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Larotrectinib versus infigratinib for adult patients with both glioma and tyrosine kinase alterations after failure of initial therapies: Efficacy and safety analysis
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The data were all measurement data expressed as mean ± standard deviation). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "XiaoQun Che, Xiao Wang, LiLian Wang, LiHua Xu, Lin Zou, TianZhong Ma, Bi Chen" "autores" => array:7 [ 0 => array:2 [ "nombre" => "XiaoQun" "apellidos" => "Che" ] 1 => array:2 [ "nombre" => "Xiao" "apellidos" => "Wang" ] 2 => array:2 [ "nombre" => "LiLian" "apellidos" => "Wang" ] 3 => array:2 [ "nombre" => "LiHua" "apellidos" => "Xu" ] 4 => array:2 [ "nombre" => "Lin" "apellidos" => "Zou" ] 5 => array:2 [ "nombre" => "TianZhong" "apellidos" => "Ma" ] 6 => array:2 [ "nombre" => "Bi" "apellidos" => "Chen" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara007" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">•</span><p id="para0001" class="elsevierStylePara elsevierViewall">Correlation analysis of miR-141-5p and serum β-HCG, P4 and E2 levels in patients with ESA.</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">•</span><p id="para0002" class="elsevierStylePara elsevierViewall">miR-141-5p as a diagnostic biomarker for ESA.</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">•</span><p id="para0003" class="elsevierStylePara elsevierViewall">β-HCG, P4 and E2 levels.</p></li></ul></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593224000048?idApp=UINPBA00004N" "url" => "/18075932/000000790000000C/v123_202411010523/S1807593224000048/v123_202411010523/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S1807593224000012" "issn" => "18075932" "doi" => "10.1016/j.clinsp.2024.100324" "estado" => "S250" "fechaPublicacion" => "2024-01-01" "aid" => "100324" "copyright" => "HCFMUSP" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original articles</span>" "titulo" => "Health-Related quality of life by 31-item Cervantes scale in breast cancer survivors undergoing adjuvant endocrine therapy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "en" ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1484 "Ancho" => 2917 "Tamanyo" => 414717 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Diagram reporting the number of survivors recruited and selected in the study, and the Cervantes’ sample. Time point: T0, Initial follow-up period; T1, Intermediate period, corresponding to 12-months after T0; and T2, Final follow-up period, corresponding to 24-months after T0; CS-31, 31-item Cervantes Scale.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Isis Danyelle Dias Custódio, Fernanda Silva Mazzutti Nunes, Mariana Tavares Miranda Lima, Kamila Pires de Carvalho, Andressa Miranda Machado, Paula Philbert Lajolo, Carlos Eduardo Paiva, Yara Cristina de Paiva Maia" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Isis Danyelle Dias" "apellidos" => "Custódio" ] 1 => array:2 [ "nombre" => "Fernanda Silva Mazzutti" "apellidos" => "Nunes" ] 2 => array:2 [ "nombre" => "Mariana Tavares Miranda" "apellidos" => "Lima" ] 3 => array:2 [ "nombre" => "Kamila Pires de" "apellidos" => "Carvalho" ] 4 => array:2 [ "nombre" => "Andressa Miranda" "apellidos" => "Machado" ] 5 => array:2 [ "nombre" => "Paula Philbert" "apellidos" => "Lajolo" ] 6 => array:2 [ "nombre" => "Carlos Eduardo" "apellidos" => "Paiva" ] 7 => array:2 [ "nombre" => "Yara Cristina de Paiva" "apellidos" => "Maia" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "HIGHLIGHTS" "clase" => "author-highlights" "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara013" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">•</span><p id="para0001" class="elsevierStylePara elsevierViewall">CS-31 seems to be appropriate for use in oncology and may help to monitoring adverse effects and HRQL.</p></li></ul></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593224000012?idApp=UINPBA00004N" "url" => "/18075932/000000790000000C/v123_202411010523/S1807593224000012/v123_202411010523/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original articles</span>" "titulo" => "Larotrectinib versus infigratinib for adult patients with both glioma and tyrosine kinase alterations after failure of initial therapies: Efficacy and safety analysis" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Yufang Chen, Jian Ma, Qianqian Gao, Yu Gai, Yichi Sun, Meihua Wang" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Yufang" "apellidos" => "Chen" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn1" ] ] ] 1 => array:3 [ "nombre" => "Jian" "apellidos" => "Ma" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0002" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn1" ] ] ] 2 => array:3 [ "nombre" => "Qianqian" "apellidos" => "Gao" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] ] ] 3 => array:3 [ "nombre" => "Yu" "apellidos" => "Gai" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] ] ] 4 => array:3 [ "nombre" => "Yichi" "apellidos" => "Sun" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] ] ] 5 => array:4 [ "nombre" => "Meihua" "apellidos" => "Wang" "email" => array:1 [ 0 => "wangmeihua1234@suda.edu.cn" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0001" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pathology, Changzhou Tumor Hospital, Changzhou, Jiangsu, China" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Department of Oncology, Changzhou Tumor Hospital, Changzhou, Jiangsu, China" "etiqueta" => "b" "identificador" => "aff0002" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2406 "Ancho" => 3167 "Tamanyo" => 275000 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">The retrospective flow chart.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Introduction</span><p id="para0011" class="elsevierStylePara elsevierViewall">Gliomas are a type of neuroepithelial tissue<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> that is about 2 % of all types of occurring cancers (rare diseases).<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Glioblastomas are aggressive and lethal types of gliomas.<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> The tyrosine kinase domains of genomic alterations in gliomas demonstrate oncogenic potential.<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> Tyrosine kinase domains are available with fibroblast growth factor receptors<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> and play a vital role in neurotrophic tyrosine receptor kinase gene encoding.<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> Tyrosine kinase alterations have a vital role in the development of glioma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> Limited literature is available on the mechanism of action of tyrosine kinase alterations responsible for the development of glioma.<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a></p><p id="para0012" class="elsevierStylePara elsevierViewall">Larotrectinib (tropomyosin receptor kinase inhibitor) monotherapy<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> and infigratinib (tyrosine kinase inhibitor) monotherapy<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> are both effective in the treatment of gliomas with tyrosine kinase alterations in adult patients. However, to date, larotrectinib monotherapy has not been compared with infigratinib monotherapy for the treatment of glioma, where tyrosine kinase alterations occur in the development of glioma.</p><p id="para0013" class="elsevierStylePara elsevierViewall">The objectives of this retrospective study were to compare progression-free survival, overall survival, treatment response, and adverse effects between adult patients with glioma with tyrosine kinase alterations who received larotrectinib and those who received infigratinib.</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Materials and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Ethics approval and consent to participate</span><p id="para0014" class="elsevierStylePara elsevierViewall">The designed protocol was prepared by the authors and approved by the Human Ethics Committee of Changzhou Tumor Hospital (Approval number CJ20220224 dated January 10, 2016) and the Chinese Society of Clinical Oncology. As this was a retrospective study, informed consent of patients and/or their legally authorized person(s) was waived by the human ethics committee of the Changzhou Tumor Hospital. The study follows the laws of China and the v2008 Declarations of Helinski.</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Inclusion criteria</span><p id="para0015" class="elsevierStylePara elsevierViewall">Adult glioma patients with pathologically confirmed tyrosine kinase alterations after failure of initial therapy were included in the study.</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Exclusion criteria</span><p id="para0016" class="elsevierStylePara elsevierViewall">Patients who required anticonvulsant drugs (e.g., carbamazepine, phenobarbital, and phenytoin) were excluded from the study (because of strong inducers of CYP3A4). In addition, patients with abnormal calcium and/or phosphate homeostasis, neurological instability, history of corneal/keratopathy, or retinal disorders were excluded from the study. Patients with a history of sensitivity to larotrectinib and infigratinib were excluded from this study.</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Cohorts</span><p id="para0017" class="elsevierStylePara elsevierViewall">A total of 125 patients received oral infigratinib 125 mg once daily on days 1–21 of each 28-day cycle until unacceptable toxicities or disease progression (IN cohort).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> The patients were recommended a low-phosphate diet. In cases of hyperphosphatemia (plasma inorganic phosphate level > 4.5 mg/dL), oral phosphate binder(s) were provided to patients. A total of 105 patients received 100 mg twice daily of oral larotrectinib until unacceptable toxicities or disease progression (LB cohort).<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> The Common Terminology Criteria for Adverse Events, version 4.03 was used to define unacceptable toxicities. Disease progression was evaluated using magnetic resonance imaging and pathology.</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">ECOG performance status</span><p id="para0018" class="elsevierStylePara elsevierViewall">ECOG (Eastern Cooperative Oncology Group) performance status was graded as 0 ‒ Fully active; 1 ‒ Unable to perform strenuous activities; 2 ‒ Capable of all self-care activities but dependent on others to carry out normal activities; 3 ‒ Capable of performing limited self-care activities; 4 ‒ Completely disabled.</p></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Treatment response evaluation</span><p id="para0019" class="elsevierStylePara elsevierViewall">Magnetic Resonance Imaging (MRI) was performed every 2 months. RECIST 1.1 criteria<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> was used to evaluate treatment response. Oncologists, in assistance with radiologists, evaluated the treatment response. The responses are listed in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1.</a><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Survival</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Progression-free survival</span><p id="para0020" class="elsevierStylePara elsevierViewall">Survival of patient without any progression of disease after treatment(s).</p></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Overall survival</span><p id="para0021" class="elsevierStylePara elsevierViewall">The detection of disease(s) to death was considered the overall survival of the patient.</p><p id="para0022" class="elsevierStylePara elsevierViewall">New disease lesions or disease progression were detected using magnetic resonance imaging scans and pathology.</p></span></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Adverse effects</span><p id="para0023" class="elsevierStylePara elsevierViewall">The Common Terminology Criteria for Adverse Events, version 4.03, was used to evaluate adverse effects during the treatment(s) and follow-up period.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a></p><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021">Hyperphosphatemia</span><p id="para0024" class="elsevierStylePara elsevierViewall">A plasma inorganic phosphate level of more than 4.5 mg/dL was considered hyperphosphatemia. Blood pathology was performed to detect the plasma inorganic phosphate levels.</p></span></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0022">Statistical analysis</span><p id="para0025" class="elsevierStylePara elsevierViewall">InStat 3.01 (GraphPad Software, San Diego, CA, USA) was used for the statistical analysis. All results were considered significant if the <span class="elsevierStyleItalic">p</span>-value was less than 0.05. Categorical, continuous normal, and continuous non-normal variables are presented as frequencies (percentages), mean±Standard Deviation (SD), and median (Q3–Q1), respectively. Fisher's exact test or the Chi-Square test (χ<span class="elsevierStyleSup">2</span>-test) was performed for categorical variables. Kolmogorov and Smirnov tests were performed to check the normality of continuous variables. The Mann-Whitney test was used for the statistical analysis of non-normal continuous variables. Multivariate analysis was used for statistical analysis of the evaluation of independent parameters (treatment, gender, ethnicity, ECOG status, and initial therapies) for higher overall survival at a 95 % Confidence Interval (95 % CI).</p></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023">Results</span><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0024">Study population</span><p id="para0026" class="elsevierStylePara elsevierViewall">From January 15, 2016, to December 17, 2018, 240 adult patients with glioma with tyrosine kinase alterations after the failure of initial therapy were available at the Changzhou Tumor Hospital, Changzhou, Jiangsu, China, and the referring hospitals. Among them (240 glioma patients), three patients were on anticonvulsant drugs, one patient had abnormal calcium homeostasis, one patient had abnormal phosphate homeostasis, one patient was neurologically unstable, one patient had a history of corneal disorders, one patient had a history of keratopathy, and two patients had a history of retinal disorders. Therefore, these patients (10 glioma patients) were excluded from the study. The medical records of progression-free survival, overall survival, treatment response, and adverse effects of 230 patients with glioma with tyrosine kinase alterations after the failure of initial therapy were included in the analysis. A retrospective flowchart of the study is presented in <a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>.</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia></span><span id="sec0017" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0025">Demographic and clinical parameters</span><p id="para0027" class="elsevierStylePara elsevierViewall">The number of male patients was higher than that of female patients. More than 50 % of patients had ECOG performance status 1. There were no significant differences in sex, age, ethnicity, ECOG performance status, initial therapies (i.e., failure) between cohorts before the start of second-line treatment for glioma (previous treatments received including radiation), the time frame of diagnosis, medicine administration, extent of surgery, prior history of cancer, and genetic background of participants. The details of the demographic and clinical parameters of the enrolled patients before the start of second-line treatment for glioma are reported in <a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>.</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia></span><span id="sec0018" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0026">Treatment response evaluation</span><p id="para0028" class="elsevierStylePara elsevierViewall">The duration of treatment was higher in the LB cohort than in the IN cohort (8 [9.5–6.25] months vs. 5.5 [6–5.25] months, <span class="elsevierStyleItalic">p</span> < 0.0001, Mann–Whitney test, Mann–Whitney U-statistic = 1811). Patients with a complete response and stable disease were statistically similar between the cohorts. However, the number of patients with partial responses was higher in the IN cohort. The number of patients with disease progression was higher in the LB cohort. The details of the treatment response evaluation after the termination of 2nd line treatment are reported in <a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>.</p><elsevierMultimedia ident="tbl0003"></elsevierMultimedia></span><span id="sec0019" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0027">Survival</span><p id="para0029" class="elsevierStylePara elsevierViewall">From the start of treatment and after the termination of 2nd line treatment in a follow-up of 18 months, a total of 14 (11 %) and 10 (10 %) patients from the IN and the LB cohorts had progression-free survival. Progression-free survival of patients was the same between cohorts from the start of treatment, during treatment, and in followed-up of 18 months after termination of 2nd line treatment (<span class="elsevierStyleItalic">p</span> = 0.999, Fisher’s exact test, 95 % CI: 0.6270 to 1.471, Relative Risk = 0.9603). From the start of treatment, during treatment, and at the follow-up of 18 months a total of 30 (24 %) and 40 (38 %) patients from the IN and the LB cohorts died. overall survival of patients in the IN cohort was higher than that of the LB cohort (<span class="elsevierStyleItalic">p</span> = 0.03, χ<span class="elsevierStyleSup">2</span>-test with Yates correction, degree of freedom: 1, 95 % CI: 0.5350 to 0.9738, χ<span class="elsevierStyleSup">2</span>-value: 4.71).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0028">Adverse effects</span><p id="para0030" class="elsevierStylePara elsevierViewall">Patients in the IN cohort reported hyperphosphatemia, diarrhea, fatigue, vomiting, hyperlipidemia, stomatitis, dry skin, alopecia, decreased appetite, dyspepsia, onycholysis, palmar-plantar erythrodysesthesia, constipation, nail disorder, and dry eyes during 2nd line treatment and 18-months of followed-up. Patients in the LB cohort reported diarrhea, fatigue, vomiting, decreased appetite, constipation, upper respiratory tract infection, pyrexia, cough, anemia, bacterial and/or viral infection, conjunctivitis, urinary tract infection, headache, ataxia, dizziness, and muscle tremor during 2nd line treatment and 18-months of followed-up. The details of the adverse effects during 2nd line treatment and 18 months of follow-up are reported in <a class="elsevierStyleCrossRef" href="#tbl0004">Table 4</a>.</p><elsevierMultimedia ident="tbl0004"></elsevierMultimedia></span><span id="sec0021" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0029">Independent parameter</span><p id="para0031" class="elsevierStylePara elsevierViewall">Patients who received bevacizumab initial therapy had higher overall survival (<span class="elsevierStyleItalic">p</span> = 0.048, Odds Ratio: 1.0241, 95 % CI: 1.0011 to 1.3211, multivariate analysis).</p></span></span><span id="sec0022" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0030">Discussions</span><p id="para0032" class="elsevierStylePara elsevierViewall">Patients with partial response were higher in the IN cohort, and patients with progression were higher in the LB cohort after termination of 2nd line treatment. The poor blood-brain barrier penetration of Larotrectinib<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> is responsible for the higher progression of disease in patients in the LB cohort. Infigratinib can penetrate the central nervous system<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> and is responsible for a higher partial response in patients in the IN cohort. Infigratinib has higher efficacy than larotrectinib in adult patients with both glioma and tyrosine kinase alterations after the failure of initial therapies.</p><p id="para0033" class="elsevierStylePara elsevierViewall">Progression-free survival was the same, but overall survival was higher among adult patients with glioma with tyrosine kinase alterations after the failure of initial therapies who received infigratinib than among those who received larotrectinib. Partial response was higher and disease progression was lower among adult patients with glioma with tyrosine kinase alterations after the failure of initial therapies who received infigratinib, which would lead to an increase in overall survival of patients, but these were not enough for progression-free survival of patients. Infigratinib increases the overall survival of adult patients with both glioma and tyrosine kinase alterations after the failure of initial therapies.</p><p id="para0034" class="elsevierStylePara elsevierViewall">Larotrectinib-emergent adverse effects were higher than infigratinib-emergent adverse effects. Larotrectinib has a favorable safety profile in both adult and pediatric patients.<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> The infigratinib-emergent adverse effects observed in the current study are consistent with those in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> Infigratinib has more adverse effects than larotrectinib in the management of both glioma and tyrosine kinase alterations after failure of initial therapies.</p><p id="para0035" class="elsevierStylePara elsevierViewall">Initial bevacizumab therapy is associated with a higher overall survival. The results of the independent parameters for overall survival in the current study are consistent with those of the phase II study.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> A combination of bevacizumab with infigratinib or larotrectinib could result in higher overall survival of patients with both glioma and tyrosine kinase alterations.</p><p id="para0036" class="elsevierStylePara elsevierViewall">Performing chi square or Mann-Whitney tests are inadequate for evaluating the overall survival in cancer treatment. In almost all clinical evaluations of overall survival, median survival times, and cancer-related survival rates, the statistical analysis for comparison between treatment options is performed by Kaplan Meier estimator curves. The possible justifications for the same are Kaplan Meier estimator curves used for predictions of overall survival and progression-free survival. However, in the current study the authors have absolute parameters for overall survival and progression-free survival because of the 18 months of followed-up period of data. As because of the availability of absolute values, the authors have evaluated overall survival and progression-free survival using Fisher’s exact test instead of Kaplan–Meier estimator curves.</p><p id="para0037" class="elsevierStylePara elsevierViewall">The study proposed to perform a clinical evaluation for efficacy and safety analysis of larotrectinib or infigratinib therapies for patients with both glioma and tyrosine kinase alterations. However, there are certain limitations of this study, for example, its retrospective design and the lack of randomized trials. The study did not report or discuss the efficacy of infigratinib and larotrectinib in recurrent disease conditions. The absence of WHO 2021 CNS tumor classification<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> applied to what seems to be collectively referred to as “glioma”, and thereby it is not possible to draw conclusions regarding the efficacy of these two drugs. What constitutes glioma is currently understood to represent a rather vast array of tumors that must be evaluated based on their molecular characteristics to draw any valid conclusions.</p></span><span id="sec0023" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0031">Conclusions</span><p id="para0038" class="elsevierStylePara elsevierViewall">Infigratinib has a higher efficacy than larotrectinib in adult patients with both glioma and tyrosine kinase alterations after the failure of initial therapies. Infigratinib increases the overall survival compared to larotrectinib in adult patients with both glioma and tyrosine kinase alterations. Infigratinib has more adverse effects than larotrectinib in the management of adult patients with both glioma and tyrosine kinase alterations after the failure of initial therapies. A combination of bevacizumab with infigratinib or larotrectinib could result in higher overall survival of patients with glioma.</p></span><span id="sec0024" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0032">Availability of data and materials</span><p id="para0039" class="elsevierStylePara elsevierViewall">The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0033">Authors’ contributions</span><p id="para0040" class="elsevierStylePara elsevierViewall">All the authors have read and approved the manuscript for publication. YC and JM were project administrators who contributed equally to the conceptualization, formal analysis, supervision, resources, methodology, validation, and literature review of the study. QG contributed to the investigation, resources, conceptualization, visualization, formal analysis, methodology, and literature review. YG contributed resources, formal analysis, conceptualization, methodology, data curation, and literature review. YS contributed to the resources, supervision, formal analysis, data curation, and literature review. MW contributed to the resources, funding acquisition, formal analysis, methodology, and literature review of the study and drafted and edited the manuscript for intellectual content. All authors agree to be accountable for all aspects of this study, ensuring its integrity and accuracy. YC and JM confirmed the authenticity of the raw data.</p></span><span id="sec0026" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0034">Funding</span><p id="para0041" class="elsevierStylePara elsevierViewall">This study was supported by the <span class="elsevierStyleGrantSponsor" id="gs0001">Changzhou Sci & Tech Program, China</span> (Grant no. <span class="elsevierStyleGrantNumber" refid="gs0001">CJ20220224</span>).</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres2290866" "titulo" => "Highlights" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abss0001" ] ] ] 1 => array:3 [ "identificador" => "xres2290865" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0002" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abss0003" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0004" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0005" "titulo" => "Conclusions" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1903279" "titulo" => "Keywords" ] 3 => array:2 [ "identificador" => "xpalclavsec1903278" "titulo" => "List of abbreviations" ] 4 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0002" "titulo" => "Materials and methods" "secciones" => array:9 [ 0 => array:2 [ "identificador" => "sec0003" "titulo" => "Ethics approval and consent to participate" ] 1 => array:2 [ "identificador" => "sec0004" "titulo" => "Inclusion criteria" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Exclusion criteria" ] 3 => array:2 [ "identificador" => "sec0006" "titulo" => "Cohorts" ] 4 => array:2 [ "identificador" => "sec0007" "titulo" => "ECOG performance status" ] 5 => array:2 [ "identificador" => "sec0008" "titulo" => "Treatment response evaluation" ] 6 => array:3 [ "identificador" => "sec0009" "titulo" => "Survival" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Progression-free survival" ] 1 => array:2 [ "identificador" => "sec0011" "titulo" => "Overall survival" ] ] ] 7 => array:3 [ "identificador" => "sec0012" "titulo" => "Adverse effects" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0013" "titulo" => "Hyperphosphatemia" ] ] ] 8 => array:2 [ "identificador" => "sec0014" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0016" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0017" "titulo" => "Demographic and clinical parameters" ] 2 => array:2 [ "identificador" => "sec0018" "titulo" => "Treatment response evaluation" ] 3 => array:2 [ "identificador" => "sec0019" "titulo" => "Survival" ] 4 => array:2 [ "identificador" => "sec0020" "titulo" => "Adverse effects" ] 5 => array:2 [ "identificador" => "sec0021" "titulo" => "Independent parameter" ] ] ] 7 => array:2 [ "identificador" => "sec0022" "titulo" => "Discussions" ] 8 => array:2 [ "identificador" => "sec0023" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0024" "titulo" => "Availability of data and materials" ] 10 => array:2 [ "identificador" => "sec0025" "titulo" => "Authors’ contributions" ] 11 => array:2 [ "identificador" => "sec0026" "titulo" => "Funding" ] 12 => array:2 [ "identificador" => "xack786216" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-09-15" "fechaAceptado" => "2023-12-21" "PalabrasClave" => array:1 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1903279" "palabras" => array:5 [ 0 => "Glioma" 1 => "Hyperphosphatemia" 2 => "Infigratinib" 3 => "Larotrectinib" 4 => "Tyrosine kinase alteration" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "List of abbreviations" "identificador" => "xpalclavsec1903278" "palabras" => array:8 [ 0 => "IN cohort" 1 => "LB cohort" 2 => "χ<span class="elsevierStyleSup">2</span>-test" 3 => "ECOG" 4 => "SD" 5 => "CI" 6 => "WHO" 7 => "CNS" ] ] ] ] "tieneResumen" => true "highlights" => array:2 [ "titulo" => "Highlights" "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara019" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">•</span><p id="para0002" class="elsevierStylePara elsevierViewall">Tyrosine kinase domains with genomic alterations have oncogenic potential.</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">•</span><p id="para0003" class="elsevierStylePara elsevierViewall">Higher efficacy for infigratinib than larotrectinib.</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">•</span><p id="para0004" class="elsevierStylePara elsevierViewall">Infigratinib has a higher overall survival than larotrectinib.</p></li><li class="elsevierStyleListItem" id="celistitem0004"><span class="elsevierStyleLabel">•</span><p id="para0005" class="elsevierStylePara elsevierViewall">Infigratinib has higher adverse effects than larotrectinib.</p></li><li class="elsevierStyleListItem" id="celistitem0005"><span class="elsevierStyleLabel">•</span><p id="para0006" class="elsevierStylePara elsevierViewall">Bevacizumab initial therapy has a higher overall survival.</p></li></ul></p></span>" ] "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Objectives</span><p id="spara020" class="elsevierStyleSimplePara elsevierViewall">To compare the efficacy and safety of larotrectinib with those of infigratinib in adult glioma patients with tyrosine kinase alterations.</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara021" class="elsevierStyleSimplePara elsevierViewall">Patients received oral infigratinib 125 mg (IN cohort, <span class="elsevierStyleItalic">n</span> = 125) or oral larotrectinib (LB cohort, <span class="elsevierStyleItalic">n</span> = 105) until unacceptable toxicity or disease progression.</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara022" class="elsevierStyleSimplePara elsevierViewall">Duration of treatment was longer in the LB cohort than in the IN cohort (8 [9.5–6.25] months vs. 5.5 [6–5.25] months, <span class="elsevierStyleItalic">p</span> < 0.0001). Patients with partial responses (<span class="elsevierStyleItalic">p</span> = 0.0424) and overall survival (<span class="elsevierStyleItalic">p</span> = 0.03) were higher in the IN cohort than those in the LB cohort. The number of patients with disease progression was higher in the LB cohort (<span class="elsevierStyleItalic">p</span> = 0.0015). All the patients reported diarrhea, fatigue, vomiting, constipation, and decreased appetite. Patients in the IN cohort reported hyperphosphatemia, hyperlipasemia, stomatitis, dry skin, alopecia, dyspepsia, onycholysis, palmar-plantar erythrodysesthesia, nail disorders, and dry eyes. Patients in the LB cohort reported upper respiratory tract infections, pyrexia, cough, anemia, bacterial/viral infections, conjunctivitis, urinary tract infections, headaches, ataxia, dizziness, and muscle tremors. A total of 30 (24 %) and 40 (38 %) patients from the IN and the LB cohorts died at the follow-up of 18 months (<span class="elsevierStyleItalic">p</span> = 0.03). Patients who received bevacizumab initial therapy had higher overall survival (<span class="elsevierStyleItalic">p</span> = 0.048).</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusions</span><p id="spara023" class="elsevierStyleSimplePara elsevierViewall">Infigratinib has higher efficacy and overall survival than larotrectinib but has higher adverse effects in the management of both glioma and tyrosine kinase alterations after failure of initial therapies. Initial bevacizumab therapy is associated with a higher overall survival.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0002" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abss0003" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0004" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0005" "titulo" => "Conclusions" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="notep0001">These two authors contributed to this work equally.</p>" "identificador" => "fn1" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2406 "Ancho" => 3167 "Tamanyo" => 275000 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">The retrospective flow chart.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Oncologists in assistance with radiologists have evaluated treatment response.</p><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Magnetic resonance imaging scans and pathology were preferred for evaluation of response.</p>" "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"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Different types of responses \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Criteria \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0003"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Complete response \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0004"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Complete invisible of all advanced measurables and unmeasurable diseases. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0005"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Partial response \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">50 % or more decrease of all advanced measurables and unmeasurable diseases. That is sustained for at least 4-weeks, with no new lesions. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0007"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Progression \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 % or more increase in all advanced measurables and unmeasurable diseases. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Stable disease \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Not qualified for partial response and no progression of the disease. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3711491.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Treatment response evaluation.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0002" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Categorial variables are depicted as frequencies (percentages). Continuous non-normal variables are depicted as median (Q3–Q1).</p><p id="spara007" class="elsevierStyleSimplePara elsevierViewall">CI, Confidence Interval (using the approximation of Katz.); Df, Degree of freedom; N/A, Not Applicable; ECOG, Eastern Cooperative Oncology Group (0: Fully active; 1: Unable to do strenuous activities; 2: Capable of all self-care but dependent on others to carry out normal activities).</p><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Test value (χ<span class="elsevierStyleSup">2</span> value for χ<span class="elsevierStyleSup">2</span>-test, Mann-Whitney U-statistic for Mann-Whitney test).</p>" "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"><a name="en0011"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup colgroup " rowspan="2" align="left" valign="top" scope="col" colspan="2" style="border-bottom: 2px solid black">Parameters</th><a name="en0012"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col">Total</th><a name="en0013"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Cohorts</th><a name="en0014"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup colgroup " rowspan="3" align="center" valign="top" scope="col" colspan="4" style="border-bottom: 2px solid black">Comparisons between cohorts</th></tr><tr title="table-row"><a name="en0017"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">IN \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0018"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">LB \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0020"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="top" scope="col">Treatment(s)</th><a name="en0021"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">2nd line \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0022"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Infigratinib \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0023"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Larotrectinib \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0025"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Numbers of patients</th><a name="en0026"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">230 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0027"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">125 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0028"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">105 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0029"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0030"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95 % CI \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0031"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Df \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0032"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Test value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0033"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top">Gender</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">135 (59) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">70 (56) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">65 (62) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top">0.4404 (χ<span class="elsevierStyleSup">2</span>-test)</td><a name="en0039"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top">0.7071 to 1.134</td><a name="en0040"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top">1</td><a name="en0041"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top">0.5952</td></tr><tr title="table-row"><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">95 (41) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">55 (44) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">40 (38) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0051"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="top">Age (years)</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">52 (57–44) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">52 (57–44) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">52 (56.5–43) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">0.5211 (Mann-Whitney test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">6239.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0059"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">Ethnicity</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Han Chinese \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">214 (93) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">117 (94) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">97 (92) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0064"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">0.7292 (χ<span class="elsevierStyleSup">2</span>-test for Trend)</td><a name="en0065"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">N/A</td><a name="en0066"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">1</td><a name="en0067"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">0.1199</td></tr><tr title="table-row"><a name="en0069"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Mongolian \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14 (6) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 (5) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 (7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0078"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Tibetan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 (1) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 (1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0086"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">ECOG performance status</td><a name="en0087"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">55 (24) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 (24) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 (24) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0091"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">0.9799 (χ<span class="elsevierStyleSup">2</span>-test for independence)</td><a name="en0092"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">N/A</td><a name="en0093"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">2</td><a name="en0094"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">0.0451</td></tr><tr title="table-row"><a name="en0096"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">140 (56) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">70 (56) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">60 (57) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0105"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">45 (20) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 (20) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20 (19) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0113"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="top">Initial Therapies</td><a name="en0114"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Radiotherapy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 (11) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 (12) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 (10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0118"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="top">0.7456 (χ<span class="elsevierStyleSup">2</span>-test for independence)</td><a name="en0119"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="top">N/A</td><a name="en0120"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="top">3</td><a name="en0121"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="top">1.231</td></tr><tr title="table-row"><a name="en0123"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Antineoplastic therapy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">60 (26) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">35 (28) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 (24) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0132"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Bevacizumab \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">85 (37) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">45 (36) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">40 (38) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0141"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Temozolomide \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">60 (26) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 (24) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0144"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 (28) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3711492.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical parameters of enrolled patients before the start of second-line treatment for glioma.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0003" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spara010" class="elsevierStyleSimplePara elsevierViewall">Variables are depicted as frequencies (percentages).</p><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">RECIST 1.1 criteria were used for the evaluation of treatment response.</p><p id="spara012" class="elsevierStyleSimplePara elsevierViewall">Oncologists in assistance with radiologists have evaluated treatment response.</p><p id="spara013" class="elsevierStyleSimplePara elsevierViewall">CI, Confidence Interval (using the approximation of Katz.); Df, Degree of freedom; N/A, Not Applicable.</p><p id="spara014" class="elsevierStyleSimplePara elsevierViewall">Test value (χ<span class="elsevierStyleSup">2</span> value or relative risk value for χ<span class="elsevierStyleSup">2</span>-test Fisher exact test).</p>" "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"><a name="en0149"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameters</th><a name="en0150"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col">Total</th><a name="en0151"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Cohorts</th><a name="en0152"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup colgroup " rowspan="3" align="center" valign="top" scope="col" colspan="4" style="border-bottom: 2px solid black">Comparisons between cohorts</th></tr><tr title="table-row"><a name="en0155"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">IN \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0156"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">LB \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0158"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Treatment(s) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0159"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">2<span class="elsevierStyleSup">nd</span> line \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0160"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Infigratinib \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0161"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Larotrectinib \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0163"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Numbers of patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0164"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">230 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0165"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">125 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0166"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">105 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0167"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0168"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">95 % CI \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0169"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Df \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0170"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Test value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0171"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Complete response \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0172"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 (10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 (10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0174"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9 (9) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0175"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.6611 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0176"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.7581 to 1.588 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0177"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0178"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.097 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0179"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Partial response \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0180"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">62 (27) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0181"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">41 (33) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0182"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 (20) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0183"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0424 (χ<span class="elsevierStyleSup">2</span>-test with Yate's correction) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0184"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.047 to 1.671 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0185"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0186"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.121 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0187"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Progression \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0188"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">69 (30) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0189"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 (21) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0190"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">43 (41) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0191"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0015 (χ<span class="elsevierStyleSup">2</span>-test with Yate's correction) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0192"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.4418 to 0.8500 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0193"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0194"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.097 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0195"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Stable disease \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0196"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">77 (33) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0197"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">45 (36) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0198"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32 (30) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0199"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.4569 (χ<span class="elsevierStyleSup">2</span>-test with Yate's correction) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0200"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.8777 to 1.423 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0201"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0202"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5535 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3711494.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Treatment response evaluation after the termination of 2nd line treatment.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0004" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spara016" class="elsevierStyleSimplePara elsevierViewall">Variables are depicted as frequencies (percentages). The Common Terminology Criteria for Adverse Events, version 4.03 was used for the evaluation of adverse effects.</p><p id="spara017" class="elsevierStyleSimplePara elsevierViewall">CI, Confidence Interval (using the approximation of Katz.); Df, Degree of freedom; N/A, Not Applicable.</p><p id="spara018" class="elsevierStyleSimplePara elsevierViewall">Test value (χ<span class="elsevierStyleSup">2</span> value or relative risk value for χ<span class="elsevierStyleSup">2</span>-test Fisher exact test).</p>" "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"><a name="en0203"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameters</th><a name="en0204"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Cohorts</th><a name="en0205"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup colgroup " rowspan="3" align="center" valign="top" scope="col" colspan="4" style="border-bottom: 2px solid black">Comparisons between cohorts</th></tr><tr title="table-row"><a name="en0207"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">IN \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0208"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">LB \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0210"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Treatment(s) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0211"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Infigratinib \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0212"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Larotrectinib \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0214"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Numbers of patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0215"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">125 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0216"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">105 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0217"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0218"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">95 % CI \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0219"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Df \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0220"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Test value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0221"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Hyperphosphatemia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0222"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">94 (75)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0223"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0224"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0225"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3.220 to 5.978 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0226"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0227"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.378 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0228"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Diarrhea \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0229"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20 (16)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0230"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">60 (57)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0231"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (χ<span class="elsevierStyleSup">2</span>-test with Yate's correction) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0232"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.2409 to 0.5295 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0233"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0234"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">40.788 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0235"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Fatigue \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0236"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 (24)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0237"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">55 (52)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0238"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (χ<span class="elsevierStyleSup">2</span>-test with Yate's correction) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0239"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.3946 to 0.7354 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0240"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0241"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">18.529 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0242"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Vomiting \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0243"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">65 (52)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0244"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">60 (57)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0245"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5176 (χ<span class="elsevierStyleSup">2</span>-test with Yate's correction) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0246"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.7185 to 1.153 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0247"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0248"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.4187 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0249"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Hyperlipasemia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0250"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 (12)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0251"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0252"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0253"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.715 to 2.227 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0254"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0255"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.955 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0256"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Stomatitis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0257"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14 (11)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0258"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0259"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0260"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.709 to 2.216 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0261"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0262"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.946 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0263"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Dry skin \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0264"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 (10)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0265"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0266"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0003 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0267"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.703 to 2.204 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0268"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0269"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.938 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0270"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Alopecia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0271"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 (18)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0272"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0273"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0274"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.760 to 2.316 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0275"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0276"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.019 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0277"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Decreased appetite \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0278"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">18 (14)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0279"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">18 (17)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0280"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5893 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0281"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.6385 to 1.287 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0282"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0283"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.9065 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0284"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Dyspepsia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0285"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9 (7)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0286"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0(0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0287"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0043 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0288"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.681 to 2.160 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0289"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0290"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.905 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0291"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Onycholysis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0292"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8 (6)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0293"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0294"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0085 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0295"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.675 to 2.149 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0296"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0297"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.897 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0298"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Palmar-plantar erythrodysesthesia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0299"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 (6)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0300"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0301"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0166 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0302"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.670 to 2.139 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0303"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0304"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0305"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Constipation \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0306"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12 (10)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0307"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32 (30)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0308"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0309"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.2733 to 0.7374 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0310"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0311"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.4489 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0312"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Nail disorder \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0313"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">11 (9)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0314"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0(0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0315"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0011 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0316"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.692 to 2.181 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0317"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0318"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.921 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0319"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Dry eye \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0320"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8 (6)<a class="elsevierStyleCrossRef" href="#tb4fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0321"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0(0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0322"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0085 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0323"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.675 to 2.149 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0324"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0325"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.897 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0326"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Upper respiratory tract infection \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0327"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0328"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">55 (54)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0329"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0330"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0331"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0332"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0333"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Pyrexia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0334"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0335"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">35 (33)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0336"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0337"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0338"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0339"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0340"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cough \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0341"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0(0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0342"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">31 (30)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0343"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0344"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0345"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0346"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0347"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Anemia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0348"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0349"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32 (30)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0350"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0351"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0352"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0353"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0354"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Bacterial/Viral infection \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0355"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0356"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 (21)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0357"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0358"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0359"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0360"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0361"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Conjunctivitis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0362"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0363"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19 (18)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0364"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0365"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0366"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0367"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0368"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Urinary tract infection \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0369"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0370"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 (14)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0371"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0372"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0373"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0374"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0375"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Headache \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0376"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0377"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 (20)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0378"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.0001 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0379"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0380"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0381"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0382"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Ataxia \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0383"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0384"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 (7)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0385"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0037 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0386"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0387"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0388"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0389"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Dizziness \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0390"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0391"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5 (3)<a class="elsevierStyleCrossRef" href="#tb4fn2"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0392"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0188 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0393"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0394"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0395"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0396"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Muscle tremor \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0397"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0398"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4 (4) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0399"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.0421 (Fisher exact test) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0400"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">-Infinity to Infinity \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0401"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0402"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3711493.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tb4fn1" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="notep0015">Infigratinib-emergent adverse effects.</p>" ] 1 => array:3 [ "identificador" => "tb4fn2" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="notep0016">Larotrectinib-emergent adverse effects.</p> <p class="elsevierStyleNotepara" id="notep0017">Hyperphosphatemia: > 4.5 mg/dL plasma inorganic phosphate level.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara015" class="elsevierStyleSimplePara elsevierViewall">Adverse effects during 2nd line treatment and 18-months of followed-up.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "QT Ostrom" 1 => "G Cioffi" 2 => "H Gittleman" 3 => "N Patil" 4 => "K Waite" 5 => "C Kruchko" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/neuonc/noz150" "Revista" => array:7 [ "tituloSerie" => "Neuro Oncol" "fecha" => "2019" "volumen" => "21" "numero" => "Suppl 5" "paginaInicial" => "v1" "paginaFinal" => "v100" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31675094" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0002" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic and molecular epidemiology of adult diffuse glioma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "AM Molinaro" 1 => "JW Taylor" 2 => "JK Wiencke" 3 => "MR. 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