Chemoprevention of keratinocyte carcinoma and actinic keratosis in solid-organ transplant recipients: Systematic review and meta-analyses

To the Editor: Skin cancers account for 40% of malignancies in solid-organ transplant recipients (SOTRs), who have an 80-fold increased risk squamous cell carcinoma (SCC) and a 16-fold basal (BCC). Systemic chemoprevention is one method to mitigate this amplified risk. Acitretin, instance, has been used prevent keratinocyte carcinomas (KC) actinic keratoses (AK) SOTRs since 1995,1Bavinck J.N. Tieben L.M. Van der Woude F.J. et al.Prevention skin cancer reduction keratotic lesions during acitretin therapy renal recipients: double-blind, placebo-controlled study.J Clin Oncol. 1995; 13: 1933-1938Crossref PubMed Google Scholar but its adverse effects include mucositis, liver lipid abnormalities, teratogenicity.2George R. Weightman W. Russ G.R. al.Acitretin non-melanoma recipients.Australas J Dermatol. 2002; 43: 269-273Crossref Scopus (130) Nicotinamide, amide form vitamin B3, newer chemoprophylaxis with fewer effects.3Chen A.C. Martin A.J. Dalziell R.A. al.A phase II randomized controlled trial nicotinamide recipients.Br 2016; 175: 1073-1075Crossref (61) Here we report results pairwise network meta-analyses summarize current evidence regarding chemoprevention. We selected studies that analyzed efficacy systemic KC/AK patients are or history 2 more KCs, both. limited our search placebo-controlled, control trials (RCTs) reported number new both arms. Two authors (L.Y.T., S.Y.C.T.) independently conducted literature search, screened titles abstracts eligibility, extracted data. Statistical synthesis was performed RevMan 5.3 software (The Nordic Cochrane Centre, The Collaboration, Copenhagen, Denmark). After 6 RCTs 734 were included quantitative (Appendix A, available via Mendeley at https://doi.org/10.17632/m6z2fzkkxn.2). Of RCTs, 3 580 (range, 17-192 patients) compared placebo, 154 19-35 placebo. Pairwise meta-analysis all using random-effects model demonstrated significant (Fig 1). overall mean difference 0.855 (95% confidence interval, 0.365-1.345; P < .001). In addition, efficacious, combined 0.792 0.298-1.286; = .00168) 4.239 0.611-7.866; .0220) nicotinamide. A comparing found no between treatments 2, Appendix B).Fig 2Network graph league table meta-analysis. Mean differences 95% intervals calculated model. >1 means top-left treatment better.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This does not address optimal dosages drugs frequency effects. owing numbers eligible unable investigate how influenced by duration type transplantation, chemoprevention, existing immunosuppressive regimens. Moving forward, topical may be suitable alternative SOTRs. Notably, large evaluated keratosis. For Veterans Affairs Keratinocyte Carcinoma Chemoprevention 5% 5-fluorouracil cream resulted 49% relative AK after months reduced SCC requiring surgery 75% 1 year did lower BCC.4Hyemin P. Hogan D. Eilers al.Long-term fluorouracil treating keratosis: clinical trial.JAMA 2015; 151: 952-960Crossref (69) Scholar,5Weinstock M.A. Thwin S.S. Siegel J.A. al.Chemoprevention single course fluorouracil, 5%, cream: 2018; 154: 167-174Crossref (54) knowledge, first statistically integrates KC/AK. study demonstrates effective lowering Yet, even advent better regular physician surveillance sun protection still key basic strategies should practiced