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DOI: 10.1055/s-0041-1728798
Skin Cancers and Lung Transplant
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Abstract
It is well known that solid-organ transplant recipients (SOTRs) have a 65- to 100-fold increase in the risk of developing skin cancer, namely, nonmelanoma skin cancers (NMSCs) such as cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). In addition, these patients are also at increased risk for development of melanoma as well as other less common cutaneous malignancies (Merkel's cell carcinoma, Kaposi's sarcoma). SOTRs with NMSC (namely cSCC) are also at significantly increased risk of poor clinical outcomes including local recurrence, nodal and distant metastasis, and disease-specific death relative to patients who are not immunosuppressed. Increased surveillance and monitoring in patients at risk of aggressive disease and poor outcomes who are on immunosuppression is essential in patients with lung transplants given the high degree of immunosuppression. Increased awareness of risks, treatments, and management allows for improved outcomes in these patients. This article will provide an overview of the risk factors for the development of cutaneous malignancies in organ transplant recipients as well as a detailed discussion of various immunosuppressant and prophylactic medications used in this patient population that contribute to the risk of developing cutaneous malignancies, with an emphasis on NMSC (cSCC and BCC) in lung transplant recipients. Finally, this article includes a discussion on the clinical and dermatologic management of this high-risk immunosuppressed population including a review of topical and systemic agents for field therapy of actinic damage and chemoprevention of keratinocyte carcinomas. In addition, indications for additional treatment and preventive measures such as adjuvant radiation treatment after surgical management of cutaneous malignancies and potential modification of immunosuppressive medication regimens are discussed.
Keywords
skin cancer - immunosuppression - lung transplant - squamous cell carcinoma - melanoma - merkel cell carcinomaPublikationsverlauf
Artikel online veröffentlicht:
24. Mai 2021
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References
- 1 Global Observatory on Donation and Transplantation. Accessed April 19, 2021 at: www.transplant-observatory.org
- 2 United Network for Organ Sharing. Accessed April 19, 2021 at: www.unos.org
- 3 Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med 2003; 348 (17) 1681-1691
- 4 Stevenson ML, Carucci J, Colegio OR. Skin cancer in transplant recipients: scientific retreat of the international immunosuppression and transplant skin cancer collaborative and skin care in organ transplant patients—Europe. Clin Transplant 2019; 33 (12) e13736
- 5 Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol 2012; 166 (05) 1069-1080
- 6 Garrett GL, Blanc PD, Boscardin J. et al. Incidence of and risk factors for skin cancer in organ transplant recipients in the United States. JAMA Dermatol 2017; 153 (03) 296-303
- 7 O'Reilly Zwald F, Brown M. Skin cancer in solid organ transplant recipients: advances in therapy and management: Part I. Epidemiology of skin cancer in solid organ transplant recipients. J Am Acad Dermatol 2011; 65 (02) 253-261
- 8 Krynitz B, Edgren G, Lindelöf B. et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish population-based study. Int J Cancer 2013; 132 (06) 1429-1438
- 9 Hartevelt MM, Bavinck JN, Kootte AM, Vermeer BJ, Vandenbroucke JP. Incidence of skin cancer after renal transplantation in the Netherlands. Transplantation 1990; 49 (03) 506-509
- 10 Green AC, Olsen CM. Increased risk of melanoma in organ transplant recipients: systematic review and meta-analysis of cohort studies. Acta Derm Venereol 2015; 95 (08) 923-927
- 11 Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol 2013; 68 (06) 957-966
- 12 Garrett GL, Lowenstein SE, Singer JP, He SY, Arron ST. Trends of skin cancer mortality after transplantation in the United States: 1987 to 2013. J Am Acad Dermatol 2016; 75 (01) 106-112
- 13 Mackenzie KA, Wells JE, Lynn KL. et al. First and subsequent nonmelanoma skin cancers: incidence and predictors in a population of New Zealand renal transplant recipients. Nephrol Dial Transplant 2010; 25 (01) 300-306
- 14 Rashtak S, Dierkhising RA, Kremers WK, Peters SG, Cassivi SD, Otley CC. Incidence and risk factors for skin cancer following lung transplantation. J Am Acad Dermatol 2015; 72 (01) 92-98
- 15 Iannacone MR, Sinnya S, Pandeya N. et al; STAR Study. Prevalence of skin cancer and related skin tumors in high-risk kidney and liver transplant recipients in Queensland, Australia. J Invest Dermatol 2016; 136 (07) 1382-1386
- 16 Navarro MD, López-Andréu M, Rodríguez-Benot A, Agüera ML, Del Castillo D, Aljama P. Cancer incidence and survival in kidney transplant patients. Transplant Proc 2008; 40 (09) 2936-2940
- 17 Kang W, Sampaio MS, Huang E, Bunnapradist S. Association of pretransplant skin cancer with posttransplant malignancy, graft failure and death in kidney transplant recipients. Transplantation 2017; 101 (06) 1303-1309
- 18 Gräger N, Leffler M, Gottlieb J. et al. Risk factors for developing nonmelanoma skin cancer after lung transplantation. J Skin Cancer 2019; 2019: 7089482
- 19 Gogia R, Binstock M, Hirose R, Boscardin WJ, Chren MM, Arron ST. Fitzpatrick skin phototype is an independent predictor of squamous cell carcinoma risk after solid organ transplantation. J Am Acad Dermatol 2013; 68 (04) 585-591
- 20 Ong CS, Keogh AM, Kossard S, Macdonald PS, Spratt PM. Skin cancer in Australian heart transplant recipients. J Am Acad Dermatol 1999; 40 (01) 27-34
- 21 Harwood CA, Mesher D, McGregor JM. et al. A surveillance model for skin cancer in organ transplant recipients: a 22-year prospective study in an ethnically diverse population. Am J Transplant 2013; 13 (01) 119-129
- 22 Ulrich C, Jürgensen JS, Degen A. et al. Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study. Br J Dermatol 2009; 161 (Suppl. 03) 78-84
- 23 Pavlick AC, Fecher L, Ascierto PA, Sullivan RJ. Frontline therapy for BRAF-mutated metastatic melanoma: How do you choose, and is there one correct answer?. Am Soc Clin Oncol Educ Book 2019; 39: 564-571
- 24 Howard MD, Su JC, Chong AH. Skin cancer following solid organ transplantation: a review of risk factors and models of care. Am J Clin Dermatol 2018; 19 (04) 585-597
- 25 Hollenbeak CS, Todd MM, Billingsley EM, Harper G, Dyer AM, Lengerich EJ. Increased incidence of melanoma in renal transplantation recipients. Cancer 2005; 104 (09) 1962-1967
- 26 Vajdic CM, Chong AH, Kelly PJ. et al. Survival after cutaneous melanoma in kidney transplant recipients: a population-based matched cohort study. Am J Transplant 2014; 14 (06) 1368-1375
- 27 Aderhold K, Wilson M, Berger AC, Levi S, Bennett J. Precision medicine in the treatment of melanoma. Surg Oncol Clin N Am 2020; 29 (01) 1-13
- 28 Lipson EJ, Bodell MA, Kraus ES, Sharfman WH. Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J Clin Oncol 2014; 32 (19) e69-e71
- 29 Herz S, Höfer T, Papapanagiotou M. et al. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer 2016; 67: 66-72
- 30 Morales RE, Shoushtari AN, Walsh MM, Grewal P, Lipson EJ, Carvajal RD. Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation. J Immunother Cancer 2015; 3: 22
- 31 Schvartsman G, Perez K, Sood G, Katkhuda R, Tawbi H. Immune checkpoint inhibitor therapy in a liver transplant recipient with melanoma. Ann Intern Med 2017; 167 (05) 361-362
- 32 Arron ST, Canavan T, Yu SS. Organ transplant recipients with Merkel cell carcinoma have reduced progression-free, overall, and disease-specific survival independent of stage at presentation. J Am Acad Dermatol 2014; 71 (04) 684-690
- 33 Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi's sarcoma after kidney transplantation: a 21-years experience. Int J Hematol Oncol Stem Cell Res 2013; 7 (04) 29-33
- 34 Clarke CA, Robbins HA, Tatalovich Z. et al. Risk of Merkel cell carcinoma after solid organ transplantation. J Natl Cancer Inst 2015; 107 (02) 107
- 35 Cahoon EK, Linet MS, Clarke CA, Pawlish KS, Engels EA, Pfeiffer RM. Risk of Kaposi sarcoma after solid organ transplantation in the United States. Int J Cancer 2018; 143 (11) 2741-2748
- 36 Moosa MR. Racial and ethnic variations in incidence and pattern of malignancies after kidney transplantation. Medicine (Baltimore) 2005; 84 (01) 12-22
- 37 Scheffert JL, Raza K. Immunosuppression in lung transplantation. J Thorac Dis 2014; 6 (08) 1039-1053
- 38 Ivulich S, Westall G, Dooley M, Snell G. The evolution of lung transplant immunosuppression. Drugs 2018; 78 (10) 965-982
- 39 Madeleine MM, Patel NS, Plasmeijer EI. et al; the Keratinocyte Carcinoma Consortium (KeraCon) Immunosuppression Working Group. Epidemiology of keratinocyte carcinomas after organ transplantation. Br J Dermatol 2017; 177 (05) 1208-1216
- 40 Liu J, Farmer Jr JD, Lane WS, Friedman J, Weissman I, Schreiber SL. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 1991; 66 (04) 807-815
- 41 Zhang Y, Baumgrass R, Schutkowski M, Fischer G. Branches on the alpha-C atom of cyclosporin A residue 3 result in direct calcineurin inhibition and rapid cyclophilin 18 binding. ChemBioChem 2004; 5 (07) 1006-1009
- 42 Yarosh DB, Pena AV, Nay SL, Canning MT, Brown DA. Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation. J Invest Dermatol 2005; 125 (05) 1020-1025
- 43 Kuschal C, Thoms KM, Schubert S. et al. Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair. Exp Dermatol 2012; 21 (01) 2-6
- 44 Marcén R, Pascual J, Tato AM. et al. Influence of immunosuppression on the prevalence of cancer after kidney transplantation. Transplant Proc 2003; 35 (05) 1714-1716
- 45 Jensen P, Hansen S, Møller B, Leivestad T, Pfeffer P, Fauchald P. Are renal transplant recipients on CsA-based immunosuppressive regimens more likely to develop skin cancer than those on azathioprine and prednisolone?. Transplant Proc 1999; 31 (1-2): 1120
- 46 Molina BD, Leiro MG, Pulpón LA. et al. Incidence and risk factors for nonmelanoma skin cancer after heart transplantation. Transplant Proc 2010; 42 (08) 3001-3005
- 47 Crespo-Leiro MG, Alonso-Pulpón L, Vázquez de Prada JA. et al. Malignancy after heart transplantation: incidence, prognosis and risk factors. Am J Transplant 2008; 8 (05) 1031-1039
- 48 Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004; 4 (06) 905-913
- 49 O'Donovan P, Perrett CM, Zhang X. et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 2005; 309 (5742): 1871-1874
- 50 Attard NR, Karran P. UVA photosensitization of thiopurines and skin cancer in organ transplant recipients. Photochem Photobiol Sci 2012; 11 (01) 62-68
- 51 Guven M, Brem R, Macpherson P, Peacock M, Karran P. Oxidative damage to RPA limits the nucleotide excision repair capacity of human cells. J Invest Dermatol 2015; 135 (11) 2834-2841
- 52 de Graaf YG, Rebel H, Elghalbzouri A. et al. More epidermal p53 patches adjacent to skin carcinomas in renal transplant recipients than in immunocompetent patients: the role of azathioprine. Exp Dermatol 2008; 17 (04) 349-355
- 53 Jiyad Z, Olsen CM, Burke MT, Isbel NM, Green AC. Azathioprine and risk of skin cancer in organ transplant recipients: systematic review and meta-analysis. Am J Transplant 2016; 16 (12) 3490-3503
- 54 Pópulo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci 2012; 13 (02) 1886-1918
- 55 Khariwala SS, Kjaergaard J, Lorenz R, Van Lente F, Shu S, Strome M. Everolimus (RAD) inhibits in vivo growth of murine squamous cell carcinoma (SCC VII). Laryngoscope 2006; 116 (05) 814-820
- 56 Meier F, Guenova E, Clasen S. et al. Significant response after treatment with the mTOR inhibitor sirolimus in combination with carboplatin and paclitaxel in metastatic melanoma patients. J Am Acad Dermatol 2009; 60 (05) 863-868
- 57 Brenneisen P, Wenk J, Wlaschek M, Krieg T, Scharffetter-Kochanek K. Activation of p70 ribosomal protein S6 kinase is an essential step in the DNA damage-dependent signaling pathway responsible for the ultraviolet B-mediated increase in interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3) protein levels in human dermal fibroblasts. J Biol Chem 2000; 275 (06) 4336-4344
- 58 Jung JW, Overgaard NH, Burke MT. et al. Does the nature of residual immune function explain the differential risk of non-melanoma skin cancer development in immunosuppressed organ transplant recipients?. Int J Cancer 2016; 138 (02) 281-292
- 59 Euvrard S, Ulrich C, Lefrancois N. Immunosuppressants and skin cancer in transplant patients: focus on rapamycin. Dermatol Surg 2004; 30 (4, Pt 2): 628-633
- 60 Karia PS, Azzi JR, Heher EC, Hills VM, Schmults CD. Association of sirolimus use with risk for skin cancer in a mixed-organ cohort of solid-organ transplant recipients with a history of cancer. JAMA Dermatol 2016; 152 (05) 533-540
- 61 Euvrard S, Morelon E, Rostaing L. et al; TUMORAPA Study Group. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367 (04) 329-339
- 62 Hoogendijk-van den Akker JM, Harden PN, Hoitsma AJ. et al. Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus. J Clin Oncol 2013; 31 (10) 1317-1323
- 63 Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant 1996; 10 (1, Pt 2): 77-84
- 64 Coghill AE, Johnson LG, Berg D, Resler AJ, Leca N, Madeleine MM. Immunosuppressive medications and squamous cell skin carcinoma: nested case-control study within the skin cancer after organ transplant (SCOT) cohort. Am J Transplant 2016; 16 (02) 565-573
- 65 O'Neill JO, Edwards LB, Taylor DO. Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2006; 25 (10) 1186-1191
- 66 Vos M, Plasmeijer EI, van Bemmel BC. et al. Azathioprine to mycophenolate mofetil transition and risk of squamous cell carcinoma after lung transplantation. J Heart Lung Transplant 2018; 37 (07) 853-859
- 67 Karagas MR, Cushing Jr GL, Greenberg ER, Mott LA, Spencer SK, Nierenberg DW. Non-melanoma skin cancers and glucocorticoid therapy. Br J Cancer 2001; 85 (05) 683-686
- 68 Ingvar A, Smedby KE, Lindelöf B. et al. Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma. Nephrol Dial Transplant 2010; 25 (08) 2764-2771
- 69 Neoh CF, Snell GI, Levvey B. et al. Lung transplant recipients receiving voriconazole and skin squamous cell carcinoma risk in Australia. Med J Aust 2014; 201 (09) 543-544
- 70 Williams K, Mansh M, Chin-Hong P, Singer J, Arron ST. Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin Infect Dis 2014; 58 (07) 997-1002
- 71 D'Arcy ME, Pfeiffer RM, Rivera DR. et al. Voriconazole and the risk of keratinocyte carcinomas among lung transplant recipients in the United States. JAMA Dermatol 2020; 156 (07) 772-779
- 72 Singer JP, Boker A, Metchnikoff C. et al. High cumulative dose exposure to voriconazole is associated with cutaneous squamous cell carcinoma in lung transplant recipients. J Heart Lung Transplant 2012; 31 (07) 694-699
- 73 Kolaitis NA, Duffy E, Zhang A. et al. Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation. Transpl Int 2017; 30 (01) 41-48
- 74 Mansh M, Binstock M, Williams K. et al. Voriconazole exposure and risk of cutaneous squamous cell carcinoma, Aspergillus colonization, invasive aspergillosis and death in lung transplant recipients. Am J Transplant 2016; 16 (01) 262-270
- 75 Jacobsen AA, Papo YB, Sarro R, Weisse K, Strasswimmer J. Posaconazole substitution for voriconazole-associated phototoxic effects. JAMA Dermatol 2016; 152 (07) 839-841
- 76 Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol 2018; 78 (02) 237-247
- 77 Schmults CD, Karia PS, Carter JB, Han J, Qureshi AA. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol 2013; 149 (05) 541-547
- 78 Karia PS, Jambusaria-Pahlajani A, Harrington DP, Murphy GF, Qureshi AA, Schmults CD. Evaluation of American Joint Committee on Cancer, International Union against Cancer, and Brigham and Women's Hospital tumor staging for cutaneous squamous cell carcinoma. J Clin Oncol 2014; 32 (04) 327-334
- 79 Schmitt AR, Brewer JD, Bordeaux JS, Baum CL. Staging for cutaneous squamous cell carcinoma as a predictor of sentinel lymph node biopsy results: meta-analysis of American Joint Committee on Cancer criteria and a proposed alternative system. JAMA Dermatol 2014; 150 (01) 19-24
- 80 Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: management of advanced and high-stage tumors. J Am Acad Dermatol 2018; 78 (02) 249-261
- 81 Bangash HK, Colegio OR. Management of non-melanoma skin cancer in immunocompromised solid organ transplant recipients. Curr Treat Options Oncol 2012; 13 (03) 354-376
- 82 Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993; 329 (16) 1147-1151
- 83 Naylor MF, Boyd A, Smith DW, Cameron GS, Hubbard D, Neldner KH. High sun protection factor sunscreens in the suppression of actinic neoplasia. Arch Dermatol 1995; 131 (02) 170-175
- 84 van der Pols JC, Williams GM, Pandeya N, Logan V, Green AC. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev 2006; 15 (12) 2546-2548
- 85 Ulrich C. Topical treatment of field cancerization. Cancer Treat Res 2009; 146: 439-446
- 86 Perrett CM, McGregor JM, Warwick J. et al. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy. Br J Dermatol 2007; 156 (02) 320-328
- 87 Firoz BF, Goldberg LH. When imiquimod fails. Dermatol Surg 2010; 36 (05) 717-720
- 88 Ulrich C, Bichel J, Euvrard S. et al. Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients. Br J Dermatol 2007; 157 (Suppl. 02) 25-31
- 89 Fallen RS, Gooderham M. Ingenol mebutate: an introduction. Skin Therapy Lett 2012; 17 (02) 1-3
- 90 Crow LD, Yuan JT, Aroyan CS. et al. Ingenol mebutate 0·015% gel is safe for short-term treatment of actinic keratoses on the face in solid organ transplant recipients. Br J Dermatol 2020; 183 (03) 575-577
- 91 Ulrich C, Hackethal M, Ulrich M. et al. Treatment of multiple actinic keratoses with topical diclofenac 3% gel in organ transplant recipients: a series of six cases. Br J Dermatol 2007; 156 (Suppl. 03) 40-42
- 92 Ulrich C, Johannsen A, Röwert-Huber J, Ulrich M, Sterry W, Stockfleth E. Results of a randomized, placebo-controlled safety and efficacy study of topical diclofenac 3% gel in organ transplant patients with multiple actinic keratoses. Eur J Dermatol 2010; 20 (04) 482-488
- 93 Gozali MV, Yi F, Zhang JA. et al. Photodynamic therapy inhibit fibroblast growth factor-10 induced keratinocyte differentiation and proliferation through ROS in fibroblast growth factor receptor-2b pathway. Sci Rep 2016; 6: 27402
- 94 Babilas P, Landthaler M, Szeimies RM. Photodynamic therapy in dermatology. Eur J Dermatol 2006; 16 (04) 340-348
- 95 Salim A, Leman JA, McColl JH, Chapman R, Morton CA. Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen's disease. Br J Dermatol 2003; 148 (03) 539-543
- 96 Basset-Seguin N, Baumann Conzett K, Gerritsen MJ. et al. Photodynamic therapy for actinic keratosis in organ transplant patients. J Eur Acad Dermatol Venereol 2013; 27 (01) 57-66
- 97 Willey A, Mehta S, Lee PK. Reduction in the incidence of squamous cell carcinoma in solid organ transplant recipients treated with cyclic photodynamic therapy. Dermatol Surg 2010; 36 (05) 652-658
- 98 Chen AC, Martin AJ, Choy B. et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015; 373 (17) 1618-1626
- 99 Surjana D, Halliday GM, Damian DL. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis 2013; 34 (05) 1144-1149
- 100 Yiasemides E, Sivapirabu G, Halliday GM, Park J, Damian DL. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis 2009; 30 (01) 101-105
- 101 Chen AC, Martin AJ, Dalziell RA. et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J Dermatol 2016; 175 (05) 1073-1075
- 102 Drago F, Ciccarese G, Cogorno L, Calvi C, Marsano LA, Parodi A. Prevention of non-melanoma skin cancers with nicotinamide in transplant recipients: a case-control study. Eur J Dermatol 2017; 27 (04) 382-385
- 103 Knip M, Douek IF, Moore WP. et al; European Nicotinamide Diabetes Intervention Trial Group. Safety of high-dose nicotinamide: a review. Diabetologia 2000; 43 (11) 1337-1345
- 104 Lens M, Medenica L. Systemic retinoids in chemoprevention of non-melanoma skin cancer. Expert Opin Pharmacother 2008; 9 (08) 1363-1374
- 105 Germain P, Chambon P, Eichele G. et al. International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol Rev 2006; 58 (04) 712-725
- 106 Mrass P, Rendl M, Mildner M. et al. Retinoic acid increases the expression of p53 and proapoptotic caspases and sensitizes keratinocytes to apoptosis: a possible explanation for tumor preventive action of retinoids. Cancer Res 2004; 64 (18) 6542-6548
- 107 Spinella MJ, Freemantle SJ, Sekula D, Chang JH, Christie AJ, Dmitrovsky E. Retinoic acid promotes ubiquitination and proteolysis of cyclin D1 during induced tumor cell differentiation. J Biol Chem 1999; 274 (31) 22013-22018
- 108 Langenfeld J, Kiyokawa H, Sekula D, Boyle J, Dmitrovsky E. Posttranslational regulation of cyclin D1 by retinoic acid: a chemoprevention mechanism. Proc Natl Acad Sci U S A 1997; 94 (22) 12070-12074
- 109 Herold M, Good AJ, Nielson CB, Longo MI. Use of topical and systemic retinoids in solid organ transplant recipients: update and review of the current literature. Dermatol Surg 2019; 45 (12) 1442-1449
- 110 Bavinck JN, Tieben LM, Van der Woude FJ. et al. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol 1995; 13 (08) 1933-1938
- 111 McKenna DB, Murphy GM. Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin. Br J Dermatol 1999; 140 (04) 656-660
- 112 George R, Weightman W, Russ GR, Bannister KM, Mathew TH. Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Australas J Dermatol 2002; 43 (04) 269-273
- 113 Hardin J, Mydlarski PR. Systemic retinoids: chemoprevention of skin cancer in transplant recipients. Skin Therapy Lett 2010; 15 (07) 1-4
- 114 Mungamuri SK, Yang X, Thor AD, Somasundaram K. Survival signaling by Notch1: mammalian target of rapamycin (mTOR)-dependent inhibition of p53. Cancer Res 2006; 66 (09) 4715-4724
- 115 Salgo R, Gossmann J, Schöfer H. et al. Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial. Am J Transplant 2010; 10 (06) 1385-1393
- 116 Alberú J, Pascoe MD, Campistol JM. et al; Sirolimus CONVERT Trial Study Group. Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial. Transplantation 2011; 92 (03) 303-310
- 117 Phan K, Moloney FJ, Hogarty DT, Lenane P, McColl D, Yazdabadi A. Mammalian target of rapamycin (mTOR) inhibitors and skin cancer risk in nonrenal solid organ transplant recipients: systematic review and meta-analysis. Int J Dermatol 2019; (epub ahead of print) DOI: 10.1111/ijd.14549.
- 118 Thompson AK, Kelley BF, Prokop LJ, Murad MH, Baum CL. Risk factors for cutaneous squamous cell carcinoma recurrence, metastasis, and disease-specific death: a systematic review and meta-analysis. JAMA Dermatol 2016; 152 (04) 419-428
- 119 Miller J, Chang T, Schwartz D, Peters M, Baum C. Outcomes of adjuvant radiotherapy following negative surgical margins for cutaneous squamous cell carcinoma. Dermatol Surg 2019; 45 (09) 1111-1116
- 120 Stevenson ML, Criscito MC, Wilken R. et al. Use of adjuvant radiotherapy in the treatment of high-risk cutaneous squamous cell carcinoma with perineural invasion. JAMA Dermatol 2020; 156 (08) 918-921