sordella"
                            3 => "S&#46; Gurubhagavatula"
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                        "tituloSerie" => "N Engl J Med"
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                        "volumen" => "350"
                        "paginaInicial" => "2129"
                        "paginaFinal" => "2139"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15118073"
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                      "titulo" => "EGFR mutations in lung cancer&#58; correlation with clinical response to gef itinib therapy"
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                            2 => "J&#46;C&#46; Lee"
                            3 => "S&#46; Tracy"
                            4 => "H&#46; Greulich"
                            5 => "S&#46; Gabriel"
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                        "tituloSerie" => "Science"
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                        "paginaInicial" => "1497"
                        "paginaFinal" => "1500"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15118125"
                            "web" => "Medline"
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            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Mutations of the epidermal growth factor receptor gene predict prolonged survival after gef itinib treatment in patients with non-small-cell lung cancer with postoperative recurrence"
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                          "etal" => true
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                            4 => "H&#46; Kuwano"
                            5 => "T&#46; Takahashi"
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                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
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                        "volumen" => "23"
                        "paginaInicial" => "2513"
                        "paginaFinal" => "2520"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15738541"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0025"
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                    0 => array:2 [
                      "titulo" => "EGF receptor gene mutations are common in lung cancers from &#8220;never smokers&#8221; and are associated with sensitivity of tumors to gef itinib and erlotinib"
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                          "etal" => true
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                            2 => "M&#46; Zakowski"
                            3 => "J&#46; Doherty"
                            4 => "K&#46; Politi"
                            5 => "I&#46; Sarkaria"
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                    0 => array:2 [
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                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "2004"
                        "volumen" => "101"
                        "paginaInicial" => "13306"
                        "paginaFinal" => "13311"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15329413"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0030"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Shigematsu"
                            1 => "L&#46; Lin"
                            2 => "T&#46; Takahashi"
                            3 => "M&#46; Nomura"
                            4 => "M&#46; Suzuki"
                            5 => "I&#46; Wistuba"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "J Nat Cancer Inst"
                        "fecha" => "2005"
                        "volumen" => "97"
                        "paginaInicial" => "339"
                        "paginaFinal" => "346"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15741570"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0035"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas"
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                        0 => array:2 [
                          "etal" => true
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                            2 => "R&#46; Rosell"
                            3 => "T&#46; Mok"
                            4 => "B&#46; Massuti"
                            5 => "L&#46; Zamora"
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                    0 => array:2 [
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                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "paginaInicial" => "5878"
                        "paginaFinal" => "5885"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16115929"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0040"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cel lung cancer patients treated with gefitinib"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "T&#46;Y&#46; Kim"
                            2 => "P&#46;G&#46; Hwang"
                            3 => "Y&#46;K&#46; Jeon"
                            4 => "D&#46;Y&#46; Oh"
                            5 => "S&#46;H&#46; Lee"
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                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "2493"
                        "paginaFinal" => "2501"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15710947"
                            "web" => "Medline"
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                            4 => "S&#46; Salvatore"
                            5 => "A&#46; Chella"
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                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
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                        "volumen" => "23"
                        "paginaInicial" => "857"
                        "paginaFinal" => "865"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15681531"
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              "identificador" => "bib0050"
              "etiqueta" => "10"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Screening for epidermal growth factor receptor mutations in lung cancer"
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                            0 => "R&#46; Rosell"
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                            3 => "R&#46; Porta"
                            4 => "F&#46; Cardenal"
                            5 => "C&#46; Camps"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2009"
                        "volumen" => "361"
                        "paginaInicial" => "958"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19692684"
                            "web" => "Medline"
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              "identificador" => "bib0055"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Update on epidermal growth factor receptor mutations in non-small cell lung cancer"
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                          "autores" => array:4 [
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                        "tituloSerie" => "Clin Cancer Res"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17189394"
                            "web" => "Medline"
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                    0 => array:2 [
                      "titulo" => "Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants"
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                            4 => "J&#46; Alvarez"
                            5 => "M&#46; Zappaterra"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16187797"
                            "web" => "Medline"
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                0 => array:2 [
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                      "titulo" => "EGFR mutation detection in NSCLC&#8212;assessment of diagnostic application and recommendations of the German Panel for Mutation Testing in NSCLC"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21057810"
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              "identificador" => "bib0070"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Novel D761Y and common secondary T790<span class="elsevierStyleHsp" style=""></span>M mutations in EGFR-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors"
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                        "paginaFinal" => "6501"
                        "link" => array:1 [
                          0 => array:2 [
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                        "paginaInicial" => "9"
                        "paginaFinal" => "10"
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                    ]
                  ]
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              "identificador" => "bib0080"
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                      "titulo" => "Ge&#64257;tinib or carboplatin-paclitaxel in pulmonary adenocarcinoma"
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                            4 => "D&#46;T&#46; Chu"
                            5 => "N&#46; Saijo"
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                        "tituloSerie" => "N Engl J Med"
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                        "volumen" => "361"
                        "paginaInicial" => "947"
                        "paginaFinal" => "957"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19692680"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer &#40;OPTIMAL CTONG-0802&#41;&#58; a multicentre&#44; open-label&#44; randomised&#44; phase 3 study"
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                        "paginaFinal" => "742"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21783417"
                            "web" => "Medline"
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                      "titulo" => "Erlotinib versus chemotherapy &#40;CT&#41; in advanced non-small cell lung cancer &#40;NSCLC&#41; patients &#40;p&#41; with epidermal growth factor receptor &#40;EGFR&#41; mutations&#58; Interim results of the European Erlotinib Versus Chemotherapy &#40;EURTAC&#41; phase III randomized trial"
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                ]
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Estudo da mutação do recetor do fator de crescimento epidérmico, durante 5 anos, numa população de doentes com cancro do pulmão de não pequenas células
Epidermal Growth Factor Recetor mutation study for 5 years, in a population of patients with non-small cell lung cancer
A.S. Castroa,
, B. Parentea,**, I. Gonçalvesa, A. Antunesa, A. Barrosoa, S. Condea, S. Nevesa, J.C. Machadob
a Unidade de Pneumologia Oncológica, Serviço de Pneumologia, Centro Hospitalar Vila Nova de Gaia-Espinho, Vila Nova de Gaia, Portugal
b Instituto de Patologia e Imunologia Molecular, Universidade do Porto, Porto, Portugal
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no tri&#233;nio de 2000 e 2002&#44; um estudo em que participaram 22 hospitais portugueses&#44; tendo-se registado 4 396 novos casos de cancro do pulm&#227;o&#59; o adenocarcinoma foi o subtipo histol&#243;gico mais frequente e&#44; em 76&#44;9&#37; dos casos os doentes&#44; encontravam-se em estadio avan&#231;ado ou metast&#225;tico de doen&#231;a&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Embora sendo do nosso conhecimento que&#44; destes indiv&#237;duos com doen&#231;a avan&#231;ada&#44; apenas 10-12&#37; poder&#227;o beneficiar dos inibidores da tirosina quinase &#40;ITK&#41; em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha&#44; o aparecimento destes f&#225;rmacos &#40;<span class="elsevierStyleItalic">EGFR</span>-ITK&#41; foi uma mais-valia no tratamento do CPNPC avan&#231;ado ou metast&#225;tico quer em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha&#44; nos doentes com a muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span>&#44; quer em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Existem v&#225;rios par&#226;metros cl&#237;nicos e moleculares que preveem quais os doentes com CPNPC doen&#231;a avan&#231;ada mais suscet&#237;veis de beneficiar do tratamento com inibidores de TK&#44; quer para a terap&#234;utica inicial quer para 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha&#46; Estes indicadores de estudos de fase <span class="elsevierStyleSmallCaps">ii</span><a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;5</span></a> e <span class="elsevierStyleSmallCaps">iii</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> que identificaram par&#226;metros cl&#237;nicos associados a melhor resposta cl&#237;nica&#44; s&#227;o adenocarcinoma&#44; sexo feminino&#44; n&#227;o fumadores e etnia asi&#225;tica<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;9</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Muta&#231;&#245;es ativadoras espec&#237;ficas no dom&#237;nio TK do <span class="elsevierStyleItalic">EGFR</span> &#40;ex&#227;o 18-21&#41; est&#227;o associadas habitualmente a aumento da resposta aos ITK&#44; erlotinib ou gefitinib&#44; ocorrendo&#44; de acordo com a literatura&#44; na Europa em 10-15&#37; dos doentes com CPNPC e com efeitos laterais facilmente manuse&#225;veis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O m&#233;todo &#171;gold-standard&#187; para an&#225;lise da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> &#233; a sequencia&#231;&#227;o direta do ADN&#44; dos ex&#245;es 18 ao 21&#46; A percentagem de muta&#231;&#245;es em cada ex&#227;o &#233; algo ainda controverso&#59; a grande maioria dos trabalhos&#44; incluindo o grupo espanhol<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; s&#243; estudaram os ex&#245;es 19 e 21 &#40;e&#44; neste&#44; s&#243; a <span class="elsevierStyleItalic">muta&#231;&#227;o Leu858Arg</span>&#41;&#46; J&#225; foi referido anteriormente que ocorriam muta&#231;&#245;es nos ex&#245;es 18 e 20 e que algumas tinham valor preditivo de resposta<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; Apontava-se para valores de 5&#37; ex&#227;o 18&#59; 49&#37; ex&#227;o 19&#59; 1&#37; ex&#227;o 20&#59; 45&#37; ex&#227;o 21&#46; O valor preditivo positivo da muta&#231;&#227;o <span class="elsevierStyleItalic">Gly719</span> no ex&#227;o 18 est&#225; bem estabelecido e o valor preditivo negativo das inser&#231;&#245;es do ex&#227;o 20<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; Penzel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; em 1047 casos analisados&#44; encontraram uma taxa de muta&#231;&#227;o de 15&#44;6&#37; &#40;ex&#227;o 18 &#8211; 10&#44;4&#37;&#59; ex&#227;o 19 &#8211; 49&#44;7&#37;&#59; ex&#227;o 20 &#8211; 5&#44;5&#37;&#59; ex&#227;o 21 &#8211; 34&#44;4&#37;&#46;&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">N&#227;o tem sido tamb&#233;m consensual a que grupo de doentes deve ser pedida a muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> e os estudos efetuados t&#234;m exclu&#237;do habitualmente os doentes com tumores epidermoides e grandes fumadores&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ainda sem defini&#231;&#227;o clara sobre qual o valor da bi&#243;psia &#40;em tumor prim&#225;rio vs&#46; met&#225;stases&#41; para o estudo da muta&#231;&#227;o&#44; no entanto&#44; sempre que poss&#237;vel&#44; o primeiro estudo da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> tem sido efetuado no tumor prim&#225;rio e n&#227;o nas met&#225;stases&#46; Tamb&#233;m sem grande tradi&#231;&#227;o entre n&#243;s&#44; efetuar nova pun&#231;&#227;o aos doentes que progridem a efetuaefetuar ITK&#46; Em cerca de 50&#37; dos casos de progress&#227;o ocorre a muta&#231;&#227;o <span class="elsevierStyleItalic">Thr790Met</span> &#40;ex&#227;o 20&#41;&#46; Esta muta&#231;&#227;o confere resist&#234;ncia ao tratamento com ITK&#44; sendo uma muta&#231;&#227;o secund&#225;ria que aparece ap&#243;s tratamento e aquisi&#231;&#227;o de resist&#234;ncia e s&#243; muito raramente uma muta&#231;&#227;o prim&#225;ria &#40;alguns autores defendem que pode j&#225; estar presente em subclones residuais de c&#233;lulas tumorais antes do tratamento com ITK&#41;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As melhores respostas ao tratamento com ITK e muta&#231;&#245;es obt&#234;m-se em doentes com dele&#231;&#245;es no ex&#227;o 19 e na muta&#231;&#227;o <span class="elsevierStyleItalic">Leu858Arg</span> do ex&#227;o 21&#44; embora tendencialmente com resultados um pouco inferiores &#224; dele&#231;&#227;o do ex&#227;o 19&#59; as muta&#231;&#245;es <span class="elsevierStyleItalic">Gly719</span> &#40;ex&#227;o 18&#41; e <span class="elsevierStyleItalic">Leu 861</span> &#40;ex&#227;o 21&#41; est&#227;o associadas a boa resposta&#46; A evid&#234;ncia &#233; cl&#237;nica e experimental <span class="elsevierStyleItalic">&#40;in vitro&#41;</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A Unidade de Pneumologia Oncol&#243;gica &#40;UPO&#41; do Servi&#231;o de Pneumologia do Centro Hospitalar Gaia-Espinho &#40;CHGE&#41; iniciou a pesquisa da muta&#231;&#227;o do gene do <span class="elsevierStyleItalic">EGFR</span> em 2006 em colabora&#231;&#227;o com o IPATIMUP &#40;Instituto de Patologia e Imunologia Molecular da Universidade do Porto&#41; em doentes selecionados e j&#225; com o uso aprovado em Portugal de erlotinib em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linhas&#46; Em 2010&#44; com a aprova&#231;&#227;o do gefitinib em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha passou a efetuar esta sequencia&#231;&#227;o em todos os doentes com CPNPC&#44; independentemente da histologia&#44; estadio&#44; h&#225;bitos tab&#225;gicos ou sexo&#44; e a tratar com gefitinib em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha todos os doentes com muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> positiva<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; Pretendia-se&#44; assim&#44; a recolha de dados epidemiol&#243;gicos de forma prospetiva&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material e m&#233;todos</span><p id="par0070" class="elsevierStylePara elsevierViewall">Apresentamos os resultados de um registo cont&#237;nuo&#44; para pesquisa de muta&#231;&#245;es do <span class="elsevierStyleItalic">EGFR</span> em doentes com CPNPC&#44; realizado no Servi&#231;o de Pneumologia do Centro Hospitalar de 2006 a 2010&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Foram avaliados os resultados obtidos ap&#243;s tratamento em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com ITK em doentes com CPNPC doen&#231;a avan&#231;ada que efetuaefetuaram a pesquisa de muta&#231;&#227;o do EGFR&#46; Os resultados em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha nos doentes mutados n&#227;o s&#227;o alvo de apresenta&#231;&#227;o&#44; dado ainda o pequeno n&#46;&#176; de casos&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">No per&#237;odo entre 2006-2009&#44; os crit&#233;rios de inclus&#227;o para o estudo da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> foram histologia adenocarcinoma&#44; n&#227;o fumadores ou ex-fumadores&#44; independentemente do sexo&#59; no ano de 2010&#44; os crit&#233;rios de inclus&#227;o foram diagn&#243;stico de CPNPC&#44; independentemente do sexo ou do estadio ou h&#225;bitos tab&#225;gicos&#46; Os doentes foram classificados de acordo com h&#225;bitos tab&#225;gicos&#44; em fumadores&#44; ex-fumadores &#40;doentes que deixaram de fumar h&#225; mais de 12 meses&#41; e n&#227;o fumadores&#46; Registo do material dispon&#237;vel para an&#225;lise e demora m&#233;dia de resultado do exame&#44; de acordo com o material enviado&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Nos doentes em estadios avan&#231;ados que efetuaram erlotinib em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha entre 2006 e 2010&#44; os par&#226;metros avaliados inclu&#237;ram idade&#44; sexo&#44; h&#225;bitos tab&#225;gicos&#44; histologia&#44; estadio TNM na apresenta&#231;&#227;o&#44; regimes pr&#233;vios de quimioterapia&#44; estado mutacional do <span class="elsevierStyleItalic">EGFR</span> e sobrevida global de acordo com o estado mutacional&#44; sobrevida mediana global ap&#243;s erlotinib&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Todos os c&#225;lculos estat&#237;sticos foram efetuados com o software <span class="elsevierStyleItalic">SPSS &#40;Statistical Package for the Social Sciences&#41;</span> vers&#227;o 17&#46;0&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Resultados</span><p id="par0095" class="elsevierStylePara elsevierViewall">No per&#237;odo entre 1 de janeiro de 2006 a 31 dezembro de 2010&#44; foi efetuada a sequencia&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> em 374 doentes com CPNPC &#40;248 doentes entre 2006-2009 e 126 doentes em 2010&#41;&#46; No total de doentes analisados&#44; 266 &#40;71&#44;1&#37;&#41; do sexo masculino e 108 &#40;28&#44;9&#37;&#41; do sexo feminino&#46; M&#233;dia de idades de 64&#44;5 &#177; 11&#44;3 anos&#46; Em rela&#231;&#227;o aos h&#225;bitos tab&#225;gicos&#44; 35&#44;8&#37; ex-fumadores&#44; 31&#44;3&#37; n&#227;o fumadores e 32&#44;9&#37; fumadores&#46; O tipo histol&#243;gico predominante &#8211; adenocarcinoma &#40;57&#44;8&#37;&#41;&#44; seguido do carcinoma epidermoide &#8211; 23&#44;5&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">10&#44;1&#37; dos doentes encontravam-se no estadio <span class="elsevierStyleSmallCaps">i</span>&#59; no estadio <span class="elsevierStyleSmallCaps">ii</span>em 2&#44;4&#37; dos casos&#59; estadio IIIA em 5&#44;8&#37; e os estadios IIIB&#47;IV em 81&#44;6&#37; dos casos&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">As muta&#231;&#245;es no gene <span class="elsevierStyleItalic">EGFR</span> foram detetadas em 49 de 374 doentes&#44; correspondendo a uma taxa de muta&#231;&#227;o de 13&#44;1&#37; &#40;a taxa de muta&#231;&#227;o foi de 9&#37; no sexo masculino e 23&#37; no sexo feminino&#41;&#46; No total de doentes mutados&#44; 46&#44;9&#37; eram n&#227;o fumadores e 59&#44;2&#37; correspondiam a adenocarcinoma &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Quando considerados separadamente&#44; a taxa de muta&#231;&#227;o nos doentes selecionados entre 2006 e 2009 foi de 16&#44;3 vs<span class="elsevierStyleItalic">&#46;</span> 10&#44;4&#37; no ano de 2010 em que o estudo da muta&#231;&#227;o come&#231;ou a ser efetuado a todos os doentes com CPNPC&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">A distribui&#231;&#227;o por ex&#245;es foi a seguinte&#58; 10&#44;2&#37; no ex&#227;o 18&#59; 38&#44;8&#37; no ex&#227;o 19&#59; 18&#44;4&#37; no ex&#227;o 20 &#40;6&#44;2&#37; foram de resist&#234;ncia&#41;&#59; 32&#44;7&#37; no ex&#227;o 21&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Os doentes do sexo feminino com muta&#231;&#227;o positiva &#40;n&#160;&#61;&#160;25&#41;&#44; a maioria n&#227;o fumadores &#40;22&#47;88&#44;0&#37;&#41; e com predom&#237;nio do adenocarcinoma &#40;20&#47;80&#44;0&#37;&#41;&#46; Neste subgrupo&#44; 44&#37; das muta&#231;&#245;es ocorreram no ex&#227;o 19&#59; 28&#37; no ex&#227;o 21&#59; 12&#37; no ex&#227;o 18 e 12&#37; no ex&#227;o 20 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Nos homens mutados &#40;n&#160;&#61;&#160;24&#41;&#44; 91&#44;7&#37; eram fumadores ou ex-fumadores e o tipo histol&#243;gico predominante foi o carcinoma epidermoide em 45&#44;8&#37; dos doentes&#46; As muta&#231;&#245;es ocorreram em 37&#44;5&#37; no ex&#227;o 21&#59; 29&#44;2&#37; no ex&#227;o 19&#59; 25&#37; ex&#227;o 20 e 8&#44;3&#37; no ex&#227;o 18 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Os doentes mutados n&#227;o fumadores &#40;23&#41;&#44; s&#227;o na sua maioria do sexo feminino &#40;21&#47;91&#44;3&#37;&#41;&#44; 78&#44;3&#37; adenocarcinomas&#44; 17&#44;4&#37; CPNPC e 4&#44;3&#37; carcinomas epiderm&#243;ides&#46; A muta&#231;&#227;o&#44; na maioria dos n&#227;o fumadores&#44; ocorreu no ex&#227;o 19 &#40;43&#44;5&#37;&#41; e ex&#227;o 21 &#40;34&#44;8&#37;&#41;&#44; seguidos do ex&#227;o 18 &#40;13&#44;0&#37;&#41; e ex&#227;o 20 &#40;4&#44;3&#37;&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">No tempo m&#233;dio de demora at&#233; ao resultado da sequencia&#231;&#227;o<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#44; verificou-se&#44; de acordo com o tipo de material dispon&#237;vel para estudo que&#44; as l&#226;minas demoram em m&#233;dia 20 dias&#59; o bloco de parafina 8&#44;32 dias e os detritos celulares &#40;com produtos a fresco &#8211; EBUS&#44; BAT e outras pun&#231;&#245;es&#44; na presen&#231;a de anatomia patol&#243;gica&#41; 6&#44;5 dias &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Do total de doentes sequenciados&#44; 71 em estadio avan&#231;ado ou metastizado efetuaram tratamento de 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com erlotinib 150<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; at&#233; &#224; morte&#44; progress&#227;o da doen&#231;a ou toxicidade inaceit&#225;vel&#46; Neste subgrupo de doentes&#44; verificou-se predom&#237;nio do sexo feminino &#40;43&#47;60&#44;6&#37;&#41;&#44; n&#227;o fumadores &#40;31&#47;43&#44;7&#37;&#41; e histologia adenocarcinoma &#40;43&#47;60&#44;6&#37;&#41;&#46; A muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> positiva em 20 doentes &#40;19&#44;2&#37;&#41;&#44; 55&#37; homens e 45&#37; mulheres&#44; na maioria n&#227;o fumadores &#40;12&#47;60&#44;0&#37;&#41; e histologia adenocarcinoma &#40;14&#47;70&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Na resposta global ao tratamento com erlotinib&#44; nos doentes com <span class="elsevierStyleItalic">muta&#231;&#227;o do EGFR</span> negativa &#40;n&#160;&#61;&#160;51&#41;&#44; verificou-se 47&#44;9&#37; &#40;24&#41; doen&#231;a progressiva&#44; 45&#44;1&#37; &#40;23&#41; doen&#231;a estacion&#225;ria e 7&#44;8&#37; &#40;4&#41; remiss&#227;o parcial&#46; No subgrupo de doentes tratados com erlotinib com muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> positiva &#40;n &#61;&#160;20&#41;&#44; 35&#44;0&#37; &#40;7&#41; apresentaram doen&#231;a progressiva&#44; 50&#44;0&#37; &#40;10&#41; doen&#231;a estacion&#225;ria e 15&#44;0&#37; &#40;3&#41; remiss&#227;o parcial&#44; ou seja&#44; como era de esperar&#44; melhor controlo da doen&#231;a em doentes com muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> positiva quando comparado com os doentes com muta&#231;&#227;o negativa &#40;65&#44;0 vs&#46; 52&#44;9&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">A sobrevida global dos doentes que efetuaram erlotinib com muta&#231;&#227;o do EGFR positiva vs&#46; doentes n&#227;o mutados foi de 47 e 22 meses &#40;p&#160;&#61;&#160;0&#44;038&#41;&#44; respetivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; A sobrevida m&#233;dia ap&#243;s o tratamento com erlotinib no grupo com muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> positiva tamb&#233;m foi superior neste subgrupo quando comparada com os doentes com muta&#231;&#227;o negativa &#40;14 vs&#46; 6 meses&#44; respetivamente p&#160;&#61;&#160;0&#44;003&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discuss&#227;o</span><p id="par0150" class="elsevierStylePara elsevierViewall">A nossa amostra revelou uma taxa de muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> global &#40;2006-2010&#41; de 13&#44;1&#37;&#46; Uma vez que de 2006 a 2009 houve sele&#231;&#227;o de doentes&#44; a taxa de muta&#231;&#227;o foi de 16&#37; vs&#46; 10&#44;4&#37; no ano de 2010 em que o estudo da muta&#231;&#227;o foi efetuado a todos os doentes com CPNPC independentemente do sexo e estadio&#46; Estes n&#250;meros parecem-nos uma mais-valia para o conhecimento da taxa de muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na popula&#231;&#227;o portuguesa&#59; os estudos de preval&#234;ncia da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> no cancro do pulm&#227;o na Europa revelaram&#44; em doentes n&#227;o selecionados&#44; taxas de muta&#231;&#227;o de 10&#37;&#59; em Espanha&#44; Rosell et al&#46;&#44; obtiveram uma taxa de muta&#231;&#227;o de 16&#44;6&#37;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; num grupo selecionado de doentes com CPNPC em estadios avan&#231;ados<span class="elsevierStyleBold">&#46;</span> A continua&#231;&#227;o deste nosso trabalho &#40;que nos anos de 2011 e 2012 se tem mantido igualmente numa popula&#231;&#227;o n&#227;o selecionada&#41; vai permitir tra&#231;ar com seguran&#231;a o perfil da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na popula&#231;&#227;o portuguesa e poder confirmar estes dados agora apresentados&#44; que mostram a presen&#231;a da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na subpopula&#231;&#227;o de doentes do sexo masculino&#44; carcinomas epidermoides e alguns fumadores&#46; A diferen&#231;a &#233;&#44; contudo&#44; muito significativa na taxa de muta&#231;&#227;o em rela&#231;&#227;o aos 2 sexos&#44; sendo o adenocarcinoma respons&#225;vel pela grande maioria dos casos&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Foi poss&#237;vel efetuar a sequencia&#231;&#227;o do gene do <span class="elsevierStyleItalic">EGFR</span> em variados tipos de amostras diagn&#243;sticas&#46; A sequencia&#231;&#227;o de DNA a partir de detritos celulares &#40;a fresco ou ap&#243;s <span class="elsevierStyleItalic">cell blok</span>&#41; foi mais r&#225;pida comparativamente a l&#226;minas ou bloco de parafina&#44; diferen&#231;a essa estatisticamente significativa e com impacto no in&#237;cio do tratamento&#46; Isto s&#243; foi poss&#237;vel com a colabora&#231;&#227;o estreita entre os v&#225;rios elementos envolvidos no diagn&#243;stico do cancro de pulm&#227;o &#40;pneumologia oncol&#243;gica&#44; broncologia&#44; radiologia de interven&#231;&#227;o e anatomia patol&#243;gica&#41;&#46; Nos tumores perif&#233;ricos&#44; ou sempre que seja poss&#237;vel efetuar pun&#231;&#245;es aspirativas&#44; deve-se dar prioridade ao envio deste material a fresco&#44; com obten&#231;&#227;o mais r&#225;pida dos resultados &#40;6&#44;5 dias ap&#243;s o envio dos produtos&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">O estudo da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> deve ser efetuado por rotina em todos os doentes com o diagn&#243;stico de CPNPC e devem ser criadas as condi&#231;&#245;es ao seu uso em todos os hospitais que tratam cancro do pulm&#227;o&#44; tendo em conta o seu correto tratamento&#44; pela possibilidade de uso dos ITK em 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha em doentes mutados&#44; com melhor controlo da doen&#231;a do que com os protocolos de quimioterapia convencional&#46; Todos estes pressupostos assentam na resposta ao tratamento e na sobrevida global no grupo de doentes tratados com ITK<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Os resultados da nossa amostra em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha mostraram significado estat&#237;stico no grupo de doentes com muta&#231;&#227;o positiva para o <span class="elsevierStyleItalic">EGFR</span>&#44; comparativamente aos doentes com muta&#231;&#227;o negativa&#44; apesar de a presen&#231;a da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> n&#227;o ser condi&#231;&#227;o obrigat&#243;ria para o in&#237;cio de tratamento&#46; Ainda n&#227;o temos n&#250;mero suficiente de doentes para apresenta&#231;&#227;o dos resultados de 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha dos doentes mutados tratados com ITK&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflito de interesses</span><p id="par0170" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflito de interesses&#46;</p></span></span>"
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    "fechaRecibido" => "2012-01-12"
    "fechaAceptado" => "2012-08-30"
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            0 => "Carcinoma pulmonar n&#227;o pequenas c&#233;lulas"
            1 => "Recetor do fator de crescimento epid&#233;rmico"
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            3 => "Sobrevida"
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          "clase" => "keyword"
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            0 => "Non Small Cell Lung Cancer"
            1 => "Epidermal Growth Factor Receptor"
            2 => "Tyrosine kinase inhibitor"
            3 => "Survival"
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    "resumen" => array:2 [
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        "titulo" => "Resumo"
        "resumen" => "<span><span class="elsevierStyleSectionTitle">Introdu&#231;&#227;o</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Em 2006&#44; a Unidade de Pneumologia Oncol&#243;gica do Servi&#231;o de Pneumologia do Centro Hospitalar de Vila Nova de Gaia&#47;Espinho iniciou a sequencia&#231;&#227;o da muta&#231;&#227;o do <span class="elsevierStyleItalic">recetor do fator de crescimento epid&#233;rmico &#40;EGFR&#41;</span> em doentes com CPNPC selecionados e desde 2010 realiza a sequencia&#231;&#227;o sistematicamente em todos os doentes&#44; independentemente da histologia&#44; h&#225;bitos tab&#225;gicos&#44; idade ou sexo&#46; O objetivo deste trabalho foi caracterizar o grupo de doentes que efetuou a sequencia&#231;&#227;o entre 2006-2010&#44; determinar a frequ&#234;ncia da muta&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span>&#44; avaliar as sobrevidas globais e ap&#243;s uso de inibidores da tirosina quinase &#40;ITK&#41;&#44; nos doentes que efetuaram esta terap&#234;utica em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com conhecimento do estado da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span>&#46;</p></span> <span><span class="elsevierStyleSectionTitle">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise estat&#237;stica descritiva dos doentes que efetuaram sequencia&#231;&#227;o <span class="elsevierStyleItalic">EGFR</span> em 2006-2010 e sobrevida mediana global nos doentes que efetuaefetuaram ITK em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha&#46; Registo do material dispon&#237;vel para an&#225;lise e demora m&#233;dia de resultado do exame&#44; de acordo com o material enviado&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A sequencia&#231;&#227;o foi efetuada em 374 doentes&#44; 71&#44;1&#37; sexo masculino&#44; 67&#44;1&#37; n&#227;o&#47;ex-fumadores&#44; 32&#44;9&#37; fumadores&#59; 57&#44;8&#37; adenocarcinoma e 23&#44;5&#37; carcinoma epidermoide &#40;CE&#41;&#46; A muta&#231;&#227;o foi detetada em 49 doentes &#40;13&#44;1&#37;&#41;&#46; No total dos doentes estudados&#44; a taxa de muta&#231;&#227;o foi de 9&#37; no sexo masculino e 23&#37; no sexo feminino&#46; A sobrevida mediana global ap&#243;s o uso de erlotinib foi de 14 meses para os doentes com muta&#231;&#227;o positiva do <span class="elsevierStyleItalic">EGFR versus</span> 6 meses nos doentes n&#227;o mutados &#40;p&#160;&#61;&#160;0&#44;003&#41;&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Conclus&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O nosso grupo teve uma taxa de muta&#231;&#227;o global de 13&#44;1&#37;&#44; com predom&#237;nio no sexo feminino&#44; n&#227;o fumadores&#44; histologia adenocarcinoma&#46; Em doentes selecionados &#40;2006&#47;2009&#41;&#44; a taxa de muta&#231;&#227;o foi de 16&#37;&#59; nos doentes n&#227;o selecionados &#40;2010&#41; foi de 10&#44;4&#37;&#46; Este estudo tem vindo a permitir um melhor conhecimento da taxa de muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> na popula&#231;&#227;o portuguesa&#44; bem como avaliar os resultados das sobrevidas dos doentes ap&#243;s uso de inibidores da tirosina quinase &#40;ITK&#41;&#44; efetuada em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> e 3&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com conhecimento pr&#233;vio do estado da muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span>&#44; tendo sido encontradas diferen&#231;as nas sobrevidas nos 2 grupos de doentes &#40;mutados e n&#227;o mutados&#41; com significado estat&#237;stico&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A pesquisa muta&#231;&#227;o do <span class="elsevierStyleItalic">EGFR</span> deve ser efetuada em todos os doentes com CPNPC&#44; dando possibilidade a um n&#250;mero consider&#225;vel de doentes de poder efetuar um tratamento de 1&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha com ITK &#40;doentes mutados&#41;&#44; bem como de poder usufruir de outros esquemas de quimioterapia&#44; quando progredirem&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span><span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In 2006&#44; the Vila Nova de Gaia&#47;Espinho Hospital Centre Pulmonary Oncology Unit started performing EGFR &#40;Epidermal Growth Factor Receptor&#41; mutation sequencing in selected patients with NSCLC and systematically in all patients since 2010&#44; regardless of histology&#44; smoking habits&#44; age or sex&#46; The aim of this study was to characterize the group of patients that carried out the sequencing between 2006-2010&#44; to determine EGFR mutation frequency&#44; to evaluate the overall survival and the survival after the use of tyrosine kinase inhibitors &#40;TKI&#41;&#44; in patients who performed this therapy in second and third line&#44; knowing the EGFR mutation status&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Descriptive statistical analysis of patients who did EGFR sequencing in 2006-2010 and of overall survival in patients treated with TKI as 2nd and 3rd line therapy&#46; Record of the material available for analysis and average delay of exam results&#44; according to the material submitted&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The sequencing was performed in 374 patients&#44; 71&#44;1&#37; males&#44; 67&#44;1&#37; non&#47;ex-smokers&#44; 32&#44;9&#37; smokers&#44; 57&#44;8&#37; adenocarcinoma and 23&#44;5&#37; squamous cell carcinoma &#40;SCC&#41;&#46; The mutation was detected in 49 patients &#40;13&#44;1&#37;&#41;&#46; In all studied patients&#44; the mutation rate was 9&#37; in males and 23&#37; in females&#46; Median overall survival after erlotinib use of was 14 months for patients with positive EGFR mutation versus 6 months in not mutated patients &#40;p &#61; 0&#46;003&#41;&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Our group had an overall mutation rate of 13&#46;1&#37; with female&#44; non-smokers&#44; adenocarcinoma histology predominance&#46; In selected patients &#40;2006&#47;2009&#41;&#44; the mutation rate was 16&#37;&#44; in not selected patients &#40;2010&#41; the mutation rate was 10&#46;4&#37;&#46; This study has permitted a better understanding of the EGFR mutation rate in the Portuguese population as welll as an evaluation of the patients survival after the use of of tyrosine kinase inhibitors&#44; in second and third line therapy with previous knowledge of the EGFR mutational status&#46; Statistical significant differences in survival were found in the two patient groups &#40;EGFR mutated and non mutated&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The EGFR mutation research should be performed in all patients with NSCLC&#44; giving the possibility to a considerable number of patients to perform a first line treatment with TKI &#40;EGFR mutated patients&#41; and the advantage of performing other chemotherapy schemes&#44; when progression occurs&#46;</p></span>"
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    ]
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          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A&#46; Curva de sobrevida global dos doentes mutados versus n&#227;o mutados &#40;47 vs&#46; 22 meses&#44; p&#160;&#61;&#160;0&#44;038&#41;&#46;</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">B&#46; Curva de sobrevida ap&#243;s tratamento com erlotinib em doentes mutados e WT &#40;14 vs&#46; 6 meses&#44; p&#160;&#61;&#160;0&#44;003&#41;&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col">Vari&#225;veis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Todos doentes &#40;n&#160;&#61;&#160;374&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Doentes mutados &#40;n&#160;&#61;&#160;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">266&#47;71&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;9&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Feminino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">108&#47;28&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#47;23&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Idade</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M&#233;dia&#177;dp&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&#44;52&#160;&#177;&#160;11&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#160;&#177;&#160;9&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M&#237;nimo&#47;m&#225;ximo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#47;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">H&#225;bitos tab&#225;gicos</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ex-fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">134&#47;35&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#47;30&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123&#47;32&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;22&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117&#47;31&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#47;46&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Tipo histol&#243;gico</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">216&#47;57&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&#47;59&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>epidermoide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&#47;23&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#47;24&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ca grandes c&#233;lulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>bronqu&#237;olo-alveolar&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CPNPC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;14&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Ex&#227;o</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;10&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#47;38&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#47;18&#44;4&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#47;32&#44;6&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Caracteriza&#231;&#227;o da amostra e frequ&#234;ncia de muta&#231;&#245;es EGFR&#46; &#40;&#42; 6&#44;2&#37; foram muta&#231;&#245;es de resist&#234;ncia&#41;</p>"
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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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Vari&#225;veis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sexo feminino &#40;n&#160;&#61;&#160;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sexo masculino &#40;n&#160;&#61;&#160;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">H&#225;bitos tab&#225;gicos</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#47;88&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;8&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ex-fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;29&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#47;62&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Tipo histol&#243;gico</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#47;80&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;37&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ca epidermoide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#47;45&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CPNPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;16&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Ex&#227;o mutado</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;8&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#47;44&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;29&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#47;25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;28&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;37&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab884897.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Caracteriza&#231;&#227;o dos doentes mutados por sexo</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Amostra utilizada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tempo m&#233;dio de demora &#40;dias&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diferen&#231;a de tempo &#40;dias&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bloco de parafina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#44;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">L&#226;mina de citologia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#44;6721&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;0255&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">L&#226;mina de histologia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#44;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#44;0888&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#44;1108&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Detritos celulares&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#44;5556&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#44;7723&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;1789&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Tempo m&#233;dio de demora at&#233; ao resultado da sequencia&#231;&#227;o do EGFR</p>"
        ]
      ]
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        "etiqueta" => "Tabela 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                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="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Total doentes &#40;n&#160;&#61;&#160;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Doentes mutados n&#160;&#61;&#160;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&#47;&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleBold">Estudo do</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">EGFR</span></span><span class="elsevierStyleBold">e terap&#234;utica com erlotinib</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#47;39&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;55&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Feminino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&#47;60&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#47;45&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Idade</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68&#160;&#177;&#160;8&#44;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">H&#225;bitos tab&#225;gicos</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ex-fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;33&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#47;22&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;15&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>N&#227;o fumador&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#47;43&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#47;60&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tipo histol&#243;gico</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&#47;60&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#47;70&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Outro tipo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#47;39&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;30&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">Resposta ao erlotinib</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">EGFR&#160;&#8722;&#160;&#61;&#160;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">EGFR&#160;&#43;&#160;&#61;&#160;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Remiss&#227;o parcial</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;7&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;15&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Doen&#231;a estacion&#225;ria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#47;45&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#47;50&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Doen&#231;a progressiva</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;47&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;35&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sobrevida global media</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sobrevida ap&#243;s uso erlotinib</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab884896.png"
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas demogr&#225;ficas e resposta ao tratamento dos doentes com estudo do <span class="elsevierStyleItalic">EGFR</span> que efetuaram terap&#234;utica com erlotinib em 2&#46;<span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span> linha</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
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                        "paginaFinal" => "10"
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                          0 => array:2 [
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Article information
ISSN: 08732159
Original language: Portuguese
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