Melanoma in Solid Organ Transplant Recipients | Actas Dermo-Sifiliográficas

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Belinchón, M. Velasco, M. Ara-Martín, S. Armesto Alonso, O. Baniandrés Rodríguez, L. Ferrándiz Pulido, M. García-Bustinduy, J.A. Martínez-López, N. Martínez Sánchez, A. Pérez Ferriols, E. Pérez Pascual, R. Rivera Díaz, R. Ruiz-Villaverde, R. Taberner Ferrer, A. Vicente Villa, J.M. Carrascosa" "autores" => array:16 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Belinchón" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Velasco" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Ara-Martín" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Armesto Alonso" ] 4 => array:2 [ "nombre" => "O." "apellidos" => "Baniandrés Rodríguez" ] 5 => array:2 [ "nombre" => "L." "apellidos" => "Ferrándiz Pulido" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "García-Bustinduy" ] 7 => array:2 [ "nombre" => "J.A." "apellidos" => "Martínez-López" ] 8 => array:2 [ "nombre" => "N." "apellidos" => "Martínez Sánchez" ] 9 => array:2 [ "nombre" => "A." 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Métodos y paradigma: tratamiento biológico de la psoriasis" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1401 "Ancho" => 2341 "Tamanyo" => 306399 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Example of an NMA network diagram for PASI 90 results at 12 or 16 weeks of biologic treatment for psoriasis.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> The size of the nodes represents the sample size of the interventions and the widths of the lines the number of studies included. Abbreviations: ADA, adalimumab; APR, apremilast; BIW, twice weekly, BRO, brodalumab; ENT, etanercept; GUS, guselkumab; IFX, infliximab; IXE, ixekizumab; PBO, placebo; QW, once a week; Q2W, every 2 weeks; SEC, secukinumab; UST, ustekinumab. Modified from Cameron et al.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Puig" "autores" => array:1 [ 0 => array:2 [ "nombre" => "L." 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González-Cruz, C. Ferrándiz-Pulido, V. García-Patos Briones" "autores" => array:3 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "González-Cruz" "email" => array:1 [ 0 => "carlos.gonzalez.cruz@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Ferrándiz-Pulido" ] 2 => array:2 [ "nombre" => "V." "apellidos" => "García-Patos Briones" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Universitari Vall d’Hebron, Facultad de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Melanoma en pacientes receptores de un trasplante de órgano sólido" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 1085 "Ancho" => 1310 "Tamanyo" => 182305 ] ] ] ] "textoCompleto" => "IntroductionApproximately 120 000 solid organ transplants (SOTs) are performed worldwide every year.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Survival in this setting has improved with time thanks to advances in surgical techniques and better immunosuppressive regimens.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Chronic immunosuppression increases the risk of malignancy, and in SOT recipients 40% to 50% of all malignancies are nonmelanoma skin cancers.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> In the general population, melanoma accounts for up to 80% of skin cancer deaths.<a class="elsevierStyleCrossRefs" href="#bib0020">4,5</a> Early diagnosis significantly reduces melanoma-specific mortality.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Because melanoma is a highly immunogenic tumor, it would be expected to be more common and more aggressive in SOT recipients due to their immunosuppressed state.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a> Melanoma accounts for 6.2% of all malignancies in adult SOT recipients and for 15% of those in pediatric recipients.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> In this review, we analyze the different clinical scenarios in which SOT recipients can develop melanoma and describe the corresponding clinical and epidemiologic characteristics, treatments, and prognosis.Search Strategy and Selection of ArticlesThe PubMed database was used to search for articles whose title or abstract contained combinations of the following MESH terms: “melanoma”, “organ transplantation”, “transplantation”, “nivolumab”, “pembrolizumab”, “ipilimumab”, “dabrafenib”, “vemurafenib”, “photocarcinogenesis”, and “voriconazole”.A hand search was also made of the articles selected to identify additional studies.Clinical ScenariosThree clinical scenarios related to the development of melanoma in SOT recipients are generally recognized: melanoma in patients with a pretransplant history of melanoma, de novo melanoma after a transplant, and melanoma of donor origin.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> In our experience, there is a fourth scenario in which an SOT recipient was not diagnosed or treated for melanoma until seen by a dermatologist after the transplantation.History of Pretransplant MelanomaUnfortunately for anyone whose survival depends on an SOT, a history of melanoma is a classic contraindication for SOT.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> There is little evidence on whether SOT recipients with a history of melanoma have an increased risk of recurrence or progression after transplantation.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> The authors of a series of 31 SOT recipients with a past history of melanoma reported an alarming recurrence rate of 19% and recommended leaving a period of at least 5 years between melanoma treatment and SOT.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The authors, however, did not provide details of Breslow depth, the most important prognostic factor in melanoma.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> These high recurrence rates were not confirmed by more recent work.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Dapprich et al.,<a class="elsevierStyleCrossRef" href="#bib0070">14</a> in a series of 12 SOT recipients previously treated for melanoma (mean Breslow depth, 0.35 mm), found no cases of posttransplant recurrence or melanoma-specific mortality. Similarly, the European Skin Care in Organ Transplant Patients, Europe (SCOPE) group reported no melanoma recurrences or deaths after SOT in a series of 9 recipients with a history of melanoma.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Brewer et al.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> found no significant differences in recurrences (after a period of 10.5 years) or metastasis rates in 59 SOT recipients with pretransplant melanoma. It should be noted, however, that Breslow depth measurements were available for just 17 cases.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> It should also be noted that the results of these studies were probably affected by selection bias, as patients with a history of melanoma selected for SOT are likely to have a better prognosis (lower Breslow depth) and to have been free of disease for longer. Another study showed that 336 SOT recipients with a history of melanoma had a higher risk of posttransplant melanoma-specific mortality (hazard ratio [HR], 27; 95% CI, 11–64; P < .0001), overall mortality, and incident melanoma than recipients without a history of melanoma.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Despite these alarming rates, the authors explained that because melanoma-specific deaths are, in absolute terms, rare among SOT recipients, the difference in 5-year mortality due to melanoma between recipients with and without pretransplant melanoma was just 1.2%. They were of the opinion that these data would probably not justify a change in patient selection strategies, although they would indicate the need for close dermatologic follow-up.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Based on these studies and the melanoma survival curves in the American Joint Commission on Cancer (AJCC) Cancer Staging Manual (7th Edition), the International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) drew up a series of recommendations on the wait time between melanoma treatment and transplant (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Based on a 5-year posttransplant survival rate of 60% and the AJCC 7th Edition survival curves, the authors proposed that patients with melanoma stages Ia, Ib, IIa, IIb, or IIIa would be candidates for SOT. They also considered that the point at which the survival curve for each stage flattened was the minimum wait time between a diagnosis of melanoma and SOT. Sentinel lymph node biopsy results are particularly useful when evaluating the candidacy of patients with a history of melanoma for SOT.<a class="elsevierStyleCrossRef" href="#bib0030">6</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>De Novo Melanoma After SOTIncidence StudiesSOT recipients have a 2- to 8-fold increased risk of developing melanoma compared with members of the general population<a class="elsevierStyleCrossRefs" href="#bib0090">18–24</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The higher number of dermatology examinations in SOT recipients has probably led to increased awareness of the risk among other health care professionals and consequently more diagnoses. The risk of melanoma may be 17.2 times higher in African American SOT recipients.<a class="elsevierStyleCrossRef" href="#bib0125">25</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>While SOT recipients have a higher risk of melanoma than immunocompetent people, they have an even higher risk of squamous cell carcinoma (50- to- 250-fold increased risk) and basal cell carcinoma (10-fold increased risk).<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Risk FactorsMelanoma is a highly immunogenic tumor and responds very well to new immunotherapies.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Like other tumors, however, it has developed mechanisms to evade immune surveillance, enabling it to spread.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In immunosuppressed patients, one would expect melanoma to have an even higher incidence and greater metastatic potential.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Apart from immunosuppression itself, other factors specific to each immunosuppressive agent may contribute to the higher incidence and faster progression of melanoma in immunosuppressed individuals,<a class="elsevierStyleCrossRef" href="#bib0040">8</a> as occurs with nonmelanoma skin cancer (NMSC). There have even been reports of good response and outcomes in patients with melanoma following withdrawal of immunosuppressants.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Calcineurin inhibitors and azathioprine increase the risk of skin cancer by reducing immune surveillance, increasing vascularization and tumor invasive capacity, and enhancing DNA damage (e.g., after exposure to UV-B radiation) or inhibiting its repair.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> Replacing classic immunosuppressive agents with a mammalian target of rapamycin (mTOR) inhibitor, which has antiproliferative properties, is known to be effective for the secondary prevention of NMSC.<a class="elsevierStyleCrossRefs" href="#bib0010">2,27,28</a> Very little data, however, are available on the benefits of switching from an immunosuppressive regimen to an mTOR inhibitor in melanoma. The current evidence is based on animal studies and the CONVERT trial, which showed a lower incidence of melanoma in kidney transplant recipients who received sirolimus than in those who did not, although the incidence was very low in both groups.<a class="elsevierStyleCrossRefs" href="#bib0145">29,30</a> It is noteworthy that a meta-analysis of data from 5876 patients from 21 randomized controlled trials showed that the use of sirolimus in SOT recipients was associated with a 43% increased risk of death (HR, 1.43; 95% CI, 1.21–1.71; P < .001) in patients treated with high doses. The main causes of death were cardiovascular or infectious disease. These data, together with a high incidence of adverse effects (many of which increase cardiovascular risk), are limiting factors for the use of sirolimus as a first-line immunosuppressive treatment.<a class="elsevierStyleCrossRef" href="#bib0140">28</a>Vajdic et al.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> showed that the risk of melanoma in SOT recipients peaked in the second year posttransplant, and then decreased linearly. Additional risk factors were age and induction immunosuppression with monoclonal antibodies. Female sex, non-Caucasian race, and a longer time since SOT, by contrast, were protective factors.Several studies have reported a possible association between a higher number of nevi in SOT recipients and duration of immunosuppressive therapy. A high number of nevi is a risk factor for melanoma.<a class="elsevierStyleCrossRefs" href="#bib0030">6,31</a> In a Swedish series, 63% of melanomas in SOT recipients were histologically associated with the presence of a dysplastic nevus.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> In another 2 series, just 33% to 36% of melanomas in SOT recipients arose in a previous nevus.<a class="elsevierStyleCrossRefs" href="#bib0090">18,24</a>A number of studies on melanoma in SOT recipients have mentioned that a past history of NMSC is common.<a class="elsevierStyleCrossRefs" href="#bib0020">4,24</a>Voriconazole is used to treat invasive fungal infections in SOT recipients, particularly following a lung transplant. Its use is considered an independent risk factor for skin cancer, in particular squamous cell carcinoma. Apart from its photosensitizing properties, voriconazole appears to enhance DNA damage when exposed to UV radiation and to inhibit its repair. Several articles thus have pointed to a possible role for voriconazole in the development of melanoma. Discontinuation of this drug is recommended in SOT recipients who develop melanoma or squamous cell carcinoma.<a class="elsevierStyleCrossRefs" href="#bib0015">3,33</a>Disease Course and PrognosisStage at diagnosis is one of the main prognostic factors in patients with melanoma, whether they are immunosuppressed or immunocompetent.<a class="elsevierStyleCrossRefs" href="#bib0085">17,34</a> Breslow depth is the most significant histologic prognostic factor.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> The 2008 multicenter SCOPE study comparing outcomes between 95 SOT recipients who developed melanoma posttransplant and a cohort of immunocompetent patients with melanoma found no significant differences in mortality rates among patients with stage T1 or T2 disease. Mortality in patients with stage T3 or T4 disease, however, was significantly higher in SOT recipients (HR, 11.49; 95% CI, 3.59–36.82). Another study found that SOT recipients had more advanced melanoma at diagnosis than members of the general population (OR for stages III-IV, 4.2; 95% CI, 1.6–10.8; P = .003).<a class="elsevierStyleCrossRef" href="#bib0160">32</a> The risk of melanoma-specific mortality was also higher in SOT recipients (adjusted HR, 3; 95% CI, 1.7–5.3; P < .001). Finally, a Canadian study of 51 patients with posttransplant melanoma also showed a higher risk of melanoma-specific mortality compared with immunocompetent individuals (adjusted HR, 1.93; 95% CI, 1.03–3.63; P = .04).<a class="elsevierStyleCrossRef" href="#bib0175">35</a> All-cause mortality was also higher (2 to 8 times depending on melanoma stage) While it is true that changes to the immunosuppressive regimen could explain some of the increase in mortality, the authors did not believe that these changes made a significant contribution.<a class="elsevierStyleCrossRef" href="#bib0175">35</a>Clinical and Histologic CharacteristicsBased on findings from the main series of posttransplant melanoma to date, the clinical and histologic characteristics of the tumors appear to be indistinguishable from those observed in immunocompetent individuals.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The mean age at diagnosis was 54 years (range, 26–77 years) and there a predominance of male patients (66%), supporting previous findings.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Mean time from the first transplant to onset of melanoma was 8.7 years (range, 0.1–24.9 years), which is somewhat shorter than the mean of 12 years reported by Brocard et al.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> Overall, 95% of patients had a Fitzpatrick skin type I-III and, contrasting with reports for the general population, there were no sex-related differences in tumor location. Park et al.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> found that SOT recipients were more likely to have melanomas on the head and neck than immunocompetent patients. In another study of melanoma in SOT recipients, the predominant locations were the trunk (51%) and the head and neck (26%) for men and the trunk (50%) and the extremities (42%) for women. The most common site for melanoma in women from the general population is the lower extremities (36%).<a class="elsevierStyleCrossRef" href="#bib0160">32</a>In the series by Brocard et al.,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> 2 (10%) of 20 SOT recipients with melanoma had mucosal melanoma.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> In our (unpublished) series of 8 patients, 2 (25%) had melanoma involving the oral mucosa. These rates of mucosal melanoma are higher than those reported for the general population (1%–2%).<a class="elsevierStyleCrossRef" href="#bib0185">37</a> Further studies, however, are needed to confirm these data, but they might indicate differential etiologic or pathogenic mechanisms for melanoma in the context of SOT.Although all histologic subtypes of melanoma were represented in the SCOPE series, superficial spreading melanoma was the most common form of invasive melanoma, supporting findings for the general population and other series.<a class="elsevierStyleCrossRefs" href="#bib0020">4,24,35</a> The mean Breslow depth observed in invasive melanomas was 1.5 to 2 mm.<a class="elsevierStyleCrossRefs" href="#bib0020">4,32</a> In the series described by Krynitz et al.,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> 82% of melanomas diagnosed in SOT recipients had a Clark level of III to V compared with 66% of those in immunocompetent patients (OR, 2.2; 95% CI, 1.01–4.7). The authors also observed a less prominent lymphocytic infiltrate in SOT recipients who died of melanoma and suggested that this feature might be of prognostic value. It is probably a reflection of the underlying iatrogenic immunosuppression.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>Management and TreatmentThe initial treatment of melanoma in SOT recipients should be no different to that in immunocompetent patients: simple excision followed by widening of margins depending on Breslow depth and, where necessary, SLN biopsy. Proper staging is essential for correct management. The worse the prognosis, the more aggressive the approach, and consequently, the greater the risk to the survival of the transplanted organ.<a class="elsevierStyleCrossRefs" href="#bib0030">6,38</a>Immunosuppressive therapy should be revised in SOT recipients following a diagnosis of melanoma. Options include drug withdrawal, reduction of drug blood levels, and switching to another drug with antiproliferative and antiangiogenic activity to reduce the risk of tumor spread. It is important to strike a balance between a level of immunosuppression that will not favor the spread of the tumor and one that will not result in rejection of the transplanted organ. Important factors to bear in mind are tumor stage and prognosis, the type of organ transplanted and the possibility of artificially reproducing its function (e.g., dialysis in the case of kidneys), and the patient’s general health. The ITSCC recommendations on the level of reduction of immunosuppression following a diagnosis of melanoma or NMSC are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.<a class="elsevierStyleCrossRefs" href="#bib0030">6,39</a> Despite the limited evidence available for melanoma, it would seem reasonable to consider an immunosuppressive regimen involving an mTOR inhibitor where possible.<a class="elsevierStyleCrossRef" href="#bib0140">28</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Survival in patients with advanced melanoma, and metastatic melanoma in particular, is very low.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> Targeted therapies and immunotherapies have revolutionized the treatment of melanoma, achieving long survival times in certain patients with disseminated disease.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> Evidence, however, is lacking on the safety and efficacy of these treatments in SOT recipients, as these patients have been systematically excluded from the clinical trials.42 Some studies have shown acceptable responses to combined BRAF and MEK inhibition in SOT recipients with advanced BRAF-mutant melanoma.<a class="elsevierStyleCrossRefs" href="#bib0200">40,43</a> Nonetheless, several studies have indicated that BRAF mutations are less common in melanomas in SOT recipients.<a class="elsevierStyleCrossRefs" href="#bib0180">36,44</a> In our unpublished series of SOT recipients with melanoma, just 29% had a BRAF mutation, compared with 54% of patients with melanoma from the general population.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> It is possible that both immunosuppression and immunosuppressive therapy might have a differential effect on the pathogenesis of melanoma in SOT recipients.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> Brocard et al.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> characterized the mutational profile of melanoma (BRAF, c-KIT, and NRAS genes) in 20 SOT recipients.<a class="elsevierStyleCrossRef" href="#bib0180">36</a>BRAF and NRAS mutations were detected in 40% and 23% of cases, respectively. No c-KIT mutations were found. One limitation of the study, however, was that a significant number of samples were inadequate for molecular analysis.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> More studies are therefore needed to investigate differences in melanoma mutations between SOT recipients and immunocompetent patients, as this information would help identify potential therapeutic targets.Immune checkpoint inhibitors (ICIs) should be considered in SOT recipients with advanced non-BRAF-mutant melanoma. The potential benefits and increased risk of organ rejection must be carefully weighed up, and it is very difficult to find the exact point at which this balance is maintained.<a class="elsevierStyleCrossRef" href="#bib0230">46</a> The decision should be taken by a multidisciplinary committee including members of the transplant team, oncologists, and dermatologists.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> It is also essential to discuss the matter with the patient and involve him or her in the decision. Evidence on the use of ICIs in SOT recipients is based on isolated clinical reports and small series.<a class="elsevierStyleCrossRefs" href="#bib0235">47–60</a> Abdel-Wahab et al.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> recently published the findings of the largest series of SOT recipients treated with ICIs to date at the University of Texas MD Anderson Cancer Center. They also performed the first systematic review of the literature on this subject.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> They analyzed organ rejection, survival, and tumor response in 39 SOT recipients with melanoma (metastatic in 62% of cases) treated with ICIs. Allograft rejection occurred in 41% of patients and the median time to rejection was 21 days after ICI initiation; 81% of the patients (10 kidney transplant recipients and 3 liver transplant recipients) experienced graft loss despite treatment (increased immunosuppression and ICI discontinuation). Rejection rates were found to be similar with anti-cytoxic T-lymphocyte antigen 4 and anti-programmed death 1 antibodies, contradicting previous findings suggesting that the former might be safer.<a class="elsevierStyleCrossRef" href="#bib0280">56</a> Of the 22 SOT recipients with metastatic melanoma, 64% experienced tumor progression, while 32% showed a partial or complete response. In a recent study, Hurkmans et al.<a class="elsevierStyleCrossRef" href="#bib0305">61</a> proposed that donor-derived cell-free DNA might be a sensitive biomarker for the early detection of transplant rejection in SOT recipients treated with ICIs.There has been a report of an immunosuppressive regimen being successfully used to preserve renal-allograft function in a recipient with metastatic adenocarcinoma of the duodenum due to receive treatment with nivolumab<a class="elsevierStyleCrossRef" href="#bib0270">54</a> (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Sunshine et al.<a class="elsevierStyleCrossRef" href="#bib0310">62</a> successfully treated a kidney transplant recipient with melanoma and in-transit metastasis with a combination of topical imiquimod 5% and talimogene laherparepvec (T-VEC) injections. No signs of rejection were observed.Based on the literature reviewed, our proposed approach to treating de nova melanoma in an SOT recipient is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Dermatologic Follow-up of SOT RecipientsSOT recipients with advanced melanoma have a significantly worse prognosis than members of the general population with advanced melanoma, and they also face a very high risk of organ rejection after ICI therapy. Close dermatologic surveillance is thus necessary to ensure that any melanoma that may occur is diagnosed early.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Frequency of follow-up should be determined by individual risk, with particular attention paid to patients with a dysplastic nevus or a personal or family history of melanoma.<a class="elsevierStyleCrossRefs" href="#bib0030">6,24</a> Follow-up with dermoscopy, in addition to body mapping and reflectance confocal microscopy, is useful for improving the ratio of melanomas to benign skin lesions excised.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Patients should be taught how to recognize suspicious lesions or recurrent tumors at previous excision sites and cautioned to avoid recreational sun exposure and to continue to use sun-protection and other measures that minimize sun exposure.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Strict sun protection measures must be accompanied by monitoring of vitamin D levels and any deficiencies corrected through supplementation.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> Finally, we believe that SOT candidates should be examined by a dermatologist before undergoing a transplant to rule out melanoma. Immunosuppression—and hence risk of tumor progression—is highest during the peritransplant period (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Donor-Derived MelanomaMelanoma can be transmitted to an SOT recipient via an organ donated by a person with melanoma. This could happen in the case of occult melanomas, which would then spread in an immunosuppressed transplant recipient. It could also happen in the case of donors (especially young donors) who died of metastatic melanoma of the brain misdiagnosed as a brain hemorrhage or a primary brain tumor. The estimated risk of occult donor malignancy is 1.3%, and the risk of transmission to a recipient, 0.2%.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Melanoma is the donor-derived tumor with the highest risk of metastasis. One review analyzed donor-to-recipient transmission of melanoma in 7 donors whose organs were provided to 44 recipients.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Thirty-five recipients (80%) developed melanoma within 3 to 24 months of the transplant, and 33 (75%) died as a result.<a class="elsevierStyleCrossRefs" href="#bib0030">6,11</a> These data indicate that anyone with a history of melanoma should not be ruled out as an organ donor. In addition, potential donors should be given a full-body examination to search for lesions or scars suspicious for melanoma.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a>The little evidence available on the treatment of donor-derived melanoma suggests that the best approach may be to excise the transplanted organ together with any resectable metastases and to discontinue immunosuppressive therapy. This approach, however, is only possible in the case of kidney recipients. Recipients of other vital organs face a grim prognosis unless there is another organ available.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Molecular biology techniques such as fluorescent in situ hybridization, polymerase chain reaction assays, and tandem repeat sequencing can be used to clarify doubts regarding whether metastatic melanoma detected in an SOT recipient is de novo or donor derived. This information has important prognostic and therapeutic implications. In addition, if the tumor is donor derived, any other organs donated by the donor, regardless of the recipient, should also be removed.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>ConclusionsAlthough evidence on the management of melanoma in SOT recipients is scarce and based on case series, it is known that in early-stage melanoma, prognosis in SOT recipients is similar to that of the general population. Dermatologists thus have an essential role in posttransplant follow-up as they are in a position to diagnose thin melanomas. Much work remains regarding the management of advanced melanoma in SOT recipients, who currently face a worse prognosis than immunocompetent patients with metastatic disease. Because SOT recipients have been excluded from clinical trials of ICIs, treatment decisions should be reached by a multidisciplinary committee, with the informed consent of the patient and knowing that there is a high risk of acute rejection. Further research is also necessary on the role of adjuvant therapy in SOT recipients as it has been demonstrated to improve survival in immunocompetent patients.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1473836" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1473834" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1341922" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1473835" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0015" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1341921" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:2 [ "identificador" => "sec0010" "titulo" => "Search Strategy and Selection of Articles" ] 7 => array:3 [ "identificador" => "sec0015" "titulo" => "Clinical Scenarios" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "History of Pretransplant Melanoma" ] 1 => array:3 [ "identificador" => "sec0025" "titulo" => "De Novo Melanoma After SOT" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Incidence Studies" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Risk Factors" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Disease Course and Prognosis" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Clinical and Histologic Characteristics" ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "Management and Treatment" ] ] ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Dermatologic Follow-up of SOT Recipients" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Donor-Derived Melanoma" ] ] ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-05-29" "fechaAceptado" => "2020-11-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1341922" "palabras" => array:8 [ 0 => "Melanoma" 1 => "Skin cancer" 2 => "Solid organ transplant" 3 => "Nivolumab" 4 => "Pembrolizumab" 5 => "Ipilimumab" 6 => "Dabrafenib" 7 => "Vemurafenib" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1341921" "palabras" => array:8 [ 0 => "Melanoma" 1 => "Cáncer cutáneo" 2 => "Trasplante de órgano sólido" 3 => "Nivolumab" 4 => "Pembrolizumab" 5 => "Ipilimumab" 6 => "Dabrafenib" 7 => "Vemurafenib" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "In this review, we analyze the 3 clinical scenarios related to the development of melanoma in solid organ transplant recipients: melanoma in patients with a history of the tumor prior to a transplant, de novo melanoma following a transplant, and melanoma of donor origin. The main factors to consider in organ-transplant candidates with a history of melanoma are tumor stage, presence or absence of residual disease, and time from diagnosis to transplantation. Solid organ transplant recipients have a greater risk of melanoma than immunocompetent individuals. Mortality is also higher in this population, especially in patients with advanced melanoma, as treatment is especially challenging. Clinical history and physical examination provide the most useful information for preventing donor-to-recipient transmission of melanoma. Donor-derived melanoma has a very poor prognosis." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El melanoma en receptores de un trasplante de órgano sólido (RTOS) puede aparecer en tres situaciones clínicas, objeto de esta revisión: pacientes con historia de melanoma previa al trasplante, pacientes que desarrollan el melanoma posteriormente al trasplante y pacientes con melanoma procedente del donante. Los factores más relevantes a considerar en pacientes con antecedentes de melanoma candidatos a un trasplante son el estadio del tumor, la presencia o no de enfermedad residual y el periodo entre el diagnóstico y el trasplante. Los RTOS tienen mayor riesgo de padecer un melanoma que la población inmunocompetente. La mortalidad por melanoma es también mayor, especialmente en aquellos con estadios avanzados, que suponen un verdadero reto terapéutico. Finalmente, la historia clínica y la exploración física del donante son las herramientas más útiles para evitar la transmisión de un melanoma al receptor, situación con pronóstico infausto." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: González-Cruz C, Ferrándiz-Pulido C, García-Patos Briones V. Melanoma en pacientes receptores de un trasplante de órgano sólido. Actas Dermosifiliogr. 2021;112:216–224." ] ] "multimedia" => array:7 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3096 "Ancho" => 2183 "Tamanyo" => 350829 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Proposed approach for treating de novo melanoma following SOT based on the literature reviewed. CTLA-4 indicates cytotoxic T-lymphocyte-associated protein 4; mTOR, mammalian target of rapamycin; PD-1, programmed death 1; SOT, solid organ transplant; T-VEC, talimogene laherparepvec." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 624 "Ancho" => 755 "Tamanyo" => 139541 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Melanoma diagnosed 4 months after a solid organ transplant, located just a few centimeters from the laparotomy scar, highlighting the importance of a full dermatologic examination before the procedure." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Abbreviations: AJCC CSM, American Joint Commission on Cancer Cancer Staging Manual; ITSCC, International Transplant Skin Cancer Collaborative; SOT, solid organ transplant.Source: Adapted from Zwald et al.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>" "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Stage (AJCC CSM, 7th Edition) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recommended Time to SOT \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage 0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No need to defer SOT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage Ia \t\t\t\t\t\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 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage Ib \t\t\t\t\t\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 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage IIa, IIb, IIIa \t\t\t\t\t\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">5-10 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stages IIc, IIIb, 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">Not candidates for SOT<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2535814.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Consider on a case-by-case basis in patients who have survived for more than 10–15 years." ] ] ] "descripcion" => array:1 [ "en" => "Minimum Time From Melanoma Treatment to SOT According to the ITSCC." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviation: SOT, solid organ transplant." "tablatextoimagen" => array:2 [ 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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No. of SOT Recipients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study Location \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidence Rate (Annual Cases per 100 000 Population) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Garret et al.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10649 \t\t\t\t\t\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">United States \t\t\t\t\t\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">75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Brown et al.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">861 \t\t\t\t\t\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">London, United Kingdom \t\t\t\t\t\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">82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vajdic et al.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8152 \t\t\t\t\t\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">Australia \t\t\t\t\t\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">134 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2535817.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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study Location \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidence Rate (Annual Cases per 100 000 Population) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tejera-Vaquerizo et al.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Meta-analysis \t\t\t\t\t\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">Spain \t\t\t\t\t\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">8.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2535815.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Studies of the Incidence of Melanoma in SOT Recipients and Immunocompetent Individuals in Spain." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: AJCC, American Joint Commission on Cancer (Cancer Staging Manual); ITSCC, International Transplant Skin Cancer Collaborative.Source: Adapted from Zwald et al.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>" "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Leve of Reduction of Immunosuppression</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Transplanted Organ</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AJCC Stage (7th Edition) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Kidney \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Heart \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Liver \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage Ia \t\t\t\t\t\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">Mild \t\t\t\t\t\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">None \t\t\t\t\t\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">Mild \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage Ib \t\t\t\t\t\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">Mild \t\t\t\t\t\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">Mild \t\t\t\t\t\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">Mild \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage IIa \t\t\t\t\t\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">Moderate \t\t\t\t\t\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">Mild \t\t\t\t\t\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">Moderate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stage IIc/III \t\t\t\t\t\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">Severe \t\t\t\t\t\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">Moderate \t\t\t\t\t\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">Moderate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">Severe \t\t\t\t\t\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">Severe \t\t\t\t\t\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">Severe \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2535816.png" ] ] ] ] "descripcion" => array:1 [ "en" => "ITSCC and SCOPE Recommendations on the Level of Reduction of Immunosuppression for Solid Organ Transplant Recipients With Nonmelanoma Skin Cancer or Melanoma." ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Source: Adapted from Barnett et al.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>" "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Timing in Relation to Treatment Initiation \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment: Dose \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 wk before \t\t\t\t\t\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">Prednisone: 40 mg/d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">During treatment \t\t\t\t\t\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">Prednisone: 20 mg/d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" 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">Sirolimus (target levels): 4–6 ng/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 wk after \t\t\t\t\t\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">Prednisone: 20 mg/d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">> 2 wk and ≤ 6 mo \t\t\t\t\t\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">Prednisone: 10 mg/d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" 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">Sirolimus (target levels): 10–12 ng/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">> 6 mo after treatment \t\t\t\t\t\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">Prednisone: progressive reduction to 5 mg/d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" 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">Sirolimus (target levels): 10–12 ng/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2535813.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Immunosuppressive Regimen for Kidney Transplant Recipients Who Are Candidates for Anti-Programmed Death-1 Antibodies." ] ] 6 => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 1085 "Ancho" => 1310 "Tamanyo" => 182305 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:62 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of keratinocyte carcinomas after organ transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.M. 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Melanoma in Solid Organ Transplant Recipients

Melanoma en pacientes receptores de un trasplante de órgano sólido

C. González-Cruz

Corresponding author

carlos.gonzalez.cruz@hotmail.com

Corresponding author.

, C. Ferrándiz-Pulido, V. García-Patos Briones

Servicio de Dermatología, Hospital Universitari Vall d’Hebron, Facultad de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Approximately 120&#8239;000 solid organ transplants &#40;SOTs&#41; are performed worldwide every year&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Survival in this setting has improved with time thanks to advances in surgical techniques and better immunosuppressive regimens&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Chronic immunosuppression increases the risk of malignancy&#44; and in SOT recipients 40&#37; to 50&#37; of all malignancies are nonmelanoma skin cancers&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In the general population&#44; melanoma accounts for up to 80&#37; of skin cancer deaths&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> Early diagnosis significantly reduces melanoma-specific mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Because melanoma is a highly immunogenic tumor&#44; it would be expected to be more common and more aggressive in SOT recipients due to their immunosuppressed state&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Melanoma accounts for 6&#46;2&#37; of all malignancies in adult SOT recipients and for 15&#37; of those in pediatric recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In this review&#44; we analyze the different clinical scenarios in which SOT recipients can develop melanoma and describe the corresponding clinical and epidemiologic characteristics&#44; treatments&#44; and prognosis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Search Strategy and Selection of Articles</span><p id="par0010" class="elsevierStylePara elsevierViewall">The PubMed database was used to search for articles whose title or abstract contained combinations of the following MESH terms&#58; <span class="elsevierStyleBold">&#8220;</span>melanoma&#8221;&#44; &#8220;organ transplantation&#8221;&#44; &#8220;transplantation&#8221;&#44; &#8220;nivolumab&#8221;&#44; &#8220;pembrolizumab&#8221;&#44; &#8220;ipilimumab&#8221;&#44; &#8220;dabrafenib&#8221;&#44; &#8220;vemurafenib&#8221;&#44; &#8220;photocarcinogenesis&#8221;&#44; and &#8220;voriconazole&#8221;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A hand search was also made of the articles selected to identify additional studies&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical Scenarios</span><p id="par0020" class="elsevierStylePara elsevierViewall">Three clinical scenarios related to the development of melanoma in SOT recipients are generally recognized&#58; melanoma in patients with a pretransplant history of melanoma&#44; de novo melanoma after a transplant&#44; and melanoma of donor origin&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In our experience&#44; there is a fourth scenario in which an SOT recipient was not diagnosed or treated for melanoma until seen by a dermatologist after the transplantation&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">History of Pretransplant Melanoma</span><p id="par0025" class="elsevierStylePara elsevierViewall">Unfortunately for anyone whose survival depends on an SOT&#44; a history of melanoma is a classic contraindication for SOT&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> There is little evidence on whether SOT recipients with a history of melanoma have an increased risk of recurrence or progression after transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The authors of a series of 31 SOT recipients with a past history of melanoma reported an alarming recurrence rate of 19&#37; and recommended leaving a period of at least 5 years between melanoma treatment and SOT&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The authors&#44; however&#44; did not provide details of Breslow depth&#44; the most important prognostic factor in melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> These high recurrence rates were not confirmed by more recent work&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Dapprich et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> in a series of 12 SOT recipients previously treated for melanoma &#40;mean Breslow depth&#44; 0&#46;35&#8239;mm&#41;&#44; found no cases of posttransplant recurrence or melanoma-specific mortality&#46; Similarly&#44; the European Skin Care in Organ Transplant Patients&#44; Europe &#40;SCOPE&#41; group reported no melanoma recurrences or deaths after SOT in a series of 9 recipients with a history of melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Brewer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> found no significant differences in recurrences &#40;after a period of 10&#46;5 years&#41; or metastasis rates in 59 SOT recipients with pretransplant melanoma&#46; It should be noted&#44; however&#44; that Breslow depth measurements were available for just 17 cases&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> It should also be noted that the results of these studies were probably affected by selection bias&#44; as patients with a history of melanoma selected for SOT are likely to have a better prognosis &#40;lower Breslow depth&#41; and to have been free of disease for longer&#46; Another study showed that 336 SOT recipients with a history of melanoma had a higher risk of posttransplant melanoma-specific mortality &#40;hazard ratio &#91;HR&#93;&#44; 27&#59; 95&#37; CI&#44; 11&#8211;64&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;0001&#41;&#44; overall mortality&#44; and incident melanoma than recipients without a history of melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Despite these alarming rates&#44; the authors explained that because melanoma-specific deaths are&#44; in absolute terms&#44; rare among SOT recipients&#44; the difference in 5-year mortality due to melanoma between recipients with and without pretransplant melanoma was just 1&#46;2&#37;&#46; They were of the opinion that these data would probably not justify a change in patient selection strategies&#44; although they would indicate the need for close dermatologic follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Based on these studies and the melanoma survival curves in the American Joint Commission on Cancer &#40;AJCC&#41; Cancer Staging Manual &#40;7th Edition&#41;&#44; the International Immunosuppression and Transplant Skin Cancer Collaborative &#40;ITSCC&#41; drew up a series of recommendations on the wait time between melanoma treatment and transplant &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Based on a 5-year posttransplant survival rate of 60&#37; and the AJCC 7th Edition survival curves&#44; the authors proposed that patients with melanoma stages Ia&#44; Ib&#44; IIa&#44; IIb&#44; or IIIa would be candidates for SOT&#46; They also considered that the point at which the survival curve for each stage flattened was the minimum wait time between a diagnosis of melanoma and SOT&#46; Sentinel lymph node biopsy results are particularly useful when evaluating the candidacy of patients with a history of melanoma for SOT&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">De Novo Melanoma After SOT</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Incidence Studies</span><p id="par0030" class="elsevierStylePara elsevierViewall">SOT recipients have a 2- to 8-fold increased risk of developing melanoma compared with members of the general population<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;24</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The higher number of dermatology examinations in SOT recipients has probably led to increased awareness of the risk among other health care professionals and consequently more diagnoses&#46; The risk of melanoma may be 17&#46;2 times higher in African American SOT recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">While SOT recipients have a higher risk of melanoma than immunocompetent people&#44; they have an even higher risk of squamous cell carcinoma &#40;50- to- 250-fold increased risk&#41; and basal cell carcinoma &#40;10-fold increased risk&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Risk Factors</span><p id="par0040" class="elsevierStylePara elsevierViewall">Melanoma is a highly immunogenic tumor and responds very well to new immunotherapies&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Like other tumors&#44; however&#44; it has developed mechanisms to evade immune surveillance&#44; enabling it to spread&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In immunosuppressed patients&#44; one would expect melanoma to have an even higher incidence and greater metastatic potential&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Apart from immunosuppression itself&#44; other factors specific to each immunosuppressive agent may contribute to the higher incidence and faster progression of melanoma in immunosuppressed individuals&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> as occurs with nonmelanoma skin cancer &#40;NMSC&#41;&#46; There have even been reports of good response and outcomes in patients with melanoma following withdrawal of immunosuppressants&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Calcineurin inhibitors and azathioprine increase the risk of skin cancer by reducing immune surveillance&#44; increasing vascularization and tumor invasive capacity&#44; and enhancing DNA damage &#40;e&#46;g&#46;&#44; after exposure to UV-B radiation&#41; or inhibiting its repair&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Replacing classic immunosuppressive agents with a mammalian target of rapamycin &#40;mTOR&#41; inhibitor&#44; which has antiproliferative properties&#44; is known to be effective for the secondary prevention of NMSC&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;27&#44;28</span></a> Very little data&#44; however&#44; are available on the benefits of switching from an immunosuppressive regimen to an mTOR inhibitor in melanoma&#46; The current evidence is based on animal studies and the CONVERT trial&#44; which showed a lower incidence of melanoma in kidney transplant recipients who received sirolimus than in those who did not&#44; although the incidence was very low in both groups&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a> It is noteworthy that a meta-analysis of data from 5876 patients from 21 randomized controlled trials showed that the use of sirolimus in SOT recipients was associated with a 43&#37; increased risk of death &#40;HR&#44; 1&#46;43&#59; 95&#37; CI&#44; 1&#46;21&#8211;1&#46;71&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41; in patients treated with high doses&#46; The main causes of death were cardiovascular or infectious disease&#46; These data&#44; together with a high incidence of adverse effects &#40;many of which increase cardiovascular risk&#41;&#44; are limiting factors for the use of sirolimus as a first-line immunosuppressive treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Vajdic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> showed that the risk of melanoma in SOT recipients peaked in the second year posttransplant&#44; and then decreased linearly&#46; Additional risk factors were age and induction immunosuppression with monoclonal antibodies&#46; Female sex&#44; non-Caucasian race&#44; and a longer time since SOT&#44; by contrast&#44; were protective factors&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Several studies have reported a possible association between a higher number of nevi in SOT recipients and duration of immunosuppressive therapy&#46; A high number of nevi is a risk factor for melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;31</span></a> In a Swedish series&#44; 63&#37; of melanomas in SOT recipients were histologically associated with the presence of a dysplastic nevus&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In another 2 series&#44; just 33&#37; to 36&#37; of melanomas in SOT recipients arose in a previous nevus&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;24</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A number of studies on melanoma in SOT recipients have mentioned that a past history of NMSC is common&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;24</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Voriconazole is used to treat invasive fungal infections in SOT recipients&#44; particularly following a lung transplant&#46; Its use is considered an independent risk factor for skin cancer&#44; in particular squamous cell carcinoma&#46; Apart from its photosensitizing properties&#44; voriconazole appears to enhance DNA damage when exposed to UV radiation and to inhibit its repair&#46; Several articles thus have pointed to a possible role for voriconazole in the development of melanoma&#46; Discontinuation of this drug is recommended in SOT recipients who develop melanoma or squamous cell carcinoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;33</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Disease Course and Prognosis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Stage at diagnosis is one of the main prognostic factors in patients with melanoma&#44; whether they are immunosuppressed or immunocompetent&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;34</span></a> Breslow depth is the most significant histologic prognostic factor&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The 2008 multicenter SCOPE study comparing outcomes between 95 SOT recipients who developed melanoma posttransplant and a cohort of immunocompetent patients with melanoma found no significant differences in mortality rates among patients with stage T1 or T2 disease&#46; Mortality in patients with stage T3 or T4 disease&#44; however&#44; was significantly higher in SOT recipients &#40;HR&#44; 11&#46;49&#59; 95&#37; CI&#44; 3&#46;59&#8211;36&#46;82&#41;&#46; Another study found that SOT recipients had more advanced melanoma at diagnosis than members of the general population &#40;OR for stages III-IV&#44; 4&#46;2&#59; 95&#37; CI&#44; 1&#46;6&#8211;10&#46;8&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;003&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> The risk of melanoma-specific mortality was also higher in SOT recipients &#40;adjusted HR&#44; 3&#59; 95&#37; CI&#44; 1&#46;7&#8211;5&#46;3&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41;&#46; Finally&#44; a Canadian study of 51 patients with posttransplant melanoma also showed a higher risk of melanoma-specific mortality compared with immunocompetent individuals &#40;adjusted HR&#44; 1&#46;93&#59; 95&#37; CI&#44; 1&#46;03&#8211;3&#46;63&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;04&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> All-cause mortality was also higher &#40;2 to 8 times depending on melanoma stage&#41; While it is true that changes to the immunosuppressive regimen could explain some of the increase in mortality&#44; the authors did not believe that these changes made a significant contribution&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Clinical and Histologic Characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">Based on findings from the main series of posttransplant melanoma to date&#44; the clinical and histologic characteristics of the tumors appear to be indistinguishable from those observed in immunocompetent individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The mean age at diagnosis was 54 years &#40;range&#44; 26&#8211;77 years&#41; and there a predominance of male patients &#40;66&#37;&#41;&#44; supporting previous findings&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Mean time from the first transplant to onset of melanoma was 8&#46;7 years &#40;range&#44; 0&#46;1&#8211;24&#46;9 years&#41;&#44; which is somewhat shorter than the mean of 12 years reported by Brocard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Overall&#44; 95&#37; of patients had a Fitzpatrick skin type I-III and&#44; contrasting with reports for the general population&#44; there were no sex-related differences in tumor location&#46; Park et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> found that SOT recipients were more likely to have melanomas on the head and neck than immunocompetent patients&#46; In another study of melanoma in SOT recipients&#44; the predominant locations were the trunk &#40;51&#37;&#41; and the head and neck &#40;26&#37;&#41; for men and the trunk &#40;50&#37;&#41; and the extremities &#40;42&#37;&#41; for women&#46; The most common site for melanoma in women from the general population is the lower extremities &#40;36&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In the series by Brocard et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> 2 &#40;10&#37;&#41; of 20 SOT recipients with melanoma had mucosal melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In our &#40;unpublished&#41; series of 8 patients&#44; 2 &#40;25&#37;&#41; had melanoma involving the oral mucosa&#46; These rates of mucosal melanoma are higher than those reported for the general population &#40;1&#37;&#8211;2&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Further studies&#44; however&#44; are needed to confirm these data&#44; but they might indicate differential etiologic or pathogenic mechanisms for melanoma in the context of SOT&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Although all histologic subtypes of melanoma were represented in the SCOPE series&#44; superficial spreading melanoma was the most common form of invasive melanoma&#44; supporting findings for the general population and other series&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;24&#44;35</span></a> The mean Breslow depth observed in invasive melanomas was 1&#46;5 to 2&#8239;mm&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;32</span></a> In the series described by Krynitz et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> 82&#37; of melanomas diagnosed in SOT recipients had a Clark level of III to V compared with 66&#37; of those in immunocompetent patients &#40;OR&#44; 2&#46;2&#59; 95&#37; CI&#44; 1&#46;01&#8211;4&#46;7&#41;&#46; The authors also observed a less prominent lymphocytic infiltrate in SOT recipients who died of melanoma and suggested that this feature might be of prognostic value&#46; It is probably a reflection of the underlying iatrogenic immunosuppression&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Management and Treatment</span><p id="par0085" class="elsevierStylePara elsevierViewall">The initial treatment of melanoma in SOT recipients should be no different to that in immunocompetent patients&#58; simple excision followed by widening of margins depending on Breslow depth and&#44; where necessary&#44; SLN biopsy&#46; Proper staging is essential for correct management&#46; The worse the prognosis&#44; the more aggressive the approach&#44; and consequently&#44; the greater the risk to the survival of the transplanted organ&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;38</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Immunosuppressive therapy should be revised in SOT recipients following a diagnosis of melanoma&#46; Options include drug withdrawal&#44; reduction of drug blood levels&#44; and switching to another drug with antiproliferative and antiangiogenic activity to reduce the risk of tumor spread&#46; It is important to strike a balance between a level of immunosuppression that will not favor the spread of the tumor and one that will not result in rejection of the transplanted organ&#46; Important factors to bear in mind are tumor stage and prognosis&#44; the type of organ transplanted and the possibility of artificially reproducing its function &#40;e&#46;g&#46;&#44; dialysis in the case of kidneys&#41;&#44; and the patient&#8217;s general health&#46; The ITSCC recommendations on the level of reduction of immunosuppression following a diagnosis of melanoma or NMSC are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;39</span></a> Despite the limited evidence available for melanoma&#44; it would seem reasonable to consider an immunosuppressive regimen involving an mTOR inhibitor where possible&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Survival in patients with advanced melanoma&#44; and metastatic melanoma in particular&#44; is very low&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> Targeted therapies and immunotherapies have revolutionized the treatment of melanoma&#44; achieving long survival times in certain patients with disseminated disease&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Evidence&#44; however&#44; is lacking on the safety and efficacy of these treatments in SOT recipients&#44; as these patients have been systematically excluded from the clinical trials&#46;<span class="elsevierStyleSup">42</span> Some studies have shown acceptable responses to combined <span class="elsevierStyleItalic">BRAF</span> and <span class="elsevierStyleItalic">MEK</span> inhibition in SOT recipients with advanced BRAF-mutant melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;43</span></a> Nonetheless&#44; several studies have indicated that <span class="elsevierStyleItalic">BRAF</span> mutations are less common in melanomas in SOT recipients&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;44</span></a> In our unpublished series of SOT recipients with melanoma&#44; just 29&#37; had a BRAF mutation&#44; compared with 54&#37; of patients with melanoma from the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> It is possible that both immunosuppression and immunosuppressive therapy might have a differential effect on the pathogenesis of melanoma in SOT recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Brocard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> characterized the mutational profile of melanoma &#40;<span class="elsevierStyleItalic">BRAF</span>&#44; <span class="elsevierStyleItalic">c-KIT</span>&#44; and <span class="elsevierStyleItalic">NRAS</span> genes&#41; in 20 SOT recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a><span class="elsevierStyleItalic">BRAF</span> and <span class="elsevierStyleItalic">NRAS</span> mutations were detected in 40&#37; and 23&#37; of cases&#44; respectively&#46; No <span class="elsevierStyleItalic">c-KIT</span> mutations were found&#46; One limitation of the study&#44; however&#44; was that a significant number of samples were inadequate for molecular analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> More studies are therefore needed to investigate differences in melanoma mutations between SOT recipients and immunocompetent patients&#44; as this information would help identify potential therapeutic targets&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Immune checkpoint inhibitors &#40;ICIs&#41; should be considered in SOT recipients with advanced non-BRAF-mutant melanoma&#46; The potential benefits and increased risk of organ rejection must be carefully weighed up&#44; and it is very difficult to find the exact point at which this balance is maintained&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> The decision should be taken by a multidisciplinary committee including members of the transplant team&#44; oncologists&#44; and dermatologists&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> It is also essential to discuss the matter with the patient and involve him or her in the decision&#46; Evidence on the use of ICIs in SOT recipients is based on isolated clinical reports and small series&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#8211;60</span></a> Abdel-Wahab et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> recently published the findings of the largest series of SOT recipients treated with ICIs to date at the University of Texas MD Anderson Cancer Center&#46; They also performed the first systematic review of the literature on this subject&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> They analyzed organ rejection&#44; survival&#44; and tumor response in 39 SOT recipients with melanoma &#40;metastatic in 62&#37; of cases&#41; treated with ICIs&#46; Allograft rejection occurred in 41&#37; of patients and the median time to rejection was 21 days after ICI initiation&#59; 81&#37; of the patients &#40;10 kidney transplant recipients and 3 liver transplant recipients&#41; experienced graft loss despite treatment &#40;increased immunosuppression and ICI discontinuation&#41;&#46; Rejection rates were found to be similar with anti-cytoxic T-lymphocyte antigen 4 and anti-programmed death 1 antibodies&#44; contradicting previous findings suggesting that the former might be safer&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> Of the 22 SOT recipients with metastatic melanoma&#44; 64&#37; experienced tumor progression&#44; while 32&#37; showed a partial or complete response&#46; In a recent study&#44; Hurkmans et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> proposed that donor-derived cell-free DNA might be a sensitive biomarker for the early detection of transplant rejection in SOT recipients treated with ICIs&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">There has been a report of an immunosuppressive regimen being successfully used to preserve renal-allograft function in a recipient with metastatic adenocarcinoma of the duodenum due to receive treatment with nivolumab<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Sunshine et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> successfully treated a kidney transplant recipient with melanoma and in-transit metastasis with a combination of topical imiquimod 5&#37; and talimogene laherparepvec &#40;T-VEC&#41; injections&#46; No signs of rejection were observed&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Based on the literature reviewed&#44; our proposed approach to treating de nova melanoma in an SOT recipient is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Dermatologic Follow-up of SOT Recipients</span><p id="par0120" class="elsevierStylePara elsevierViewall">SOT recipients with advanced melanoma have a significantly worse prognosis than members of the general population with advanced melanoma&#44; and they also face a very high risk of organ rejection after ICI therapy&#46; Close dermatologic surveillance is thus necessary to ensure that any melanoma that may occur is diagnosed early&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Frequency of follow-up should be determined by individual risk&#44; with particular attention paid to patients with a dysplastic nevus or a personal or family history of melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;24</span></a> Follow-up with dermoscopy&#44; in addition to body mapping and reflectance confocal microscopy&#44; is useful for improving the ratio of melanomas to benign skin lesions excised&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Patients should be taught how to recognize suspicious lesions or recurrent tumors at previous excision sites and cautioned to avoid recreational sun exposure and to continue to use sun-protection and other measures that minimize sun exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Strict sun protection measures must be accompanied by monitoring of vitamin D levels and any deficiencies corrected through supplementation&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Finally&#44; we believe that SOT candidates should be examined by a dermatologist before undergoing a transplant to rule out melanoma&#46; Immunosuppression&#8212;and hence risk of tumor progression&#8212;is highest during the peritransplant period &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Donor-Derived Melanoma</span><p id="par0125" class="elsevierStylePara elsevierViewall">Melanoma can be transmitted to an SOT recipient via an organ donated by a person with melanoma&#46; This could happen in the case of occult melanomas&#44; which would then spread in an immunosuppressed transplant recipient&#46; It could also happen in the case of donors &#40;especially young donors&#41; who died of metastatic melanoma of the brain misdiagnosed as a brain hemorrhage or a primary brain tumor&#46; The estimated risk of occult donor malignancy is 1&#46;3&#37;&#44; and the risk of transmission to a recipient&#44; 0&#46;2&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Melanoma is the donor-derived tumor with the highest risk of metastasis&#46; One review analyzed donor-to-recipient transmission of melanoma in 7 donors whose organs were provided to 44 recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Thirty-five recipients &#40;80&#37;&#41; developed melanoma within 3 to 24 months of the transplant&#44; and 33 &#40;75&#37;&#41; died as a result&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;11</span></a> These data indicate that anyone with a history of melanoma should not be ruled out as an organ donor&#46; In addition&#44; potential donors should be given a full-body examination to search for lesions or scars suspicious for melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The little evidence available on the treatment of donor-derived melanoma suggests that the best approach may be to excise the transplanted organ together with any resectable metastases and to discontinue immunosuppressive therapy&#46; This approach&#44; however&#44; is only possible in the case of kidney recipients&#46; Recipients of other vital organs face a grim prognosis unless there is another organ available&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Molecular biology techniques such as fluorescent in situ hybridization&#44; polymerase chain reaction assays&#44; and tandem repeat sequencing can be used to clarify doubts regarding whether metastatic melanoma detected in an SOT recipient is de novo or donor derived&#46; This information has important prognostic and therapeutic implications&#46; In addition&#44; if the tumor is donor derived&#44; any other organs donated by the donor&#44; regardless of the recipient&#44; should also be removed&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusions</span><p id="par0135" class="elsevierStylePara elsevierViewall">Although evidence on the management of melanoma in SOT recipients is scarce and based on case series&#44; it is known that in early-stage melanoma&#44; prognosis in SOT recipients is similar to that of the general population&#46; Dermatologists thus have an essential role in posttransplant follow-up as they are in a position to diagnose thin melanomas&#46; Much work remains regarding the management of advanced melanoma in SOT recipients&#44; who currently face a worse prognosis than immunocompetent patients with metastatic disease&#46; Because SOT recipients have been excluded from clinical trials of ICIs&#44; treatment decisions should be reached by a multidisciplinary committee&#44; with the informed consent of the patient and knowing that there is a high risk of acute rejection&#46; Further research is also necessary on the role of adjuvant therapy in SOT recipients as it has been demonstrated to improve survival in immunocompetent patients&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of Interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "xres1473836"
          "titulo" => "Graphical abstract"
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          "identificador" => "xres1473834"
          "titulo" => "Abstract"
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              "identificador" => "abst0010"
            ]
          ]
        ]
        2 => array:2 [
          "identificador" => "xpalclavsec1341922"
          "titulo" => "Keywords"
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          "identificador" => "xres1473835"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0015"
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        4 => array:2 [
          "identificador" => "xpalclavsec1341921"
          "titulo" => "Palabras clave"
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        5 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        6 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Search Strategy and Selection of Articles"
        ]
        7 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Clinical Scenarios"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "History of Pretransplant Melanoma"
            ]
            1 => array:3 [
              "identificador" => "sec0025"
              "titulo" => "De Novo Melanoma After SOT"
              "secciones" => array:5 [
                0 => array:2 [
                  "identificador" => "sec0030"
                  "titulo" => "Incidence Studies"
                ]
                1 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Risk Factors"
                ]
                2 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Disease Course and Prognosis"
                ]
                3 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Clinical and Histologic Characteristics"
                ]
                4 => array:2 [
                  "identificador" => "sec0050"
                  "titulo" => "Management and Treatment"
                ]
              ]
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Dermatologic Follow-up of SOT Recipients"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Donor-Derived Melanoma"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclusions"
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        9 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Conflicts of Interest"
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        10 => array:1 [
          "titulo" => "References"
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    ]
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    "fechaRecibido" => "2020-05-29"
    "fechaAceptado" => "2020-11-02"
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          "clase" => "keyword"
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            0 => "Melanoma"
            1 => "Skin cancer"
            2 => "Solid organ transplant"
            3 => "Nivolumab"
            4 => "Pembrolizumab"
            5 => "Ipilimumab"
            6 => "Dabrafenib"
            7 => "Vemurafenib"
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          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1341921"
          "palabras" => array:8 [
            0 => "Melanoma"
            1 => "C&#225;ncer cut&#225;neo"
            2 => "Trasplante de &#243;rgano s&#243;lido"
            3 => "Nivolumab"
            4 => "Pembrolizumab"
            5 => "Ipilimumab"
            6 => "Dabrafenib"
            7 => "Vemurafenib"
          ]
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">In this review&#44; we analyze the 3 clinical scenarios related to the development of melanoma in solid organ transplant recipients&#58; melanoma in patients with a history of the tumor prior to a transplant&#44; de novo melanoma following a transplant&#44; and melanoma of donor origin&#46; The main factors to consider in organ-transplant candidates with a history of melanoma are tumor stage&#44; presence or absence of residual disease&#44; and time from diagnosis to transplantation&#46; Solid organ transplant recipients have a greater risk of melanoma than immunocompetent individuals&#46; Mortality is also higher in this population&#44; especially in patients with advanced melanoma&#44; as treatment is especially challenging&#46; Clinical history and physical examination provide the most useful information for preventing donor-to-recipient transmission of melanoma&#46; Donor-derived melanoma has a very poor prognosis&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El melanoma en receptores de un trasplante de &#243;rgano s&#243;lido &#40;RTOS&#41; puede aparecer en tres situaciones cl&#237;nicas&#44; objeto de esta revisi&#243;n&#58; pacientes con historia de melanoma previa al trasplante&#44; pacientes que desarrollan el melanoma posteriormente al trasplante y pacientes con melanoma procedente del donante&#46; Los factores m&#225;s relevantes a considerar en pacientes con antecedentes de melanoma candidatos a un trasplante son el estadio del tumor&#44; la presencia o no de enfermedad residual y el periodo entre el diagn&#243;stico y el trasplante&#46; Los RTOS tienen mayor riesgo de padecer un melanoma que la poblaci&#243;n inmunocompetente&#46; La mortalidad por melanoma es tambi&#233;n mayor&#44; especialmente en aquellos con estadios avanzados&#44; que suponen un verdadero reto terap&#233;utico&#46; Finalmente&#44; la historia cl&#237;nica y la exploraci&#243;n f&#237;sica del donante son las herramientas m&#225;s &#250;tiles para evitar la transmisi&#243;n de un melanoma al receptor&#44; situaci&#243;n con pron&#243;stico infausto&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Gonz&#225;lez-Cruz C&#44; Ferr&#225;ndiz-Pulido C&#44; Garc&#237;a-Patos Briones V&#46; Melanoma en pacientes receptores de un trasplante de &#243;rgano s&#243;lido&#46; Actas Dermosifiliogr&#46; 2021&#59;112&#58;216&#8211;224&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Proposed approach for treating de novo melanoma following SOT based on the literature reviewed&#46; CTLA-4 indicates cytotoxic T-lymphocyte-associated protein 4&#59; mTOR&#44; mammalian target of rapamycin&#59; PD-1&#44; programmed death 1&#59; SOT&#44; solid organ transplant&#59; T-VEC&#44; talimogene laherparepvec&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Melanoma diagnosed 4 months after a solid organ transplant&#44; located just a few centimeters from the laparotomy scar&#44; highlighting the importance of a full dermatologic examination before the procedure&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AJCC CSM&#44; American Joint Commission on Cancer Cancer Staging Manual&#59; ITSCC&#44; International Transplant Skin Cancer Collaborative&#59; SOT&#44; solid organ transplant&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Adapted from Zwald et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Stage &#40;AJCC CSM&#44; 7th Edition&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recommended Time to SOT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage 0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No need to defer SOT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage Ia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage Ib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage IIa&#44; IIb&#44; IIIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5-10 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stages IIc&#44; IIIb&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not candidates for SOT<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Consider on a case-by-case basis in patients who have survived for more than 10&#8211;15 years&#46;</p>"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Minimum Time From Melanoma Treatment to SOT According to the ITSCC&#46;</p>"
        ]
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        "etiqueta" => "Table 2"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abbreviation&#58; SOT&#44; solid organ transplant&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46; of SOT Recipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study Location&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidence Rate &#40;Annual Cases per 100&#8239;000 Population&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Garret et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10649&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">United States&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brown et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">861&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">London&#44; United Kingdom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vajdic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8152&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Australia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2535817.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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidence Rate &#40;Annual Cases per 100&#8239;000 Population&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tejera-Vaquerizo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Meta-analysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Spain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2535815.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Studies of the Incidence of Melanoma in SOT Recipients and Immunocompetent Individuals in Spain&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AJCC&#44; American Joint Commission on Cancer &#40;Cancer Staging Manual&#41;&#59; ITSCC&#44; International Transplant Skin Cancer Collaborative&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Adapted from Zwald et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Leve of Reduction of Immunosuppression</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Transplanted Organ</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AJCC Stage &#40;7th Edition&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Kidney&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Heart&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Liver&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage Ia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage Ib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage IIc&#47;III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stage IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2535816.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">ITSCC and SCOPE Recommendations on the Level of Reduction of Immunosuppression for Solid Organ Transplant Recipients With Nonmelanoma Skin Cancer or Melanoma&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0030"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Adapted from Barnett et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Timing in Relation to Treatment Initiation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&#58; Dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 wk before&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&#58; 40&#8239;mg&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">During treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&#58; 20&#8239;mg&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sirolimus &#40;target levels&#41;&#58; 4&#8211;6&#8239;ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 wk after&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&#58; 20&#8239;mg&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2021.01.011

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Year/Month	Html	Pdf	Total

2024 November	6	2	8
2024 October	138	52	190
2024 September	117	33	150
2024 August	140	58	198
2024 July	98	34	132
2024 June	140	44	184
2024 May	104	36	140
2024 April	82	25	107
2024 March	113	35	148
2024 February	123	38	161
2024 January	141	35	176
2023 December	128	17	145
2023 November	132	28	160
2023 October	132	35	167
2023 September	112	34	146
2023 August	78	29	107
2023 July	87	40	127
2023 June	96	31	127
2023 May	109	35	144
2023 April	93	33	126
2023 March	90	34	124
2023 February	77	29	106
2023 January	44	35	79
2022 December	56	53	109
2022 November	69	78	147
2022 October	36	31	67
2022 September	36	43	79
2022 August	28	38	66
2022 July	35	35	70
2022 June	49	48	97
2022 May	76	48	124
2022 April	76	54	130
2022 March	67	67	134
2022 February	59	32	91
2022 January	73	29	102
2021 December	55	39	94
2021 November	60	39	99
2021 October	63	63	126
2021 September	50	46	96
2021 August	47	36	83
2021 July	56	29	85
2021 June	40	30	70
2021 May	50	42	92
2021 April	161	89	250
2021 March	164	69	233
2021 February	59	27	86
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