Acta Dermato-Venereologica 97-6 97-6CompleteContent | Page 24

751 SHORT COMMUNICATION Risk Factors for De Novo Squamous Cell Carcinoma Development in Renal Transplant Recipients with a Previous Squamous Cell Carcinoma Vivan C. HELLSTRÖM 1 , Ylva ENSTRÖM 2 , Gunilla ENBLAD 3 , Gunnar TUFVESON 1 , Henrik RENLUND 4 , Tomas LORANT 1 and Filippa NYBERG 5 1 Department of Surgical Sciences, Section of Transplantation Surgery, 2 Department of Medical Sciences, Section of Dermatology and Venereology, 3 Department of Immunology, Genetics and Pathology, Section of Experimental and Clinical Oncology, 4 Uppsala Clinical Research Centre, Uppsala University, SE-751 85 Uppsala, and 5 Institution for Clinical Sciences, Unit for Dermatology, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden. E-mail: [email protected] Accepted Jan 12, 2017; Epub ahead of print Jan 17, 2017 Cutaneous squamous cell carcinoma (SCC) is the most common post-transplant tumour in renal transplanted re- cipients in Sweden. Five percent of the renal transplanted population develop SCC within 10 years of transplanta- tion. Five years after transplantation the incidence of a first SCC is increased 52-fold, and the incidence of all SCCs is increased 121-fold in renal transplant recipients compared with the general population (1). Half of the patients with a first SCC and three-quarters of those with 2 or 3 SCCs are at risk of multiple subsequent SCC and, finally, of metastatic SCC within 10 years after transplantation. These patients are in need of intense skin surveillance. However, the risk factors that indicate the need for intensified skin surveillance have not been completely identified (1–3). Table I. Analysed risk factor Age at 1 st transplantation a Age at 1 st SCC a Time 1 st transplantation to 1 st SCC a Age at baseline SCC a Time 1 st transplantation to baseline SCC a Skin type (Fitzpatrick’s), n (%) I–II III–IV Sun exposure, n (%) Low to moderate Hig h Clinical assessment of skin, n (%) Normal or aged skin AK, solar lentigines, field cancerization Histology of base SCC, n (%) In situ Invasive Number previous SCC, n (%) 1 2 > 2 Azathioprine, n (%) No Yes previously Mycophenolate mofetil, n (%) No or stopped Yes mTOR inhibitor, n (%) No or <  3 months Yes > 15 months Sex, n (%) Female Male All (n  = 73) No Dn SCC (n  = 42) 51.9 (38–62) 53.1 (38–61) 60.8 (54–66) 61.8 (54–66) 9.4 (4–16) 9.8 (4–15) 65.2 (58–69) 64.5 (57–68) 11.6 (6–23) 10.3 (6–19) 40 (55) 33 (45) 24 (57) 18 (43) 36 (49) 37 (51) 21 (50) 21 (50) 21 (29) 52 (71) 15 (36) 27 (64) 37 (51) 36 (49) 21 (50) 21 (50) 25 (34) 14 (19) 34 (47) 21 (50) 9 (21) 12 (29) 47 (64) 26 (36) 29 (69) 13 (31) 43 (59) 30 (41) MATERIALS AND METHODS In this prospective clinical observational study at Uppsala Univer- sity Hospital, Sweden, 73 kidney or simultaneous pancreas and kidney transplanted patients were included. All patients had at least one post-transplant SCC in situ or invasive SCC diagnosed from September 2006 to December 2012 and they were followed for 2 years (4). The aim was to identify the risk factor or risk factors that are the most significant in predicting de novo SCC. This study was approved by the Regional Ethical Review Board in Uppsala (Dnr 2007/032) and registered with ClinicalTrials.gov (NCT02241564). The recorded risk factors for de novo SCC, as well as a compari- son between patients developing and not developing de novo SCC are presented in Table I. Skin types were assessed according to Fitzpatrick’s classification (5). Sun exposure was assessed based on anamnestic information. Patients with low and medium sun exposure were classified as Group 1 (low risk) and those with a history of active sun bathing (before transplantation or continu- ously) were classified as Group 2 (high risk). Group 1 had normal skin status according to age or minor skin lesions such as aged skin, telangiectases, elas- Dn SCC tosis, and some solar lentigines. Group 2 had actinic (n  = 31) p-value keratosis, many solar lentigines or more advanced 50.8 (38–63) 0.97 lesions, such as numerous actinic keratoses and 60.7 (54–66) 0.96 field cancerization. 8.1 (4–16) 0.68 Immunosuppression. All patients except one had 65.4 (60–72) 0.36 calcineurin inhibitor (CNI)-based maintenance im- 14.1 (7–24) 0.31 munosuppression, and all patients except 4 (5%) had 16 (52) 0.80 corticosteroids in combination with CNI at inclusion. 15 (48) Nineteen patients in the study used everolimus as maintenance immunosuppression for > 21 months. 15 (48) 1.00 Statistical analyses were performed using softwa- 16 (52) re R version 3.1.1 (The R Foundation for Statistical Computing, Vienna, Austria). 6 (19) 0.19 25 (81) The sample size was small compared with the number of potential explanatory variables and it was 16 (52) 1.00 unlikely a priori that statistical significance alone 15 (48) would be able to identify all prognostic covariates. Therefore, besides Cox regression analysis of all 4 (13) <0.001 candidate variables, we removed covariates 1 at the 5 (16) 22 (71) time to determine which could be excluded with the smallest deterioration in predictive value. 18 (58) 13 (42) 0.46 27 (64) 15 (36) 16 (52) 15 (48) 0.34 54 (74) 19 (26 32 (76) 10 (24) 22 (71) 9 (29) 0.79 21 (29) 52 (71) 10 (24) 32 (76) 11 (36) 20 (64) 0.31 a years, median (IQR) Dn: de novo; IQR: interquartile range; SCC: squamous cell cancer; AK: actinic keratosis. RESULTS During follow-up 31 patients (42%) develo- ped de novo SCC, of which 15 (48%) were in situ SCC and 16 (52%) were invasive SCC (Table I). Patients with more than one previous cu- taneous SCC had a 5-fold (1–21) higher risk This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340/00015555-2606 Acta Derm Venereol 2017; 97: 751–753