Efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma

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Hoff, Jorge Sabbaga" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Guilherme Nader" "apellidos" => "Marta" ] 1 => array:4 [ "nombre" => "Leonardo G." "apellidos" => "da Fonseca" "email" => array:1 [ 0 => "l.fonseca@fm.usp.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 2 => array:2 [ "nombre" => "Maria Ignez" "apellidos" => "Braghiroli" ] 3 => array:2 [ "nombre" => "Fernando" "apellidos" => "Moura" ] 4 => array:2 [ "nombre" => "Paulo M." "apellidos" => "Hoff" ] 5 => array:2 [ "nombre" => "Jorge" "apellidos" => "Sabbaga" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 284 "Ancho" => 673 "Tamanyo" => 25265 ] ] "descripcion" => array:1 [ "en" => "Time to treatment failure and overall survival curves for patients with advanced HCC under 70 years of age (Group A) and for patients 70 years of age or older (Group B) treated with sorafenib in the first-line setting." ] ] ] "textoCompleto" => "INTRODUCTIONApproximately 70% of the patients with cancer are aged 65 years and older, and the number of patients with cancer in this age group is projected to significantly increase over the next decades (<a class="elsevierStyleCrossRef" href="#bib1">1</a>). Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide (<a class="elsevierStyleCrossRef" href="#bib2">2</a>). Although the mean age of HCC presentation is between 50 and 60 years (<a class="elsevierStyleCrossRef" href="#bib3">3</a>), a substantial proportion of HCC patients is older. Sorafenib was the first systemic agent to improve survival and has been the backbone of advanced HCC treatment over the past decade (<a class="elsevierStyleCrossRef" href="#bib4">4</a>). Recently, an expansion in systemic treatment options (<a class="elsevierStyleCrossRef" href="#bib5">5</a>) has increased the complexity of therapeutic decisions for the management of HCC. This scenario is even more complex in older patients because of the scarce representation of this population in clinical trials. Furthermore, concomitant advanced age with chronic liver disease increase concerns about toxicity and clinical benefits in this subgroup (<a class="elsevierStyleCrossRef" href="#bib6">6</a>). Therefore, it is of utmost importance to broaden the available evidence to support the management of elderly patients with advanced HCC. Here, we analyzed a cohort of HCC patients with the aim of evaluating the efficacy and safety of sorafenib in this specific population.MATERIAL AND METHODSStudy Design and ParticipantsWe retrospectively evaluated a cohort of advanced HCC patients treated between October 2007 and January 2017 at the Instituto do Câncer do Estado de São Paulo (ICESP), Universidade de São Paulo, Brazil. All patients included in the analysis met the diagnostic criteria for HCC based on radiological and/or histological findings (<a class="elsevierStyleCrossRef" href="#bib7">7</a>). Clinical characteristics related to the underlying liver disease, information on treatments, and clinical outcomes were collected from medical records at the beginning of the systemic therapy.Patients were excluded in case of: (<a class="elsevierStyleCrossRef" href="#bib1">1</a>) diagnosis of fibrolamellar carcinoma, (<a class="elsevierStyleCrossRef" href="#bib2">2</a>) exposure to systemic therapy for less than 30 days, (<a class="elsevierStyleCrossRef" href="#bib3">3</a>) insufficient data in medical records, or (<a class="elsevierStyleCrossRef" href="#bib4">4</a>) loss to follow-up, long enough to impair outcome assessment.Patients were divided into two groups, (Group A) individuals <70 years of age and (Group B) individuals who were 70-years old or older at the time of initiation of sorafenib treatment. Efficacy and safety were compared between Groups A and B. The study was approved by the institutional ethics committee (3.807.496).TreatmentAccording to the institutional protocol, patients who are candidates for systemic treatment receive first-line therapy with sorafenib at a dose of 400 mg twice daily, and this is continued until evidence of disease progression, unacceptable adverse events, or death. The use of reduced doses was permitted both from the beginning of the treatment and during the course of treatment (depending on tolerability and side effects) at the discretion of the treating physician. The follow-up consisted of regular clinical visits and laboratory assessments every three to four weeks and assessment of radiological response (computed tomography or magnetic resonance) every eight to 12 weeks. After sorafenib discontinuation, patients received best supportive care or were enrolled in clinical trials whenever available in the institution.Statistical AnalysisOverall survival (OS) was calculated from the first day of treatment until death from any cause. Patients without the event were censored at the time of the last follow-up. Time to treatment failure (TTF) because of disease progression or toxicity was calculated from the first to the last day on sorafenib.Categorical variables were compared using the χ2-test or Fischer's exact test, where appropriate. TTF and OS were estimated using the Kaplan-Meier method and curves were compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards model were performed to evaluate the prognostic factors. Variables were included in the multivariate analyses if they presented a p-value <0.05 in the univariate analysis and were not associated with each other. Statistical analyses were performed using SPSS software, version 22.0 (IBM SPSS Chicago, IL). A p-value <0.05 was considered significant.RESULTSPatient CharacteristicsFrom October 2007 to January 2017, 238 patients with advanced HCC who were not suitable candidates for—or had progressed after—locoregional therapies received first-line sorafenib at Instituto do Câncer do Estado de São Paulo (ICESP) and were included in the present analysis. The median age for Group A was 59.1 years and for Group B 73.6 years. The proportion of patients with preserved performance status (ECOG performance status 0) was significantly higher in Group A than that in Group B (75.3% vs 56.8%, p=0.014), respectively. The distribution of the etiologies of chronic liver diseases was homogeneous between the groups, although a higher proportion of patients with hepatitis C virus infection was observed in Group A (51.5% vs 27.3%, p=0.004). Important prognostic markers, such as staging according to the Barcelona Clinic Liver Cancer (BCLC) staging system (p=0.831), the presence of elevated α-fetoprotein levels (p=0.481), or the presence of extrahepatic spread of the disease (p=0.115) were balanced between groups. Locoregional treatments performed prior to systemic therapy had been delivered to 46.4% of patients in Group A and to 43.1% in Group B. Patients in Group B were more likely to receive sorafenib at reduced doses (<800 mg daily) than patients in Group A (27.3% vs 11.3%, p=0.006). The demographic and treatment characteristics are presented in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>.<elsevierMultimedia ident="tbl1"></elsevierMultimedia>Efficacy and Adverse EventsAt the time of the final analysis, 156 (92.9%) deaths occurred in Group A and 28 (90.3%) in Group B. The median follow-up period was 7.0 months. No significant difference was observed in TTF between Group A (3.0 months, 95%CI 2.39-3.60) and Group B (3.0 months, 95%CI 1.68-4.32), p=0.936. Similarly, no significant difference was observed in the median OS between Group A (8.0 months, 95%CI 6.34-9.3) and Group B (9.0 months, 95% CI 5.38-12.62), p=0.433 (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>).<elsevierMultimedia ident="fig1"></elsevierMultimedia>The incidence of dermatological adverse events (38.5% vs 33.3%, p=0.532), hypertension (6.9% vs 4.9%, p=0.746), and diarrhea (37.8% vs 26.8%, p=0.186) did not differ significantly between Groups A and B, respectively. Intolerance leading to sorafenib discontinuation occurred in 11.3% and 9.1% of the patients in Groups A and B, respectively (p=0.794). Temporary interruptions of at least 1 week were observed at least once in 6.7% of the patients in Group A versus 13.6% of the patients in Group B (p=0.131). The distribution of the most common toxicities is described in <a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>.<elsevierMultimedia ident="tbl2"></elsevierMultimedia>Factors associated with OS in patients with advanced hepatocellular carcinomaThe variables included in the univariate analysis were age, Eastern Cooperative Oncology Group performance status (ECOG PS) etiology of hepatopathy (HCV, HBV, alcohol), initial dose of sorafenib, BCLC stage, Child-Pugh score, presence of extrahepatic metastasis, and serum levels of alpha-fetoprotein. In the univariate analysis, ECOG PS (HR 1.45, 95% CI 1.1-2.0, p=0.021), Child-Pugh (HR 2.93, 95% CI 1.9-4.5, p<0.001), and AFP levels (HR 1.53, 95% CI 1.1-2.0, p=0.004) achieved the significance threshold for inclusion in the multivariate analysis.In the multivariate analysis, ECOG PS (HR 1.42, 95% CI 1.1-1.9, p=0.025), Child-Pugh (HR 2.59, 95% CI 1.7-3.9, p<0.001), and AFP levels (HR 1.48, 95% CI 1.1-1.9, p=0.006) exhibited a significant association with poor OS. <a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a> summarizes the results of the univariate and multivariate analyses.<elsevierMultimedia ident="tbl3"></elsevierMultimedia>DISCUSSIONOur study focused on assessing the impact of age on the efficacy and safety of sorafenib in patients with advanced HCC. Although patients over 70 years of age more frequently received sorafenib with dose reductions, no significant OS or TTF differences were observed between patients over 70 years of age and their younger counterparts. Similarly, the frequency of adverse events occurred at comparable rates between the groups. In multivariate analysis, known prognostic factors such as ECOG PS 1-2 and Child-Pugh B and elevated serum levels of AFP (>400 ng/mL) were associated with lower survival in the entire cohort.Liver cancer was the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide in 2018 (<a class="elsevierStyleCrossRef" href="#bib2">2</a>). The incidence and mortality rates of HCC are increasing in many parts of the world, including North America, Latin America, and central Europe (<a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib9">9</a>). Although the median age for diagnosis of HCC in the United States is 62 years, more than 30% of patients are currently diagnosed at >70 years of age (<a class="elsevierStyleCrossRef" href="#bib10">10</a>), emphasizing the need for data that support the clinical management of this population.Upon using a cutoff point of 70 years of age, we did not find a significant difference in the clinical outcomes, i.e., OS and TTF between younger and older patients who received sorafenib for advanced HCC. The absence of difference between age groups becomes even more pronounced when we consider that the group of younger patients (Group A) more frequently received full doses of sorafenib (800 mg daily) and was enriched with a higher proportion of patients with preserved performance status, a known favorable prognostic factor (<a class="elsevierStyleCrossRef" href="#bib11">11</a>), in addition to presenting a higher proportion of patients with HCC because of hepatitis C infection, a subgroup that was shown to derive greater benefit from sorafenib treatment (<a class="elsevierStyleCrossRef" href="#bib12">12</a>).Although different age cutoff points have been used, other authors have already sought to evaluate the efficacy of sorafenib in older patients with advanced HCC. Novel treatment strategies such as the combination of atezolizumab plus bevacizumab, have been shown to be associated with a favorable safety profile and a meaningful benefit in adults ≥65 years of age in a subgroup analysis in the IMbrave150 trial (<a class="elsevierStyleCrossRef" href="#bib13">13</a>).<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a> summarizes the findings of studies comparing the clinical outcomes of young and old patients with HCC who received first-line sorafenib. Heterogeneity in survival across different cohorts is likely to reflect variations in epidemiological and clinical contexts, including improved management of treatment-related adverse events with tailored dosing (<a class="elsevierStyleCrossRef" href="#bib14">14</a>). Most of these studies also did not find any significant correlation between age and OS subgroups (<a class="elsevierStyleCrossRefs" href="#bib15">15–21</a>). Hajiev et al. analyzed a large cohort of 5598 patients, including 792 patients aged ≥75 years and found equivalent outcomes in the groups < or ≥75 years, independent of dose (<a class="elsevierStyleCrossRef" href="#bib15">15</a>). In this cohort, a higher rate of discontinuation because of toxicity in the older subgroup was observed, which indicates that physicians may be inclined to discontinue treatment in older patients who experience an adverse event, fearing further severe complications. In addition, they observed that patients aged ≥75 years who received sorafenib had lower alpha-fetoprotein levels, less portal invasion, and better liver function. This probably reflects the reason why physicians tend to prescribe sorafenib for older patients because of these favorable prognostic factors (<a class="elsevierStyleCrossRef" href="#bib15">15</a>).<elsevierMultimedia ident="tbl4"></elsevierMultimedia>In contrast, Morimoto et al. (<a class="elsevierStyleCrossRef" href="#bib18">18</a>) reported a survival benefit in favor of the subgroup of younger patients. In this respect, the following limitations of this study should be taken into consideration when interpreting the results: (<a class="elsevierStyleCrossRef" href="#bib1">1</a>) this study included a relatively small population (n=76) comprising exclusively of Asian patients; (<a class="elsevierStyleCrossRef" href="#bib2">2</a>) treatment compliance was poor (less than 50% of patients received more than 80% of the prescribed dose of sorafenib); and (<a class="elsevierStyleCrossRef" href="#bib3">3</a>) the median duration of treatment was short (only 1.7 months), possibly because of a high rate of adverse events.In the present analysis, although older patients more frequently received lower doses of sorafenib, such dose reductions did not significantly impact efficacy or toxicity. The prescription of a reduced initial dose in 27% of our cohort might reflect a common perception of physicians that elderly patients are at increased risk of adverse events. In addition, a higher proportion of ECOG PS 2 among the older group might also explain this finding.Aging has been associated with changes in the pharmacokinetics of antineoplastic agents because of a number of age-related changes, including modifications in renal function and excretion, changes in liver function and metabolism, drug absorption and distribution alterations, among others (<a class="elsevierStyleCrossRefs" href="#bib22">22–24</a>). For this reason, the doses of drugs provided to younger patients are not necessarily extrapolatable to older patients. In addition—specifically regarding the use of sorafenib in the treatment of HCC—recent evidence suggests that no significant efficacy impairment might be observed when starting treatment at doses below 800 mg daily (<a class="elsevierStyleCrossRef" href="#bib25">25</a>).Older cancer patients are often at a higher risk of “undertreatment” because of exaggerated clinical estimation of their frailty, as well as “overtreatment” because of inappropriate evaluation of their fitness to receive intensive treatment regimens (<a class="elsevierStyleCrossRef" href="#bib26">26</a>,<a class="elsevierStyleCrossRef" href="#bib27">27</a>). As reinforced by our data, age alone is not a reliable predictor of efficacy or adverse events in advanced HCC patients treated with sorafenib. Specific geriatric assessment tools that are not widely used in routine oncology assessments have been validated to predict adverse outcomes in patients being considered for cancer treatments (<a class="elsevierStyleCrossRef" href="#bib26">26</a>). Evidence suggests that geriatric assessment should include—at a minimum—evaluation of function, comorbidity, falls, depression, cognition, and nutrition (<a class="elsevierStyleCrossRef" href="#bib28">28</a>). Finally, the underrepresentation of patients over 65 years in clinical cancer trials is a major issue because it weakens the evidence supporting the therapeutic decisions in this population (<a class="elsevierStyleCrossRef" href="#bib29">29</a>,<a class="elsevierStyleCrossRef" href="#bib30">30</a>). Thus, the use of inclusion or exclusion criteria based exclusively on age should be discouraged, and clinical trials in oncology should be performed without an upper age limit to allow inclusion of eligible older adults (<a class="elsevierStyleCrossRef" href="#bib31">31</a>).It has been demonstrated that specific types of adverse events have a prognostic value, such as skin toxicities and hypertension (<a class="elsevierStyleCrossRef" href="#bib32">32</a>). A longer follow-up of the present cohort can aid us in understanding whether these observations apply to the elderly population, as the incidence of some specific events in this study was low. Further, worse liver function is a key prognostic factor in advanced HCC (<a class="elsevierStyleCrossRef" href="#bib33">33</a>) and is of particular relevance in older patients, as suggested by our multivariate analysis.Our study has limitations that should be considered when interpreting the results. This was a single-center retrospective analysis, which may hinder the external validity of our results. We excluded patients with exposure to systemic therapy for less than 30 days to minimize the inclusion of patients with premature loss to follow-up, which may have underrepresented patients with rapidly progressive disease. In addition, because of its retrospective nature, there was no randomization between the treatment arms, which may have influenced our outcomes.CONCLUSIONSAlthough older patients received reduced starting doses of sorafenib and presented lower performance status at the start of systemic treatment, these patients did not exhibit a significant difference in OS and TTF in comparison with younger patients in the present retrospective analysis. The safety of sorafenib treatment was similar between younger and older patients, with similar toxicity-related discontinuation rates between groups. Our results suggest that age alone should not be used to determine the therapeutic strategy for patients with advanced HCC being considered for sorafenib therapy.CONFLICTS OF INTERESTGuilherme Nader Marta has received travel/accommodation grants from Bayer Schering Pharma and Roche. Leonardo Gomes da Fonseca received lecture fees from Bayer and travel grants from Bayer and Ipsen. Maria Ignez Braghiroli received grants from Merck Sharp and Dohme and Bristol-Myers Squibb for clinical trials at her institution and from Merck Sharp and Dohme, Bayer, and Astra Zeneca for being a member of their advisory boards. Paulo M. Hoff has no conflicts of interest to declare. Jorge Sabbaga received grants from Bayer for being a member of its advisory board.AUTHOR CONTRIBUTIONSMarta GN, Fonseca LG, Sabbaga J contributed in study concepts. Fonseca LG, Braghiroli MI contributed in study design. Marta GN, Fonseca LG, Moura F contributed in data acquisition. Braghiroli MI, Hoff PM, Sabbaga J contributed in quality control of data and algorithms. Marta GN, Fonseca LG, Sabbaga J contributed in data analysis and interpretation. Marta GN, Fonseca LG, Moura F contributed in statistical analysis. Marta GN, Fonseca LG contributed in manuscript preparation. Moura F, Braghiroli MI, Hoff PM, Sabbaga J contributed in manuscript editing. Braghiroli MI, Hoff PM, Sabbaga J contributed in manuscript review." 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METHODS:We analyzed data from a cohort of patients with advanced HCC treated using systemic treatment according to the local institutional protocol. Patients were divided into two groups, Group A, individuals <70 years of age, and Group B, individuals 70 years of age or older at the time of treatment initiation. Efficacy, measured based on overall survival (OS) and time to treatment failure (TTF), and toxicity were compared between groups. RESULTS:A total of 238 patients with advanced HCC who received sorafenib between 2007 and 2018 were evaluated. The median age for Group A was 59.1 years and that for Group B 73.6 years. The major prognostic characteristics were balanced between the groups. There were no significant differences in OS between Group A (8.0 months, 95%CI 6.34-9.3) and Group B (9.0 months, 95%CI 5.38-12.62), p=0.433, or in TTF between Group A (3.0 months, 95%CI 2.39-3.60) and Group B (3.0 months, 95%CI 1.68-4.32), p=0.936. There were no significant differences between Groups A and B with respect to the incidence of adverse events or treatment discontinuation because of toxicity. CONCLUSION:Efficacy and safety of sorafenib did not differ significantly between younger and older patients with HCC. Our data suggest that age alone should not restrict clinical decision-making for patients with advanced HCC." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVES:" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS:" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS:" ] 3 => array:2 [ "identificador" => "ceabs40" "titulo" => "CONCLUSION:" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "No potential conflict of interest was reported." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 284 "Ancho" => 673 "Tamanyo" => 25265 ] ] "descripcion" => array:1 [ "en" => "Time to treatment failure and overall survival curves for patients with advanced HCC under 70 years of age (Group A) and for patients 70 years of age or older (Group B) treated with sorafenib in the first-line setting." ] ] 1 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ECOG PS (Eastern Cooperative Oncology Group performance status); CLD (chronic liver disease); NAFLD (nonalcoholic fatty liver disease); APF, α-fetoprotein; TACE (transarterial chemoembolization); BCLC (Barcelona Clinic Liver Cancer); BID, twice a day." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group A <70 yr \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group B ≥70 yr \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of patients (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N=238 (100) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N=194 (81.5) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N=44 (18.5) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">189 (79.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">154 (79.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 (79.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 (20.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (20.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (20.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean Age (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 (10.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.8 (8.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74.8 (3.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median Age, years (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.8 (18.9-84.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.1 (18.9-69.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73.6 (70.0-84.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ECOG PS [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">171 (71.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">146 (75.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (56.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 (23.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (22.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.742 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (2.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (18.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Underlying CLD [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatitis C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">112 (47.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 (51.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (27.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatitis B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (19.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (19.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (20.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.834 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alcohol-related CLD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 (15.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (13.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (20.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.275 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NAFLD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (8.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (6.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.131 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (10.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (8.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (18.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.097 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extrahepatic disease [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">112 (47.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 (49.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (36.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.115 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AFP ≥400 ng/mL [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">125 (52.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">104 (53.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (47.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.481 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Child-Pugh score [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.664 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">205 (86.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">168 (86.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (84.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (13.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (13.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (15.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Local treatments [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Transplant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (5.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (6.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.472 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Resection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (11.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (11.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.686 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Radiofrequency ablation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.215 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TACE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 (29.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (29.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (29.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.963 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BCLC stage [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (19.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (19.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (18.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.831 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 (17.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (15.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.130 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">151 (63.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">126 (64.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (56.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.312 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sorafenib dose [n (%)] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Initial dose 400 mg BID \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">204 (85.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">172 (88.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (72.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Initial reduced dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (11.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (27.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline patient demographics and disease characteristics at the beginning of systemic treatment." ] ] 2 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group A \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group B \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Skin rash \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 (38.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.532 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.746 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diarrhea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 (37.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (26.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.746 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Toxicities leading to discontinuation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (11.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.794 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Adverse events (any grade) most commonly reported by patients and severe toxicities leading to discontinuation of sorafenib." ] ] 3 => array:7 [ "identificador" => "tbl3" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ECOG PS (Eastern Cooperative Oncology Group performance status); CLD (Chronic Liver Disease); BCLC (Barcelona Clinic Liver Cancer); APF, α-fetoprotein. HR (hazard ratio); CI (confidence interval)." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Unvariate</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Multivariate</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR (95% CI) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR (95% CI) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (<70 yr vs ≥70 yr) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.81 (0.5-1.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.268 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ECOG PS (0 vs 1-2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.45 (1.1-2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.021 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.42 (1.1-1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.025 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatitis C (no vs yes) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.77 (0.5-1.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.190 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatitis B (no vs yes) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.89 (0.6-1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.615 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alcohol-related CLD (no vs yes) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.26 (0.8-2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.332 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sorafenib dose-daily (800 mg vs <800 mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.28 (0.8-1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.220 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BCLC stage (A-B vs C) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.22 (0.9-1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.218 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Child-Pugh (A vs B) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.93 (1.9-4.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.59 (1.7-3.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extrahepatic disease (no vs yes) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.14 (0.8-1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.363 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AFP (<400 vs ≥400 ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.53 (1.1-2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.48 (1.1-1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Univariate and multivariate analyses of factors associated with overall survival." ] ] 4 => array:7 [ "identificador" => "tbl4" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age cutoff \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OS, months (younger vs older) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hajiev et al. [15] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5598 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.3 vs 7.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.97 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Wong H et al. [16] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">309 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.32 vs 5.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.310 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Edeline J et al. [17] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">129 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.6 vs 12.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.250 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Morimoto M et al. [18] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR<a class="elsevierStyleCrossRef" href="#tbl4fn1">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.022 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ziogas et al. [19] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">190 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.1 vs 10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.360 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nishikawa H et al. [20] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">458 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.7 vs 8.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.641 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Jo M et al. [21] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">185 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.5 vs 11.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.450 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tbl4fn1" "etiqueta" => "a" "nota" => "Not reported." ] ] ] "descripcion" => array:1 [ "en" => "Studies comparing the clinical outcomes of younger and older patients with HCC treated with sorafenib." ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Future of cancer incidence in the United States: burdens upon an aging, changing nation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ BD Smith \n \t\t\t\t\t\t\t\t """ 1 => """ GL Smith \n \t\t\t\t\t\t\t\t """ 2 => """ A Hurria \n \t\t\t\t\t\t\t\t """ 3 => """ GN Hortobagyi \n \t\t\t\t\t\t\t\t """ 4 => """ TA Buchholz \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.20.8983" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "numero" => "17" "paginaInicial" => "2758" "paginaFinal" => "2765" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19403886" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1200/JCO.2008.20.8983" "WWW" => array:1 [ "link" => "https://doi.org/10.1200/JCO.2008.20.8983" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ F Bray \n \t\t\t\t\t\t\t\t """ 1 => """ J Ferlay \n \t\t\t\t\t\t\t\t """ 2 => """ I Soerjomataram \n \t\t\t\t\t\t\t\t """ 3 => """ RL Siegel \n \t\t\t\t\t\t\t\t """ 4 => """ LA Torre \n \t\t\t\t\t\t\t\t """ 5 => """ A Jemal \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.3322/caac.21492" "Revista" => array:7 [ "tituloSerie" => "CA Cancer J Clin" "fecha" => "2018" "volumen" => "68" "numero" => "6" "paginaInicial" => "394" "paginaFinal" => "424" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30207593" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.3322/caac.21492" "WWW" => array:1 [ "link" => "https://doi.org/10.3322/caac.21492" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma in Italian patients with cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ M Colombo \n \t\t\t\t\t\t\t\t """ 1 => """ R de Franchis \n \t\t\t\t\t\t\t\t """ 2 => """ E Del Ninno \n \t\t\t\t\t\t\t\t """ 3 => """ A Sangiovanni \n \t\t\t\t\t\t\t\t """ 4 => """ C De Fazio \n \t\t\t\t\t\t\t\t """ 5 => """ M Tommasini \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1056/NEJM199109053251002" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "1991" "volumen" => "325" "numero" => "10" "paginaInicial" => "675" "paginaFinal" => "680" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1651452" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1056/NEJM199109053251002" "WWW" => array:1 [ "link" => "https://doi.org/10.1056/NEJM199109053251002" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sorafenib in advanced hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ JM Llovet \n \t\t\t\t\t\t\t\t """ 1 => """ S Ricci \n \t\t\t\t\t\t\t\t """ 2 => """ V Mazzaferro \n \t\t\t\t\t\t\t\t """ 3 => """ P Hilgard \n \t\t\t\t\t\t\t\t """ 4 => """ E Gane \n \t\t\t\t\t\t\t\t """ 5 => """ JF Blanc \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0708857" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2008" "volumen" => "359" "numero" => "4" "paginaInicial" => "378" "paginaFinal" => "390" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18650514" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1056/NEJMoa0708857" "WWW" => array:1 [ "link" => "https://doi.org/10.1056/NEJMoa0708857" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New trials and results in systemic treatment of HCC" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ M Reig \n \t\t\t\t\t\t\t\t """ 1 => """ LG da Fonseca \n \t\t\t\t\t\t\t\t """ 2 => """ S Faivre \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2018.03.028" "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "2018" "volumen" => "69" "numero" => "2" "paginaInicial" => "525" "paginaFinal" => "533" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29653122" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jhep.2018.03.028" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jhep.2018.03.028" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical features and prognosis of elderly patients with hepatocellular carcinoma not indicated for surgical resection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ A Kinoshita \n \t\t\t\t\t\t\t\t """ 1 => """ K Koike \n \t\t\t\t\t\t\t\t """ 2 => """ H Nishino \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/ggi.12747" "Revista" => array:7 [ "tituloSerie" => "Geriatr Gerontol Int" "fecha" => "2017" "volumen" => "17" "numero" => "2" "paginaInicial" => "189" "paginaFinal" => "201" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26847184" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/ggi.12747" "WWW" => array:1 [ "link" => "https://doi.org/10.1111/ggi.12747" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of hepatocellular carcinoma: An update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ J Bruix \n \t\t\t\t\t\t\t\t """ 1 => """ M Sherman \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/hep.24199" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2011" "volumen" => "53" "numero" => "3" "paginaInicial" => "1020" "paginaFinal" => "1022" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21374666" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/hep.24199" "WWW" => array:1 [ "link" => "https://doi.org/10.1002/hep.24199" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Global Burden of Disease Liver Cancer Collaboration" "etal" => true "autores" => array:5 [ 0 => """ T Akinyemiju \n \t\t\t\t\t\t\t\t """ 1 => """ S Abera \n \t\t\t\t\t\t\t\t """ 2 => """ M Ahmed \n \t\t\t\t\t\t\t\t """ 3 => """ N Alam \n \t\t\t\t\t\t\t\t """ 4 => """ MA Alemayohu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1001/jamaoncol.2017.3055" "Revista" => array:7 [ "tituloSerie" => "JAMA Oncol" "fecha" => "2017" "volumen" => "3" "numero" => "12" "paginaInicial" => "1683" "paginaFinal" => "1691" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28983565" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1001/jamaoncol.2017.3055" "WWW" => array:1 [ "link" => "https://doi.org/10.1001/jamaoncol.2017.3055" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ AB Ryerson \n \t\t\t\t\t\t\t\t """ 1 => """ CR Eheman \n \t\t\t\t\t\t\t\t """ 2 => """ SF Altekruse \n \t\t\t\t\t\t\t\t """ 3 => """ JW Ward \n \t\t\t\t\t\t\t\t """ 4 => """ A Jemal \n \t\t\t\t\t\t\t\t """ 5 => """ RL Sherman \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/cncr.29936" "Revista" => array:7 [ "tituloSerie" => "Cancer" "fecha" => "2016" "volumen" => "122" "numero" => "9" "paginaInicial" => "1312" "paginaFinal" => "1337" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26959385" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/cncr.29936" "WWW" => array:1 [ "link" => "https://doi.org/10.1002/cncr.29936" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic Treatment of Advanced Hepatocellular Carcinoma in Older Adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ LM Arellano \n \t\t\t\t\t\t\t\t """ 1 => """ SP Arora \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Nat Sci" "fecha" => "2018" "volumen" => "4" "numero" => "8" "paginaInicial" => "e518" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30211314" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Performance status in patients with hepatocellular carcinoma: determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ CY Hsu \n \t\t\t\t\t\t\t\t """ 1 => """ YH Lee \n \t\t\t\t\t\t\t\t """ 2 => """ CY Hsia \n \t\t\t\t\t\t\t\t """ 3 => """ YH Huang \n \t\t\t\t\t\t\t\t """ 4 => """ CW Su \n \t\t\t\t\t\t\t\t """ 5 => """ HC Lin \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/hep.25950" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2013" "volumen" => "57" "numero" => "1" "paginaInicial" => "112" "paginaFinal" => "119" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22806819" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/hep.25950" "WWW" => array:1 [ "link" => "https://doi.org/10.1002/hep.25950" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ J Bruix \n \t\t\t\t\t\t\t\t """ 1 => """ AL Cheng \n \t\t\t\t\t\t\t\t """ 2 => """ G Meinhardt \n \t\t\t\t\t\t\t\t """ 3 => """ K Nakajima \n \t\t\t\t\t\t\t\t """ 4 => """ Y De Sanctis \n \t\t\t\t\t\t\t\t """ 5 => """ J Llovet \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2017.06.026" "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "2017" "volumen" => "67" "numero" => "5" "paginaInicial" => "999" "paginaFinal" => "1008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687477" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jhep.2017.06.026" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jhep.2017.06.026" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "O-8 Atezolizumab + bevacizumab vs sorafenib for unresectable hepatocellular carcinoma: Results from older adults enrolled in IMbrave150" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ D Li \n \t\t\t\t\t\t\t\t """ 1 => """ H Toh \n \t\t\t\t\t\t\t\t """ 2 => """ P Merle \n \t\t\t\t\t\t\t\t """ 3 => """ K Tsuchiya \n \t\t\t\t\t\t\t\t """ 4 => """ S Hernandez \n \t\t\t\t\t\t\t\t """ 5 => """ H Shao \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Ann Oncol" "fecha" => "2020" "volumen" => "31" "paginaInicial" => "234" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.annonc.2020.04.061" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of adverse events with tailored sorafenib dosing prolongs survival of hepatocellular carcinoma patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ F Tovoli \n \t\t\t\t\t\t\t\t """ 1 => """ L Ielasi \n \t\t\t\t\t\t\t\t """ 2 => """ A Casadei-Gardini \n \t\t\t\t\t\t\t\t """ 3 => """ A Granito \n \t\t\t\t\t\t\t\t """ 4 => """ FG Foschi \n \t\t\t\t\t\t\t\t """ 5 => """ G Rovesti \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2019.08.015" "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "2019" "volumen" => "71" "numero" => "6" "paginaInicial" => "1175" "paginaFinal" => "1183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31449860" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jhep.2019.08.015" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jhep.2019.08.015" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ S Hajiev \n \t\t\t\t\t\t\t\t """ 1 => """ E Allara \n \t\t\t\t\t\t\t\t """ 2 => """ L Motedayen Aval \n \t\t\t\t\t\t\t\t """ 3 => """ T Arizumi \n \t\t\t\t\t\t\t\t """ 4 => """ D Bettinger \n \t\t\t\t\t\t\t\t """ 5 => """ M Pirisi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bjc.1990.181" "Revista" => array:3 [ "tituloSerie" => "Br J Cancer" "fecha" => "2020" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1695521" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The outcomes and safety of single-agent sorafenib in the treatment of elderly patients with advanced hepatocellular carcinoma (HCC)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ H Wong \n \t\t\t\t\t\t\t\t """ 1 => """ YF Tang \n \t\t\t\t\t\t\t\t """ 2 => """ TJ Yao \n \t\t\t\t\t\t\t\t """ 3 => """ J Chiu \n \t\t\t\t\t\t\t\t """ 4 => """ R Leung \n \t\t\t\t\t\t\t\t """ 5 => """ P Chan \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1634/theoncologist.2011-0192" "Revista" => array:7 [ "tituloSerie" => "Oncologist" "fecha" => "2011" "volumen" => "16" "numero" => "12" "paginaInicial" => "1721" "paginaFinal" => "1728" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22135121" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1634/theoncologist.2011-0192" "WWW" => array:1 [ "link" => "https://doi.org/10.1634/theoncologist.2011-0192" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sorafenib use in elderly patients with hepatocellular carcinoma: caution about use of platelet aggregation inhibitors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ J Edeline \n \t\t\t\t\t\t\t\t """ 1 => """ L Crouzet \n \t\t\t\t\t\t\t\t """ 2 => """ S Le Sourd \n \t\t\t\t\t\t\t\t """ 3 => """ C Larible \n \t\t\t\t\t\t\t\t """ 4 => """ A Brunot \n \t\t\t\t\t\t\t\t """ 5 => """ F Le Roy \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1007/s00280-014-2645-z" "Revista" => array:7 [ "tituloSerie" => "Cancer Chemother Pharmacol" "fecha" => "2015" "volumen" => "75" "numero" => "1" "paginaInicial" => "215" "paginaFinal" => "219" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25477009" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1007/s00280-014-2645-z" "WWW" => array:1 [ "link" => "https://doi.org/10.1007/s00280-014-2645-z" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Higher discontinuation and lower survival rates are likely in elderly Japanese patients with advanced hepatocellular carcinoma receiving sorafenib" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ M Morimoto \n \t\t\t\t\t\t\t\t """ 1 => """ K Numata \n \t\t\t\t\t\t\t\t """ 2 => """ M Kondo \n \t\t\t\t\t\t\t\t """ 3 => """ H Hidaka \n \t\t\t\t\t\t\t\t """ 4 => """ J Takada \n \t\t\t\t\t\t\t\t """ 5 => """ A Shibuya \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/j.1872-034X.2011.00778.x" "Revista" => array:7 [ "tituloSerie" => "Hepatol Res" "fecha" => "2011" "volumen" => "41" "numero" => "4" "paginaInicial" => "296" "paginaFinal" => "302" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21348907" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/j.1872-034X.2011.00778.x" "WWW" => array:1 [ "link" => "https://doi.org/10.1111/j.1872-034X.2011.00778.x" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: age is not a problem" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ DC Ziogas \n \t\t\t\t\t\t\t\t """ 1 => """ D Papadatos-Pastos \n \t\t\t\t\t\t\t\t """ 2 => """ K Thillai \n \t\t\t\t\t\t\t\t """ 3 => """ I Korantzis \n \t\t\t\t\t\t\t\t """ 4 => """ R Chowdhury \n \t\t\t\t\t\t\t\t """ 5 => """ A Suddle \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/MEG.0000000000000739" "Revista" => array:7 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2017" "volumen" => "29" "numero" => "1" "paginaInicial" => "48" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27623000" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/MEG.0000000000000739" "WWW" => array:1 [ "link" => "https://doi.org/10.1097/MEG.0000000000000739" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sorafenib Therapy for BCLC Stage B/C Hepatocellular Carcinoma; Clinical Outcome and Safety in Aged Patients: A Multicenter Study in Japan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ H Nishikawa \n \t\t\t\t\t\t\t\t """ 1 => """ H Takeda \n \t\t\t\t\t\t\t\t """ 2 => """ K Tsuchiya \n \t\t\t\t\t\t\t\t """ 3 => """ K Joko \n \t\t\t\t\t\t\t\t """ 4 => """ C Ogawa \n \t\t\t\t\t\t\t\t """ 5 => """ H Taniguchi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.7150/jca.9257" "Revista" => array:7 [ "tituloSerie" => "J Cancer" "fecha" => "2014" "volumen" => "5" "numero" => "7" "paginaInicial" => "499" "paginaFinal" => "509" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24963354" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.7150/jca.9257" "WWW" => array:1 [ "link" => "https://doi.org/10.7150/jca.9257" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of sorafenib in very elderly patients aged 80 years and older with advanced hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ M Jo \n \t\t\t\t\t\t\t\t """ 1 => """ K Yasui \n \t\t\t\t\t\t\t\t """ 2 => """ T Kirishima \n \t\t\t\t\t\t\t\t """ 3 => """ T Shima \n \t\t\t\t\t\t\t\t """ 4 => """ T Niimi \n \t\t\t\t\t\t\t\t """ 5 => """ T Katayama \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/hepr.12308" "Revista" => array:7 [ "tituloSerie" => "Hepatol Res" "fecha" => "2014" "volumen" => "44" "numero" => "13" "paginaInicial" => "1329" "paginaFinal" => "1338" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24528772" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/hepr.12308" "WWW" => array:1 [ "link" => "https://doi.org/10.1111/hepr.12308" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Physiologic aspects of aging: impact on cancer management and decision making, part I" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ R Sawhney \n \t\t\t\t\t\t\t\t """ 1 => """ M Sehl \n \t\t\t\t\t\t\t\t """ 2 => """ A Naeim \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/00130404-200511000-00004" "Revista" => array:7 [ "tituloSerie" => "Cancer J" "fecha" => "2005" "volumen" => "11" "numero" => "6" "paginaInicial" => "449" "paginaFinal" => "460" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16393479" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/00130404-200511000-00004" "WWW" => array:1 [ "link" => "https://doi.org/10.1097/00130404-200511000-00004" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal insufficiency in elderly cancer patients: International Society of Geriatric Oncology clinical practice recommendations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ V Launay-Vacher \n \t\t\t\t\t\t\t\t """ 1 => """ E Chatelut \n \t\t\t\t\t\t\t\t """ 2 => """ SM Lichtman \n \t\t\t\t\t\t\t\t """ 3 => """ H Wildiers \n \t\t\t\t\t\t\t\t """ 4 => """ C Steer \n \t\t\t\t\t\t\t\t """ 5 => """ M Aapro \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdm011" "Revista" => array:7 [ "tituloSerie" => "Ann Oncol" "fecha" => "2007" "volumen" => "18" "numero" => "8" "paginaInicial" => "1314" "paginaFinal" => "1321" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17631561" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1093/annonc/mdm011" "WWW" => array:1 [ "link" => "https://doi.org/10.1093/annonc/mdm011" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacology of cancer chemotherapy in the older person" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ SD Baker \n \t\t\t\t\t\t\t\t """ 1 => """ LB Grochow \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Clin Geriatr Med" "fecha" => "1997" "volumen" => "13" "numero" => "1" "paginaInicial" => "169" "paginaFinal" => "183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8995106" "web" => "Medline" ] ] ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1016/S0749-0690(18)30188-5" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ KA Reiss \n \t\t\t\t\t\t\t\t """ 1 => """ S Yu \n \t\t\t\t\t\t\t\t """ 2 => """ R Mamtani \n \t\t\t\t\t\t\t\t """ 3 => """ R Mehta \n \t\t\t\t\t\t\t\t """ 4 => """ K D’Addeo \n \t\t\t\t\t\t\t\t """ 5 => """ EP Wileyto \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1200/JCO.2017.73.8245" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2017" "volumen" => "35" "numero" => "31" "paginaInicial" => "3575" "paginaFinal" => "3581" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28872925" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1200/JCO.2017.73.8245" "WWW" => array:1 [ "link" => "https://doi.org/10.1200/JCO.2017.73.8245" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ SG Mohile \n \t\t\t\t\t\t\t\t """ 1 => """ W Dale \n \t\t\t\t\t\t\t\t """ 2 => """ MR Somerfield \n \t\t\t\t\t\t\t\t """ 3 => """ MA Schonberg \n \t\t\t\t\t\t\t\t """ 4 => """ CM Boyd \n \t\t\t\t\t\t\t\t """ 5 => """ PS Burhenn \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1200/JCO.2018.78.8687" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2018" "volumen" => "36" "numero" => "22" "paginaInicial" => "2326" "paginaFinal" => "2347" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29782209" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1200/JCO.2018.78.8687" "WWW" => array:1 [ "link" => "https://doi.org/10.1200/JCO.2018.78.8687" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Geriatric oncology research to improve clinical care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ S Mohile \n \t\t\t\t\t\t\t\t """ 1 => """ W Dale \n \t\t\t\t\t\t\t\t """ 2 => """ A Hurria \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/nrclinonc.2012.125" "Revista" => array:7 [ "tituloSerie" => "Nat Rev Clin Oncol" "fecha" => "2012" "volumen" => "9" "numero" => "10" "paginaInicial" => "571" "paginaFinal" => "578" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22825377" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/nrclinonc.2012.125" "WWW" => array:1 [ "link" => "https://doi.org/10.1038/nrclinonc.2012.125" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ H Wildiers \n \t\t\t\t\t\t\t\t """ 1 => """ P Heeren \n \t\t\t\t\t\t\t\t """ 2 => """ M Puts \n \t\t\t\t\t\t\t\t """ 3 => """ E Topinkova \n \t\t\t\t\t\t\t\t """ 4 => """ ML Janssen-Heijnen \n \t\t\t\t\t\t\t\t """ 5 => """ M Extermann \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1200/JCO.2013.54.8347" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2014" "volumen" => "32" "numero" => "24" "paginaInicial" => "2595" "paginaFinal" => "2603" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25071125" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1200/JCO.2013.54.8347" "WWW" => array:1 [ "link" => "https://doi.org/10.1200/JCO.2013.54.8347" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" 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array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer–Alliance for Clinical Trials in Oncology–International Society Of Geriatric Oncology position article" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ H Wildiers \n \t\t\t\t\t\t\t\t """ 1 => """ M Mauer \n \t\t\t\t\t\t\t\t """ 2 => """ A Pallis \n \t\t\t\t\t\t\t\t """ 3 => """ A Hurria \n \t\t\t\t\t\t\t\t """ 4 => """ SG Mohile \n \t\t\t\t\t\t\t\t """ 5 => """ A Luciani \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1200/JCO.2013.49.6125" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2013" "volumen" => "31" "numero" => "29" "paginaInicial" => "3711" "paginaFinal" => "3718" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24019549" "web" => "Medline" ] ] ] ] 1 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array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26929785" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1177/1756283X15618129" "WWW" => array:1 [ "link" => "https://doi.org/10.1177/1756283X15618129" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib33" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ A Granito \n \t\t\t\t\t\t\t\t """ 1 => """ L Bolondi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(16)30569-1" "Revista" => array:7 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2017" "volumen" => "18" "numero" => "2" "paginaInicial" => "e101" "paginaFinal" => "e112" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28214411" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/S1470-2045(16)30569-1" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/S1470-2045(16)30569-1" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/000000760000000C/v1_202211191031/S1807593222001120/v1_202211191031/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/000000760000000C/v1_202211191031/S1807593222001120/v1_202211191031/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222001120?idApp=UINPBA00004N"]

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Guilherme Nader Marta, Leonardo G. da Fonseca

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l.fonseca@fm.usp.br

Corresponding author.

, Maria Ignez Braghiroli, Fernando Moura, Paulo M. Hoff, Jorge Sabbaga

Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR

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Recently&#44; an expansion in systemic treatment options &#40;<a class="elsevierStyleCrossRef" href="#bib5">5</a>&#41; has increased the complexity of therapeutic decisions for the management of HCC&#46; This scenario is even more complex in older patients because of the scarce representation of this population in clinical trials&#46; Furthermore&#44; concomitant advanced age with chronic liver disease increase concerns about toxicity and clinical benefits in this subgroup &#40;<a class="elsevierStyleCrossRef" href="#bib6">6</a>&#41;&#46; Therefore&#44; it is of utmost importance to broaden the available evidence to support the management of elderly patients with advanced HCC&#46; Here&#44; we analyzed a cohort of HCC patients with the aim of evaluating the efficacy and safety of sorafenib in this specific population&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIAL AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Study Design and Participants</span><p id="para20" class="elsevierStylePara elsevierViewall">We retrospectively evaluated a cohort of advanced HCC patients treated between October 2007 and January 2017 at the Instituto do C&#226;ncer do Estado de S&#227;o Paulo &#40;ICESP&#41;&#44; Universidade de S&#227;o Paulo&#44; Brazil&#46; All patients included in the analysis met the diagnostic criteria for HCC based on radiological and&#47;or histological findings &#40;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#41;&#46; Clinical characteristics related to the underlying liver disease&#44; information on treatments&#44; and clinical outcomes were collected from medical records at the beginning of the systemic therapy&#46;</p><p id="para30" class="elsevierStylePara elsevierViewall">Patients were excluded in case of&#58; &#40;<a class="elsevierStyleCrossRef" href="#bib1">1</a>&#41; diagnosis of fibrolamellar carcinoma&#44; &#40;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#41; exposure to systemic therapy for less than 30 days&#44; &#40;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#41; insufficient data in medical records&#44; or &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#41; loss to follow-up&#44; long enough to impair outcome assessment&#46;</p><p id="para40" class="elsevierStylePara elsevierViewall">Patients were divided into two groups&#44; &#40;Group A&#41; individuals &#60;70 years of age and &#40;Group B&#41; individuals who were 70-years old or older at the time of initiation of sorafenib treatment&#46; Efficacy and safety were compared between Groups A and B&#46; The study was approved by the institutional ethics committee &#40;3&#46;807&#46;496&#41;&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Treatment</span><p id="para50" class="elsevierStylePara elsevierViewall">According to the institutional protocol&#44; patients who are candidates for systemic treatment receive first-line therapy with sorafenib at a dose of 400 mg twice daily&#44; and this is continued until evidence of disease progression&#44; unacceptable adverse events&#44; or death&#46; The use of reduced doses was permitted both from the beginning of the treatment and during the course of treatment &#40;depending on tolerability and side effects&#41; at the discretion of the treating physician&#46; The follow-up consisted of regular clinical visits and laboratory assessments every three to four weeks and assessment of radiological response &#40;computed tomography or magnetic resonance&#41; every eight to 12 weeks&#46; After sorafenib discontinuation&#44; patients received best supportive care or were enrolled in clinical trials whenever available in the institution&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Statistical Analysis</span><p id="para60" class="elsevierStylePara elsevierViewall">Overall survival &#40;OS&#41; was calculated from the first day of treatment until death from any cause&#46; Patients without the event were censored at the time of the last follow-up&#46; Time to treatment failure &#40;TTF&#41; because of disease progression or toxicity was calculated from the first to the last day on sorafenib&#46;</p><p id="para70" class="elsevierStylePara elsevierViewall">Categorical variables were compared using the &#967;<span class="elsevierStyleSup">2</span>-test or Fischer&#39;s exact test&#44; where appropriate&#46; TTF and OS were estimated using the Kaplan-Meier method and curves were compared using the log-rank test&#46; Univariate and multivariate analyses using the Cox proportional hazards model were performed to evaluate the prognostic factors&#46; Variables were included in the multivariate analyses if they presented a p-value &#60;0&#46;05 in the univariate analysis and were not associated with each other&#46; Statistical analyses were performed using SPSS software&#44; version 22&#46;0 &#40;IBM SPSS Chicago&#44; IL&#41;&#46; A <span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05 was considered significant&#46;</p></span></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">RESULTS</span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Patient Characteristics</span><p id="para80" class="elsevierStylePara elsevierViewall">From October 2007 to January 2017&#44; 238 patients with advanced HCC who were not suitable candidates for&#8212;or had progressed after&#8212;locoregional therapies received first-line sorafenib at Instituto do C&#226;ncer do Estado de S&#227;o Paulo &#40;ICESP&#41; and were included in the present analysis&#46; The median age for Group A was 59&#46;1 years and for Group B 73&#46;6 years&#46; The proportion of patients with preserved performance status &#40;ECOG performance status 0&#41; was significantly higher in Group A than that in Group B &#40;75&#46;3&#37; <span class="elsevierStyleItalic">vs</span> 56&#46;8&#37;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;014&#41;&#44; respectively&#46; The distribution of the etiologies of chronic liver diseases was homogeneous between the groups&#44; although a higher proportion of patients with hepatitis C virus infection was observed in Group A &#40;51&#46;5&#37; <span class="elsevierStyleItalic">vs</span> 27&#46;3&#37;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;004&#41;&#46; Important prognostic markers&#44; such as staging according to the Barcelona Clinic Liver Cancer &#40;BCLC&#41; staging system &#40;<span class="elsevierStyleItalic">p&#61;</span>0&#46;831&#41;&#44; the presence of elevated &#945;-fetoprotein levels &#40;<span class="elsevierStyleItalic">p&#61;</span>0&#46;481&#41;&#44; or the presence of extrahepatic spread of the disease &#40;<span class="elsevierStyleItalic">p&#61;</span>0&#46;115&#41; were balanced between groups&#46; Locoregional treatments performed prior to systemic therapy had been delivered to 46&#46;4&#37; of patients in Group A and to 43&#46;1&#37; in Group B&#46; Patients in Group B were more likely to receive sorafenib at reduced doses &#40;&#60;800 mg daily&#41; than patients in Group A &#40;27&#46;3&#37; <span class="elsevierStyleItalic">vs</span> 11&#46;3&#37;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;006&#41;&#46; The demographic and treatment characteristics are presented in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Efficacy and Adverse Events</span><p id="para90" class="elsevierStylePara elsevierViewall">At the time of the final analysis&#44; 156 &#40;92&#46;9&#37;&#41; deaths occurred in Group A and 28 &#40;90&#46;3&#37;&#41; in Group B&#46; The median follow-up period was 7&#46;0 months&#46; No significant difference was observed in TTF between Group A &#40;3&#46;0 months&#44; 95&#37;CI 2&#46;39-3&#46;60&#41; and Group B &#40;3&#46;0 months&#44; 95&#37;CI 1&#46;68-4&#46;32&#41;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;936&#46; Similarly&#44; no significant difference was observed in the median OS between Group A &#40;8&#46;0 months&#44; 95&#37;CI 6&#46;34-9&#46;3&#41; and Group B &#40;9&#46;0 months&#44; 95&#37; CI 5&#46;38-12&#46;62&#41;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;433 &#40;<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p id="para100" class="elsevierStylePara elsevierViewall">The incidence of dermatological adverse events &#40;38&#46;5&#37; <span class="elsevierStyleItalic">vs</span> 33&#46;3&#37;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;532&#41;&#44; hypertension &#40;6&#46;9&#37; <span class="elsevierStyleItalic">vs</span> 4&#46;9&#37;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;746&#41;&#44; and diarrhea &#40;37&#46;8&#37; <span class="elsevierStyleItalic">vs</span> 26&#46;8&#37;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;186&#41; did not differ significantly between Groups A and B&#44; respectively&#46; Intolerance leading to sorafenib discontinuation occurred in 11&#46;3&#37; and 9&#46;1&#37; of the patients in Groups A and B&#44; respectively &#40;<span class="elsevierStyleItalic">p&#61;</span>0&#46;794&#41;&#46; Temporary interruptions of at least 1 week were observed at least once in 6&#46;7&#37; of the patients in Group A <span class="elsevierStyleItalic">versus</span> 13&#46;6&#37; of the patients in Group B &#40;<span class="elsevierStyleItalic">p&#61;</span>0&#46;131&#41;&#46; The distribution of the most common toxicities is described in <a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Factors associated with OS in patients with advanced hepatocellular carcinoma</span><p id="para110" class="elsevierStylePara elsevierViewall">The variables included in the univariate analysis were age&#44; Eastern Cooperative Oncology Group performance status &#40;ECOG PS&#41; etiology of hepatopathy &#40;HCV&#44; HBV&#44; alcohol&#41;&#44; initial dose of sorafenib&#44; BCLC stage&#44; Child-Pugh score&#44; presence of extrahepatic metastasis&#44; and serum levels of alpha-fetoprotein&#46; In the univariate analysis&#44; ECOG PS &#40;HR 1&#46;45&#44; 95&#37; CI 1&#46;1-2&#46;0&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;021&#41;&#44; Child-Pugh &#40;HR 2&#46;93&#44; 95&#37; CI 1&#46;9-4&#46;5&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41;&#44; and AFP levels &#40;HR 1&#46;53&#44; 95&#37; CI 1&#46;1-2&#46;0&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;004&#41; achieved the significance threshold for inclusion in the multivariate analysis&#46;</p><p id="para120" class="elsevierStylePara elsevierViewall">In the multivariate analysis&#44; ECOG PS &#40;HR 1&#46;42&#44; 95&#37; CI 1&#46;1-1&#46;9&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;025&#41;&#44; Child-Pugh &#40;HR 2&#46;59&#44; 95&#37; CI 1&#46;7-3&#46;9&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41;&#44; and AFP levels &#40;HR 1&#46;48&#44; 95&#37; CI 1&#46;1-1&#46;9&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;006&#41; exhibited a significant association with poor OS&#46; <a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a> summarizes the results of the univariate and multivariate analyses&#46;</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia></span></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">DISCUSSION</span><p id="para130" class="elsevierStylePara elsevierViewall">Our study focused on assessing the impact of age on the efficacy and safety of sorafenib in patients with advanced HCC&#46; Although patients over 70 years of age more frequently received sorafenib with dose reductions&#44; no significant OS or TTF differences were observed between patients over 70 years of age and their younger counterparts&#46; Similarly&#44; the frequency of adverse events occurred at comparable rates between the groups&#46; In multivariate analysis&#44; known prognostic factors such as ECOG PS 1-2 and Child-Pugh B and elevated serum levels of AFP &#40;&#62;400 ng&#47;mL&#41; were associated with lower survival in the entire cohort&#46;</p><p id="para140" class="elsevierStylePara elsevierViewall">Liver cancer was the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide in 2018 &#40;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#41;&#46; The incidence and mortality rates of HCC are increasing in many parts of the world&#44; including North America&#44; Latin America&#44; and central Europe &#40;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#41;&#46; Although the median age for diagnosis of HCC in the United States is 62 years&#44; more than 30&#37; of patients are currently diagnosed at &#62;70 years of age &#40;<a class="elsevierStyleCrossRef" href="#bib10">10</a>&#41;&#44; emphasizing the need for data that support the clinical management of this population&#46;</p><p id="para150" class="elsevierStylePara elsevierViewall">Upon using a cutoff point of 70 years of age&#44; we did not find a significant difference in the clinical outcomes&#44; i&#46;e&#46;&#44; OS and TTF between younger and older patients who received sorafenib for advanced HCC&#46; The absence of difference between age groups becomes even more pronounced when we consider that the group of younger patients &#40;Group A&#41; more frequently received full doses of sorafenib &#40;800 mg daily&#41; and was enriched with a higher proportion of patients with preserved performance status&#44; a known favorable prognostic factor &#40;<a class="elsevierStyleCrossRef" href="#bib11">11</a>&#41;&#44; in addition to presenting a higher proportion of patients with HCC because of hepatitis C infection&#44; a subgroup that was shown to derive greater benefit from sorafenib treatment &#40;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#41;&#46;</p><p id="para160" class="elsevierStylePara elsevierViewall">Although different age cutoff points have been used&#44; other authors have already sought to evaluate the efficacy of sorafenib in older patients with advanced HCC&#46; Novel treatment strategies such as the combination of atezolizumab plus bevacizumab&#44; have been shown to be associated with a favorable safety profile and a meaningful benefit in adults &#8805;65 years of age in a subgroup analysis in the IMbrave150 trial &#40;<a class="elsevierStyleCrossRef" href="#bib13">13</a>&#41;&#46;</p><p id="para170" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a> summarizes the findings of studies comparing the clinical outcomes of young and old patients with HCC who received first-line sorafenib&#46; Heterogeneity in survival across different cohorts is likely to reflect variations in epidemiological and clinical contexts&#44; including improved management of treatment-related adverse events with tailored dosing &#40;<a class="elsevierStyleCrossRef" href="#bib14">14</a>&#41;&#46; Most of these studies also did not find any significant correlation between age and OS subgroups &#40;<a class="elsevierStyleCrossRefs" href="#bib15">15&#8211;21</a>&#41;&#46; Hajiev et al&#46; analyzed a large cohort of 5598 patients&#44; including 792 patients aged &#8805;75 years and found equivalent outcomes in the groups &#60; or &#8805;75 years&#44; independent of dose &#40;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#41;&#46; In this cohort&#44; a higher rate of discontinuation because of toxicity in the older subgroup was observed&#44; which indicates that physicians may be inclined to discontinue treatment in older patients who experience an adverse event&#44; fearing further severe complications&#46; In addition&#44; they observed that patients aged &#8805;75 years who received sorafenib had lower alpha-fetoprotein levels&#44; less portal invasion&#44; and better liver function&#46; This probably reflects the reason why physicians tend to prescribe sorafenib for older patients because of these favorable prognostic factors &#40;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#41;&#46;</p><elsevierMultimedia ident="tbl4"></elsevierMultimedia><p id="para180" class="elsevierStylePara elsevierViewall">In contrast&#44; Morimoto et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib18">18</a>&#41; reported a survival benefit in favor of the subgroup of younger patients&#46; In this respect&#44; the following limitations of this study should be taken into consideration when interpreting the results&#58; &#40;<a class="elsevierStyleCrossRef" href="#bib1">1</a>&#41; this study included a relatively small population &#40;n&#61;76&#41; comprising exclusively of Asian patients&#59; &#40;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#41; treatment compliance was poor &#40;less than 50&#37; of patients received more than 80&#37; of the prescribed dose of sorafenib&#41;&#59; and &#40;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#41; the median duration of treatment was short &#40;only 1&#46;7 months&#41;&#44; possibly because of a high rate of adverse events&#46;</p><p id="para190" class="elsevierStylePara elsevierViewall">In the present analysis&#44; although older patients more frequently received lower doses of sorafenib&#44; such dose reductions did not significantly impact efficacy or toxicity&#46; The prescription of a reduced initial dose in 27&#37; of our cohort might reflect a common perception of physicians that elderly patients are at increased risk of adverse events&#46; In addition&#44; a higher proportion of ECOG PS 2 among the older group might also explain this finding&#46;</p><p id="para200" class="elsevierStylePara elsevierViewall">Aging has been associated with changes in the pharmacokinetics of antineoplastic agents because of a number of age-related changes&#44; including modifications in renal function and excretion&#44; changes in liver function and metabolism&#44; drug absorption and distribution alterations&#44; among others &#40;<a class="elsevierStyleCrossRefs" href="#bib22">22&#8211;24</a>&#41;&#46; For this reason&#44; the doses of drugs provided to younger patients are not necessarily extrapolatable to older patients&#46; In addition&#8212;specifically regarding the use of sorafenib in the treatment of HCC&#8212;recent evidence suggests that no significant efficacy impairment might be observed when starting treatment at doses below 800 mg daily &#40;<a class="elsevierStyleCrossRef" href="#bib25">25</a>&#41;&#46;</p><p id="para210" class="elsevierStylePara elsevierViewall">Older cancer patients are often at a higher risk of &#8220;undertreatment&#8221; because of exaggerated clinical estimation of their frailty&#44; as well as &#8220;overtreatment&#8221; because of inappropriate evaluation of their fitness to receive intensive treatment regimens &#40;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#44;<a class="elsevierStyleCrossRef" href="#bib27">27</a>&#41;&#46; As reinforced by our data&#44; age alone is not a reliable predictor of efficacy or adverse events in advanced HCC patients treated with sorafenib&#46; Specific geriatric assessment tools that are not widely used in routine oncology assessments have been validated to predict adverse outcomes in patients being considered for cancer treatments &#40;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#41;&#46; Evidence suggests that geriatric assessment should include&#8212;at a minimum&#8212;evaluation of function&#44; comorbidity&#44; falls&#44; depression&#44; cognition&#44; and nutrition &#40;<a class="elsevierStyleCrossRef" href="#bib28">28</a>&#41;&#46; Finally&#44; the underrepresentation of patients over 65 years in clinical cancer trials is a major issue because it weakens the evidence supporting the therapeutic decisions in this population &#40;<a class="elsevierStyleCrossRef" href="#bib29">29</a>&#44;<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#41;&#46; Thus&#44; the use of inclusion or exclusion criteria based exclusively on age should be discouraged&#44; and clinical trials in oncology should be performed without an upper age limit to allow inclusion of eligible older adults &#40;<a class="elsevierStyleCrossRef" href="#bib31">31</a>&#41;&#46;</p><p id="para220" class="elsevierStylePara elsevierViewall">It has been demonstrated that specific types of adverse events have a prognostic value&#44; such as skin toxicities and hypertension &#40;<a class="elsevierStyleCrossRef" href="#bib32">32</a>&#41;&#46; A longer follow-up of the present cohort can aid us in understanding whether these observations apply to the elderly population&#44; as the incidence of some specific events in this study was low&#46; Further&#44; worse liver function is a key prognostic factor in advanced HCC &#40;<a class="elsevierStyleCrossRef" href="#bib33">33</a>&#41; and is of particular relevance in older patients&#44; as suggested by our multivariate analysis&#46;</p><p id="para230" class="elsevierStylePara elsevierViewall">Our study has limitations that should be considered when interpreting the results&#46; This was a single-center retrospective analysis&#44; which may hinder the external validity of our results&#46; We excluded patients with exposure to systemic therapy for less than 30 days to minimize the inclusion of patients with premature loss to follow-up&#44; which may have underrepresented patients with rapidly progressive disease&#46; In addition&#44; because of its retrospective nature&#44; there was no randomization between the treatment arms&#44; which may have influenced our outcomes&#46;</p></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">CONCLUSIONS</span><p id="para240" class="elsevierStylePara elsevierViewall">Although older patients received reduced starting doses of sorafenib and presented lower performance status at the start of systemic treatment&#44; these patients did not exhibit a significant difference in OS and TTF in comparison with younger patients in the present retrospective analysis&#46; The safety of sorafenib treatment was similar between younger and older patients&#44; with similar toxicity-related discontinuation rates between groups&#46; Our results suggest that age alone should not be used to determine the therapeutic strategy for patients with advanced HCC being considered for sorafenib therapy&#46;</p></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">CONFLICTS OF INTEREST</span><p id="para250" class="elsevierStylePara elsevierViewall">Guilherme Nader Marta has received travel&#47;accommodation grants from Bayer Schering Pharma and Roche&#46; Leonardo Gomes da Fonseca received lecture fees from Bayer and travel grants from Bayer and Ipsen&#46; Maria Ignez Braghiroli received grants from Merck Sharp and Dohme and Bristol-Myers Squibb for clinical trials at her institution and from Merck Sharp and Dohme&#44; Bayer&#44; and Astra Zeneca for being a member of their advisory boards&#46; Paulo M&#46; Hoff has no conflicts of interest to declare&#46; Jorge Sabbaga received grants from Bayer for being a member of its advisory board&#46;</p></span><span id="cesec130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle180">AUTHOR CONTRIBUTIONS</span><p id="para260" class="elsevierStylePara elsevierViewall">Marta GN&#44; Fonseca LG&#44; Sabbaga J contributed in study concepts&#46; Fonseca LG&#44; Braghiroli MI contributed in study design&#46; Marta GN&#44; Fonseca LG&#44; Moura F contributed in data acquisition&#46; Braghiroli MI&#44; Hoff PM&#44; Sabbaga J contributed in quality control of data and algorithms&#46; Marta GN&#44; Fonseca LG&#44; Sabbaga J contributed in data analysis and interpretation&#46; Marta GN&#44; Fonseca LG&#44; Moura F contributed in statistical analysis&#46; Marta GN&#44; Fonseca LG contributed in manuscript preparation&#46; Moura F&#44; Braghiroli MI&#44; Hoff PM&#44; Sabbaga J contributed in manuscript editing&#46; Braghiroli MI&#44; Hoff PM&#44; Sabbaga J contributed in manuscript review&#46;</p></span></span>"
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          "titulo" => "MATERIAL AND METHODS"
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          "titulo" => "RESULTS"
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              "titulo" => "Patient Characteristics"
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              "identificador" => "cesec80"
              "titulo" => "Efficacy and Adverse Events"
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              "titulo" => "Factors associated with OS in patients with advanced hepatocellular carcinoma"
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          "titulo" => "DISCUSSION"
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          "titulo" => "CONFLICTS OF INTEREST"
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    "fechaRecibido" => "2020-10-08"
    "fechaAceptado" => "2020-11-25"
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          "palabras" => array:5 [
            0 => "Hepatocellular Carcinoma"
            1 => "Older Adults"
            2 => "Sorafenib"
            3 => "Safety"
            4 => "Efficacy"
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVES&#58;</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">To evaluate the efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma &#40;HCC&#41;&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">We analyzed data from a cohort of patients with advanced HCC treated using systemic treatment according to the local institutional protocol&#46; Patients were divided into two groups&#44; Group A&#44; individuals &#60;70 years of age&#44; and Group B&#44; individuals 70 years of age or older at the time of treatment initiation&#46; Efficacy&#44; measured based on overall survival &#40;OS&#41; and time to treatment failure &#40;TTF&#41;&#44; and toxicity were compared between groups&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara100" class="elsevierStyleSimplePara elsevierViewall">A total of 238 patients with advanced HCC who received sorafenib between 2007 and 2018 were evaluated&#46; The median age for Group A was 59&#46;1 years and that for Group B 73&#46;6 years&#46; The major prognostic characteristics were balanced between the groups&#46; There were no significant differences in OS between Group A &#40;8&#46;0 months&#44; 95&#37;CI 6&#46;34-9&#46;3&#41; and Group B &#40;9&#46;0 months&#44; 95&#37;CI 5&#46;38-12&#46;62&#41;&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;433&#44; or in TTF between Group A &#40;3&#46;0 months&#44; 95&#37;CI 2&#46;39-3&#46;60&#41; and Group B &#40;3&#46;0 months&#44; 95&#37;CI 1&#46;68-4&#46;32&#41;&#44; <span class="elsevierStyleItalic">p&#61;</span>0&#46;936&#46; There were no significant differences between Groups A and B with respect to the incidence of adverse events or treatment discontinuation because of toxicity&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSION&#58;</span><p id="spara110" class="elsevierStyleSimplePara elsevierViewall">Efficacy and safety of sorafenib did not differ significantly between younger and older patients with HCC&#46; Our data suggest that age alone should not restrict clinical decision-making for patients with advanced HCC&#46;</p></span>"
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            "titulo" => "RESULTS&#58;"
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            "titulo" => "CONCLUSION&#58;"
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Time to treatment failure and overall survival curves for patients with advanced HCC under 70 years of age &#40;Group A&#41; and for patients 70 years of age or older &#40;Group B&#41; treated with sorafenib in the first-line setting&#46;</p>"
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          "leyenda" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">ECOG PS &#40;Eastern Cooperative Oncology Group performance status&#41;&#59; CLD &#40;chronic liver disease&#41;&#59; NAFLD &#40;nonalcoholic fatty liver disease&#41;&#59; APF&#44; &#945;-fetoprotein&#59; TACE &#40;transarterial chemoembolization&#41;&#59; BCLC &#40;Barcelona Clinic Liver Cancer&#41;&#59; BID&#44; twice a day&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group A &#60;70 yr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group B &#8805;70 yr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of patients &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#61;238 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#61;194 &#40;81&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#61;44 &#40;18&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">189 &#40;79&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154 &#40;79&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;79&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;20&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;20&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;20&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mean Age &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61 &#40;10&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#46;8 &#40;8&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#46;8 &#40;3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Median Age&#44; years &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&#46;8 &#40;18&#46;9-84&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;1 &#40;18&#46;9-69&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#46;6 &#40;70&#46;0-84&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ECOG PS &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">171 &#40;71&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">146 &#40;75&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;56&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;23&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;22&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;742&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;5&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Underlying CLD &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hepatitis C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">112 &#40;47&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;51&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hepatitis B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;19&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;19&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;20&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;834&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alcohol-related CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;15&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;20&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;275&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NAFLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;8&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;13&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;131&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;10&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;18&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;097&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Extrahepatic disease &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">112 &#40;47&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96 &#40;49&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;115&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AFP &#8805;400 ng&#47;mL &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">125 &#40;52&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">104 &#40;53&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;47&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;481&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Child-Pugh score &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;664&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">205 &#40;86&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">168 &#40;86&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;84&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;13&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;15&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Local treatments &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Transplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;6&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;472&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Resection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;11&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;11&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;13&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;686&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Radiofrequency ablation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;215&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>TACE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71 &#40;29&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;29&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;29&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;963&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BCLC stage &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;19&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;19&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;831&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;17&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;15&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">151 &#40;63&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">126 &#40;64&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;56&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;312&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sorafenib dose &#91;n &#40;&#37;&#41;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Initial dose 400 mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">204 &#40;85&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">172 &#40;88&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;72&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Initial reduced dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;11&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Baseline patient demographics and disease characteristics at the beginning of systemic treatment&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl2"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;38&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;532&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;6&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;746&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;26&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;746&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Toxicities leading to discontinuation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;11&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;794&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Adverse events &#40;any grade&#41; most commonly reported by patients and severe toxicities leading to discontinuation of sorafenib&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl3"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spara60" class="elsevierStyleSimplePara elsevierViewall">ECOG PS &#40;Eastern Cooperative Oncology Group performance status&#41;&#59; CLD &#40;Chronic Liver Disease&#41;&#59; BCLC &#40;Barcelona Clinic Liver Cancer&#41;&#59; APF&#44; &#945;-fetoprotein&#46; HR &#40;hazard ratio&#41;&#59; CI &#40;confidence interval&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Unvariate</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Multivariate</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;&#60;70 yr <span class="elsevierStyleItalic">vs</span> &#8805;70 yr&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;81 &#40;0&#46;5-1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;268&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ECOG PS &#40;0 <span class="elsevierStyleItalic">vs</span> 1-2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;45 &#40;1&#46;1-2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;42 &#40;1&#46;1-1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;025&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatitis C &#40;no <span class="elsevierStyleItalic">vs</span> yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;77 &#40;0&#46;5-1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;190&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatitis B &#40;no <span class="elsevierStyleItalic">vs</span> yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;89 &#40;0&#46;6-1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;615&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alcohol-related CLD &#40;no <span class="elsevierStyleItalic">vs</span> yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;26 &#40;0&#46;8-2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;332&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sorafenib dose-daily &#40;800 mg <span class="elsevierStyleItalic">vs</span> &#60;800 mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;28 &#40;0&#46;8-1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;220&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BCLC stage &#40;A-B <span class="elsevierStyleItalic">vs</span> C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;22 &#40;0&#46;9-1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;218&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Child-Pugh &#40;A <span class="elsevierStyleItalic">vs</span> B&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;93 &#40;1&#46;9-4&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;59 &#40;1&#46;7-3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Extrahepatic disease &#40;no <span class="elsevierStyleItalic">vs</span> yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;14 &#40;0&#46;8-1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;363&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AFP &#40;&#60;400 <span class="elsevierStyleItalic">vs</span> &#8805;400 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;53 &#40;1&#46;1-2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;48 &#40;1&#46;1-1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Univariate and multivariate analyses of factors associated with overall survival&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl4"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age cutoff&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OS&#44; months &#40;younger <span class="elsevierStyleItalic">vs</span> older&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hajiev et al&#46; &#91;15&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 years old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5598&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;3 <span class="elsevierStyleItalic">vs</span> 7&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wong H et al&#46; &#91;16&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 years old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">309&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;32 <span class="elsevierStyleItalic">vs</span> 5&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;310&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Edeline J et al&#46; &#91;17&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 years old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;6 <span class="elsevierStyleItalic">vs</span> 12&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;250&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morimoto M et al&#46; &#91;18&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 years old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR<a class="elsevierStyleCrossRef" href="#tbl4fn1">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ziogas et al&#46; &#91;19&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 years old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">190&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;1 <span class="elsevierStyleItalic">vs</span> 10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;360&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nishikawa H et al&#46; &#91;20&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 years old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">458&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;7 <span class="elsevierStyleItalic">vs</span> 8&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;641&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Jo M et al&#46; &#91;21&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 years old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;5 <span class="elsevierStyleItalic">vs</span> 11&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;450&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">Not reported&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Studies comparing the clinical outcomes of younger and older patients with HCC treated with sorafenib&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:33 [
            0 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Future of cancer incidence in the United States&#58; burdens upon an aging&#44; changing nation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              BD Smith \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              GL Smith \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Hurria \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              GN Hortobagyi \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              TA Buchholz \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
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                    ]
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                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2008.20.8983"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "numero" => "17"
                        "paginaInicial" => "2758"
                        "paginaFinal" => "2765"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19403886"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1200/JCO.2008.20.8983"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1200&#47;JCO&#46;2008&#46;20&#46;8983"
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            ]
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              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global cancer statistics 2018&#58; GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              F Bray \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Ferlay \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              I Soerjomataram \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              RL Siegel \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              LA Torre \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Jemal \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.3322/caac.21492"
                      "Revista" => array:7 [
                        "tituloSerie" => "CA Cancer J Clin"
                        "fecha" => "2018"
                        "volumen" => "68"
                        "numero" => "6"
                        "paginaInicial" => "394"
                        "paginaFinal" => "424"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30207593"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                      "doi" => "10.3322/caac.21492"
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            2 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatocellular carcinoma in Italian patients with cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              M Colombo \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              R de Franchis \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              E Del Ninno \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Sangiovanni \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              C De Fazio \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              M Tommasini \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199109053251002"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1991"
                        "volumen" => "325"
                        "numero" => "10"
                        "paginaInicial" => "675"
                        "paginaFinal" => "680"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1651452"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1056/NEJM199109053251002"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1056&#47;NEJM199109053251002"
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              ]
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            3 => array:3 [
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              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sorafenib in advanced hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              JM Llovet \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Ricci \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              V Mazzaferro \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              P Hilgard \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              E Gane \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              JF Blanc \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0708857"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2008"
                        "volumen" => "359"
                        "numero" => "4"
                        "paginaInicial" => "378"
                        "paginaFinal" => "390"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18650514"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1056/NEJMoa0708857"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1056&#47;NEJMoa0708857"
                      ]
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              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New trials and results in systemic treatment of HCC"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              M Reig \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              LG da Fonseca \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              S Faivre \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2018.03.028"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2018"
                        "volumen" => "69"
                        "numero" => "2"
                        "paginaInicial" => "525"
                        "paginaFinal" => "533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29653122"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.jhep.2018.03.028"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;jhep&#46;2018&#46;03&#46;028"
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                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical features and prognosis of elderly patients with hepatocellular carcinoma not indicated for surgical resection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              A Kinoshita \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              K Koike \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              H Nishino \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/ggi.12747"
                      "Revista" => array:7 [
                        "tituloSerie" => "Geriatr Gerontol Int"
                        "fecha" => "2017"
                        "volumen" => "17"
                        "numero" => "2"
                        "paginaInicial" => "189"
                        "paginaFinal" => "201"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26847184"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/ggi.12747"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1111&#47;ggi&#46;12747"
                      ]
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                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of hepatocellular carcinoma&#58; An update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              J Bruix \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Sherman \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.24199"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2011"
                        "volumen" => "53"
                        "numero" => "3"
                        "paginaInicial" => "1020"
                        "paginaFinal" => "1022"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21374666"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1002/hep.24199"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1002&#47;hep&#46;24199"
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            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global&#44; Regional&#44; and National Level&#58; Results From the Global Burden of Disease Study 2015"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Global Burden of Disease Liver Cancer Collaboration"
                          "etal" => true
                          "autores" => array:5 [
                            0 => """
                              T Akinyemiju \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Abera \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Ahmed \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              N Alam \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              MA Alemayohu \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1001/jamaoncol.2017.3055"
                      "Revista" => array:7 [
                        "tituloSerie" => "JAMA Oncol"
                        "fecha" => "2017"
                        "volumen" => "3"
                        "numero" => "12"
                        "paginaInicial" => "1683"
                        "paginaFinal" => "1691"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28983565"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1001/jamaoncol.2017.3055"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1001&#47;jamaoncol&#46;2017&#46;3055"
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                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Annual Report to the Nation on the Status of Cancer&#44; 1975-2012&#44; featuring the increasing incidence of liver cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              AB Ryerson \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              CR Eheman \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              SF Altekruse \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JW Ward \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              A Jemal \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              RL Sherman \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1002/cncr.29936"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "2016"
                        "volumen" => "122"
                        "numero" => "9"
                        "paginaInicial" => "1312"
                        "paginaFinal" => "1337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26959385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1002/cncr.29936"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1002&#47;cncr&#46;29936"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systemic Treatment of Advanced Hepatocellular Carcinoma in Older Adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              LM Arellano \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              SP Arora \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Nat Sci"
                        "fecha" => "2018"
                        "volumen" => "4"
                        "numero" => "8"
                        "paginaInicial" => "e518"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30211314"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Performance status in patients with hepatocellular carcinoma&#58; determinants&#44; prognostic impact&#44; and ability to improve the Barcelona Clinic Liver Cancer system"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              CY Hsu \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              YH Lee \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CY Hsia \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              YH Huang \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              CW Su \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              HC Lin \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.25950"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2013"
                        "volumen" => "57"
                        "numero" => "1"
                        "paginaInicial" => "112"
                        "paginaFinal" => "119"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22806819"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1002/hep.25950"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1002&#47;hep&#46;25950"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma&#58; Analysis of two phase III studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              J Bruix \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AL Cheng \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              G Meinhardt \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              K Nakajima \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              Y De Sanctis \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              J Llovet \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2017.06.026"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2017"
                        "volumen" => "67"
                        "numero" => "5"
                        "paginaInicial" => "999"
                        "paginaFinal" => "1008"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687477"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.jhep.2017.06.026"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;jhep&#46;2017&#46;06&#46;026"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "O-8 Atezolizumab &#43; bevacizumab vs sorafenib for unresectable hepatocellular carcinoma&#58; Results from older adults enrolled in IMbrave150"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              D Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              H Toh \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              P Merle \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              K Tsuchiya \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              S Hernandez \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              H Shao \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2020"
                        "volumen" => "31"
                        "paginaInicial" => "234"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;annonc&#46;2020&#46;04&#46;061"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of adverse events with tailored sorafenib dosing prolongs survival of hepatocellular carcinoma patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              F Tovoli \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              L Ielasi \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Casadei-Gardini \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Granito \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              FG Foschi \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              G Rovesti \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2019.08.015"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2019"
                        "volumen" => "71"
                        "numero" => "6"
                        "paginaInicial" => "1175"
                        "paginaFinal" => "1183"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31449860"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.jhep.2019.08.015"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;jhep&#46;2019&#46;08&#46;015"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of age on sorafenib outcomes in hepatocellular carcinoma&#58; an international cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              S Hajiev \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              E Allara \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              L Motedayen Aval \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              T Arizumi \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              D Bettinger \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              M Pirisi \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bjc.1990.181"
                      "Revista" => array:3 [
                        "tituloSerie" => "Br J Cancer"
                        "fecha" => "2020"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1695521"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The outcomes and safety of single-agent sorafenib in the treatment of elderly patients with advanced hepatocellular carcinoma &#40;HCC&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              H Wong \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              YF Tang \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              TJ Yao \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              J Chiu \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              R Leung \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              P Chan \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1634/theoncologist.2011-0192"
                      "Revista" => array:7 [
                        "tituloSerie" => "Oncologist"
                        "fecha" => "2011"
                        "volumen" => "16"
                        "numero" => "12"
                        "paginaInicial" => "1721"
                        "paginaFinal" => "1728"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22135121"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1634/theoncologist.2011-0192"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1634&#47;theoncologist&#46;2011-0192"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sorafenib use in elderly patients with hepatocellular carcinoma&#58; caution about use of platelet aggregation inhibitors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              J Edeline \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              L Crouzet \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              S Le Sourd \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              C Larible \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              A Brunot \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              F Le Roy \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1007/s00280-014-2645-z"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cancer Chemother Pharmacol"
                        "fecha" => "2015"
                        "volumen" => "75"
                        "numero" => "1"
                        "paginaInicial" => "215"
                        "paginaFinal" => "219"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25477009"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1007/s00280-014-2645-z"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1007&#47;s00280-014-2645-z"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Higher discontinuation and lower survival rates are likely in elderly Japanese patients with advanced hepatocellular carcinoma receiving sorafenib"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              M Morimoto \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              K Numata \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Kondo \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              H Hidaka \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              J Takada \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Shibuya \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1872-034X.2011.00778.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatol Res"
                        "fecha" => "2011"
                        "volumen" => "41"
                        "numero" => "4"
                        "paginaInicial" => "296"
                        "paginaFinal" => "302"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21348907"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/j.1872-034X.2011.00778.x"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1111&#47;j&#46;1872-034X&#46;2011&#46;00778&#46;x"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma&#58; age is not a problem"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              DC Ziogas \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              D Papadatos-Pastos \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              K Thillai \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              I Korantzis \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              R Chowdhury \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Suddle \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/MEG.0000000000000739"
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur J Gastroenterol Hepatol"
                        "fecha" => "2017"
                        "volumen" => "29"
                        "numero" => "1"
                        "paginaInicial" => "48"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27623000"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/MEG.0000000000000739"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1097&#47;MEG&#46;0000000000000739"
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                ]
              ]
            ]
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              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sorafenib Therapy for BCLC Stage B&#47;C Hepatocellular Carcinoma&#59; Clinical Outcome and Safety in Aged Patients&#58; A Multicenter Study in Japan"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              H Nishikawa \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              H Takeda \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              K Tsuchiya \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              K Joko \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              C Ogawa \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              H Taniguchi \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.7150/jca.9257"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Cancer"
                        "fecha" => "2014"
                        "volumen" => "5"
                        "numero" => "7"
                        "paginaInicial" => "499"
                        "paginaFinal" => "509"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24963354"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.7150/jca.9257"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;7150&#47;jca&#46;9257"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of sorafenib in very elderly patients aged 80 years and older with advanced hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              M Jo \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              K Yasui \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              T Kirishima \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              T Shima \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              T Niimi \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              T Katayama \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/hepr.12308"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatol Res"
                        "fecha" => "2014"
                        "volumen" => "44"
                        "numero" => "13"
                        "paginaInicial" => "1329"
                        "paginaFinal" => "1338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24528772"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/hepr.12308"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1111&#47;hepr&#46;12308"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Physiologic aspects of aging&#58; impact on cancer management and decision making&#44; part I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              R Sawhney \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Sehl \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Naeim \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/00130404-200511000-00004"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cancer J"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "numero" => "6"
                        "paginaInicial" => "449"
                        "paginaFinal" => "460"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16393479"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/00130404-200511000-00004"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1097&#47;00130404-200511000-00004"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal insufficiency in elderly cancer patients&#58; International Society of Geriatric Oncology clinical practice recommendations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              V Launay-Vacher \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              E Chatelut \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              SM Lichtman \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              H Wildiers \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              C Steer \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              M Aapro \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdm011"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2007"
                        "volumen" => "18"
                        "numero" => "8"
                        "paginaInicial" => "1314"
                        "paginaFinal" => "1321"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17631561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1093/annonc/mdm011"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1093&#47;annonc&#47;mdm011"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacology of cancer chemotherapy in the older person"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              SD Baker \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              LB Grochow \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Geriatr Med"
                        "fecha" => "1997"
                        "volumen" => "13"
                        "numero" => "1"
                        "paginaInicial" => "169"
                        "paginaFinal" => "183"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8995106"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;S0749-0690&#40;18&#41;30188-5"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma&#58; A Retrospective&#44; Multi-Institutional Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              KA Reiss \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Yu \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              R Mamtani \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              R Mehta \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              K D&#8217;Addeo \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              EP Wileyto \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2017.73.8245"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "numero" => "31"
                        "paginaInicial" => "3575"
                        "paginaFinal" => "3581"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28872925"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1200/JCO.2017.73.8245"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1200&#47;JCO&#46;2017&#46;73&#46;8245"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy&#58; ASCO Guideline for Geriatric Oncology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              SG Mohile \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              W Dale \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              MR Somerfield \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              MA Schonberg \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              CM Boyd \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              PS Burhenn \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2018.78.8687"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2018"
                        "volumen" => "36"
                        "numero" => "22"
                        "paginaInicial" => "2326"
                        "paginaFinal" => "2347"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29782209"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1200/JCO.2018.78.8687"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1200&#47;JCO&#46;2018&#46;78&#46;8687"
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                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Geriatric oncology research to improve clinical care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              S Mohile \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              W Dale \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Hurria \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1038/nrclinonc.2012.125"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nat Rev Clin Oncol"
                        "fecha" => "2012"
                        "volumen" => "9"
                        "numero" => "10"
                        "paginaInicial" => "571"
                        "paginaFinal" => "578"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22825377"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1038/nrclinonc.2012.125"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1038&#47;nrclinonc&#46;2012&#46;125"
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                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              H Wildiers \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              P Heeren \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Puts \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              E Topinkova \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              ML Janssen-Heijnen \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              M Extermann \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2013.54.8347"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2014"
                        "volumen" => "32"
                        "numero" => "24"
                        "paginaInicial" => "2595"
                        "paginaFinal" => "2603"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25071125"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1200/JCO.2013.54.8347"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1200&#47;JCO&#46;2013&#46;54&#46;8347"
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                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Participation in cancer clinical trials&#58; race-&#44; sex-&#44; and age-based disparities"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              VH Murthy \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              HM Krumholz \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CP Gross \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.291.22.2720"
                      "Revista" => array:7 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2004"
                        "volumen" => "291"
                        "numero" => "22"
                        "paginaInicial" => "2720"
                        "paginaFinal" => "2726"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15187053"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1001/jama.291.22.2720"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1001&#47;jama&#46;291&#46;22&#46;2720"
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                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Underrepresentation of patients 65 years of age or older in cancer-treatment trials"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              LF Hutchins \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JM Unger \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JJ Crowley \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              CA Coltman Jr \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              KS Albain \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199912303412706"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1999"
                        "volumen" => "341"
                        "numero" => "27"
                        "paginaInicial" => "2061"
                        "paginaFinal" => "2067"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10615079"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1056/NEJM199912303412706"
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1056&#47;NEJM199912303412706"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "End points and trial design in geriatric oncology research&#58; a joint European organisation for research and treatment of cancer&#8211;Alliance for Clinical Trials in Oncology&#8211;International Society Of Geriatric Oncology position article"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              H Wildiers \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              M Mauer \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Pallis \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Hurria \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SG Mohile \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Luciani \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
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                              \t\t\t\t\t\t\t\t
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Article information

ISSN: 18075932
Original language: English

DOI:10.6061/clinics/2021/e2498

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	2	1	3
2024 October	20	17	37
2024 September	27	18	45
2024 August	29	29	58
2024 July	24	17	41
2024 June	32	14	46
2024 May	28	16	44
2024 April	26	18	44
2024 March	20	15	35
2024 February	26	14	40
2024 January	25	14	39
2023 December	20	21	41
2023 November	17	18	35
2023 October	31	29	60
2023 September	26	25	51
2023 August	26	5	31
2023 July	28	25	53
2023 June	25	6	31
2023 May	44	0	44
2023 April	39	2	41
2023 March	36	2	38
2023 February	22	0	22
2023 January	22	6	28
2022 December	12	1	13
2022 November	9	1	10

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