E- Case Report
Clinical Response to Ingenol Mebutate in Patients With Actinic Keratoses
Respuesta a ingenol mebutato en los pacientes con queratosis actínicas en la práctica clínica
A. Batalla
, Á. Flórez, C. Feal, G. Peón, M.T. Abalde, L. Salgado-Boquete, C. de la Torre
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Servicio de Dermatología, Centro de Especialidades de Mollabao, Xestión Integrada Pontevedra-Salnés, Pontevedra, Spain
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5811
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2021
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A. Queratosis actínica no hiperqueratósica malar izquierda. B. Reacción local tipo <span class="elsevierStyleSmallCaps">iv</span> tras administración de la primera monodosis de ingenol mebutato (suspensión de las 2 siguientes aplicaciones). C. Queratosis actínica residual. La paciente requirió una sesión de crioterapia adicional.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Batalla, Á. Flórez, C. Feal, G. Peón, M.T. Abalde, L. Salgado-Boquete, C. de la Torre" "autores" => array:7 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Batalla" ] 1 => array:2 [ "nombre" => "Á." "apellidos" => "Flórez" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Feal" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Peón" ] 4 => array:2 [ "nombre" => "M.T." "apellidos" => "Abalde" ] 5 => array:2 [ "nombre" => "L." "apellidos" => "Salgado-Boquete" ] 6 => array:2 [ "nombre" => "C." 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Batalla, Á. Flórez, C. Feal, G. Peón, M.T. Abalde, L. Salgado-Boquete, C. de la Torre" "autores" => array:7 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Batalla" "email" => array:1 [ 0 => "anacebey@yahoo.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Á." "apellidos" => "Flórez" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Feal" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Peón" ] 4 => array:2 [ "nombre" => "M.T." "apellidos" => "Abalde" ] 5 => array:2 [ "nombre" => "L." "apellidos" => "Salgado-Boquete" ] 6 => array:2 [ "nombre" => "C." "apellidos" => "de la Torre" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Centro de Especialidades de Mollabao, Xestión Integrada Pontevedra-Salnés, Pontevedra, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta a ingenol mebutato en los pacientes con queratosis actínicas en la práctica clínica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 514 "Ancho" => 1600 "Tamanyo" => 179442 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Partial Response to ingenol mebutate following treatment that was not completed due to a type <span class="elsevierStyleSmallCaps">iv</span> local reaction. A, Non-hyperkeratotic actinic keratosis on the left malar. B, Type <span class="elsevierStyleSmallCaps">iv</span> local reaction after administration of the first single dose of ingenol mebutate; the following 2 applications were not administered. C, Residual actinic keratosis. The patient required an additional session of cryotherapy.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Actinic keratoses (AK) are considered by most authors to be premalignant lesions that can progress to invasive squamous cell carcinoma.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In addition to lesion-directed therapies such as cryotherapy, the available treatment options for AK also include topical treatments that act on both the isolated—clinically visible—lesions and on the surrounding area of skin with chronic actinic damage and subclinical AK. Treatments include 5-fluorouracil, imiquimod (IMQ), diclofenac (DCF), and photodynamic therapy.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Ingenol mebutate is a treatment indicated for AK that has only recently become available. It has been shown to be effective in the treatment of both individual lesions and the cancerization field, with treatment cycles of 3 consecutive days for the face and scalp and 2-day cycles for the trunk or limbs, achieving a complete cure rate of around 40%.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The main difference between ingenol mebutate and other field cancerization therapies is that the treatment cycle is shorter and adherence to the dosing schedule is easier.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Descriptions</span><p id="par0015" class="elsevierStylePara elsevierViewall">We present a series of 17 patients treated with ingenol mebutate. Demographic and clinical characteristics were evaluated as well as treatment-related data (effectiveness, adherence to treatment, and tolerance) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Effectiveness was evaluated at 2 months<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and was classified as follows: complete response if no abnormalities were detected in the treated area (normal skin); partial response if the abnormalities had diminished but were still present to some degree, making a cycle of any other treatment necessary; and no response if the lesions were unchanged. The regimen prescribed was 3 doses for facial lesions and 2 doses if the site affected was on the body. Correct adherence to treatment was defined as the application by the patient of all the doses prescribed; if any dose was skipped, adherence was defined as partial. To assess tolerance, the patients were asked about localized irritation at the site of application using the terminology specified in the Summary of Product Characteristics (minimum, type I; mild, type II; moderate, type III; and severe, type IV).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The mean age of the group of patients treated was 76 years. Only 1 patient had a history of melanoma skin cancer, and 3 patients a history of non-melanoma skin cancer. None of the prior skin cancer lesions were located in the area treated with ingenol mebutate. Fourteen of the 17 patients (82%) had previously received treatment for AKs, mainly cryotherapy (76%), imiquimod (29%), or diclofenac (29%). The mean interval between the last prior treatment and application of ingenol mebutate was 20 months (median, 6 months). All the patients in the present study received treatment with ingenol mebutate for AK lesions on the face (76%; 13/17) or scalp (24%; 4/17). The response to treatment was complete in 35% (6/17) and partial in 53% (9/17). In 2 cases (12%), there was no response. <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a> shows a case of complete response to ingenol mebutate. Long-term follow-up was variable after the assessment of response at 2 months post-treatment. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the maximum follow-up period and the clinical outcome at the end of follow-up for the patients who presented a complete response (mean: 10 mo, median: 11 mo; complete remission in 67% of cases). Adherence was correct in 94% (16/17) of the patients. The only case in which there was partial compliance was due to a type IV local reaction after application of the first dose; the following 2 applications were not administered because of the severe symptoms associated with that reaction (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). In addition to that case, 2 other patients had local type IV reactions (3/17 in total, 18%). The rates for type III and type I/II reactions were similar: 41% in both groups. No relationship was observed between the severity of the reaction and a better or worse response (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.4; Fisher test). None of the patients reported cosmetic alterations or scarring in the treated area.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">In this case series of patients treated with ingenol mebutate in routine clinical practice, we observed a response rate of 88% (complete response, 35%; partial response, 53%), high adherence (94%), and frequent local skin reactions (minimal to mild, 41%; moderate to severe, 59%).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The response rates in this study were slightly lower than those reported in the literature (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> It has been observed that the success rate may be higher when ingenol mebutate is combined with other therapies (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">It is difficult to perform a direct comparison of the different treatment options for AK due to the heterogeneity of the available studies.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes the results of studies which, based on the best scientific evidence, analyze the effectiveness of various interventions, including ingenol mebutate. In terms of effectiveness, ingenol mebutate is ranked midway between the most effective treatment (5-fluorouracil) and the least effective options (cryotherapy and diclofenac), achieving results comparable to treatments of intermediate effectiveness (photodynamic therapy and IMQ).<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> In the case of ingenol mebutate, relative effectiveness is influenced by the site of treatment, with higher rates of clearance for the head region, for which it has proved more effective than 5% IMQ.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">With respect to adherence to treatment, 94% of our patients completed treatment, a percentage similar to that reported by other authors.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Adherence to treatment with ingenol mebutate is much higher than with other patient-applied topical therapies (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>),<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> a phenomenon that can be explained by the short treatment cycle required.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Although localized skin reactions at the site of application of ingenol mebutate are common (>96%), these usually occur after the treatment cycle has been completed and do not, therefore, lead the patients to abandon treatment.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Local inflammatory reactions in the treated area are also common during the administration of the other topical treatments used to treat AK.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The retrospective design of the present study has allowed us to describe the characteristics of treatment with ingenol mebutate in clinical practice. However, it also has several limitations. Since no histological analysis is available of the lesions in the treated area, the selection of non-hyperkeratotic or “superficial” AKs was necessarily subjective. This subjectivity may have given rise to minor differences in the severity of the treated area and could therefore have affected our results. In the absence of any exact count of the number of lesions at baseline, there was also a degree of subjectivity in the assessment of whether response was complete or partial. The early assessment of response to treatment (at 2 months) may also have positively influenced our results. Nonetheless, we considered 2 months to be the best moment for this evaluation because it allowed us to assess all the patients in the study at the same time point since the prescribing physicians followed the indications of the Summary of Product Characteristics with respect to the timing of follow-up. Finally, the small number of patients treated makes it difficult to compare our results with other studies.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Our conclusion is that ingenol mebutate is useful in the treatment of AKs and field cancerization, and that the dosage used favors adherence to treatment.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical Disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animal subjects</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed adhered to the ethical guidelines of the responsible committee on human experimentation and comply with the Declaration of Helsinki of the World Medical Association.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Data confidentiality</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they followed the protocols of their institution with respect to the publication of private patient data.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors obtained the informed consent of the patients and/or subjects referred to in this article. These documents are in the possession of the corresponding author.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of Interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">Ana Batalla and Ángeles Flórez have received lecture fees from Leo-Pharma Spain for interventions on the topic of actinic keratosis.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The other authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres586320" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec602166" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres586321" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec602165" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Descriptions" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec602166" "palabras" => array:4 [ 0 => "Actinic keratosis" 1 => "Effectiveness" 2 => "Ingenol mebutate" 3 => "Treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec602165" "palabras" => array:4 [ 0 => "Queratosis actínica" 1 => "Efectividad" 2 => "Ingenol mebutato" 3 => "Tratamiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cryotherapy is the most common treatment for actinic keratosis, but its effect is limited to individual lesions. Several topical drugs, however, are available that, in addition to treating individual actinic keratoses, target field cancerization and thereby act on subclinical lesions. Examples are 5-fluorouracil, imiquimod, diclofenac, and ingenol mebutate. We report on 17 patients with actinic keratoses treated with ingenol mebutate and describe our findings on treatment effectiveness, adherence, and tolerance. Complete and partial response rates were 35% and 53%, respectively. Ninety-four percent of patients fully adhered to treatment and 18% developed severe local reactions. Ingenol mebutate is an effective treatment for actinic keratosis. Although it has a similar rate of local reactions to other treatments available for actinic keratosis, its short treatment regimen favors better adherence.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La crioterapia es el tratamiento más frecuentemente utilizado para las queratosis actínicas, ejerciendo su efecto únicamente sobre lesiones individuales. Existen fármacos tópicos que tratan además el campo de cancerización, actuando sobre queratosis actínicas no clínicamente evidentes, entre los que se encuentran el 5-fluorouracilo, el imiquimod, el diclofenaco o el ingenol mebutato.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Presentamos 17 pacientes con queratosis actínicas tratados con ingenol mebutato y describimos las observaciones en relación con la efectividad, el cumplimiento terapéutico y la tolerancia del fármaco. Las tasas de respuesta completa y parcial fueron del 35% y del 53%, respectivamente. El cumplimiento fue correcto en un 94% de los casos. En el 18% de los pacientes existieron reacciones locales intensas.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El ingenol mebutato es efectivo para el tratamiento de las queratosis actínicas. Aunque presenta similar tasa de reacciones locales a los restantes tratamientos disponibles para esta indicación, su pauta corta de administración favorece el cumplimiento.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Batalla A, Flórez Á, Feal C, Peón G, Abalde MT, Salgado-Boquete L, et al. Respuesta a ingenol mebutato en los pacientes con queratosis actínicas en la práctica clínica. Actas Dermosifiliogr. 2015;106:e55–e61.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 975 "Ancho" => 1300 "Tamanyo" => 223019 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Complete response to ingenol mebutate. A, Actinic keratosis on the nasal pyramid. B, Complete response at 2 months.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 514 "Ancho" => 1600 "Tamanyo" => 179442 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Partial Response to ingenol mebutate following treatment that was not completed due to a type <span class="elsevierStyleSmallCaps">iv</span> local reaction. A, Non-hyperkeratotic actinic keratosis on the left malar. B, Type <span class="elsevierStyleSmallCaps">iv</span> local reaction after administration of the first single dose of ingenol mebutate; the following 2 applications were not administered. C, Residual actinic keratosis. The patient required an additional session of cryotherapy.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: 5-FU, 5-fluorouracil; BCC, basal cell carcinoma; CT, Cryotherapy; DCF, diclofenac; ELC, electrocoagulation; IMQ, imiquimod; LM, lentigo maligna; M, Man; NMSC, nonmelanoma skin cancer; PDT, photodynamic therapy; SCC, squamous cell carcinoma; W, woman.</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">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Past History of Skin Cancer</th><th class="td" title="table-head " align="left" valign="top" scope="col">Previous Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Time Since Last Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Site \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Adherence<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Tolerance<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> (Severity of Reaction) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Effectiveness<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Maximum Follow-up \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Melanoma \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NMSC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" 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="" 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="" 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="" 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="" 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="" 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="" 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" title="table-entry " align="left" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (LM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (BCC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \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">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 months (No recurrence) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \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">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 months (no recurrence) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (BCC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, IMQ, 5-FU) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 months (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I/II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, DCF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 months (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 months (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I/II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, ELC, IMQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 y (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Scalp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, DCF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 months (DCF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I/II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, IMQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 months (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Scalp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \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">Scalp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, DIC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 months (DCF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, DCF, PDT) \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">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I/II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, IMQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 months (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 months (no recurrence) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (BCC, SCC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, IMQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 months (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Scalp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I/II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 months (relapse: 3 lesions) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 months (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \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">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 y (CT) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (CT, DCF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 months (DCF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Correct \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 months (relapse: 1 lesion) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab957420.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">The definitions used to classify adherence, tolerability, and effectiveness are described in the text.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Patients Treated With Ingenol Mebutate.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: 5-FU, 5-fluorouracil; ALA, 5-aminolaevulinic acid; AK, actinic keratosis; CT, cryotherapy; DCF, diclofenac; IM, ingenol mebutate; IMQ, imiquimod; MAL, methyl aminolaevulinate; PDT, photodynamic therapy; RCT, randomized clinical trial.</p>" "tablatextoimagen" => array:5 [ 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">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intervention \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Effectiveness \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lebwohl et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Phase 3 RCT- Effectiveness on face and scalp: n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>547 (277 IM, 270 placebo)-Effectiveness on trunk and limbs<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>458 (226 IM, 232 placebo) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IM vs placeboObjective: complete clearance rate (assessment at 57 days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete clearance:AK on face and scalp: 42%AK on trunk and limbs: 34%Partial response (clearance ≥ 75%):AK on face and scalp: 64%AK on trunk and limbs: 49% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Berman et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Phase 3 RCTn<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>329 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IM<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>CT vs CTObjectives:- Complete clearance rate at wk 11- Effectiveness at 12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete clearance at wk 11CT and IM: 61%CT: 49%Complete clearance at 12 monthsCT and IM: 55%CT: 40% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vegter et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Meta-analysis25 RCTsn<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5562 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Treatments for AK on face or scalp.Objective: to achieve complete clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ALA-PDT gel: 85.3%MAL-PDT: 65.9%ALA-PDT patch: 62%5% IMQ 4-wk: 57.2%0.5% 5-FU: 54.6%CT: 49.1%5% IMQ 16-wk: 45.1%IM: 43%3% DCF: 35.4%3.75% IMQ 2- or 3-wk: 34.8%Placebo: 6.9% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab957418.png" ] ] 1 => 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">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intervention \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Effectiveness \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Gupta and Paquet<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> (Cochrane review update) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Meta-analysis of36 RCTsn<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6473Data Collection: up till April 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Treatments for AKObjective: to achieve complete clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No clearance percentage specified. Treatments are shown in order of effectiveness \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab957419.png" ] ] 2 => 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">All Sites \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Scalp Only \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Overall \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5% 5-FU ><span class="elsevierStyleMonospace">0.5%</span>5-FU, ALA-PDT ><span class="elsevierStyleMonospace">5%</span> IMQ<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>IM<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>MAL PDT<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>CT<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>DCF<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5% 5-FU<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">0.5%</span>5-FU<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>IM<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">ALA</span>-PDT<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">5%</span>IMQ<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">MAL-P</span>DT<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>CT<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5-FU<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>ALA-PDT≈<span class="elsevierStyleMonospace">5%</span>IMQ ≈ IM≈MAL-PDT >CT<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>DCF \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab957416.png" ] ] 3 => 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">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics and Intervention \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Local Adverse Effects \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lebwohl et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">See above \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Local reactions:-AK, face and scalp: 98%Moderate-intense reactions in a “minority” of casesAK trunk and limbs: 96%70% moderate to intense \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab957417.png" ] ] 4 => 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">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intervention \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adherence \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lebwohl et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">See above \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">See above \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>98% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Shergill et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cross-sectional studyn<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>305DCF, 5% 5-FU, 5% IMQ, 0.5% 5-FU \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Objective: To identify adherence rate and factors conditioning adherence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Percentage of non-adherence or abandonment<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>88%Percentage of non-adherence by length of treatment52% in treatments of 3-4 wks duration69% in treatments of 6-8 wks duration71% in treatments of 6-12 wks duration \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab957415.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Non-adherence indicates not using the correct dosage and abandoment indicates not completing the treatment cycle.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p 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| 2020 Agosto | 30 | 31 | 61 |
| 2020 Julio | 29 | 16 | 45 |
| 2020 Junio | 65 | 39 | 104 |
| 2020 Mayo | 41 | 20 | 61 |
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| 2020 Febrero | 5 | 3 | 8 |
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| 2019 Febrero | 2 | 0 | 2 |
| 2019 Enero | 1 | 0 | 1 |
| 2018 Diciembre | 11 | 0 | 11 |
| 2018 Octubre | 5 | 0 | 5 |
| 2018 Septiembre | 8 | 0 | 8 |
| 2018 Junio | 0 | 1 | 1 |
| 2018 Marzo | 1 | 0 | 1 |
| 2018 Febrero | 23 | 4 | 27 |
| 2018 Enero | 30 | 7 | 37 |
| 2017 Diciembre | 33 | 9 | 42 |
| 2017 Noviembre | 31 | 6 | 37 |
| 2017 Octubre | 21 | 8 | 29 |
| 2017 Septiembre | 20 | 6 | 26 |
| 2017 Agosto | 19 | 10 | 29 |
| 2017 Julio | 16 | 8 | 24 |
| 2017 Junio | 26 | 12 | 38 |
| 2017 Mayo | 19 | 8 | 27 |
| 2017 Abril | 37 | 13 | 50 |
| 2017 Marzo | 17 | 45 | 62 |
| 2017 Febrero | 18 | 10 | 28 |
| 2017 Enero | 22 | 9 | 31 |
| 2016 Diciembre | 17 | 13 | 30 |
| 2016 Noviembre | 25 | 34 | 59 |
| 2016 Octubre | 18 | 28 | 46 |
| 2016 Septiembre | 0 | 5 | 5 |
| 2016 Agosto | 0 | 2 | 2 |
| 2016 Julio | 2 | 4 | 6 |
| 2016 Junio | 1 | 4 | 5 |
| 2016 Mayo | 0 | 2 | 2 |
| 2016 Abril | 0 | 9 | 9 |
| 2016 Marzo | 0 | 7 | 7 |
| 2016 Febrero | 0 | 12 | 12 |
| 2016 Enero | 0 | 3 | 3 |
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