Letter to the Editor
Value of rebiopsy in advanced Epidermal Growth Factor Receptor mutated Non-Small Cell Lung Cancer: Real-world data
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A) On admission with bilateral opacities with air bronchogram. B) On discharge day showing almost complete resolution of the previously described lesions.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Thoracic computed tomography</span>. C) On final days of hospitalization by varicella-zoster pneumonia showing multiple small nodules scattered in the pulmonary parenchyma, some forming small conglomerates, and surrounding ground glass with bilateral distribution, but predominantly in the lower lobes. The largest conglomerate measuring 15 mm in the lower left lobe (arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Oliveira, S. Braga, F. Fernandes, J.M. Silva" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Oliveira" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Braga" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Fernandes" ] 3 => array:2 [ "nombre" => "J.M." 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"apellidos" => "Antunes" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043720302063?idApp=UINPBA00004E" "url" => "/25310437/0000002700000002/v2_202105110755/S2531043720302063/v2_202105110755/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Value of rebiopsy in advanced Epidermal Growth Factor Receptor mutated Non-Small Cell Lung Cancer: Real-world data" "tieneTextoCompleto" => true "saludo" => "Letter to the Editor" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "177" "paginaFinal" => "180" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "R. Saúde-Conde, S. Cristóvão-Ferreira, E. Campoa, M.T. Almodovar" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Saúde-Conde" "email" => array:1 [ 0 => "rconde@ipolisboa.min-saude.pt" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Cristóvão-Ferreira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Campoa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M.T." "apellidos" => "Almodovar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Medical Oncology, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisbon, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Medical Oncology, Centro Hospitalar Universitário do Algarve, Faro, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Pulmonology, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisbon, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1883 "Ancho" => 2508 "Tamanyo" => 254216 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Study flow chart.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: n: number of patients; N: number of biopsies.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acquisition of Epidermal Growth Factor Receptor (EGFR) mutation resistance (mainly T790M) to EGFR tyrosine kinase inhibitors (TKI) occurs in about half of Non-Small Cell Lung Cancer (NSCLC) patients treated with TKI.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Mutational status is important to guide therapy.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Pirker stated that while tissue biopsy is currently the main source for molecular analyses, liquid biopsies will gain importance for diagnosis and disease monitoring in the future.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The aim of this study was to analyse the value of liquid and tissue rebiopsy for evaluation of EGFR mutational status in a real-world setting.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We carried out a retrospective identification of patients tested for EGFR mutation at a Portuguese cancer center between January 2015 and October 2019. We collected clinical data from patients with advanced EGFR mutation NSCLC. Descriptive statistic was used to analyse patients’ characteristics.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Of the 824 patients that were evaluated for EGFR mutation, 160 (19%) had EGFR-mutant NSCLC.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Eighty-five of 160 patients (53%) had advanced disease (11 patients with stage III, 65 patients with stage IV and 9 patients presented a relapsing NSCLC). All neoplasms were adenocarcinomas due to a selection bias of our institution (only adenocarcinmomas are tested for EGFR mutation. The median age at diagnosis was 69 years old [range: 39–95] and 66% of patients were female. History of tobacco use was reported as 42%.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The most common EGFR mutation was exon 19 deletion (del19) (33 patients) followed by L858R point mutation on exon 21 (24 patients) and del19 plus de novo T790M mutation (7 patients). Other uncommon mutations identified were L858R plus T790M, G719X on exon 18, del19 plus insertion of 20 and S7681 on exon 20 plus L858R.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Sixty-nine of 85 patients (81%) received EGFR-TKI and 46 patients (67%) developed disease progression on TKI. All 46 patients were submitted to a first (1st) rebiopsy, corresponding to a total of 50 rebiopsies: 25liquid biopsies and 25 tissue biopsies/cytologies (some patients had both). Eighteen patients underwent a second and third (2nd/3rd) rebiopsy, corresponding to a total of 34 rebiopsies: 25 liquid biopsies and 9 tissue biopsies/cytologies.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The most common sampling method was liquid biopsy both for 1st (50%) and 2nd/3rd rebiopsies (74%). Bronchial tissue was the most common site for tissue biopsy/cytology followed by pleural fluid both in 1st and 2nd/3rd rebiopsies. Less common sites were cerebrospinal fluid, thoracic lymph nodes and bronchial secretions for 1st rebiopsy and brain and bone for 2nd/3rd rebiopsies.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We analysed the proportion of T790M mutation identified for each rebiopsy site as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In 1st rebiopsy, bronchial tissue was the site where T790M mutation was most frequently identified (62%), followed by pleural fluid (38%) and liquid biopsies (24%). No T790M mutation was identified in other sites, corresponding to a T790M mutation detection rate of 44% for 1st tissue rebiopsy</p><p id="par0050" class="elsevierStylePara elsevierViewall">In 2nd/3rd rebiopsy, T790M mutation was identified in the only brain biopsy performed and in 16% of the liquid biopsies. No T790M mutation was identified in other sites, meaning the detection rate for T90M mutation 2nd/3rd tissue rebiopsies was only 11%.</p><p id="par0055" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, 16 of 46 patients (35%) undergoing a 1st rebiopsy harbored a T790M mutation. Among the 30 remaining patients, 12 did not repeat biopsy and 18 were submitted to a 2nd/3rd biopsy. Five of those 18 patients (28%) were submitted to 2nd/3rd biopsies harbored a T790M mutation.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Furthermore, 18 of 46 patients undergoing rebiopsy presented exclusive intrathoracic disease. In this setting, T790M mutation was detected in 5 of 40 all rebiopsies (13%).</p><p id="par0065" class="elsevierStylePara elsevierViewall">In patients with exclusive intrathoracic disease, liquid biopsy failed to identify T790M mutation, regardless of the number of rebiopsies. However, out of those 20 negative liquid biopsies, one had a positive matched tissue biopsy/cytology. T790M mutation was identified in 5 of 20 tissue rebiopsies/citologies performed (25%).</p><p id="par0070" class="elsevierStylePara elsevierViewall">Among 28 patients with extrathoracic disease, T790M mutation was detected in 17 of 44 rebiopsies performed (39%). T790M mutation was found in 10 of 30 liquid biopsies (33%) and in 10 of 14 tissue biopsies/citologies (50%).</p><p id="par0075" class="elsevierStylePara elsevierViewall">The overall survival was higher among patients submitted to rebiopsy [28.9 months (95%CI 21.2–35.0)] than among those were not [18.6 months (95%CI 9.87-NR)]. Although the increase of 10 months in overall survival was not statistically significant (p = 0.3116), this lack of significance might be related with the small number of our cohort. Additionally, we may consider that this tendency towards overall survival benefit could be related with a better performance status of the rebiopsied patients (fit to receive treatment). Also, we can hypothesize that rebiopsy might guide the physician to choose the best treatment, which would l lead to a better overall survival.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Our results suggest that 2nd/3rd biopsies are worth performing, as the proportion of patients with mutation identified is still significant and have a clinical impact in therapeutic choices and prognosis.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">T790M mutation is less identified in patients with exclusive intrathoracic disease. Liquid biopsy might not add value in this setting but tissue biopsy/cytology must be considered.</p><p id="par0090" class="elsevierStylePara elsevierViewall">In extrathoracic disease, a higher proportion of T90M mutation was identified both in tissue biopsy/cytology and liquid biopsy. Although tissue biopsy/cytology was better than liquid biopsy, it is more difficult to perform and more invasive.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Furthermore <span class="elsevierStyleItalic">EGFR</span> mutant patients undergoing rebiopsy can present different resistance mechanisms, which reflects intratumoral and intertumoral heterogeneity, as well as dynamic changes in the relative populations of resistant clones over time.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Despite the retrospective single center nature and small sample of our study, it is the first to present rebiopsy data of EGFR mutated NSCLC patients in Portugal and it is in line with other similar studies.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Eun Kyong Goag et al. also reported a sample with a similar prevalence of EGFR mutations, with 561% in exon 19 del 34,1% in L858R or L861Q (compared with 47,8% of del19 and 34,8% in L858R in our sample) and the T790M mutation was identified in 43.9% patients with exon 19 del as the most significant factor affecting T790M mutation development (hazard ratio: 6.875, P = 0.014). Similarly, our detection rate of T790M was 44% after the first tissue rebiopsy and the T790M mutation was detected in 50% of patients with an initial del19 mutation (compared with 65% in Goag’s study) and in 26% of patients with and an initial L858R mutation (vs. 21,5%).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Similarly in another Japanese study, the T790M mutation was also more frequent with an exon 19 deletion mutation (63%) than in those with a L858R mutation (38%) (p = 0.035).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Prospective, multicenter studies are needed to validate these findings.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-04-13" "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1883 "Ancho" => 2508 "Tamanyo" => 254216 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Study flow chart.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: n: number of patients; N: number of biopsies.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1st rebiopsy site \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of biopsies \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T790M + \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Tissue biopsy/cytology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">25</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">11 (</span>44%<span class="elsevierStyleBold">)</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bronchial tissue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (62%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pleural fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (38%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cerebrospinal fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bronchial secretions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thoracic Lymph node \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Liquid biopsy</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">25</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">6 (</span>24%<span class="elsevierStyleBold">)</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2nd/3rd rebiopsy site \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of biopsies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T790M+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Tissue biopsy/cytology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">9</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">1 (</span>11%<span class="elsevierStyleBold">)</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bronchial tissue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pleural fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Brain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (100%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Liquid biopsy</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">25</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">4 (</span>16%<span class="elsevierStyleBold">)</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2592392.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Rebiopsy sites and T90M detection success rate.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Real-World EGFR T790M testing in advanced non- small-cell lung cancer: a prospective observational study in Japan" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 6 | 11 |
| 2024 October | 40 | 31 | 71 |
| 2024 September | 45 | 28 | 73 |
| 2024 August | 60 | 34 | 94 |
| 2024 July | 39 | 37 | 76 |
| 2024 June | 34 | 27 | 61 |
| 2024 May | 43 | 33 | 76 |
| 2024 April | 30 | 37 | 67 |
| 2024 March | 47 | 27 | 74 |
| 2024 February | 37 | 24 | 61 |
| 2024 January | 25 | 33 | 58 |
| 2023 December | 23 | 24 | 47 |
| 2023 November | 42 | 50 | 92 |
| 2023 October | 30 | 27 | 57 |
| 2023 September | 23 | 38 | 61 |
| 2023 August | 34 | 28 | 62 |
| 2023 July | 33 | 35 | 68 |
| 2023 June | 42 | 15 | 57 |
| 2023 May | 50 | 47 | 97 |
| 2023 April | 36 | 23 | 59 |
| 2023 March | 69 | 32 | 101 |
| 2023 February | 57 | 23 | 80 |
| 2023 January | 31 | 12 | 43 |
| 2022 December | 48 | 21 | 69 |
| 2022 November | 45 | 36 | 81 |
| 2022 October | 63 | 39 | 102 |
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| 2022 July | 102 | 54 | 156 |
| 2022 June | 49 | 37 | 86 |
| 2022 May | 76 | 50 | 126 |
| 2022 April | 51 | 44 | 95 |
| 2022 March | 46 | 41 | 87 |
| 2022 February | 34 | 44 | 78 |
| 2022 January | 48 | 50 | 98 |
| 2021 December | 27 | 39 | 66 |
| 2021 November | 33 | 44 | 77 |
| 2021 October | 43 | 61 | 104 |
| 2021 September | 32 | 41 | 73 |
| 2021 August | 30 | 32 | 62 |
| 2021 July | 26 | 17 | 43 |
| 2021 June | 45 | 49 | 94 |
| 2021 May | 48 | 49 | 97 |
| 2021 April | 144 | 187 | 331 |
| 2021 March | 109 | 68 | 177 |
| 2021 February | 75 | 64 | 139 |
| 2021 January | 46 | 42 | 88 |
| 2020 December | 26 | 14 | 40 |
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