Case and Research Letter
KIT Mutations in a Series of Melanomas and Their Impact on Treatment With Imatinib
Mutaciones en KIT en una serie de melanomas y repercusiones en el tratamiento con imatinib
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Botella-Estrada, V. Soriano, L. Rubio, E. Nagore" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Botella-Estrada" "email" => array:1 [ 0 => "rbotellaes@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "V." "apellidos" => "Soriano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "L." "apellidos" => "Rubio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Nagore" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Oncología, Instituto Valenciano de Oncología, Valencia, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Biología Molecular, Instituto Valenciano de Oncología, Valencia, Spain" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Mutaciones en KIT en una serie de melanomas y repercusiones en el tratamiento con imatinib" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 740 "Ancho" => 2168 "Tamanyo" => 120584 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Disappearance of most of the lung metastases following 3 months of imatinib therapy in patient no. 1. A, Computed tomography (CT) scan performed on November 23, 2009, prior to treatment. B, CT scan performed on March 2, 2010, after 3 months of treatment with imatinib.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The first studies on the use of imatinib in patients with metastatic melanoma were published in 2005 and 2006 and reported that the drug was not effective in this setting.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> However, a study published in 2006, which analyzed 102 primary melanomas, described <span class="elsevierStyleItalic">KIT</span> mutations or copy number increases in 39% of mucosal melanomas, 36% of acral melanomas, and 28% of melanomas arising on chronically sun-damaged skin, but in 0% of those arising on skin without chronic sun damage.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In addition to isolated cases in which patients with metastatic melanoma who had <span class="elsevierStyleItalic">KIT</span> mutations achieved partial or complete regression with imatinib,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> results were recently published of 2 series of patients with metastatic melanoma who received imatinib after their tumors were found to contain genetic alterations (mutations or amplifications) in <span class="elsevierStyleItalic">KIT</span>.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> Carvajal and coworkers<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> achieved an overall durable response rate of 16% in a group of 25 patients. In a group of 43 patients of Asian origin, Guo and coworkers<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> reported a disease control rate of 53.5% (partial response in 10 patients and stable disease in 13). In a recent publication in The Lancet, Romano and colleagues<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> reported that, based on their experience at Memorial Sloan-Kettering Cancer Center, mutations in exons 11 and 13 of <span class="elsevierStyleItalic">KIT</span> better predict response to imatinib treatment than do amplifications in this gene.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Several studies have demonstrated that the mere immunohistochemical expression of KIT does not correlate with response to imatinib.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Given the limited experience with imatinib in the treatment of metastatic melanoma, we believe it is important to present our data concerning the frequency of <span class="elsevierStyleItalic">KIT</span> mutations (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), and our results describing the response to imatinib of a small group of patients with confirmed mutations. We present the case of a patient treated with imatinib who achieved a temporary partial response in the form of a reduction in the number and size of visceral metastases. The key data for 2 other patients treated with imatinib are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The present case report concerns patient number 1. The patient was a 49-year-old man with melanoma of the penis (9<span class="elsevierStyleHsp" style=""></span>mm Breslow thickness, ulceration, and 6 mitoses/mm<span class="elsevierStyleSup">2</span>) and multiple bilateral inguinal-iliac metastases (stage IIIC; pT4b, N3, M0). After surgical treatment, the patient commenced adjuvant therapy with high-dose interferon. After 7 months of interferon treatment, skin metastases were observed in the scrotum, the lung, and the lymph nodes of the left groin. The disease progressed after two lines of chemotherapy (dacarbazine followed by carboplatin). At this point, analysis of <span class="elsevierStyleItalic">KIT</span> in the patient's tumor using molecular biology techniques identified a mutation in exon 11, for which the patient was treated with imatinib (400<span class="elsevierStyleHsp" style=""></span>mg twice a day). In the course of the disease, progressive increases were observed in the levels of S100 (up to 2.49: normal value,<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.4<span class="elsevierStyleHsp" style=""></span>μg/L) and lactate dehydrogenase (LDH) (up to 434: normal value, 100-250 U/L). After 1 month of treatment with imatinib, clinical observation revealed a partial response of the skin lesions and lymph nodes, normalization of S100 levels (0.22), and a decrease in LDH levels (303). A computed tomography scan 3 months later also identified a partial response of the lung metastases (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). However, 3 months later further increases in S100 (0.71) and LDH (378) were observed and 4 weeks later progression of lung disease and new metastases of the mediastinum were confirmed. The patient was treated as a last resort with ipilimumab. Several weeks later, multiple metastases were detected in the central nervous system and treated with palliative radiotherapy and systemic corticosteroids; the patient died 2 months later.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In view of our results (temporary partial response, a lasting stabilization of disease, and eventual progression), we believe that drugs that act by inhibiting KIT should be evaluated in patients with melanoma in whom disease has progressed despite conventional chemotherapy and in those with <span class="elsevierStyleItalic">KIT</span> mutations. Our results confirm the finding of other groups that this mutation occurs in acral and mucosal melanoma. Although one of the melanomas in which we detected a <span class="elsevierStyleItalic">KIT</span> mutation corresponded to a superficial spreading melanoma, the tumor was located on the forehead of a 55-year-old patient with moderate solar elastosis. While acral and mucous melanomas are relatively infrequent, they do not usually harbor <span class="elsevierStyleItalic">BRAF</span> mutations and thus are not susceptible to treatment with the new inhibitors of this tyrosine kinase, such as vemurafenib. Thus, confirmation of a <span class="elsevierStyleItalic">KIT</span> mutation opens the door to an additional treatment option for this group of melanomas. In the near future, these new KIT inhibitors, used both alone and in conjunction with traditional chemotherapy, will likely improve upon the results achieved to date.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Botella-Estrada R, et al. Mutaciones en KIT en una serie de melanomas y repercusiones en el tratamiento con imatinib. Actas Dermosifiliogr. 2012;103:839-41.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 740 "Ancho" => 2168 "Tamanyo" => 120584 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Disappearance of most of the lung metastases following 3 months of imatinib therapy in patient no. 1. A, Computed tomography (CT) scan performed on November 23, 2009, prior to treatment. B, CT scan performed on March 2, 2010, after 3 months of treatment with imatinib.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">DNA was extracted from the primary tumor or, when this was not possible, from any other metastatic implant, and sequencing was performed on exons 9, 11, 13 and 17.</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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No KIT Mutation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">KIT Mutation (Exon) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Location</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Head and neck \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (11) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Upper extremities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Trunk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lower extremities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hands and feet \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (1 in 11, 1 in 13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mucosae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (1 in 11, 1 in 13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Unknown primary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Histological Type</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lentigo maligna melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Superficial spreading melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (11) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nodular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acral lentiginous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (1 in 11, 1 in 13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mucosal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (1 in 11, 1 in 13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab182586.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Results of the Molecular Analysis of <span class="elsevierStyleItalic">KIT</span> Status in 56 Patients with Melanoma by Site and Histological Type.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Primary Melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Spread \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Course \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">KIT</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Imatinib Treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patient 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acral lentiginous malignant melanoma, Breslow thickness 7<span class="elsevierStyleHsp" style=""></span>mm, ulcerated, sole of right foot, with satellitosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Metastases in 8 lymph nodes in the right groin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adjuvant high-dose interferon. Cutaneous recurrence at 5 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mutation in exon 11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imatinib 400 mg/12 h. Diarrhea, adjusted to 400<span class="elsevierStyleHsp" style=""></span>mg in the morning and 200<span class="elsevierStyleHsp" style=""></span>mg in the evening \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female, 72 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage IIIC (T4b, N3, M0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imiquimod<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>dacarbazine Cutaneous progression at 8 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stable disease in lung and liver with a decrease in the size and number of cutaneous metastases up to the present (11 months) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Temozolomide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Visceral spread (lung, liver) at 6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patient 3 Female, 38 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulcerated perianal malignant melanoma, Breslow thickness 22 mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regional lymph node metastases, lung and liver (stage IV) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dacarbazine Progression after 2 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mutation in exon 13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imatinib 400 mg/12 h. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Progression at 3 months. Palliative radiotherapy. Death 3 months later \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab182585.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Summary of Clinical History and Response to Imatinib Treatment in Patients 2 and 3.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lack of clinical efficacy of imatinib in metastatic melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Ugurel" 1 => "R. Hildenbrand" 2 => "A. Zimpfer" 3 => "P. La Rosée" 4 => "P. Paschka" 5 => "A. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 6 | 8 | 14 |
| 2024 Octubre | 90 | 36 | 126 |
| 2024 Septiembre | 77 | 23 | 100 |
| 2024 Agosto | 113 | 71 | 184 |
| 2024 Julio | 88 | 26 | 114 |
| 2024 Junio | 79 | 37 | 116 |
| 2024 Mayo | 73 | 26 | 99 |
| 2024 Abril | 73 | 30 | 103 |
| 2024 Marzo | 68 | 23 | 91 |
| 2024 Febrero | 56 | 28 | 84 |
| 2024 Enero | 43 | 32 | 75 |
| 2023 Diciembre | 54 | 15 | 69 |
| 2023 Noviembre | 75 | 21 | 96 |
| 2023 Octubre | 65 | 32 | 97 |
| 2023 Septiembre | 75 | 37 | 112 |
| 2023 Agosto | 53 | 19 | 72 |
| 2023 Julio | 47 | 34 | 81 |
| 2023 Junio | 45 | 25 | 70 |
| 2023 Mayo | 50 | 24 | 74 |
| 2023 Abril | 37 | 17 | 54 |
| 2023 Marzo | 31 | 22 | 53 |
| 2023 Febrero | 32 | 21 | 53 |
| 2023 Enero | 53 | 30 | 83 |
| 2022 Diciembre | 39 | 35 | 74 |
| 2022 Noviembre | 32 | 23 | 55 |
| 2022 Octubre | 35 | 22 | 57 |
| 2022 Septiembre | 29 | 36 | 65 |
| 2022 Agosto | 32 | 20 | 52 |
| 2022 Julio | 31 | 37 | 68 |
| 2022 Junio | 22 | 21 | 43 |
| 2022 Mayo | 45 | 29 | 74 |
| 2022 Abril | 34 | 28 | 62 |
| 2022 Marzo | 34 | 60 | 94 |
| 2022 Febrero | 40 | 35 | 75 |
| 2022 Enero | 27 | 29 | 56 |
| 2021 Diciembre | 35 | 36 | 71 |
| 2021 Noviembre | 57 | 42 | 99 |
| 2021 Octubre | 92 | 53 | 145 |
| 2021 Septiembre | 30 | 41 | 71 |
| 2021 Agosto | 33 | 34 | 67 |
| 2021 Julio | 30 | 30 | 60 |
| 2021 Junio | 29 | 22 | 51 |
| 2021 Mayo | 30 | 25 | 55 |
| 2021 Abril | 35 | 53 | 88 |
| 2021 Marzo | 37 | 34 | 71 |
| 2021 Febrero | 50 | 19 | 69 |
| 2021 Enero | 25 | 17 | 42 |
| 2020 Diciembre | 30 | 12 | 42 |
| 2020 Noviembre | 27 | 13 | 40 |
| 2020 Octubre | 25 | 8 | 33 |
| 2020 Septiembre | 25 | 11 | 36 |
| 2020 Agosto | 21 | 16 | 37 |
| 2020 Julio | 32 | 11 | 43 |
| 2020 Junio | 41 | 29 | 70 |
| 2020 Mayo | 35 | 23 | 58 |
| 2020 Abril | 45 | 22 | 67 |
| 2020 Marzo | 35 | 21 | 56 |
| 2020 Febrero | 6 | 10 | 16 |
| 2020 Enero | 4 | 9 | 13 |
| 2019 Diciembre | 8 | 0 | 8 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 0 | 3 | 3 |
| 2019 Septiembre | 8 | 2 | 10 |
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| 2019 Enero | 2 | 3 | 5 |
| 2018 Diciembre | 2 | 7 | 9 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 1 | 0 | 1 |
| 2018 Septiembre | 4 | 0 | 4 |
| 2018 Marzo | 5 | 2 | 7 |
| 2018 Febrero | 33 | 6 | 39 |
| 2018 Enero | 32 | 7 | 39 |
| 2017 Diciembre | 41 | 5 | 46 |
| 2017 Noviembre | 20 | 4 | 24 |
| 2017 Octubre | 35 | 7 | 42 |
| 2017 Septiembre | 44 | 7 | 51 |
| 2017 Agosto | 80 | 8 | 88 |
| 2017 Julio | 65 | 9 | 74 |
| 2017 Junio | 40 | 6 | 46 |
| 2017 Mayo | 30 | 3 | 33 |
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| 2017 Marzo | 27 | 12 | 39 |
| 2017 Febrero | 26 | 7 | 33 |
| 2017 Enero | 20 | 3 | 23 |
| 2016 Diciembre | 38 | 6 | 44 |
| 2016 Noviembre | 53 | 7 | 60 |
| 2016 Octubre | 58 | 7 | 65 |
| 2016 Septiembre | 51 | 13 | 64 |
| 2016 Agosto | 51 | 4 | 55 |
| 2016 Julio | 44 | 8 | 52 |
| 2016 Junio | 15 | 12 | 27 |
| 2016 Mayo | 10 | 9 | 19 |
| 2016 Abril | 8 | 6 | 14 |
| 2016 Marzo | 23 | 1 | 24 |
| 2016 Febrero | 11 | 9 | 20 |
| 2016 Enero | 8 | 10 | 18 |
| 2015 Diciembre | 10 | 7 | 17 |
| 2015 Noviembre | 25 | 1 | 26 |
| 2015 Octubre | 17 | 1 | 18 |
| 2015 Septiembre | 7 | 7 | 14 |
| 2015 Agosto | 15 | 2 | 17 |
| 2015 Julio | 52 | 12 | 64 |
| 2015 Junio | 38 | 9 | 47 |
| 2015 Mayo | 85 | 10 | 95 |
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| 2015 Marzo | 77 | 13 | 90 |
| 2015 Febrero | 50 | 15 | 65 |
| 2015 Enero | 55 | 17 | 72 |
| 2014 Diciembre | 68 | 12 | 80 |
| 2014 Noviembre | 44 | 11 | 55 |
| 2014 Octubre | 24 | 4 | 28 |
| 2014 Septiembre | 11 | 2 | 13 |
| 2014 Agosto | 19 | 3 | 22 |
| 2014 Julio | 16 | 8 | 24 |
| 2014 Junio | 29 | 4 | 33 |
| 2014 Mayo | 54 | 4 | 58 |
| 2014 Abril | 36 | 2 | 38 |
| 2014 Marzo | 49 | 8 | 57 |
| 2014 Febrero | 46 | 7 | 53 |
| 2014 Enero | 47 | 9 | 56 |
| 2013 Diciembre | 45 | 6 | 51 |
| 2013 Noviembre | 20 | 10 | 30 |
| 2013 Octubre | 12 | 5 | 17 |
| 2013 Septiembre | 14 | 6 | 20 |
| 2013 Agosto | 8 | 11 | 19 |
| 2013 Julio | 10 | 15 | 25 |
| 2013 Junio | 11 | 1 | 12 |
| 2013 Mayo | 13 | 3 | 16 |
| 2013 Abril | 9 | 8 | 17 |
| 2013 Marzo | 18 | 3 | 21 |
| 2013 Febrero | 34 | 6 | 40 |
| 2013 Enero | 29 | 10 | 39 |
| 2012 Diciembre | 18 | 8 | 26 |
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