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Comparison of Skin Cancer Incidence in Caucasian and Non-Caucasian Liver Vs. Lung Transplant Recipients: A Tale of Two Regimens

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Abstract

Background

Organ transplantation is a significant risk factor for the development of skin cancer. The impact of skin type, immunosuppressive regimens, and photosensitizing agents requires further study.

Objective

The objective of this study was to compare skin cancer development between Caucasian and non-Caucasian transplant recipients at the University of Southern California.

Methods

We performed a retrospective chart review of lung and liver transplantations to determine the incidence of post-transplant skin cancer. Participants included patients who underwent lung or liver transplantation between 2005 and 2013 at our institution. Patients included in the study were limited to those who survived through the study observation period.

Results

We analyzed 475 patients who underwent transplantation, including 370 liver transplant recipients and 105 lung transplant recipients. Among these, 46.3% identified as Caucasian, while 53.7% were non-Caucasian. Over a mean follow-up of 7.9 years, 11.8% of Caucasian patients developed at least one skin cancer, compared with 2.7% of non-Caucasians (p < 0.001). However, irrespective of race, skin cancer development was significantly greater in lung compared with liver transplant recipients (20.0% vs. 3.2%, p < 0.001). The standard immunosuppressive and prophylactic regimens were mycophenolate mofetil and tacrolimus based for both transplants. Mycophenolate mofetil was maintained throughout the course in lung transplant patients, whereas this agent was reduced and terminated when possible in liver transplant recipients. In addition, during the years examined, voriconazole, a known photosensitizing agent, was used in lung transplant recipients to prevent aspergillosis.

Conclusions

Fair skin type increases post-transplant skin cancer development, irrespective of the immunosuppressive regimen. A higher risk of skin cancer is associated with different regimens; in particular photosensitizing agents may increase risk in transplant recipients.

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References

  1. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003;348(17):1681–91.

    Article  Google Scholar 

  2. Hanlon A, Colegio OR. The cutting edge of skin cancer in transplant recipients: scientific retreat of international transplant Skin Cancer Collaborative and Skin Cancer in Organ Transplant Patients Europe. Am J Transplant. 2014;14(5):1012–5.

    Article  CAS  Google Scholar 

  3. Ho WL, Murphy GM. Update on the pathogenesis of post-transplant skin cancer in renal transplant recipients. Br J Dermatol. 2008;158(2):217–24.

    Article  CAS  Google Scholar 

  4. Alam M, Brown RN, Silber DH, Mullen GM, Feldman DS, Oren RM, et al. Increased incidence and mortality associated with skin cancers after cardiac transplant. Am J Transplant. 2011;11(7):1488–97.

    Article  CAS  Google Scholar 

  5. Chockalingam R, Downing C, Tyring SK. Cutaneous squamous cell carcinomas in organ transplant recipients. J Clin Med. 2015;4(6):1229–39.

    Article  CAS  Google Scholar 

  6. Bouwes Bavinck JN, Euvrard S, Naldi L, Nindl I, Proby CM, Neale R, et al. Keratotic skin lesions and other risk factors are associated with skin cancer in organ-transplant recipients: a case-control study in The Netherlands, United Kingdom, Germany, France, and Italy. J Invest Dermatol. 2007;127(7):1647–56.

    Article  CAS  Google Scholar 

  7. Feist A, Lee R, Osborne S, Lane J, Yung G. Increased incidence of cutaneous squamous cell carcinoma in lung transplant recipients taking long-term voriconazole. J Heart Lung Transplant. 2012;31(11):1177–81.

    Article  Google Scholar 

  8. Ramsay HM, Fryer AA, Reece S, Smith AG, Harden PN. Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. Am J Kidney Dis. 2000;36(1):167–76.

    Article  CAS  Google Scholar 

  9. Zwald FO, Spratt M, Lemos BD, Veledar E, Lawrence C, Marshall Lyon G, et al. Duration of voriconazole exposure: an independent risk factor for skin cancer after lung transplantation. Dermatol Surg. 2012;38(8):1369–74.

    Article  CAS  Google Scholar 

  10. 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(1):106–12.

    Article  Google Scholar 

  11. Hufbauer M, Cooke J, van der Horst GT, Pfister H, Storey A, Akgul B. Human papillomavirus mediated inhibition of DNA damage sensing and repair drives skin carcinogenesis. Mol Cancer. 2015;14:183.

    Article  Google Scholar 

  12. Vadnerkar A, Nguyen MH, Mitsani D, Crespo M, Pilewski J, Toyoda Y, et al. Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients. J Heart Lung Transplant. 2010;29(11):1240–4.

    Article  Google Scholar 

  13. McLaughlin JM, Equils O, Somerville KT, Aram JA, Schlamm HT, Welch VL, et al. Risk-adjusted relationship between voriconazole utilization and non-melanoma skin cancer among lung and heart/lung transplant patients. Transpl Infect Dis. 2013;15(4):329–43.

    Article  CAS  Google Scholar 

  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(1):92–8.

    Article  Google Scholar 

  15. Krynitz B, Edgren G, Lindelof B, Baecklund E, Brattstrom C, Wilczek H, 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(6):1429–38.

    Article  CAS  Google Scholar 

  16. 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(7):997–1002.

    Article  Google Scholar 

  17. Cowen EW, Nguyen JC, Miller DD, McShane D, Arron ST, Prose NS, et al. Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole. J Am Acad Dermatol. 2010;62(1):31–7.

    Article  CAS  Google Scholar 

  18. Epaulard O, Villier C, Ravaud P, Chosidow O, Blanche S, Mamzer-Bruneel MF, et al. A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: results from a French nationwide study. Clin Infect Dis. 2013;57(12):e182–8.

    Article  CAS  Google Scholar 

  19. Hamandi B, Fegbeutel C, Silveira FP, Verschuuren EA, Younus M, Mo J, et al. Voriconazole and squamous cell carcinoma after lung transplantation: a multicenter study. Am J Transplant. 2018;18(1):113–24.

    Article  CAS  Google Scholar 

  20. Ibrahim SF, Singer JP, Arron ST. Catastrophic squamous cell carcinoma in lung transplant patients treated with voriconazole. Dermatol Surg. 2010;36(11):1752–5.

    Article  CAS  Google Scholar 

  21. Singer JP, Boker A, Metchnikoff C, Binstock M, Boettger R, Golden JA, 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(7):694–9.

    Article  Google Scholar 

  22. Clancy CJ, Nguyen MH. Long-term voriconazole and skin cancer: is there cause for concern? Curr Infect Dis Rep. 2011;13(6):536–43.

    Article  Google Scholar 

  23. Cho HG, Kuo KY, Xiao K, Batra P, Li S, Tang JY, et al. Azathioprine and risk of multiple keratinocyte cancers. J Am Acad Dermatol. 2018;78(1):27–8.

    Article  Google Scholar 

  24. 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):3490–503.

    Article  CAS  Google Scholar 

  25. Setshedi M, Epstein D, Winter TA, Myer L, Watermeyer G, Hift R. Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non-melanoma skin cancer in an at-risk population: a cohort study. J Gastroenterol Hepatol. 2012;27(2):385–9.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge Griselda Hagmaier, MBA, MHA for administrative support in the process of obtaining study approval. Findings of this study have been presented in part at the American Academy of Dermatology 2018 annual meeting in San Diego, California by Cohen et al. and Krivitskiy et al.

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Authors and Affiliations

  1. Department of Dermatology, University of Southern California, 1975 Zonal Ave, Los Angeles, CA, 90033, USA

    Brandon E. Cohen & Binh Ngo

  2. School of Medicine, University of Southern California, Los Angeles, CA, USA

    Igor Krivitskiy, Sarah Bui & Kevin Forrester

  3. Department of Pharmacy, University of Southern California, Los Angeles, CA, USA

    Kevin Forrester

  4. Department of Hepatology, University of Southern California, Los Angeles, CA, USA

    Jeffrey Kahn

  5. Department of Pulmonology, University of Southern California, Los Angeles, CA, USA

    Richard Barbers

  6. Rose Salter Medical Research Foundation, Newport Coast, CA, USA

    Binh Ngo

Authors
  1. Brandon E. Cohen
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  2. Igor Krivitskiy
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  3. Sarah Bui
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  4. Kevin Forrester
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  5. Jeffrey Kahn
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  6. Richard Barbers
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  7. Binh Ngo
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Corresponding author

Correspondence to Brandon E. Cohen.

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Funding

No sources of funding were received for the preparation of this article.

Conflict of interest

Brandon E. Cohen, Igor Krivitskiy, Sarah Bui, Kevin Forrester, Jeffrey Kahn, Richard Barbers, and Binh Ngo have no conflicts of interest that are directly relevant to the contents of this article.

Ethics approval

The Institutional Review Board of the University of Southern California approved this study.

Consent to participate

Informed consent was not obtained because of the retrospective nature of this study and the determination of lack of potential harm to subjects.

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Cohen, B.E., Krivitskiy, I., Bui, S. et al. Comparison of Skin Cancer Incidence in Caucasian and Non-Caucasian Liver Vs. Lung Transplant Recipients: A Tale of Two Regimens. Clin Drug Investig 39, 197–203 (2019). https://doi.org/10.1007/s40261-018-0732-3

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  • DOI: https://doi.org/10.1007/s40261-018-0732-3

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