{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T23:41:39Z","timestamp":1788392499073,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:00:00Z","timestamp":1768608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:00:00Z","timestamp":1768608000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Dermatology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Kidney transplant recipients (KTRs) are at increased risk of developing cutaneous squamous cell carcinoma (cSCC), particularly when treated with calcineurin inhibitors (CNI), which are strongly associated with tumorigenesis. In contrast, mTOR inhibitors such as sirolimus have demonstrated antitumor activity, but their role in secondary prevention of cSCC remains unclear. We conducted a systematic review and meta\u2010analysis of randomized controlled trials (RCTs) to evaluate the impact of switching from a CNI\u2010based to an mTOR inhibitor\u2010based immunosuppressive regimen on the incidence of cSCC in KTRs with prior cSCC. MEDLINE, EMBASE, CENTRAL, and trial registries were searched through June 2025. Incidence rate ratios (IRRs) for cSCC and risk ratios (RRs) for adverse events (AEs) were pooled using a random\u2010effects model. Risk of bias was assessed with Cochrane RoB2. The study was registered in PROSPERO prior to data extraction (CRD42024583966). The study was unfunded. Four RCTs (393 patients) were included. Sirolimus significantly reduced 2\u2010year cSCC incidence (IRR 0.51, 95% CI 0.39\u20130.67). However, discontinuation was more frequent (RR 8.60, 95% CI 1.95\u201337.93) due to AEs. No significant differences in mortality or graft rejection were found. Certainty of evidence was high for cSCC incidence and low for adverse events due to heterogeneity and selective reporting. In conclusion, sirolimus reduces secondary cSCC risk but increases AEs; patient selection and monitoring are essential.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    PROSPERO number: CRD42024583966\n                  <\/jats:p>","DOI":"10.1111\/ijd.70285","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T11:54:31Z","timestamp":1768650871000},"page":"952-962","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sirolimus for Secondary Prevention of Cutaneous Squamous Cell Carcinoma in Kidney Transplant Recipients: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5383-2263","authenticated-orcid":false,"given":"Yannick","family":"Foerster","sequence":"first","affiliation":[{"name":"Department of Dermatology TUM School of Medicine and Health  Munich Germany"},{"name":"Institute of Medical Biostatistics, Epidemiology and Informatics  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9774-7352","authenticated-orcid":false,"given":"Julia","family":"Palaras","sequence":"additional","affiliation":[{"name":"Department of Dermatology TUM School of Medicine and Health  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-5347","authenticated-orcid":false,"given":"Kristine","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Dermatology TUM School of Medicine and Health  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5352-5105","authenticated-orcid":false,"given":"Tilo","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Department of Dermatology TUM School of Medicine and Health  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1469-4464","authenticated-orcid":false,"given":"Oana\u2010Diana","family":"Persa","sequence":"additional","affiliation":[{"name":"Department of Dermatology TUM School of Medicine and Health  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022137"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2002.125579"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15931"},{"issue":"3","key":"e_1_2_10_5_1","first-page":"S1","article-title":"KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients","volume":"9","author":"Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group","year":"2009","journal-title":"American Journal of Transplantation"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/17401"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1479627"},{"issue":"5","key":"e_1_2_10_8_1","first-page":"180","article-title":"MTOR, but Not Calcineurin, Inhibition Safeguards Anti\u2010Tumoral CD8 Immunity in Transplant Recipients","volume":"13","author":"Rovira J.","year":"2013","journal-title":"American Journal of Transplantation"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2012.13.9.4335"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199904150-00017"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00190116"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2023.2029"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181d84cdc"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2016.4920"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2901"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0585-1"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.01.008"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2022.2118516"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01498"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182247ae2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.03994.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005090993"},{"issue":"3","key":"e_1_2_10_23_1","first-page":"16","article-title":"Sirolimus\u2010Based, Calcineurin Inhibitor\u2014Free Regimen in Kidney Transplant Patients: An Open\u2010Label, Randomized, Controlled Trial","volume":"13","author":"El\u2010Agroudy A. 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