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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Presentación de 2 casos y revisión de la literatura" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 2285 "Ancho" => 1632 "Tamanyo" => 393591 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Patient 2. A, Erythematous papule in the gray area of a petal of the flower. B, Accumulation of acid-alcohol-fast bacteria in the area with abscess formation (Kinyoun, original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>400).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "N. Curcó, C. Prat, X. Tarroch, P. 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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. Sucker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bjc.6602529" "Revista" => array:6 [ "tituloSerie" => "Br J Cancer" "fecha" => "2005" "volumen" => "92" "paginaInicial" => "1398" "paginaFinal" => "1405" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15846297" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicenter phase <span class="elsevierStyleSmallCaps">ii</span> trial of high-dose imatinib mesylate in metastatic melanoma: significant toxicity with no clinical efficacy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Wyman" 1 => "M.B. Atkins" 2 => "V. Prieto" 3 => "O. Eton" 4 => "D.F. McDermott" 5 => "F. Hubbard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.21834" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2006" "volumen" => "106" "paginaInicial" => "2005" "paginaFinal" => "2011" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16565971" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Somatic activation of KIT in distinct subtypes of melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.A. Curtin" 1 => "K. Busam" 2 => "D. Pinkel" 3 => "B.C. Bastian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2006.06.2984" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "4340" "paginaFinal" => "4346" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16908931" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0015028203007970" "estado" => "S300" "issn" => "00150282" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Major response to imatinib mesylate in KIT-mutated melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.S. Hodi" 1 => "P. Friedlander" 2 => "C.L. Corless" 3 => "M.C. Heinrich" 4 => "S. Mac Rae" 5 => "A. Kruse" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.14.0707" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "2046" "paginaFinal" => "2051" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18421059" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Lutzky" 1 => "J. Bauer" 2 => "B.C. Bastian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1755-148X.2008.00475.x" "Revista" => array:6 [ "tituloSerie" => "Pigment Cell Melanoma Res" "fecha" => "2008" "volumen" => "21" "paginaInicial" => "492" "paginaFinal" => "499" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18510589" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "KIT as a therapeutic target in metastatic melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.D. Carvajal" 1 => "C.R. Antonescu" 2 => "J.D. Wolchok" 3 => "P.B. Chapman" 4 => "R.A. Roman" 5 => "J. Teitcher" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JAMA" "fecha" => "2011" "volumen" => "3051" "paginaInicial" => "2327" "paginaFinal" => "2334" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Guo" 1 => "L. Si" 2 => "Y. Kong" 3 => "K.T. Flaherty" 4 => "X. Xu" 5 => "Y. Zhu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2010.33.9275" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "2904" "paginaFinal" => "2909" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21690468" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment implications of the emerging molecular classification system for melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E. Romano" 1 => "G.K. Schwartz" 2 => "P.B. Chapman" 3 => "J.D. Wolchock" 4 => "R.D. Carvajal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(10)70274-6" "Revista" => array:6 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2011" "volumen" => "12" "paginaInicial" => "913" "paginaFinal" => "922" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21349766" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010300000009/v1_201304241357/S1578219012002855/v1_201304241357/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010300000009/v1_201304241357/S1578219012002855/v1_201304241357/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219012002855?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 8 | 15 |
| 2024 October | 90 | 36 | 126 |
| 2024 September | 77 | 23 | 100 |
| 2024 August | 113 | 71 | 184 |
| 2024 July | 88 | 26 | 114 |
| 2024 June | 79 | 37 | 116 |
| 2024 May | 73 | 26 | 99 |
| 2024 April | 73 | 30 | 103 |
| 2024 March | 68 | 23 | 91 |
| 2024 February | 56 | 28 | 84 |
| 2024 January | 43 | 32 | 75 |
| 2023 December | 54 | 15 | 69 |
| 2023 November | 75 | 21 | 96 |
| 2023 October | 65 | 32 | 97 |
| 2023 September | 75 | 37 | 112 |
| 2023 August | 53 | 19 | 72 |
| 2023 July | 47 | 34 | 81 |
| 2023 June | 45 | 25 | 70 |
| 2023 May | 50 | 24 | 74 |
| 2023 April | 37 | 17 | 54 |
| 2023 March | 31 | 22 | 53 |
| 2023 February | 32 | 21 | 53 |
| 2023 January | 53 | 30 | 83 |
| 2022 December | 39 | 35 | 74 |
| 2022 November | 32 | 23 | 55 |
| 2022 October | 35 | 22 | 57 |
| 2022 September | 29 | 36 | 65 |
| 2022 August | 32 | 20 | 52 |
| 2022 July | 31 | 37 | 68 |
| 2022 June | 22 | 21 | 43 |
| 2022 May | 45 | 29 | 74 |
| 2022 April | 34 | 28 | 62 |
| 2022 March | 34 | 60 | 94 |
| 2022 February | 40 | 35 | 75 |
| 2022 January | 27 | 29 | 56 |
| 2021 December | 35 | 36 | 71 |
| 2021 November | 57 | 42 | 99 |
| 2021 October | 92 | 53 | 145 |
| 2021 September | 30 | 41 | 71 |
| 2021 August | 33 | 34 | 67 |
| 2021 July | 30 | 30 | 60 |
| 2021 June | 29 | 22 | 51 |
| 2021 May | 30 | 25 | 55 |
| 2021 April | 35 | 53 | 88 |
| 2021 March | 37 | 34 | 71 |
| 2021 February | 50 | 19 | 69 |
| 2021 January | 25 | 17 | 42 |
| 2020 December | 30 | 12 | 42 |
| 2020 November | 27 | 13 | 40 |
| 2020 October | 25 | 8 | 33 |
| 2020 September | 25 | 11 | 36 |
| 2020 August | 21 | 16 | 37 |
| 2020 July | 32 | 11 | 43 |
| 2020 June | 41 | 29 | 70 |
| 2020 May | 35 | 23 | 58 |
| 2020 April | 45 | 22 | 67 |
| 2020 March | 35 | 21 | 56 |
| 2020 February | 6 | 10 | 16 |
| 2020 January | 4 | 9 | 13 |
| 2019 December | 8 | 0 | 8 |
| 2019 November | 4 | 0 | 4 |
| 2019 October | 0 | 3 | 3 |
| 2019 September | 8 | 2 | 10 |
| 2019 August | 4 | 10 | 14 |
| 2019 July | 4 | 10 | 14 |
| 2019 June | 6 | 23 | 29 |
| 2019 May | 4 | 33 | 37 |
| 2019 April | 2 | 24 | 26 |
| 2019 March | 2 | 6 | 8 |
| 2019 February | 2 | 3 | 5 |
| 2019 January | 2 | 3 | 5 |
| 2018 December | 2 | 7 | 9 |
| 2018 November | 2 | 0 | 2 |
| 2018 October | 1 | 0 | 1 |
| 2018 September | 4 | 0 | 4 |
| 2018 March | 5 | 2 | 7 |
| 2018 February | 33 | 6 | 39 |
| 2018 January | 32 | 7 | 39 |
| 2017 December | 41 | 5 | 46 |
| 2017 November | 20 | 4 | 24 |
| 2017 October | 35 | 7 | 42 |
| 2017 September | 44 | 7 | 51 |
| 2017 August | 80 | 8 | 88 |
| 2017 July | 65 | 9 | 74 |
| 2017 June | 40 | 6 | 46 |
| 2017 May | 30 | 3 | 33 |
| 2017 April | 33 | 6 | 39 |
| 2017 March | 27 | 12 | 39 |
| 2017 February | 26 | 7 | 33 |
| 2017 January | 20 | 3 | 23 |
| 2016 December | 38 | 6 | 44 |
| 2016 November | 53 | 7 | 60 |
| 2016 October | 58 | 7 | 65 |
| 2016 September | 51 | 13 | 64 |
| 2016 August | 51 | 4 | 55 |
| 2016 July | 44 | 8 | 52 |
| 2016 June | 15 | 12 | 27 |
| 2016 May | 10 | 9 | 19 |
| 2016 April | 8 | 6 | 14 |
| 2016 March | 23 | 1 | 24 |
| 2016 February | 11 | 9 | 20 |
| 2016 January | 8 | 10 | 18 |
| 2015 December | 10 | 7 | 17 |
| 2015 November | 25 | 1 | 26 |
| 2015 October | 17 | 1 | 18 |
| 2015 September | 7 | 7 | 14 |
| 2015 August | 15 | 2 | 17 |
| 2015 July | 52 | 12 | 64 |
| 2015 June | 38 | 9 | 47 |
| 2015 May | 85 | 10 | 95 |
| 2015 April | 73 | 10 | 83 |
| 2015 March | 77 | 13 | 90 |
| 2015 February | 50 | 15 | 65 |
| 2015 January | 55 | 17 | 72 |
| 2014 December | 68 | 12 | 80 |
| 2014 November | 44 | 11 | 55 |
| 2014 October | 24 | 4 | 28 |
| 2014 September | 11 | 2 | 13 |
| 2014 August | 19 | 3 | 22 |
| 2014 July | 16 | 8 | 24 |
| 2014 June | 29 | 4 | 33 |
| 2014 May | 54 | 4 | 58 |
| 2014 April | 36 | 2 | 38 |
| 2014 March | 49 | 8 | 57 |
| 2014 February | 46 | 7 | 53 |
| 2014 January | 47 | 9 | 56 |
| 2013 December | 45 | 6 | 51 |
| 2013 November | 20 | 10 | 30 |
| 2013 October | 12 | 5 | 17 |
| 2013 September | 14 | 6 | 20 |
| 2013 August | 8 | 11 | 19 |
| 2013 July | 10 | 15 | 25 |
| 2013 June | 11 | 1 | 12 |
| 2013 May | 13 | 3 | 16 |
| 2013 April | 9 | 8 | 17 |
| 2013 March | 18 | 3 | 21 |
| 2013 February | 34 | 6 | 40 |
| 2013 January | 29 | 10 | 39 |
| 2012 December | 18 | 8 | 26 |
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