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1
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Hren MG, Silva I, Gulati N, Ungar J, Lewin J, Ji A. Utilization of an Email-Based Referral System to Streamline Skin Cancer Screenings Among Solid Organ Transplant Recipients. J Cutan Med Surg 2025:12034754251336200. [PMID: 40304237 DOI: 10.1177/12034754251336200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2025]
Affiliation(s)
- M Grace Hren
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Renaissance School of Medicine, Stony Brook University, Stony Brook NY, USA
| | - Isabel Silva
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Rutgers New Jersey Medical School, Newark, NJ, USA
| | | | - Jonathan Ungar
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jesse Lewin
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Andrew Ji
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
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2
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Mansilla-Polo M. Should patients undergoing hematopoietic stem cell transplantation undergo screening and monitoring for skin cancer? An Bras Dermatol 2025; 100:372-373. [PMID: 39799031 PMCID: PMC11963109 DOI: 10.1016/j.abd.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/19/2024] [Accepted: 06/25/2024] [Indexed: 01/15/2025] Open
Affiliation(s)
- Miguel Mansilla-Polo
- Department of Dermatology, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Instituto de Investigación Sanitaria (IIS) La Fe, Valencia, Spain; Universitat de València, Valencia, Spain, Dermatology, Valencia, Spain.
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3
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Broman KK, Meng Q, Holmqvist A, Balas N, Richman J, Landier W, Hageman L, Ross E, Bosworth A, Te HS, Hollenquest B, Wong FL, Bhatia R, Forman SJ, Armenian SH, Weisdorf DJ, Bhatia S. Incidence of and Risk Factors for Cutaneous Malignant Neoplasms After Blood or Marrow Transplant. JAMA Dermatol 2025; 161:265-273. [PMID: 39693095 PMCID: PMC11923705 DOI: 10.1001/jamadermatol.2024.5129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 10/08/2024] [Indexed: 12/19/2024]
Abstract
Importance Cutaneous malignant neoplasms are the most common subsequent neoplasm after blood or marrow transplant (BMT), but a full assessment among survivors is lacking. Objective To identify risk factors for subsequent cutaneous malignant neoplasms using the BMT Survivor Study (BMTSS). Design, Setting, and Participants This retrospective cohort study included patients who underwent transplant from 1974 to 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and survived 2 years or longer, as well as a comparison cohort of siblings. Both groups completed the BMTSS survey. Data analysis took place from October 2022 to October 2024. Exposures Demographics, pre-BMT and BMT-related therapeutic exposures, chronic graft-vs-host disease (cGVHD), and posttransplant immunosuppression. Main Outcomes and Measures Incident cutaneous malignant neoplasms (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) after BMT. Exposures were evaluated for association with subsequent neoplasms using proportional subdistribution hazards models (reported as subdistribution hazard ratio [SHR] and 95% CI). Results Among the 3880 BMT survivors (median [range] age at BMT, 44.0 [0-78.0] years; 2165 [55.8%] male; 190 [4.9%] Black, 468 [12.1%] Hispanic, 2897 [74.7%] non-Hispanic White, and 325 [8.4%] of other race [including Asian and Pacific Islander] and multiracial) who were followed up for a median (range) of 9.5 (2.0-46.0) years, 605 developed 778 distinct cutaneous neoplasms (BCC, 321; SCC, 231; melanoma, 78; and unknown type, 148). The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% (BCC, 18.0%; SCC, 9.8%; and melanoma, 3.7%). Seventy-year cumulative probabilities of BCC, SCC, and melanoma were considerably higher in BMT survivors than siblings (18.1% vs 8.2%, 14.7% vs 4.2%, and 4.2% vs 2.4%, respectively). Among BMT survivors, risk factors for subsequent cutaneous malignant neoplasms included age of 50 years and older at BMT (BCC: SHR, 1.76; 95% CI, 1.36-2.29; SCC: SHR, 3.37; 95% CI, 2.41-4.72), male sex (BCC: SHR, 1.39; 95% CI, 1.10-1.75; SCC: SHR, 1.85; 95% CI, 1.39-2.45), pre-BMT monoclonal antibody exposure (BCC: SHR, 1.71; 95% CI, 1.27-2.31), allogeneic BMT with cGVHD (BCC: SHR, 1.48; 95% CI, 1.06-2.08; SCC: SHR, 2.61; 95% CI, 1.68-4.04 [reference: autologous BMT]), post-BMT immunosuppression (BCC: SHR, 1.63; 95% CI, 1.24-2.14; SCC: SHR, 1.48; 95% CI, 1.09-2.02; melanoma: SHR, 1.90; 95% CI, 1.16-3.12), and transplant at City of Hope (BCC: SHR, 3.55; 95% CI, 2.58-4.89; SCC: SHR, 3.57; 95% CI, 2.34-5.47 [reference: University of Minnesota]) or University of Alabama at Birmingham (BCC: SHR, 2.35; 95% CI, 1.35-4.23; SCC: SHR, 2.63; 95% CI, 1.36-5.08 [reference: University of Minnesota]). Race and ethnicity other than non-Hispanic White were protective for BCC (Black: no cases; Hispanic: SHR, 0.27; 95% CI, 0.16-0.44; other race and multiracial: SHR, 0.26; 95% CI, 0.14-0.50 [reference: non-Hispanic White]) and SCC (Black: SHR, 0.17; 95% CI, 0.04-0.67; Hispanic: SHR, 0.28; 95% CI, 0.16-0.50; other race and multiracial: SHR, 0.13; 95% CI, 0.05-0.37 [reference: non-Hispanic White]). Total body irradiation was associated with BCC risk among those younger than 50 years at BMT (SHR, 1.92; 95% CI, 1.27-2.92). Conclusions and Relevance In this cohort study, the high risk of cutaneous malignant neoplasms and malignant-specific risk factors suggest a need for personalized patient counseling and posttransplant dermatologic surveillance.
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Affiliation(s)
- Kristy K. Broman
- University of Alabama at Birmingham, Birmingham
- Birmingham VA Medical Center, US Department of Veterans Affairs, Birmingham, Alabama
| | | | - Anna Holmqvist
- Childhood Cancer Center, Skane University Hospital, Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Nora Balas
- University of Alabama at Birmingham, Birmingham
| | | | | | | | | | | | | | | | | | - Ravi Bhatia
- University of Alabama at Birmingham, Birmingham
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Navsaria LJ, Liao K, Veerabagu S, Hinkston CL, Wehner MR. Actinic Keratosis Incidence in Solid Organ Transplant Recipients. JAMA Dermatol 2025; 161:334-336. [PMID: 39937503 PMCID: PMC11822593 DOI: 10.1001/jamadermatol.2024.5997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/01/2024] [Indexed: 02/13/2025]
Abstract
This cohort study examines the incidence of actinic keratoses, which are possible precursors to skin cancer, especially squamous cell carcinoma, after solid organ transplant.
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Affiliation(s)
- Lucy J. Navsaria
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston
| | - Kaiping Liao
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston
| | - Surya Veerabagu
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston
- Department of Dermatology, University of New Mexico, Albuquerque
| | - Candice L. Hinkston
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston
| | - Mackenzie R. Wehner
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston
- Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston
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5
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Mansilla-Polo M, López-Davia J, Morgado-Carrasco D. Mucocutaneous Alterations After Hematopoietic Stem Cell Transplantation: Literature Update and Review. ACTAS DERMO-SIFILIOGRAFICAS 2025:S0001-7310(25)00108-5. [PMID: 40024597 DOI: 10.1016/j.ad.2024.09.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 09/22/2024] [Indexed: 03/04/2025] Open
Abstract
In recent years, hematopoietic stem cell transplantation (HSCT) has revolutionized the treatment of various hematological and non-hematological diseases. Its implementation is not stranger to risks and involves a significant rate of complications, including mucocutaneous adverse events. We present a narrative review of the mucocutaneous alterations observed after HSCT. Among these, acute and chronic graft-versus-host disease (GVHD) stand out, whose diagnosis and treatment can be challenging. Other common conditions include cutaneous adverse reactions and infections with mucocutaneous involvement. Additionally, various studies indicate that these individuals may have a higher rate of mucocutaneous neoplasms. Early identification and management of these complications, along with a multidisciplinary approach, are essential to improving these patients' quality of life and long-term outcomes. Furthermore, it is advisable to screen for skin cancer in these individuals, especially if they have other associated risk factors.
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Affiliation(s)
- M Mansilla-Polo
- Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, España; Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, España; Departamento de Dermatología, Facultad de Medicina, Universidad de Valencia, Valencia, España
| | - J López-Davia
- Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, España; Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, España
| | - D Morgado-Carrasco
- Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España; Servicio de Dermatología, Hospital de Figueres, Fundació Salut Empordà, Figueres, España.
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6
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Mohr C, Li Y, Navsaria LJ, Hinkston CL, Wehner MR. Allogeneic Hematopoietic Stem Cell Transplant Recipients and Skin Cancer Risk: A Commercial Claims Cohort Study. J Invest Dermatol 2025:S0022-202X(25)00002-8. [PMID: 39798785 DOI: 10.1016/j.jid.2024.10.617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 10/25/2024] [Accepted: 10/29/2024] [Indexed: 01/15/2025]
Affiliation(s)
| | - Yao Li
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Lucy J Navsaria
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Candice L Hinkston
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Mackenzie R Wehner
- Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
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Mosley D, Madden C, Ike J, Smith IT, Grossarth S, Wheless L. Human leukocyte antigen type does not improve risk stratification for SUNTRAC score in solid organ transplant recipients: A cohort study. JAAD Int 2024; 17:80-81. [PMID: 39411238 PMCID: PMC11474204 DOI: 10.1016/j.jdin.2024.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024] Open
Affiliation(s)
| | - Christopher Madden
- State University of New York Downstate College of Medicine, Brooklyn, New York
| | | | - Isabelle T. Smith
- Vanderbilt University College of Arts and Sciences, Nashville, Tennessee
| | - Sarah Grossarth
- Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee
| | - Lee Wheless
- Tennessee Valley Healthcare System VA Medical Center, Nashville, Tennessee
- Department of Medicine, Division of Epidemiology and Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee
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8
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Struckmeier AK, Gosau M, Smeets R. Cutaneous squamous cell carcinoma in solid organ transplant recipients: Current therapeutic and screening strategies. Transplant Rev (Orlando) 2024; 38:100882. [PMID: 39348772 DOI: 10.1016/j.trre.2024.100882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 10/02/2024]
Abstract
Solid organ transplant recipients (SOTRs) are particularly prone to developing malignancies, often manifesting multiple tumors and tumors with a heightened susceptibility to metastasis, resulting in much lower survival rates when compared to the general population. Among these, cutaneous squamous cell carcinoma (CSCC) respresent a major challenge in terms of morbidity and mortality following organ transplantation. The management of post-transplant CSCC requires expertise from various disciplines, including dermatology, maxillofacial surgery, transplant medicine, radiation oncology, and medical oncology. Furthermore, the unique behaviors and prevalence of tumors in SOTRs necessitate tailored pathways for screening and treatment, distinct from those designed for immunocompetent patients. Despite the proven efficacy of immune checkpoint inhibitors (ICIs) in several cancers, SOTRs have often been systematically excluded from clinical trials due to concerns about potential allograft rejection and loss. Consequently, most data on the safety and efficacy of ICIs in SOTRs are derived from case series and reports. Given the significant risks involved, alternative therapeutic options should be thoroughly discussed with patients before considering ICI therapy. This literature review aims to provide an overview of CSCC in SOTRs, with a specific emphasis on therapeutic and screening strategies, particularly highlighting immunotherapy.
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Affiliation(s)
- Ann-Kristin Struckmeier
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
| | - Martin Gosau
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
| | - Ralf Smeets
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Department of Oral and Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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9
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Korzeniowski P, Griffith C, Young PA. Update on skin cancer prevention modalities and screening protocols in solid organ transplant recipients: a scoping review. Arch Dermatol Res 2024; 317:52. [PMID: 39589541 DOI: 10.1007/s00403-024-03551-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 10/25/2024] [Accepted: 11/12/2024] [Indexed: 11/27/2024]
Abstract
Solid organ transplant recipients (SOTRs) are at significantly increased risk for skin cancer, particularly due to lifelong immunosuppressant use. Despite this risk, standardized guidelines for skin cancer risk stratification and screening in SOTRs are lacking in the United States. This scoping review aims to summarize existing evidence on skin cancer prevention and screening protocols to inform the development of standardized guidelines. A systematic search was conducted using OVID, MEDLINE, and CINAHL Plus databases, focusing on English-language articles published between January 1, 2019, and February 12, 2023. The review included studies addressing skin cancer risk stratification, screening, and preventive therapies in adult SOTRs. Data extraction followed the JBI Manual for Evidence Synthesis PRISMA guidelines, with articles graded for quality using the Strength of Recommendation Taxonomy (SORT). Thirty-six articles were included in the review. The findings revealed that most studies focused on skin cancer screening protocols (36%) and chemoprevention treatments (31%) for SOTRs. The SUNTRAC tool, developed in 2019, emerged as a validated risk stratification model. Preventive strategies identified include systemic treatments like low-dose acitretin, capecitabine, niacinamide, and topical therapies such as 5-fluorouracil and photodynamic therapy. Preventive strategy strength of evidence was graded and summarized into a practical reference table. Patient education, particularly through electronic methods, was highlighted as essential for fostering photoprotective behaviors. The review highlights the need for standardized skin cancer screening and prevention guidelines for SOTRs, with the SUNTRAC tool providing a robust model for risk stratification. Future research should focus on validating the SUNTRAC tool across diverse populations, conducting randomized controlled trials on topical chemoprevention, and enhancing patient education, particularly among Skin of Color patients.
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Affiliation(s)
- Pamela Korzeniowski
- Department of Dermatology, Veterans Administration of North Texas, Fort Worth, TX, USA.
| | - Cynthia Griffith
- Department of Dermatology, University of Texas Southwestern, Dallas, TX, USA
| | - Peter A Young
- Department of Dermatology, Kaiser Permanente, Roseville, CA, USA
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10
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Anderson JR, Demehri S. Time to first skin cancer diagnosis following kidney transplant. J Am Acad Dermatol 2024; 91:973-974. [PMID: 39025265 DOI: 10.1016/j.jaad.2024.06.085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 04/16/2024] [Accepted: 06/24/2024] [Indexed: 07/20/2024]
Affiliation(s)
| | - Shadmehr Demehri
- Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts.
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Veerabagu SA, Liao KP, Jambusaria-Pahlajani A, Wheless L, Wehner MR. Dermatology Encounters After Solid Organ Transplant. JAMA Dermatol 2024; 160:1246-1248. [PMID: 39320874 PMCID: PMC11425182 DOI: 10.1001/jamadermatol.2024.3173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 07/09/2024] [Indexed: 09/26/2024]
Abstract
This cohort study describes the use of the Skin and UV Neoplasia Transplant Risk Assessment Calculator tool for transplant recipients.
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Affiliation(s)
- Surya A. Veerabagu
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston
| | - Kai-Ping Liao
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston
| | | | - Lee Wheless
- Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Mackenzie R. Wehner
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston
- Department of Health Services Research, Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston
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12
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Jew OS, Liu WW, Stamey C, Kheterpal M, Myers SA, Ellis MJ, Byrns J, Wheless L, Whitley MJ. De novo belatacept does not reduce the rate of skin cancer in renal transplant recipients compared to standard therapy. J Am Acad Dermatol 2024; 91:720-722. [PMID: 38844009 PMCID: PMC11416314 DOI: 10.1016/j.jaad.2024.05.068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/22/2024] [Accepted: 05/07/2024] [Indexed: 06/19/2024]
Affiliation(s)
- Olivia S Jew
- Department of Dermatology, Duke University Health System, Durham, North Carolina
| | - Winston W Liu
- Duke University School of Medicine, Durham, North Carolina
| | - Christopher Stamey
- Department of Dermatology, Duke University Health System, Durham, North Carolina
| | - Meenal Kheterpal
- Department of Dermatology, Duke University Health System, Durham, North Carolina
| | - Sarah A Myers
- Department of Dermatology, Duke University Health System, Durham, North Carolina
| | - Matthew J Ellis
- Department of Medicine, Duke University Health System, Durham, North Carolina
| | - Jennifer Byrns
- Department of Pharmacy, Duke University Health System, Durham, North Carolina
| | - Lee Wheless
- Tennessee Valley Healthcare System VA Medical Center, Nashville, Tennessee; Department of Dermatology, Vanderbilt University Medicine Center, Nashville, Tennessee
| | - Melodi Javid Whitley
- Department of Dermatology, Duke University Health System, Durham, North Carolina.
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13
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Rosenthal BE, Schaubel DE, Lewis JD, Margolis DJ, Goldberg DS, Bittermann T. Immunosuppression regimen and latitude impact keratinocyte carcinoma risk in U.S. liver transplant recipients. Arch Dermatol Res 2024; 316:641. [PMID: 39325226 PMCID: PMC11427564 DOI: 10.1007/s00403-024-03404-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 09/05/2024] [Accepted: 09/14/2024] [Indexed: 09/27/2024]
Abstract
Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54-66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02-1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34-1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02-1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08-1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management.
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Affiliation(s)
| | - Douglas E Schaubel
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA
| | - James D Lewis
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - David J Margolis
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, Miami, FL, USA
| | - Therese Bittermann
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Hospital of the University of Pennsylvania, 2 Dulles - Penn Transplant Institute, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
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14
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Brufau-Cochs M, Mansilla-Polo M, Morgado-Carrasco D. [Translated article] Risk of Skin Cancer Associated with Disease-Modifying Therapies in Multiple Sclerosis: A Comprehensive Evidence Review. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:T781-T790. [PMID: 38972584 DOI: 10.1016/j.ad.2024.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 12/04/2023] [Accepted: 01/10/2024] [Indexed: 07/09/2024] Open
Abstract
The use of disease-modifying therapies (DMT) has led to a paradigm shift in the management of multiple sclerosis. A comprehensive narrative review was conducted through an extensive literature search including Medline and Google Scholar to elucidate the link between DMT and the propensity of cutaneous malignancies. Sphingosine-1-phosphate receptor modulators, such as fingolimod and siponimod are associated with a higher risk of basal cell carcinoma (BCC), but not squamous cell carcinoma, or melanoma. The associated physiopathological mechanisms are not fully understood. Alemtuzumab and cladribine show isolated associations with skin cancer. Regarding other DMT, no increased risk has ever been found. Given the evidence currently available, it is of paramount importance to advocate for necessary dermatological assessments that should be individualized to the risk profile of each patient. Nonetheless, additional prospective studies are still needed to establish efficient dermatological follow-up protocols.
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Affiliation(s)
- M Brufau-Cochs
- Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - M Mansilla-Polo
- Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Instituto de Investigación Sanitaria (IIS) La Fe, Valencia, Spain
| | - D Morgado-Carrasco
- Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain; Servicio de Dermatología, Hospital de Figueres, Fundació Salut Empordá, Figueres, Girona, Spain.
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15
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Brufau-Cochs M, Mansilla-Polo M, Morgado-Carrasco D. Risk of skin cancer associated with disease-modifying therapies in multiple sclerosis: a comprehensive evidence review. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:781-790. [PMID: 38307166 DOI: 10.1016/j.ad.2024.01.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 12/04/2023] [Accepted: 01/10/2024] [Indexed: 02/04/2024] Open
Abstract
The use of disease-modifying therapies (DMT) has led to a paradigm shift in the management of multiple sclerosis. A comprehensive narrative review was conducted through an extensive literature search including Medline and Google Scholar to elucidate the link between DMT and the propensity of cutaneous malignancies. Sphingosine-1-phosphate receptor modulators, such as fingolimod and siponimod are associated with a higher risk of basal cell carcinoma (BCC), but not squamous cell carcinoma, or melanoma. The associated physiopathological mechanisms are not fully understood. Alemtuzumab and cladribine show isolated associations with skin cancer. Regarding other DMT, no increased risk has ever been found. Given the evidence currently available, it is of paramount importance to advocate for necessary dermatological assessments that should be individualized to the risk profile of each patient. Nonetheless, additional prospective studies are still needed to establish efficient dermatological follow-up protocols.
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Affiliation(s)
- M Brufau-Cochs
- Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España
| | - M Mansilla-Polo
- Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, España; Instituto de Investigación Sanitaria (IIS) La Fe, Valencia, España
| | - D Morgado-Carrasco
- Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España; Servicio de Dermatología, Hospital de Figueres, Fundació Salut Empordá, Figueres, Girona, España.
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16
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Szeimies RM, Ulrich C, Ferrándiz-Pulido C, Hofbauer GFL, Lear JT, Lebbé C, Piaserico S, Hædersdal M. The "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) Project: An Expert Panel Opinion. Dermatol Ther (Heidelb) 2024; 14:1739-1753. [PMID: 38902589 PMCID: PMC11264500 DOI: 10.1007/s13555-024-01215-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 06/11/2024] [Indexed: 06/22/2024] Open
Abstract
Actinic keratosis (AK) is an intraepithelial condition characterized by the development of scaly, erythematous lesions after repeated exposure to ultraviolet radiation. Significant immunosuppression is a risk factor for the development of AK and subsequent lesion progression to squamous cell carcinoma. Immunocompromised patients (ICPs), particularly organ transplant recipients, often have more advanced or complex AK presentations and an increased risk of skin carcinomas versus non-ICPs with AK, making lesions more difficult to treat and resulting in worse treatment outcomes. The recent "Personalising Actinic Keratosis Treatment" (PAKT) consensus reported that delivering patient-centric care may play a role in supporting better clinical outcomes and patient satisfaction with treatments for chronic dermatologic conditions such as AK, which require repeated cycles of treatment. Additionally, currently published guidance and recommendations were considered by the PAKT panel to be overly broad for managing ICPs with their unique and complex needs. Therefore, the "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) panel was established to build upon general recommendations from the PAKT consensus. The panel identified current gaps in guidance for AK care in ICPs, offered practical care approaches based on typical ICP scenarios, and highlighted the need to adapt AK management to optimize care and improve treatment outcomes in ICPs. In particular, dermatologists should establish collaborative and transparent relationships with patients' multidisciplinary teams to enhance overall care for patients' comorbidities: given their increased risk of progression to malignancy, earlier assessments/interventions and frequent follow-ups are vital.The panel also developed a novel "triage" tool outlining effective treatment follow-up and disease surveillance plans tailored to patients' risk profiles, guided by current clinical presentation and relevant medical history. Additionally, we present the panel's expert opinion on three fictional ICP scenarios to explain their decision-making process for assessing and managing typical ICPs that they may encounter in clinical practice.
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Affiliation(s)
- Rolf-Markus Szeimies
- Department of Dermatology & Allergology, Klinikum Vest GmbH Academic Teaching Hospital, Recklinghausen, Germany.
| | - Claas Ulrich
- GmbH & Department of Dermatology, Collegium Medicum, Charité Universitätsmedizin, Berlin, Germany
| | - Carla Ferrándiz-Pulido
- Department of Dermatology, University Hospital Vall d'Hebron, Barcelona, Spain
- Factultad de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Gunther F L Hofbauer
- Universität Zürich, Zurich, Switzerland
- Dermatologische Klinik, Universitätsspital Zürich, Zurich, Switzerland
| | - John Thomas Lear
- Department of Dermatology, Mid Cheshire Hospitals NHS Foundation Trust, Crewe, UK
- Manchester Academic Health Science Centre, Manchester, UK
| | - Celeste Lebbé
- Dermato-Oncology and CIC AP-HP Hôpital Saint Louis, INSERM U976, Université Paris Cite, Paris, France
| | - Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - Merete Hædersdal
- Department of Dermatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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17
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Zwald FO, Sargen MR, Austin AA, Hsieh MC, Pawlish K, Li J, Lynch CF, Yu KJ, Engels EA. Outcomes in solid organ transplant recipients with a pretransplant diagnosis of melanoma. Am J Transplant 2024; 24:993-1002. [PMID: 38387619 PMCID: PMC11144558 DOI: 10.1016/j.ajt.2024.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 02/05/2024] [Accepted: 02/05/2024] [Indexed: 02/24/2024]
Abstract
Melanoma causes significant morbidity in solid organ transplant recipients (SOTRs). Melanomas diagnosed before transplantation can recur with intensive immunosuppression, but outcomes have not been well studied. We evaluated 901 non-Hispanic White SOTRs with a pretransplant melanoma identified using linked transplant and cancer registry data in the United States. Most pretransplant melanomas were invasive (60.7%), and the median time from diagnosis to transplantation was 5.1 years. After transplantation, 41 SOTRs developed a new invasive melanoma, corresponding to 9-fold increased risk compared with the general population (standardized incidence ratio, 9.2; 95% confidence interval [CI], 6.6-12). Twenty-two SOTRs died from melanoma after transplantation, corresponding to 52-fold increased risk (standardized mortality ratio, 52; 95% CI, 33-79). Risk factors for posttransplant melanoma included age at transplantation (adjusted hazard ratio [HR], 2.86; 95% CI, 1.24-6.60; for age 55+ vs <55 years) and maintenance immunosuppression with cyclosporine/azathioprine (adjusted HR, 2.53; 95% CI, 1.08-5.90). Melanoma mortality was strongly elevated after a posttransplant melanoma diagnosis (HR, 35.6; 95% CI, 14.0-90.4; adjusted for cyclosporine/azathioprine maintenance therapy and calendar year of transplantation). In conclusion, SOTRs with a pretransplant melanoma are at risk of adverse melanoma-related outcomes after transplantation. These findings support thorough dermatologic evaluation prior to transplantation and frequent posttransplant surveillance.
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Affiliation(s)
- Fiona O Zwald
- Department of Dermatology, University of Colorado, Aurora, Colorado, USA
| | - Michael R Sargen
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
| | | | - Mei-Chin Hsieh
- Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
| | - Karen Pawlish
- New Jersey Department of Health, New Jersey State Cancer Registry, Trenton, New Jersey, USA
| | - Jie Li
- New Jersey Department of Health, New Jersey State Cancer Registry, Trenton, New Jersey, USA
| | - Charles F Lynch
- Department of Epidemiology, The University of Iowa, Iowa City, Iowa, USA
| | - Kelly J Yu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
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18
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de Jong E, Genders R, Harwood CA, Green AC, Plasmeijer EI, Proby C, Geissler E, Ferrándiz-Pulido C, Ducroux E, Euvrard S, Geusau A, Jahn-Bassler K, Borik-Heil L, Rácz E, Nägeli M, Hofbauer GFL, Piaserico S, Russo I, Mackintosh L, Borges-Costa J, Angeliki-Gkini M, Zavattaro E, Savoia P, Imko-Walszuk B, Dębska-Slizień A, Garmyn M, van Kelst S, Ricar J, Cetkovska P, Matin R, Güleç AT, Seçkin D, Anene CA, Oliveira WRP, Rademaker M, Goeman J, van Geloven N, Ruiz E, Murad F, Karn E, Schmults CD, Bouwes Bavinck JN. Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study. J Am Acad Dermatol 2024; 90:1200-1209. [PMID: 38301923 DOI: 10.1016/j.jaad.2024.01.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 11/23/2023] [Accepted: 01/07/2024] [Indexed: 02/03/2024]
Abstract
INTRODUCTION Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.
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Affiliation(s)
- Estella de Jong
- Department of Dermatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
| | - Roel Genders
- Department of Dermatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Catherine A Harwood
- Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
| | - Adèle C Green
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Elsemieke I Plasmeijer
- Department of Dermatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands; Department of Dermatology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Charlotte Proby
- Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Edward Geissler
- Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | | | - Emilie Ducroux
- Department of Dermatology, Edouard Herriot Hospital, Lyon, France
| | - Sylvie Euvrard
- Department of Dermatology, Edouard Herriot Hospital, Lyon, France
| | - Alexandra Geusau
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Karin Jahn-Bassler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Liliane Borik-Heil
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Emõke Rácz
- Department of Dermatology, University Medical Centre Groningen (UMCG), University of Groningen, Groningen, The Netherlands
| | - Mirjam Nägeli
- Department of Dermatology, University Hospital of Zürich, University of Zürich, Zürich, Switzerland
| | - Günther F L Hofbauer
- Department of Dermatology, University Hospital of Zürich, University of Zürich, Zürich, Switzerland
| | - Stefano Piaserico
- Unit of Dermatology, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Irene Russo
- Unit of Dermatology, Department of Medicine (DIMED), University of Padua, Padua, Italy; Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, IOV-IRCSS, Padua, Italy
| | - Lorna Mackintosh
- Department of Dermatology, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
| | - João Borges-Costa
- Department of Dermatology, Hospital de Santa Maria and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Maria Angeliki-Gkini
- Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
| | - Elisa Zavattaro
- Dermatology Unit, Departments of Translational Medicine and Health Science, University of Eastern Piedmont, Novara, Italy
| | - Paola Savoia
- Dermatology Unit, Departments of Translational Medicine and Health Science, University of Eastern Piedmont, Novara, Italy
| | - Beata Imko-Walszuk
- N Dermatology and STD Outpatient Clinic, Copernicus Medical Centre, Gdansk, Poland
| | - Alicja Dębska-Slizień
- Department of Nephrology, Transplantology and Internal Medicine, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland
| | - Marjan Garmyn
- Department of Dermatology, University Hospitals Leuven, Leuven, Belgium
| | - Sofie van Kelst
- Department of Dermatology, University Hospitals Leuven, Leuven, Belgium
| | - Jan Ricar
- Department of Dermatovenereology, Charles University Hospital, Pilsen, Czech Republic
| | - Petra Cetkovska
- Department of Dermatovenereology, Charles University Hospital, Pilsen, Czech Republic
| | - Rubeta Matin
- Department of Dermatology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Ayşe Tülin Güleç
- Department of Dermatology, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Deniz Seçkin
- Department of Dermatology, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Chinedu Anthony Anene
- Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Centre for Cancer Biology and Therapy, School of Applied Sciences, London South Bank University, London, United Kingdom
| | | | - Marius Rademaker
- Department of Dermatology, Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand
| | - Jelle Goeman
- Department of Biomedical Data Sciences, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Nan van Geloven
- Department of Biomedical Data Sciences, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Emily Ruiz
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Fadi Murad
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Emily Karn
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts
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19
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Eggermont CJ, Hollestein LM, Hollatz A, Louwman M, Mooyaart AL, Nijsten T, Wakkee M. Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies: A nationwide cohort study. J Am Acad Dermatol 2024; 90:530-536. [PMID: 37871807 DOI: 10.1016/j.jaad.2023.10.036] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 10/01/2023] [Accepted: 10/16/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. OBJECTIVE To investigate the cumulative incidence and timing of subsequent cSCCs. METHODS Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. RESULTS Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. LIMITATIONS Only histopathologically confirmed cSCCs were included. CONCLUSION The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.
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Affiliation(s)
- Celeste J Eggermont
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Loes M Hollestein
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | - Andrya Hollatz
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Marieke Louwman
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | - Antien L Mooyaart
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Tamar Nijsten
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Marlies Wakkee
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands.
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20
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Wunderlich K, Suppa M, Gandini S, Lipski J, White JM, Del Marmol V. Risk Factors and Innovations in Risk Assessment for Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma. Cancers (Basel) 2024; 16:1016. [PMID: 38473375 DOI: 10.3390/cancers16051016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/22/2024] [Accepted: 02/28/2024] [Indexed: 03/14/2024] Open
Abstract
Skin cancer is the most frequently diagnosed cancer globally and is preventable. Various risk factors contribute to different types of skin cancer, including melanoma, basal cell carcinoma, and squamous cell carcinoma. These risk factors encompass both extrinsic, such as UV exposure and behavioral components, and intrinsic factors, especially involving genetic predisposition. However, the specific risk factors vary among the skin cancer types, highlighting the importance of precise knowledge to facilitate appropriate early diagnosis and treatment for at-risk individuals. Better understanding of the individual risk factors has led to the development of risk scores, allowing the identification of individuals at particularly high risk. These advances contribute to improved prevention strategies, emphasizing the commitment to mitigating the impact of skin cancer.
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Affiliation(s)
- K Wunderlich
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - M Suppa
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
- Department of Dermatology, Institute Jules Bordet, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - S Gandini
- Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology, IRCCS, 20139 Milan, Italy
| | - J Lipski
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - J M White
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - V Del Marmol
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
- Department of Dermatology, Institute Jules Bordet, Université Libre de Bruxelles, 1070 Brussels, Belgium
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21
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O'Connell KA, Groover MK, Lim S, Kus KJB, Gupta N, Murad F, Ruiz ES. Cost of skin cancer-related dermatological care is higher in transplant recipients compared with nonimmunosuppressed patients. J Am Acad Dermatol 2024; 90:150-152. [PMID: 37666426 DOI: 10.1016/j.jaad.2023.08.077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 08/23/2023] [Accepted: 08/27/2023] [Indexed: 09/06/2023]
Affiliation(s)
- Katie A O'Connell
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Morgan K Groover
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Subin Lim
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; School of Medicine, Eastern Virginia Medical School, Norfolk, Virginia
| | - Kylee J B Kus
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Neha Gupta
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Fadi Murad
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Emily S Ruiz
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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22
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Yoo LJH, Bowe S, Quigley C, Victory L, Devenney C, Lenane P. Assessing the Skin and UV Neoplasia Transplant Risk Assessment Calculator in an Irish cohort of thoracic organ transplant recipients. Clin Exp Dermatol 2023; 49:68-70. [PMID: 37656020 DOI: 10.1093/ced/llad298] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 08/20/2023] [Accepted: 08/24/2023] [Indexed: 09/02/2023]
Abstract
The Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) is a tool that can be used to decide when to first screen for skin cancer in organ transplant recipients (OTRs). The objective of this study was to assess the applicability of this tool in thoracic OTRs. Based on data from patient files, the OTRs were categorized into four risk groups according to the SUNTRAC tool. The time of the first post-transplant skin cancer in each OTR was recorded. The proportion of OTRs with post-transplant skin cancer in the low-, medium-, high- and very high-risk groups was 0%, 28.3%, 58.3% and 100%, respectively. This positive correlation suggests that SUNTRAC can be used to determine when to first screen for skin cancer in heart and lung OTRs.
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Affiliation(s)
- Li Jie Helena Yoo
- Department of Dermatology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Stephanie Bowe
- Department of Dermatology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Claire Quigley
- Department of Dermatology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Liana Victory
- Department of Dermatology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Ciara Devenney
- Department of Dermatology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Patsy Lenane
- Department of Dermatology, Mater Misericordiae University Hospital, Dublin, Ireland
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23
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Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, van Akkooi A, Bataille V, Bastholt L, Dreno B, Dummer R, Fargnoli MC, Forsea AM, Harwood CA, Hauschild A, Hoeller C, Kandolf-Sekulovic L, Kaufmann R, Kelleners-Smeets NW, Lallas A, Leiter U, Malvehy J, Del Marmol V, Moreno-Ramirez D, Pellacani G, Peris K, Saiag P, Tagliaferri L, Trakatelli M, Ioannides D, Vieira R, Zalaudek I, Arenberger P, Eggermont AMM, Röcken M, Grob JJ, Lorigan P. European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention-Update 2023. Eur J Cancer 2023; 193:113251. [PMID: 37717283 DOI: 10.1016/j.ejca.2023.113251] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 07/18/2023] [Indexed: 09/19/2023]
Abstract
Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in white populations, accounting for 20% of all cutaneous malignancies. Overall, cSCC mostly has very good prognosis after treatment, with 5-year cure rates greater than 90%. Despite the overall favourable prognosis and the proportionally rare deaths, cSCC is associated with a high total number of deaths due to its high incidence. A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS), the European Academy of Dermatology and Venereology (EADV) and the European Organization of Research and Treatment of Cancer (EORTC), was formed to update recommendations on cSCC, based on current literature and expert consensus. Part 1 of the guidelines addresses the updates on classification, epidemiology, diagnosis, risk stratification, staging and prevention in immunocompetent as well as immunosuppressed patients.
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Affiliation(s)
- Alexander J Stratigos
- First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece.
| | - Claus Garbe
- Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | - Clio Dessinioti
- First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece
| | - Celeste Lebbe
- Université Paris Cite, Dermato-Oncology AP-HP Hôpital Saint Louis, Cancer Institute APHP. Nord-Université Paris Cite, INSERM U976, Paris, France
| | - Alexander van Akkooi
- Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia
| | | | - Lars Bastholt
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Brigitte Dreno
- Nantes Université, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes, France
| | - Reinhard Dummer
- Skin Cancer Centre at University Hospital Zurich, Zurich, Switzerland
| | - Maria Concetta Fargnoli
- Dermatology Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Ana Maria Forsea
- Carol Davila University of Medicine and Pharmacy Bucharest, Department of Oncologic Dermatology, Elias University Hospital Bucharest, Bucharest, Romania
| | - Catherine A Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Axel Hauschild
- Department of Dermatology, University Hospital (UKSH), Kiel, Germany
| | - Christoph Hoeller
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | | | - Roland Kaufmann
- Department of Dermatology, Venereology and Allergology, Frankfurt University Hospital, Frankfurt, Germany
| | - Nicole Wj Kelleners-Smeets
- GROW-School for Oncology and Reproduction, Maastricht, the Netherlands; Department of Dermatology, Maastricht University Medical Centre+, Maastricht University, Maastricht, the Netherlands
| | - Aimilios Lallas
- First Department of Dermatology, Aristotle University, Thessaloniki, Greece
| | - Ulrike Leiter
- Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | - Josep Malvehy
- Dermatology Department of Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBER de enfermedades raras, Instituto Carlos III, Barcelona Spain
| | - Veronique Del Marmol
- Department of Dermatology, University Hospital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - David Moreno-Ramirez
- Department of Medical and Surgical Dermatology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | | | - Ketty Peris
- UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy; Dermatologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Philippe Saiag
- Department of General and Oncologic Dermatology, Ambroise-Paré hospital, APHP, and EA 4340 'Biomarkers in Cancerology and Hemato-oncology', UVSQ, Université Paris-Saclay, Boulogne-Billancourt, France
| | - Luca Tagliaferri
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Myrto Trakatelli
- Department of Dermatology, Papageorgiou Hospital, Aristotle University Department of Medicine, Thessaloniki, Greece
| | | | - Ricardo Vieira
- Department of Dermatology Coimbra Hospital and University Centre, Coimbra, Portugal
| | - Iris Zalaudek
- Department of Dermatology, University of Trieste, Trieste, Italy
| | - Petr Arenberger
- Department of Dermatovenereology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Alexander M M Eggermont
- University Medical Center Utrecht and Princess Máxima Center, Utrecht, the Netherlands; Comprehensive Cancer Center Munich, Technical University Munich and Ludwig Maximilian University, Munich, Germany
| | - Martin Röcken
- Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | | | - Paul Lorigan
- Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, UK
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Yumeen S, Kahn BJ, Deng F, Blalock TW. Transplant Center Access to Dermatology. Prog Transplant 2023; 33:275-276. [PMID: 37469145 DOI: 10.1177/15269248231189874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Affiliation(s)
- Sara Yumeen
- Department of Dermatology, Brown University School of Medicine, Providence, RI, USA
| | - Benjamin J Kahn
- Department of Dermatology, Brown University School of Medicine, Providence, RI, USA
| | - Frank Deng
- Department of Dermatology, Brown University School of Medicine, Providence, RI, USA
| | - Travis W Blalock
- Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA
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Isa RS, Clarke E, Fanous H, Jambusaria-Pahlajani A. Catastrophic Merkel Cell Carcinoma in a Liver Transplant Recipient. Cureus 2023; 15:e45133. [PMID: 37842425 PMCID: PMC10569819 DOI: 10.7759/cureus.45133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/12/2023] [Indexed: 10/17/2023] Open
Abstract
Merkel cell carcinoma (MCC) is a rare skin cancer, is difficult to diagnose, and carries a high mortality rate. Solid organ transplant recipients (SOTR) are at a disproportionately increased risk of MCC and other malignancies due to chronic immunosuppression. We discuss the case of a 47-year-old woman with a remote history of liver transplant on chronic immunosuppression with tacrolimus for over a decade who presented for a third recurrence of MCC on her left forearm. This case report underscores the importance of a risk-stratified approach to regular dermatologic care and skin cancer screening in this vulnerable population.
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Affiliation(s)
- Rabab S Isa
- Department of Internal Medicine, Division of Dermatology, Dell Medical School at the University of Texas at Austin, Austin, USA
| | - Emily Clarke
- Department of Internal Medicine, Division of Dermatology, Dell Medical School at the University of Texas at Austin, Austin, USA
| | - Hanna Fanous
- Department of Internal Medicine, Division of Dermatology, Dell Medical School at the University of Texas at Austin, Austin, USA
| | - Anokhi Jambusaria-Pahlajani
- Department of Internal Medicine, Division of Dermatology, Dell Medical School at the University of Texas at Austin, Austin, USA
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Sunder-Plassmann R, Geusau A, Endler G, Weninger W, Wielscher M. Identification of Genetic Risk Factors for Keratinocyte Cancer in Immunosuppressed Solid Organ Transplant Recipients: A Case-Control Study. Cancers (Basel) 2023; 15:3354. [PMID: 37444464 DOI: 10.3390/cancers15133354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/21/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients (n = 150), cases with keratinocyte cancers and tumor-free controls, considering the most important risk factors for keratinocyte cancer in solid organ transplant recipients. Using whole exome data of germline DNA from this patient cohort, we identified several genetic loci associated with the occurrence of multiple keratinocyte cancers. We found one genome-wide significant association of a common single nucleotide polymorphism located in EXOC3 (rs72698504). In addition, we found several variants with a p-value of less than 10-5 associated with the number of keratinocyte cancers. These variants were located in the genes CYB561, WASHC1, PITRM1-AS1, MUC8, ABI3BP, and THBS2-AS1. Using whole exome sequencing data, we performed groupwise tests for rare missense variants in our dataset and found robust associations (p < 10-6, Burden Zeggini test) between MC1R, EPHA8, EPO, MYCT1, ADGRG3, and MGME1 and keratinocyte cancer. Thus, overall, we detected genes involved in pigmentation/UV protection, tumor suppression, immunomodulation, intracellular traffic, and response to UV as genetic risk factors for multiple keratinocyte cancers in solid organ transplant recipients. We also grouped selected genes to pathways and found a selection of genes involved in the "cellular response to UV" to be significantly associated with multiple keratinocyte cancers.
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Affiliation(s)
| | - Alexandra Geusau
- Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria
| | - Georg Endler
- Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Wolfgang Weninger
- Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria
| | - Matthias Wielscher
- Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
- Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria
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Shope C, Andrews L, Atherton K, Ritter A, LaPorte M, Lee LW. Comparison of Patient and Provider Practices between Bone Marrow and Solid Organ Transplantation Programs for Patient Education on Increased Risk of Skin Cancer. Transplant Cell Ther 2023:S2666-6367(23)00060-X. [PMID: 36736430 DOI: 10.1016/j.jtct.2023.01.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/15/2023] [Accepted: 01/20/2023] [Indexed: 02/05/2023]
Abstract
Patients receiving immunosuppressive therapy following transplantation are at risk for skin cancer owing to dampened tumor surveillance. As long-term immunotherapy is necessary to prevent graft rejection, transplantation providers and recipients are expected to perform regular surveillance for the development of suspicious lesions, and recipients are encouraged to practice preventative sun safe behaviors. No consensus exists regarding the timing of full body skin exams, and despite the well-established risk, patient education is not always prioritized. We investigated whether differences exist between bone marrow transplant (BMT) and organ transplant (OT) recipients and their providers regarding prevention and screening. We distributed surveys to adult and pediatric BMT and OT recipients, as well as their providers, at a single academic institution. Results were evaluated using the chi-square test. The survey results show that most BMT recipients (69%) and OT recipients (77%) were aware of their increased risk for skin cancer, but despite this knowledge, only 13% of patients overall reported using sunscreen, 29% reported reapplying sunscreen, and 48% reported wearing sun protective clothing. Most OT recipients (63%) reported never having a total body skin exam, whereas only 34% BMT recipients reported having a total body skin exam every 6 months (P = .006). BMT providers recommended a total body skin exam every 6 or 12 months (44.4% each), and OT providers recommended a total body skin exam every 12 months (58.3%). Only 11.1% of BMT providers and 8.3% of OT providers reported performing a total body skin exam at each visit. Despite results indicating widespread patient knowledge of skin cancer risk, most patients do not practice adequate prevention. Inclusion of a transplantation dermatologist in the care team or use of risk stratification tools by providers may help streamline timely referrals to Dermatology.
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Affiliation(s)
- Chelsea Shope
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Laura Andrews
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Kelly Atherton
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Alexandra Ritter
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Margaret LaPorte
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Lara Wine Lee
- Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
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Wang LL, Lin SK, Stull CM, Shin TM, Higgins HW, Giordano CN, McMurray SL, Etzkorn JR, Miller CJ, Walker JL. Cutaneous Oncology in the Immunosuppressed. Dermatol Clin 2023; 41:141-162. [DOI: 10.1016/j.det.2022.07.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Nair N, Hu Z, Du D. Skin Cancer Risk Prediction in Heart Transplant Recipients. EXP CLIN TRANSPLANT 2023; 21:41-46. [PMID: 36757167 DOI: 10.6002/ect.2022.0252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
OBJECTIVES This study was undertaken to derive a risk prediction model for skin cancer utilizing the United Network for Organ Sharing database population. MATERIALS AND METHODS Of the 24734 adults (>18 years old) heart transplant recipients (2000-2015) in the United Network for Organ Sharing database, 2625 recipients developed skin cancer. Univariate and multivariate Cox regression analyses were performed; P values, hazard ratios, and confidence intervals were derived. The model was tested using receiver operating characteristics curves and area under the curves. MATLAB software (MathWorks) was used for analyses. RESULTS Multivariate analysis showed that White patients had a hazard ratio of 31.7 compared with Black patients (P < .001). Male patients had a hazard ratio of 2.52 (P < .001) compared with female patients. Malignancy at listing showed a hazard ratio of 1.77 (P < .001). Thymoglobulin had a hazard ratio of 1.19 (P = .005) compared with other induction agents. The receiver operating characteristic curves generated for 5 years, 8 years, and 10 years after transplant showed area under the curve values of 0.78, 0.77, and 0.76, respectively, in the training set and 0.75, 0.75, and 0.74, respectively, in the validation set. CONCLUSIONS Male sex, White ethnicity, older age, malignancy at the time of listing or at time of transplant, and thymoglobulin induction are major risk factors for skin cancers after transplant. This risk prediction model has a C statistic of 0.75. To our knowledge,this is the firsttime such a model has been generated for skin cancers in this population.
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Affiliation(s)
- Nandini Nair
- From the Division of Cardiology, Department of Internal Medicine, Texas Tech Health Sciences Center, Texas, USA
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Characterizing Skin Cancer in Transplant Recipients by Fitzpatrick Skin Phototype. Dermatol Ther (Heidelb) 2022; 13:147-154. [PMID: 36469283 PMCID: PMC9823165 DOI: 10.1007/s13555-022-00858-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 11/07/2022] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Nearly half of organ transplants occur annually in patients with Fitzpatrick skin phototypes (Fitz type) III-VI. Organ transplant recipients (OTRs) are at risk for sequelae of chronic immunosuppression, of which skin cancer is common. As literature regarding skin cancer risk is largely conducted in OTRs with Fitz types I and II, we aimed to further characterize the incidence and risk factors for skin cancer in OTRs with higher Fitz types. METHODS We conducted a retrospective review of OTRs with Fitz types III-VI evaluated by dermatology between 1 January 2012 and 1 June 2022. The primary outcome of this study was development of skin cancer post-transplant. Secondary outcomes included risk factors for skin cancer development. Data were analyzed using two-sample t-tests and Pearson's chi-squared. RESULTS Of 530 OTRs, 193 had Fitz type III or higher. Ten patients (5.18%) developed 87 skin cancers and one recurrence at a mean of 5.17 years posttransplant. Patients with skin cancer self-identified as Black (70%, p-value ≤ 0.001), male (70%, p-value ≤ 0.001), and kidney transplant recipients (70%, p-value ≤ 0.001), with a mean age of 58.20 years at transplant (p-value ≤ 0.001). Subjects with skin cancer were more likely to be former smokers (60%) and prescribed tacrolimus (p-value ≤ 0.001 each). Development of cutaneous squamous cell carcinoma (66, 75.86%) was most common, followed by basal cell carcinoma (17, 19.54%), and malignant melanoma (3, 3.45%). Skin cancer most often occurred on the face or scalp (60%, p-value = 0.027), though also developed in sun-protected sites (30%, p-value = 0.002). Verruca vulgaris was present in 10% of patients (p-value = 0.028). CONCLUSIONS Risk factors for skin cancer post-transplant differ in OTRs with higher Fitz types. Our results suggest that among OTRs who self-identified as Black, kidney recipients are at increased risk for skin cancer in non-sun-exposed regions. These cancers may be associated with human papillomavirus (HPV). Education is key for preventing morbidity and mortality secondary to skin cancer.
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Bottomley MJ, Massey PR, Thuraisingham R, Doyle A, Rao S, Bibee KP, Bouwes Bavinck JN, Jambusaria-Pahlajani A, Harwood CA. Interventions After First Post-Transplant Cutaneous Squamous Cell Carcinoma: A Proposed Decision Framework. Transpl Int 2022; 35:10880. [PMID: 36484063 PMCID: PMC9722441 DOI: 10.3389/ti.2022.10880] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 11/10/2022] [Indexed: 11/23/2022]
Abstract
Cutaneous squamous cell carcinoma (CSCC) is a major cause of morbidity and mortality after organ transplant. Many patients subsequently develop multiple CSCC following a first CSCC, and the risk of metastasis and death is significantly increased compared to the general population. Post-transplant CSCC represents a disease at the interface of dermatology and transplant medicine. Both systemic chemoprevention and modulation of immunosuppression are frequently employed in patients with multiple CSCC, yet there is little consensus on their use after first CSCC to reduce risk of subsequent tumors. While relatively few controlled trials have been undertaken, extrapolation of observational data suggests the most effective interventions may be at the time of first CSCC. We review the need for intervention after a first post-transplant CSCC and evidence for use of various approaches as secondary prevention, before discussing barriers preventing engagement with this approach and finally highlight areas for future research. Close collaboration between specialties to ensure prompt deployment of these interventions after a first CSCC may improve patient outcomes.
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Affiliation(s)
- Matthew J. Bottomley
- Chinese Academy of Medical Sciences Oxford Institute (CAMS-COI), Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom,Oxford Transplant Unit, Oxford University Hospitals, NHS Foundation Trust, Oxford, United Kingdom,*Correspondence: Matthew J. Bottomley,
| | | | - Raj Thuraisingham
- Department of Renal Medicine and Transplantation, Barts Health NHS Trust, London, United Kingdom
| | - Alden Doyle
- Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Swati Rao
- Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Kristin P. Bibee
- Department of Dermatology, School of Medicine, John Hopkins University, Baltimore, MD, United States
| | | | - Anokhi Jambusaria-Pahlajani
- Division of Dermatology, Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX, United States
| | - Catherine A. Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
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Griffin L, Ho L, Akhurst RJ, Arron ST, Boggs JME, Conlon P, O'Kelly P, Toland AE, Epstein EH, Balmain A, Bastian BC, Moloney FJ, Murphy GM, Laing ME. Genetic polymorphism in Methylenetetrahydrofolate Reductase chloride transport protein 6 ( MTHFR CLCN6) gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients. SKIN HEALTH AND DISEASE 2022; 2:e95. [PMID: 35677930 PMCID: PMC9168012 DOI: 10.1002/ski2.95] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 01/10/2022] [Accepted: 01/13/2022] [Indexed: 12/18/2022]
Abstract
Background Renal transplant recipients (RTRs) are at increased risk of keratinocyte cancer (KC), especially cutaneous squamous cell carcinoma (cSCC). Previous studies identified a genetic variant of the Methylenetetrahydrofolate Reductase (MTHFR) gene, C677T, which conferred a risk for diagnosis of cSCC in Irish RTRs. Objective We sought to find further genetic variation in MTHFR and overlap genes that may be associated with a diagnosis of KC in RTRs. Methods Genotyping of a combined RTR population (n = 821) from two centres, Ireland (n = 546) and the USA (n = 275), was performed. This included 290 RTRs with KC and 444 without. Eleven single nucleotide polymorphisms (SNPs) in the MTHFR gene and seven in the overlap gene MTHFR Chloride transport protein 6 (CLCN6) were evaluated and association explored by time to event analysis (from transplant to first KC) using Cox proportional hazards model. Results Polymorphism at MTHFR CLCN6 (rs9651118) was significantly associated with KC in RTRs (HR 1.50, 95% CI 1.17–1.91, p < 0.00061) and cSCC (HR 1.63, 95% CI 1.14–2.34, p = 0.007). A separate SNP, MTHFR C677T, was also significantly associated with KC in the Irish population (HR 1.31, 95% CI 1.05–1.63, p = 0.016), but not American RTRs. Conclusions We report the association of a SNP in the MTHFR overlap gene, CLCN6 and KC in a combined RTR population. While the exact function of CLCN6 is not known, it is proposed to be involved in folate availability. Future applications could include incorporation in a polygenic risk score for KC in RTRs to help identify those at increased risk beyond traditional risk factor assessment.
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Affiliation(s)
- L Griffin
- Department of Dermatology University Hospital Galway Galway Ireland
| | - L Ho
- Department of Dermatology Beaumont Hospital Dublin 9 Ireland
| | - R J Akhurst
- Helen Diller Family Comprehensive Cancer Center University of California San Francisco California USA
| | - S T Arron
- Helen Diller Family Comprehensive Cancer Center University of California San Francisco California USA
| | - J M E Boggs
- Department of Dermatology University Hospital Galway Galway Ireland
| | - P Conlon
- Department of Nephrology Beaumont Hospital Dublin 9 Ireland
| | - P O'Kelly
- Department of Nephrology Beaumont Hospital Dublin 9 Ireland
| | - A E Toland
- Department of Molecular Virology, Immunology and Medical Genetics Comprehensive Cancer Centre Ohio State University Columbus Ohio USA
| | - E H Epstein
- Helen Diller Family Comprehensive Cancer Center University of California San Francisco California USA
| | - A Balmain
- Helen Diller Family Comprehensive Cancer Center University of California San Francisco California USA
| | - B C Bastian
- Helen Diller Family Comprehensive Cancer Center University of California San Francisco California USA
| | - F J Moloney
- Department of Dermatology Beaumont Hospital Dublin 9 Ireland
| | - G M Murphy
- Department of Dermatology Beaumont Hospital Dublin 9 Ireland
| | - M E Laing
- Department of Dermatology University Hospital Galway Galway Ireland.,Department of Dermatology Beaumont Hospital Dublin 9 Ireland.,Department of Medicine National University of Ireland Galway Ireland
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Thaniyavarn T, Grewal HS, Goldberg HJ, Arcasoy SM. Nonallograft Complications of Lung Transplantation. Thorac Surg Clin 2022; 32:243-258. [PMID: 35512942 DOI: 10.1016/j.thorsurg.2022.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Long-term exposure to immunosuppressive therapy may exacerbate pre-existing medical comorbidities or result in the development of new chronic medical conditions after lung transplantation. This article focuses on common nonallograft complications with the highest impact on short- and long-term outcomes after transplantation. These include diabetes mellitus, hypertension, dyslipidemia, kidney disease (acute and chronic), and malignancy. We discuss evidence-based strategies for the prevention, diagnosis, and management of these nonallograft complications in this article.
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Affiliation(s)
- Tany Thaniyavarn
- Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, PBB Clinic 3, Boston, MA 02115, USA.
| | - Harpreet Singh Grewal
- Lung Transplant Program, Columbia University Irving Medical Center, 622 W 168th Street, PH 14E, Suite 104, New York, NY 10032, USA
| | - Hilary J Goldberg
- Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, PBB Clinic 3, Boston, MA 02115, USA
| | - Selim M Arcasoy
- Lung Transplant Program, Columbia University Irving Medical Center, 622 W 168th Street, PH 14E, Suite 104, New York, NY 10032, USA
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Cohort and Nested Case-Control Study of Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Recipients, by Medication. J Am Acad Dermatol 2021; 86:598-606. [PMID: 34384835 DOI: 10.1016/j.jaad.2021.07.065] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/20/2021] [Accepted: 07/22/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Knowledge is needed about squamous cell carcinoma (cSCC) risk in solid organ transplant recipients (SOTRs) using contemporary immunosuppressive regimens. OBJECTIVE Evaluate risk of cSCC in relation to medications used by SOTRs. METHODS The cohort and nest case-control study included 3,308 SOTRs and 65,883 persons without transplantation during 2009-2019. Incident cSCC was identified from pathology data and medications from pharmacy data. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards analysis, with voriconazole examined as a time-dependent variable. RESULTS The annual incidence of cSCC was 1.69% in SOTRs and 0.30% in persons without transplantation. The adjusted HR of cSCC associated with lung transplant was 14.83 (CI 9.85-22.33) for lung and 6.53 to 10.69 for other organs. Risk in Latinx persons was higher than in other non-white groups. Among lung recipients, the HR was 1.14 for each month of voriconazole use (95% CI: 1.04-1.26). Azathioprine use for ≥7 months, relating to mycophenolate mofetil intolerance, was associated with 4.22-fold increased risk of cSCC (95% CI 1.90-9.40). Belatacept and other immunsuppressive medications were not associated with risk. LIMITATIONS The number of events was somewhat small. CONCLUSIONS Knowledge of risks and benefits in diverse patients can translate to care improvements.
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Robinson C, Chanchlani R, Kitchlu A. Malignancies after pediatric solid organ transplantation. Pediatr Nephrol 2021; 36:2279-2291. [PMID: 33057766 DOI: 10.1007/s00467-020-04790-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/28/2020] [Accepted: 09/18/2020] [Indexed: 12/19/2022]
Abstract
As life expectancy among pediatric solid organ transplant recipients (SOTRs) improves, the risk of comorbid conditions such as malignancy post-transplantation has also increased. SOTRs are at elevated risks of post-transplantation lymphoproliferative disorders (PTLDs), and skin and solid cancers. PTLDs typically occur early following transplantation, while skin and solid cancers frequently arise in young adulthood (25-40 years). By 30 years following transplantation, 26-41% of pediatric SOTRs have developed cancer. Different risk factors exist for PTLD, and skin and solid cancers, which are modified by cumulative immunosuppression, infections, transplanted organ, and the underlying disease process associated with initial organ failure (e.g., kidney failure). Optimal cancer treatment strategies depend on the specific cancer type, stage, and patient comorbidities. Immunosuppression reduction may be beneficial for certain cancers but must be considered against the risks of acute and chronic rejection and allograft loss. Lifestyle counseling regarding smoking avoidance and sun protection, as well as human papillomavirus vaccination, is an important aspect of cancer prevention. Currently, no cancer screening guidelines exist specifically for pediatric SOTRs. Adult population screening guidelines have not been validated in transplant populations. Therefore, an individualized approach should be taken to cancer screening for pediatric SOTRs, accounting for other cancer risk factors.
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Affiliation(s)
- Cal Robinson
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Rahul Chanchlani
- Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- ICES McMaster, Hamilton, Ontario, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, 200 Elizabeth Street, 8 Eaton North, 8 N-842, Toronto, Ontario, M5G 2C4, Canada.
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Low ESL, Gow PJ, Testro A, Sinclair M. Low participation in preventative health measures in a cohort of liver transplant recipients: A cross-sectional analysis. Clin Transplant 2021; 35:e14257. [PMID: 33605483 DOI: 10.1111/ctr.14257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 01/20/2021] [Accepted: 02/13/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Despite high rates of infection and malignancy post-solid organ transplant, there are little data on patient participation in preventative health care. METHODS We conducted a cross-sectional survey of post-liver transplant patients to evaluate insight into transplant-associated infective and neoplastic risks, and receipt of vaccination and cancer surveillance in accordance with Australian and local institution-specific guidelines. Descriptive analyses were used to assess characteristics potentially influencing adherence. RESULTS Of 219 patients surveyed, adherence to bowel cancer surveillance was significantly reduced in those distant from transplantation compared with those recently transplanted (95.8% if transplanted ≤ 5 years ago vs. 68.3% if transplanted > 5 years ago, P < .001). Skin cancer surveillance participation with annual physician-directed examination was low (42.9%), particularly in younger patients (29.5% in < 50yo vs. 48.1% in ≥ 50yo, P = .01), who were also less adherent to vaccination recommendations (72.1% in < 50yo vs. 87.3% in ≥ 50yo, P = .008). CONCLUSIONS This is the first analysis of preventative healthcare participation in a cohort of Australian liver transplant recipients, revealing concerning adherence to bowel and skin cancer surveillance recommendations. Major interventions to avoid preventable disease in this high-risk cohort are warranted.
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Affiliation(s)
| | - Paul J Gow
- Austin Health Liver Transplant Unit, Heidelberg, Vic, Australia
- Department of Medicine, The University of Melbourne, Parkville, Vic, Australia
| | - Adam Testro
- Austin Health Liver Transplant Unit, Heidelberg, Vic, Australia
- Department of Medicine, The University of Melbourne, Parkville, Vic, Australia
| | - Marie Sinclair
- Austin Health Liver Transplant Unit, Heidelberg, Vic, Australia
- Department of Medicine, The University of Melbourne, Parkville, Vic, Australia
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Nair N, Hu Z, Du D, Gongora E. Risk Prediction Model for Basal Cell Carcinoma in Cardiac Allograft Recipients. Transplant Proc 2021; 53:1981-1988. [PMID: 33931248 DOI: 10.1016/j.transproceed.2021.02.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 01/09/2021] [Accepted: 02/25/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Basal cell carcinoma (BCC) is the second most common skin cancers in posttransplant patients. Long-term immunosuppression predisposes the patients to higher risk. This study was undertaken to develop a risk prediction model using the United Network for Organ Sharing (UNOS) database. MATERIALS AND METHODS Heart transplant recipients (2000~2015) from the UNOS database were analyzed. The Cox proportional hazards model was applied to screen the predictors associated with the development of BCC. Stepwise forward selection with Akaike information criterion was done to obtain the multivariate model. Area under the curve was derived from the receiver operating characteristics curve to assess the quality of the prediction model. A risk scoring system was developed to stratify patients into different risk groups, and the occurrence rates of posttransplant BCC among different groups were compared. RESULTS There were 24,374 patients who received heart transplantation within this study period, and 1211 recipients have been reported with BCC. The multivariate model provides area under the curves at 5, 8, and 10 years posttransplant of 0.77, 0.76, and 0.76, respectively, in the derivation set and 0.75, 0.74, and 0.74, respectively, in the validation set. The predicted and observed probabilities of developing BCC in 5 years agree well across different risk groups. Kaplan-Meier survival curves were generated, which demonstrate significant differences between subjects in different risk groups. CONCLUSION A risk prediction model has been generated for the first time for BCC with a c-statistic of ≥0.74 in both derivation and validation sets, making it a good tool for risk stratification.
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Affiliation(s)
- Nandini Nair
- Division of Cardiology, Department of Internal Medicine, Texas Tech Health Sciences Center, Lubbock, Texas.
| | - Zhiyong Hu
- Department of Industrial, Manufacturing and Systems Engineering, Texas Tech University, Lubbock, Texas
| | - Dongping Du
- Department of Industrial, Manufacturing and Systems Engineering, Texas Tech University, Lubbock, Texas
| | - Enrique Gongora
- Department of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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Nair N, Hu Z, Du D, Gongora E. Risk prediction model for cutaneous squamous cell carcinoma in adult cardiac allograft recipients. World J Transplant 2021; 11:54-69. [PMID: 33816146 PMCID: PMC8009060 DOI: 10.5500/wjt.v11.i3.54] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 12/25/2020] [Accepted: 02/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Heart transplant recipients are at higher risk of developing skin cancer than the general population due to the long-term immunosuppression treatment. Cancer has been reported as one of the major causes of morbidity and mortality for patients after heart transplantation. Among different types of skin cancers, cutaneous squamous cell carcinoma (cSCC) is the most common one, which requires timely screening and better management.
AIM To identify risk factors and predict the incidence of cSCC for heart transplant recipients.
METHODS We retrospectively analyzed adult heart transplant recipients between 2000 and 2015 extracted from the United Network for Organ Sharing registry. The whole dataset was randomly divided into a derivation set (80%) and a validation set (20%). Uni- and multivariate Cox regression were done to identify significant risk factors associated with the development of cSCC. Receiver operating charac-teristics curves were generated and area under the curve (AUC) was calculated to assess the accuracy of the prediction model. Based on the selected risk factors, a risk scoring system was developed to stratify patients into different risk groups. A cumulative cSCC-free survival curve was generated using the Kaplan-Meier method for each group, and the log-rank test was done to compare the inter-group cSCC rates.
RESULTS There were 23736 heart-transplant recipients during the study period, and 1827 of them have been reported with cSCC. Significant predictors of post-transplant cSCC were older age, male sex, white race, recipient and donor human leukocyte antigen (HLA) mismatch level, malignancy at listing, diagnosis with restrictive myopathy or hypertrophic myopathy, heart re-transplant, and induction therapy with OKT3 or daclizumab. The multivariate model was used to predict the 5-, 8- and 10-year incidence of cSCC and respectively provided AUC of 0.79, 0.78 and 0.77 in the derivation set and 0.80, 0.78 and 0.77 in the validation set. The risk scoring system assigned each patient with a risk score within the range of 0-11, based on which they were stratified into 4 different risk groups. The predicted and observed 5-year probability of developing cSCC match well among different risk groups. In addition, the log-rank test indicated significantly different cSCC-free survival across different groups.
CONCLUSION A risk prediction model for cSCC among heart-transplant recipients has been generated for the first time. It offers a c-statistic of ≥ 0.77 in both derivation and validation sets.
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Affiliation(s)
- Nandini Nair
- Division of Cardiology, Department of Internal Medicine, Texas Tech Health Sciences Center, Lubbock, TX 79430, United States
| | - Zhiyong Hu
- Department of Industrial, Manufacturing and Systems Engineering, Texas Tech University, Lubbock, TX 79409, United States
| | - Dongping Du
- Department of Industrial, Manufacturing and Systems Engineering, Texas Tech University, Lubbock, TX 79409, United States
| | - Enrique Gongora
- Department of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, United States
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Scott JF, Brough KR, Grigoryan KV, Muzic JG, Kim GY, Conic RRZ, Hill ST, Brewer JD, Baum CL, Litzow MR, Hogan WJ, Patnaik MS, Hashmi SK, Lazarus HM, Bordeaux JS, Thompson CL, Gerstenblith MR, Lehman JS. Risk Factors for Keratinocyte Carcinoma in Recipients of Allogeneic Hematopoietic Cell Transplants. JAMA Dermatol 2021; 156:631-639. [PMID: 32267479 DOI: 10.1001/jamadermatol.2020.0559] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Importance Allogeneic hematopoietic cell transplant (alloHCT) is known to increase the risk for keratinocyte carcinoma. The extent to which host characteristics, including pigmentary phenotype and UV radiation exposure, contribute is unknown. Objective To identify and validate independent risk factors for keratinocyte carcinoma after alloHCT, including those associated with the transplant and the host. Design, Setting, and Participants This retrospective cohort study analyzed a consecutive sample of alloHCT recipients from January 1, 2000, to December 31, 2014, at the Mayo Clinic, Rochester, Minnesota (n = 872) and University Hospitals Cleveland Medical Center, Cleveland, Ohio (n = 147). Participants from the Mayo Clinic were randomly allocated (2:1) into discovery (n = 581) and validation (n = 291) cohorts. Time to first keratinocyte carcinoma and information about transplant- and host-associated risk factors were extracted. A multivariate keratinocyte carcinoma risk model was created using a stepwise Cox proportional hazards regression model with P ≤ .05 for entry that incorporated all covariates that were individually statistically significant at α = 0.05 in the discovery cohort. The risk model was first internally validated using the Mayo Clinic validation cohort and then externally validated using the independent cohort of alloHCT recipients at University Hospitals Cleveland Medical Center. Data were analyzed from March 13, 2018, to June 12, 2019. Exposures Allogeneic hematopoietic cell transplant. Main Outcomes and Measures The primary outcome was time to development of the first cutaneous keratinocyte carcinoma after alloHCT; secondary outcome, time to development of the first individual basal and/or squamous cell carcinoma after alloHCT. Results Of the 872 alloHCT recipients identified in the Mayo Clinic cohort (520 men [59.6%]; mean [SD] age, 48.3 [12.6] years), 95 (10.9%) developed keratinocyte carcinoma after alloHCT during 5349 person-years of follow-up. Of the 147 alloHCT recipients in the exernal validation cohort (86 men [58.5%]; mean [SD] age, 47.9 [17.5] years), 18 (12.2%) developed keratinocyte carcinoma after alloHCT in 880 person-years of follow up. Risk factors independently associated with keratinocyte carcinoma after alloHCT included age (hazard ratio [HR] per 10 years, 1.72; 95% CI, 1.21-2.42), chronic lymphocytic leukemia (HR, 2.47; 95% CI, 1.20-5.09), clinically photodamaged skin (HR, 3.47; 95% CI, 1.87-6.41), and history of cutaneous squamous cell carcinoma (HR, 2.60; 95% CI, 1.41-5.91). Harrell concordance statistics were 0.81 (95% CI, 0.72-0.90) and 0.86 (95% CI, 0.74-0.98) for internal and external validation of the keratinocyte carcinoma risk model, respectively. Conclusions and Relevance This study found validated independent risk factors for keratinocyte carcinoma after alloHCT that are enriched with host- compared with transplant-associated risk factors. These findings highlight the importance of assessing host-associated risk factors for keratinocyte carcinoma in patients eligible for alloHCT. Future studies should examine whether keratinocyte carcinoma risk stratification before alloHCT may inform long-term surveillance strategies.
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Affiliation(s)
- Jeffrey F Scott
- Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio.,Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kevin R Brough
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | | | - John G Muzic
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | - Grace Y Kim
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Rosalynn R Z Conic
- Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Sheena T Hill
- Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Jerry D Brewer
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | | | - Mark R Litzow
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - William J Hogan
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Mrinal S Patnaik
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Shahrukh K Hashmi
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Hillard M Lazarus
- Division of Hematology and Oncology, Case Western Reserve University, Cleveland, Ohio
| | - Jeremy S Bordeaux
- Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio.,Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Cheryl L Thompson
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio
| | - Meg R Gerstenblith
- Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio.,Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Julia S Lehman
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
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Robinson CH, Coughlin CC, Chanchlani R, Dharnidharka VR. Post-transplant malignancies in pediatric organ transplant recipients. Pediatr Transplant 2021; 25:e13884. [PMID: 33111463 DOI: 10.1111/petr.13884] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 09/13/2020] [Accepted: 09/24/2020] [Indexed: 12/11/2022]
Abstract
The majority of cancer diagnoses in pediatric solid organ transplant recipients (SOTRs) are post-transplantation lymphoproliferative disorders (PTLD) or skin cancers. However, pediatric SOTRs are also at significantly elevated risk for multiple other solid and hematological cancers. The risks of specific cancers vary by transplanted organ, underlying disease, and immunosuppression factors. More than one-quarter of pediatric SOTRs develop cancer within 30 years of transplantation and their risk of solid cancer is 14 times greater than the general population. Pediatric SOTRs are at significantly higher risk of cancer-associated death. Improving patient survival among pediatric SOTRs puts them at risk of adult epithelial cancers associated with environmental carcinogenic exposures. Vaccination against oncogenic viruses and avoidance of excessive immunosuppression may reduce the risk of solid cancers following transplantation. Patient and family education regarding photoprotection is an essential component of skin cancer prevention. There is significant variability in cancer screening recommendations for SOTRs and general population approaches are typically not validated for transplant populations. An individualized approach to cancer screening should be developed based on estimated cancer risk, patient life expectancy, and screening test performance.
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Affiliation(s)
- Cal H Robinson
- Department of Pediatrics, McMaster University, Hamilton, ON, Canada
| | - Carrie C Coughlin
- Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Rahul Chanchlani
- Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, ON, Canada.,Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.,ICES McMaster, Hamilton, ON, Canada
| | - Vikas R Dharnidharka
- Division of Pediatric Nephrology, Hypertension and Pheresis, Washington University School of Medicine, Saint Louis, MO, USA
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Gjersvik P. How to take the skin cancer risk of your transplant patient seriously. Transpl Int 2019; 32:1244-1246. [PMID: 31610049 DOI: 10.1111/tri.13541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 10/10/2019] [Indexed: 11/29/2022]
Affiliation(s)
- Petter Gjersvik
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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