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"apellidos" => "Espejo-Arjona" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Oftalmología, Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Oncología radioterápica, Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio miembro de RETICS OptaRed, Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Retinoblastoma: la importancia de su diagnóstico precoz" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 505 "Ancho" => 1200 "Tamanyo" => 85628 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">RB in stage E with orbit, intracranial and cerebrospinal fluid invasion before and after chemoreduction with modified ARET protocol. July to September: 4 cycles.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Retinoblastoma (RB) is the most frequent malignant intraocular tumor in childhood, of which 30% are bilateral and 40% hereditary. The most common initial sign (60%) is leukocoria.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Early diagnostic is crucial for therapeutic success. RB is usually diagnosed between the first and third year of life and rarely after 5 years of age.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a> In the country of the authors, the incidence is of 1:17,000 live births (in Andalucia, 4 new cases per year).<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">There is no worldwide consensus for RB treatment.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">1,3,4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The objectives of the present study are to:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Determine epidemiology and geographical distribution, laterality and genetics of patients treated at an Ocular Oncology Reference Unit from April 2006 to April 2013;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">assess treatments on the basis of their staging;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">quantify functional results such as visual acuity (VA), anatomic results (preservation of the ocular globe), local recurrences and/or development of new tumors in treated eyes and survival, as well as a comparison with other studies.</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">A descriptive study of a series of cases, diagnosed and treated at the authors’ department since being designated as Regional Reference for Tumors by the SNS Quality Agency in April 2006 up to April 2013.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Since 1998 up to April 2013, 60 children received attention at the authors’ unit. During the period of the study, 39 patients with RB and 58 eyes received attention, excluding patients with benign tumors, those initially treated at another hospital and prior to April 2006.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Pediatric oncologists completed the general examination and discarded metastatic extensions.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ocular examination had to be complete and for this reason many were performed at the operating theater due to poor patient cooperation. When detecting intralesional calcium with echography, CT were not required. In all cases NMR of cranium and orbits were requested with/without contract with fat suppression, and when extraocular or metastatic RB was suspected bone marrow aspiration was performed together with lumbar puncture and PET, NMR or full CT.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Treatment is complex and depends on staging, laterality, inheritance, age at diagnostic and parental decisions, therefore requiring individualized management. Since April 2003, a group of experts reached a consensus to establish a classification system, i.e., the International Classification of Retinoblastoma (ICRB). Eyes were classified on the basis of disease extension and intraocular tumor dissemination. Each group can comprise elements of preceding groups although the classification is based on tumor development (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The study variables comprised sex, age of onset and diagnostic confirmation, origin, most frequent debut, RB1 gene mutation, laterality and staging, VA, treatments according to staging and laterality, results of administered therapies and survival.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Sample description</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Demographic characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">Overall, 61.5% of the sample was females. The first symptoms appeared at 5.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.2 months in bilateral RB and 8.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.5 months in the unilateral cases. The definitive diagnostic for bilateral RB cases was 8.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.8 months and in unilateral cases 11.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.8 months.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In Andalucia, the 2 provinces with the highest number of cases were Málaga and Sevilla (11 and 10 cases, respectively), followed by Granada with 3 cases. The incidence rate per million inhabitants was headed by Malaga<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>Sevilla<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>Huelva.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Initial clinic signs</span><p id="par0080" class="elsevierStylePara elsevierViewall">The majority of patients debuted with leukocoria (71.8%) followed by strabismus (17.9%), while the debut of the rest was extraocular (5.1%) or were casual findings.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Retinoblastoma genetics and characteristics</span><p id="par0085" class="elsevierStylePara elsevierViewall">All patients with bilateral tumors exhibited germinal mutation of the RB1 gene (20 patients), of which 4 (20%) had familial antecedents. Only 2 patients (10.5%) of the unilateral group had positive results for said mutation and only one (5.3%) had relatives with RB.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">A.</span><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Laterality:</span> 58 eyes, 32 right eyes (RE) and 26 left eyes (LE).</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">B.</span><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Staging</span> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>): 3 cases with stage A, 10 B, one C, 12 D and unfortunately 32 cases, 55%, with stage E. Only 2 exhibited extraocular presentations.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Visual acuity</span><p id="par0100" class="elsevierStylePara elsevierViewall">Results were based on VA measurements of only 24 (61.5%) patients due to poor cooperation or bilateral enucleation. Of these, all but 2 had bilateral RB. Final mean VA in diseased eyes was 0.6. In the case of healthy fellow eyes in patients with unilateral disease, all VA readings were one.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Treatments</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Systemic chemotherapy</span><p id="par0105" class="elsevierStylePara elsevierViewall">With the exception of 4 patients (10.3%), all patients with unilateral disease (2 in stage D and 2 in stage E) were administered chemotherapy. <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a> detail the protocols and cycles received by patients according to staging and laterality (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Enucleation</span><p id="par0110" class="elsevierStylePara elsevierViewall">Thirty-six of the 44 advanced cases and one mild case underwent enucleation.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The most utilized bioceramics prosthesis was 18<span class="elsevierStyleHsp" style=""></span>mm (47%). The most frequent complication in enucleated patients was prosthesis exposure (29.7%).</p><p id="par0120" class="elsevierStylePara elsevierViewall">A tendency was observed toward enucleation in the unilateral cases, the vast majority (74%) due to reaching advanced stages: D (one eye; 7%) or E (13 eyes; 93%).</p><p id="par0125" class="elsevierStylePara elsevierViewall">Treatments for bilateral cases were more diverse, and enucleation was carried out in 38.5% of cases, mostly for eyes at advanced stages, while the contralateral eyes in milder stages or with better prognosis were administered a broad range of therapeutic combinations to preserve the eyes as well as vision as much as possible (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Carboplatin subtenon</span><p id="par0130" class="elsevierStylePara elsevierViewall">Utilized in 4 patients. At present it is not used due to complications. The mean number of injections was 2.4 per eye.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Cryotherapy</span><p id="par0135" class="elsevierStylePara elsevierViewall">Performed on 9 patients, with the triple freezing technique in each session, requiring in some cases more than one session to achieve complete remission.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Trans-pupil thermotherapy and laser</span><p id="par0140" class="elsevierStylePara elsevierViewall">Fifteen patients were administered conservative treatments with 810<span class="elsevierStyleHsp" style=""></span>nm diode laser, requiring 3 sessions to achieve control.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Brachytherapy</span><p id="par0145" class="elsevierStylePara elsevierViewall">29.3% were treated with plates, of which 30.8% in both eyes and 23% required more than one session in the same eye due to exhibiting multifocal lesions. The isotope was ruthenium 106 in all cases. The most frequent location (38%) was the posterior pole, the majority being multifocal (70.6%). The mean height of tumors was 3.5<span class="elsevierStyleHsp" style=""></span>mm.</p><p id="par0150" class="elsevierStylePara elsevierViewall">The most widely used plate was CCD (43%), with the mean prescribed dose applied at the apex of tumors was 40<span class="elsevierStyleHsp" style=""></span>Gy. Mean implants time was 24<span class="elsevierStyleHsp" style=""></span>h and 34<span class="elsevierStyleHsp" style=""></span>min.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Selective ophthalmic artery intra-arterial chemotherapy</span><p id="par0155" class="elsevierStylePara elsevierViewall">Only one patient received treatment with 3 selective ophthalmic artery intra-arterial chemotherapy sessions (the RE was at stage D and the LE was in E stage, multifocal in both cases).</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">External radiotherapy</span><p id="par0160" class="elsevierStylePara elsevierViewall">Only 2 patients were administered this therapy for advanced extraocular cases. Radiotherapy was applied according to the COG ARET 0321 protocol.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Results of different types of treatment administered to the patients of the study:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0170" class="elsevierStylePara elsevierViewall">The percentage of preserved eyes at mild stages (57%) was higher than that of eyes at advanced stages (43%).</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0175" class="elsevierStylePara elsevierViewall">Overall, the most indicated treatment was enucleation (29 eyes; 50%). The majority of enucleations (82.7%) were performed in eyes at stage E, while the remaining 5 were in stage D (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>). Eight of the 29 eyes that initially received conservative treatments were finally enucleated.</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0180" class="elsevierStylePara elsevierViewall">The second most used treatment was a combination of chemoreduction associated to more than one consolidation treatment (32.8%).</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0185" class="elsevierStylePara elsevierViewall">During 7 years follow-up, 6 eyes (20.7%) had to be treated again due to relapse which occurred within the first year post-diagnostic in all cases.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0190" class="elsevierStylePara elsevierViewall">As for unilateral or bilateral cases:</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">of the 39 bilateral cases, 18 were preserved (46%). And of the 19 unilateral cases, only 3 were preserved (15.8%).</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">Sixteen unilateral (43.2%) and 21 bilateral (56.8%) eyes were enucleated.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall">Two unilateral (10.5%) and 4 bilateral eyes (10.2%) required treatment due to relapse.</p></li></ul></p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Survival</span><p id="par0210" class="elsevierStylePara elsevierViewall">Only 3 patients died (7.69%), one due to sepsis as a complication of systemic chemotherapy, and the other 2 due to delayed diagnostic and presentation with extraocular extension (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). One case was treated for bilateral RB and the other 2 were unilateral cases.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Discussion</span><p id="par0215" class="elsevierStylePara elsevierViewall">The age of onset of the first symptoms was 5.4 months in bilateral RB and 8.4 months in unilateral RB. The definitive diagnostic was at 8.6 months in bilateral cases, matching reports in the literature<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">2,5</span></a> and at almost 12 months in unilateral cases, with a period of 3.4 months since the onset of symptoms and the first medical consultation (higher than the period described by Shields et al. who reported the first visit at 2 months), considering the importance of this factor for reaching an early diagnostic and higher successful treatments.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">The majority of cases (almost 72%) debuted with leukocoria, with strabismus being the second form of presentation (18%), matching the literature.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">All (100%) bilateral cases exhibited germinal RB1 gene mutation. Only 13% had familiar antecedents (4 bilateral and one unilateral), the majority being the result of a germinal de novo mutation in the RB1 gene, matching the results reported in the literature.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> One of the 19 patients with unilateral disease had positive results for the mutation, which matches the reports by other authors that range between 2 and 10–15%.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5,8,9</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Three (5.2%) of 58 eyes belonged to group A, 10 to group B (17.2%), one to group C (1.7%), 12 to group D (21%) and the vast majority, 32 (55%) to group E, showing a high predominance of advanced stages (D and E) of 76% compared to reports at other hospitals with 30%.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a> This clearly has a bearing on all evaluated results (VA, ocular globe preservation and survival). The percentage of patients with bilateral disease in this study is somewhat higher than the percentage described in the literature, i.e. 51.3% bilateral and 48.7% unilateral.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">2,8,11</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">There are no records on baseline VA due to the age of diagnostic and cooperation of patients for measuring VA.</p><p id="par0240" class="elsevierStylePara elsevierViewall">VA could only be measured in 24 patients (61.5%). The mean VA was 0.6, better than the results obtained by Shields et al. in a larger series of cases, with 14% exhibiting VA between 0.4–1.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> The results of the present study are higher because the majority of eyes that could be measured were at mild stages (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9–60%), with only 6 eyes at severe stages (40%). Of these 6, 3 (20%) preserved VA above 0.4, while another (6–7%) had a VA of 0.05 and an additional one (6.7%) finger counting, while the sixth patient (6.7%) had perception of light.</p><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Treatment options</span><p id="par0245" class="elsevierStylePara elsevierViewall">Nearly all centers demonstrate that short-term tumor control with a systemic chemoreduction is achievable, particularly in A or B group tumors. However, C–E group tumors proved to be problematic.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">13–17</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">The battlefield of this tumor continues to be <span class="elsevierStyleItalic">diffuse intraocular seeding.</span> Several strategies have been devised in an attempt to avoid enucleation. Subconjunctival carboplatin aroused interest in recent years, leading to experimental studies in which vitreous seeding responded in 60% of cases.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a> This percentage far exceeds the results obtained by the authors with this local treatment, as only one eye (20%) of the 5 treated eyes could be preserved.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">19,20</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Even though this study includes only one patient treated with intra-arterial chemotherapy, due to the increasing use of this new therapeutic option it is worthwhile noting that it was possible to preserve the only eye the patient had (a 5.5 months old patient, stage D in RE and E in LE, treated with chemoreduction<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>consolidation treatment). Two years after said treatment the patient did not exhibit relapse, the RE was preserved and enabled walking vision. In a series of 9 eyes at high stages (D–E) previously treated with chemoreduction, TTT, brachytherapy and RTE, Abramson et al. were able to preserve 7 (77%) eyes.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">21</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Unresolved issues include long-term tumor control and the consequences of chemotherapy. The majority of these patients are exposed to the etoposide, related to the risk of secondary leukemia in patients without predisposition to cancer.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5,21–23</span></a> To date, no secondary leukemia has been identified in the patients of the present study.</p><p id="par0265" class="elsevierStylePara elsevierViewall">Recent studies report on the efficacy of intravitreal injection of chemotherapy agents. Their long-term results are still being assessed, together with the risk of extraocular dissemination of the disease.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Comparison of obtained results</span><p id="par0270" class="elsevierStylePara elsevierViewall">Half (50%) of eyes were initially enucleated. The remaining 50% of eyes were assessed as follows:</p><p id="par0275" class="elsevierStylePara elsevierViewall">The most interesting results were obtained when assessing the combination of CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>focal therapies with an 85.6% of ability of preserving the eye, a percentage similar to those described in other studies.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">13,21,24</span></a> However, in order to perform an adequate comparison it is crucial to know the stage of the disease.</p><p id="par0280" class="elsevierStylePara elsevierViewall">A comparison of results vis-à-vis the literature based on the initial tumor stage follows.</p><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conservative treatment at mild stages</span><p id="par0285" class="elsevierStylePara elsevierViewall">In the majority of articles, groups A and B were correlated to successful chemoreduction. Demirci et al. achieved control with chemotherapy in 75–85% of macular RB, applying thermal therapy “respecting the fovea”. In the present study said percentage is higher, as 92.3% of cases in stage A or B were controlled with conservative treatment (primary chemoreduction and/or focal consolidation), although with a higher percentage of relapses: 38.5% against 26%, with the difference that the present study comprised 7 years and said study only comprised 4 and that all patients were controlled with additional focal therapy.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conservative treatment at severe stages</span><p id="par0290" class="elsevierStylePara elsevierViewall">Shin et al. reported an ocular preservation of 46.56% of the entire study group, which diminished to 37.25% in eyes at D and E stages.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">23</span></a> The present study obtained better results, i.e., 57% at mild stages (A and B), and 43% at severe stages (C, D and E).</p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Survival</span><p id="par0295" class="elsevierStylePara elsevierViewall">Survival is directly proportional to individual income. In developing countries, survival is 40–77% while in developed countries it ranges between 85 and 95%.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">2,26–28</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">During the 2006–2013 period, 3 of 36 patients died (survival probability of 92.3% at 7 years). In 2010, Shields et al. published very similar results based on the North American population with a percentage of 96% at 5 years.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a></p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conclusions</span><p id="par0305" class="elsevierStylePara elsevierViewall">The present study comprises multiple limitations, the main one being the low prevalence of RB. Precisely for this reason it is difficult to obtain series with 58 eyes, the present being the first study referring to the disease in the authors’ region and one of the few carried out in Spain.</p><p id="par0310" class="elsevierStylePara elsevierViewall">The present retrospective and nonrandomized analysis comprises an added difficulty, i.e., treatments are not standardized but rather individualized according to each case.</p><p id="par0315" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chemoreduction associated to various consolidation treatments</span> has demonstrated very encouraging results, particularly for mild-moderate stages. Enucleation continues to be regarded as the main treatment for cases with difficult to control diffused vitreous seeding and for tumors that invade a high percentage of the vitreous cavity. However, the combination of chemotherapy and focal therapies is a good option for more severe cases for patients who have already undergone enucleation of one eye and the preservation of the remaining one is crucial whenever there is a possibility of maintaining a minimum VA and the life of the patient is not in danger.</p><p id="par0320" class="elsevierStylePara elsevierViewall">Treatment with radioactive plates<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>chemotherapy has demonstrated very positive results, particularly in cases without vitreous or subretinal seeding. However, indications must be very well assessed by a multidisciplinary team due to the risk of complications and the difficulty of intraocular control.</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Funding</span><p id="par0325" class="elsevierStylePara elsevierViewall">The present study has not received specific funding from public sector agencies, private companies or nonprofit organizations.</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Conflict of interests</span><p id="par0330" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1075930" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1022232" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1075929" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1022231" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0020" "titulo" => "Sample description" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Demographic characteristics" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Initial clinic signs" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Retinoblastoma genetics and characteristics" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Visual acuity" ] ] ] 1 => array:3 [ "identificador" => "sec0045" "titulo" => "Treatments" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Systemic chemotherapy" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Enucleation" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Carboplatin subtenon" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Cryotherapy" ] 4 => array:2 [ "identificador" => "sec0070" "titulo" => "Trans-pupil thermotherapy and laser" ] 5 => array:2 [ "identificador" => "sec0075" "titulo" => "Brachytherapy" ] 6 => array:2 [ "identificador" => "sec0080" "titulo" => "Selective ophthalmic artery intra-arterial chemotherapy" ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "External radiotherapy" ] ] ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Survival" ] ] ] 7 => array:3 [ "identificador" => "sec0095" "titulo" => "Discussion" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "Treatment options" ] 1 => array:3 [ "identificador" => "sec0105" "titulo" => "Comparison of obtained results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0110" "titulo" => "Conservative treatment at mild stages" ] 1 => array:2 [ "identificador" => "sec0115" "titulo" => "Conservative treatment at severe stages" ] ] ] 2 => array:2 [ "identificador" => "sec0120" "titulo" => "Survival" ] ] ] 8 => array:2 [ "identificador" => "sec0125" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0130" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0135" "titulo" => "Conflict of interests" ] 11 => array:2 [ "identificador" => "xack364393" "titulo" => "Acknowledgments" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-03-06" "fechaAceptado" => "2018-04-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1022232" "palabras" => array:4 [ 0 => "Retinoblastoma" 1 => "Early diagnosis" 2 => "Leukocoria" 3 => "RB1" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1022231" "palabras" => array:4 [ 0 => "Retinoblastoma" 1 => "Diagnóstico precoz" 2 => "Leucocoria" 3 => "RB1" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Retinoblastoma is the most frequent malignant intraocular tumor in childhood, and both its cure and the sequelae arising from it, mainly depend on an early diagnosis. There is currently no consensus on its diagnostic and therapeutic management.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A descriptive, retrospective, and non-randomised study was conducted on a series of cases (39 patients – 58 eyes), treated during the period 2006–2013, in the Regional Reference Center for Tumors of the National Health Service Quality Agency.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The most frequent presentation sign is leukocoria (71.8%), followed by strabismus (17.9%). All cases of bilateral tumor had a germline mutation of the RB1 gene, and 20% had a family history. Stage E was observed in 55% of the patients, and 90% required chemotherapy treatment. The eye was maintained in 57% of those who had mild stages, compared to 43% who maintained it in advanced stages.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This analysis included 58 eyes. There are no previous studies in our community and there are few series so numerous throughout the country. Based on non-standardised treatment, the most appropriate is chosen according to the characteristics of the tumor. The multidisciplinary management, formed by ophthalmology, pediatric oncology, radiotherapy, and radiophysical oncology, is fundamental for the selection of the most appropriate treatment. Chemo-reduction, along with consolidation treatments, offers encouraging results in the control of these tumors, especially in those of less severity. Enucleation continues to be the method of choice in the most advanced staging with vitreous involvement, with the importance of early diagnosis being highlighted.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El retinoblastoma es el tumor intraocular maligno más frecuente en la infancia y tanto su curación como las secuelas derivadas del mismo dependen fundamentalmente de un diagnóstico precoz. En la actualidad, no existe consenso en su manejo diagnóstico y terapéutico.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio descriptivo, retrospectivo, no aleatorizado, de serie de casos (39 pacientes-58 ojos), tratados durante el período 2006-2013 en nuestro servicio, nombrado centro de Referencia Regional de Tumores por la Agencia de Calidad del SNS.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El signo más frecuente de comienzo es la leucocoria (71,8%), seguido de estrabismo (17,9%). Todos los casos de tumoración bilateral presentaban mutación germinal del gen RB1 y un 20% tenían antecedentes familiares. El 55% de los pacientes presentaron estadio E, y el 90% precisó tratamiento quimioterápico. Un 57% de los que presentaban estadios leves, conservaron su ojo respecto al 43% que lo conservó en estadios avanzados.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este análisis consta de 58 ojos, sin que existan estudios previos en nuestra comunidad y pocas series tan numerosas en todo el país. Basado en tratamiento no estandarizados, eligiendo el más adecuado según las características del tumor. El manejo multidisciplinar, formado por oftalmología, oncología pediátrica, oncología radioterápica y radiofísica, es fundamental para la elección de tratamiento más correcta. La quimiorreducción junto a tratamientos de consolidación ofrece resultados esperanzadores en el control de los mismos, sobre todo en los de menor severidad. La enucleación continúa siendo de elección en las estadificaciones más avanzadas con afectación vítrea, poniendo de manifiesto la importancia de su diagnóstico precoz.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Parrilla-Vallejo M, Perea-Pérez R, Relimpio-López I, Montero-de-Espinosa I, Rodríguez-de-la-Rúa E, Terrón-León JA, et al. Retinoblastoma: la importancia de su diagnóstico precoz. Arch Soc Esp Oftalmol. 2018;93:423–430.</p>" ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 923 "Ancho" => 1273 "Tamanyo" => 40183 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Proportion of tumors based on staging.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 503 "Ancho" => 1200 "Tamanyo" => 54732 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">unilateral RB in RE stage B before and after treatment, showing type 1 regression pattern.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 505 "Ancho" => 1200 "Tamanyo" => 85628 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">RB in stage E with orbit, intracranial and cerebrospinal fluid invasion before and after chemoreduction with modified ARET protocol. July to September: 4 cycles.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">RB international classification: groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Size (mm) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Location \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Vitreous subretinal seeding \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Retina, far:<br>Optic N.: >1.5<span class="elsevierStyleHsp" style=""></span>mm<br>Fovea: >3<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Retinal, near:<br>Optic N.: ≤1.5<span class="elsevierStyleHsp" style=""></span>mm<br>Fovea: ≤3<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Focal ≤3<span class="elsevierStyleHsp" style=""></span>mm from tumor<br>vitreous or subretinal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><1 quadrant \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diffuse >3<span class="elsevierStyleHsp" style=""></span>mm from tumor<br>vitreous or subretinal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">Touching the lens<br>GNV<br>Anterior vitreous: ciliary body or anterior segment<br>diffuse infiltrating RB</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">Hemorrhage<br>Tumor necrosis: aseptic orbit cellulite<br>invasion of optic nerve, choroids (>2<span class="elsevierStyleHsp" style=""></span>mm), sclera and orbit<br>Phthisis bulbi</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1836565.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">International Classification for Retinoblastoma (ICRB).</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">COG (<span class="elsevierStyleItalic">Children Oncology group</span>)-ARET 0332 VEC: vincristin, carboplatin and etoposide (0.05<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1, 18.6<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1. 5<span class="elsevierStyleHsp" style=""></span>mg/kg; days 1 and 2, 6 cycles); COG-CEV: vincristin, carboplatin and etoposide (0.05<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1, 14<span class="elsevierStyleHsp" style=""></span>mg/kg; days 1 and 2, 5<span class="elsevierStyleHsp" style=""></span>mg/kg; days 1 and 2, 3–6 cycles); COG-CV: carboplatin and vincristin (dose: 18.6<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1 and 0.05<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1, 2–6 cycles).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unilateral stage (n.° eyes) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CV<br>x4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CEV<br>x6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">ARET \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No CT \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1836569.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Treatments with systemic chemotherapy based on staging (unilateral stage).</p>" ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">COG (<span class="elsevierStyleItalic">Children Oncology group</span>)-ARET 0332 VEC: vincristin, carboplatin and etoposide (0.05<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1, 18.6<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1, 5<span class="elsevierStyleHsp" style=""></span>mg/kg; days 1 and 2, 6 cycles); COG-CEV: vincristin, carboplatin and etoposide (0.05<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1, 14<span class="elsevierStyleHsp" style=""></span>mg/kg; days 1 and 2, 5<span class="elsevierStyleHsp" style=""></span>mg/kg; days 1 and 2, 3–6 cycles); COG-CV: carboplatino and vincristina (dose: 18.6<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1 and 0.05<span class="elsevierStyleHsp" style=""></span>mg/kg; day 1, 2–6 cycles); ?: protocol unknown at the authors’ Dept.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Bilateral stage (n.° eyes) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CV<br>x4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CEV \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">ARET \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">? \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No CT \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Totales \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1836568.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Treatment with systemic chemotherapy based on staging (bilateral stage).</p>" ] ] 6 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatments</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Unilateral</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Bilateral</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total</th></tr><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Enucleation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>BCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>TTT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>cryotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>several treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>RTE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1836567.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Distribution of patients per laterality, based on initial treatment administered to each eye.</p>" ] ] 7 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatments</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">A</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">B</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">C</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">D</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">E</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total</th></tr><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Enucleation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>BCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>TTT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>Cryo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>various tts. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>RTE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1836566.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Distribution of patients per stage based on initial treatment per eye.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Tumores oculares y perioculares en la infancia. 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Retinoblastoma: The importance of early diagnosis
Retinoblastoma: la importancia de su diagnóstico precoz