Acta Dermato-Venereologica 99-7CompleteContent | Page 29

707 SHORT COMMUNICATION Characteristics of Keratinocyte Carcinomas and Patients with Keratinocyte Carcinomas Following a Single 2–4 Week Course of Topical 5-fluorouracil on the Face and Ears Meghan BEATSON 1–3 , Alexander D. MEANS 1,2,4 , Nicholas F. LEADER 1,2 , Leslie ROBINSON-BOSTOM 1,2 , Martin A. WEINSTOCK 1,2 ; VAKCC Trial group Center for Dermatoepidemiology-111D, Veterans Affairs Medical Center, 830 Chalkstone Avenue, Providence, RI 02908-4799, 2 Department of Dermatology, Alpert Medical School of Brown University, Providence, RI, 3 George Washington University School of Medicine, Washington, DC, and 4 Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. E-mail: [email protected] 1 Accepted Mar 21, 2019; E-published Mar 21, 2019 It was recently reported that 5-fluorouracil (5-FU) is effective for prevention of squamous cell carcinoma (SCC) for one year, but not for basal cell carcinoma (BCC) (1). Additionally, a history of 5-FU exposure has been associated with more aggressive BCC subtypes, and we wanted to confirm this finding prospectively by determining the influence of 5-FU on the histopatholo- gic characteristics of BCC and SCC (2). We evaluated whether 5-FU was effective for prevention of specific subtypes of BCC or SCC or was effective in specific subpopulations of our high risk group of veterans with at least 2 prior keratinocyte carcinomas (KCs) in the Veterans Affairs Keratinocyte Carcinoma Chemopreven- tion (VAKCC) Trial. The VAKCC Trial followed 932 veterans at high risk for development of KC for a median of 2.8 years, where participants were randomized to apply topical 5-FU or vehicle control cream to the face and ears twice daily for up to 4 and at least 2 weeks (1). All participants were free of suspicious skin lesions suggestive of any type of skin cancer at the initial full body skin examination. Total body skin examinations, with biopsies as clinically indicated, were performed every 6–12 months. All skin biopsies were read by a single central board-certified dermatopathologist. The Veteran’s Affairs Central Institutional Review Board approved this trial, all par- ticipants gave written, informed consent, and Declara- tion of Helsinki Principles were followed, as described elsewhere (1). MATERIAL, METHODS AND RESULTS Data for patient age, tumor size, anatomic location, and histo- pathologic subtypes were collected (1). Anatomic locations were first divided into left and right halves of the head, and then sub- classified based on eye, ear, nose, cheek, chin, forehead, temple, or mouth location. Histopathologic subtypes were classified ac- cording to commonly utilized dermatopathology criteria noted in the legend of Table I (3). All analyses were done using Stata statistical software (release 8.0, StataCorp, College Station, TX). To determine the charac- teristics of BCC and SCC in year 1 and overall, t-tests were performed comparing 5-FU to control groups for lesion size by individual participant and total lesion count. Age was stratified a posteriori into “very old” ≥ 85 years old, as defined by Linos et al. (4) and “not very old” (< 85 years old). Pearson’s chi-squared tests and Fischer’s exact tests were performed comparing 5-FU to control groups for development of BCC and SCC by location and histopathologic subtype by participant and total lesion count in year 1 and overall. We assigned an alpha value of 0.05. This alpha value should be interpreted in the context of our exploratory examination with multiple comparisons performed. Participants had a mean age of 71.1 years and 98% were men (1). There were no significant differences between the 5-FU and control groups with respect to other demographic characteristics such as age, education, military service history, self-reported Fitz- patrick skin type, sunburn, marital status, geographic residence, weight, height, or skin cancer history, as previously reported (1). There were fewer superficial BCCs in the 5-FU group vs. control group (Table I). In year 1, there was a smaller number of total BCCs among those at least 85 years old in the 5-FU group vs. control group, but there was no substantial difference in the risk of these individuals at least 85 years old developing a BCC (Table II). One of the BCCs in the participants ≥ 85 years old was superficial type. Among the same elderly group, there was also Table I. Histopathologic subtype of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) 5-FU Control p-value Number of BCCs by subtype Year 1 Overall study period Nodular or micronodular Aggressive a Superficial Nodular or micronodular Aggressive Superficial Overall study period Nodular or micronodular Aggressive Superficial Nodular or micronodular Aggressive Superficial p-value d 4 13 0.62 0 1 46 5 20 0 10 42 10 27 0.29 Number of SCCs by subtype 36 45 20 1 182 57 7 17 5 162 69 17 0.21 0.04 Number of participants with BCC by subtype c Year 1 Control 5-FU 30 15 0 118 32 1 SCC invasive or transected Aggressive b SCCIS/KA SCC invasive or transected Aggressive SCCIS/KA Number of participants with SCC by subtype c 33 13 3 94 43 9 0.21 0.005 SCC invasive or transected Aggressive SCCIS/KA SCC invasive or transected Aggressive SCCIS/KA 0 4 1 33 5 14 2 10 8 29 7 20 0.45 0.47 a Aggressive BCC subtypes: infiltrative/morpheaform, nodular/infiltrative, basosquamous. b Aggressive SCC subtypes: sclerosing, basosquamous, small cell, poorly or undifferentiated (high mitotic rate, high degree of nuclear polymorphism), perineural/perivascular, spindle cell, pagetoid, infiltrating, centrofacial keratoacanthoma, single cell, clear cell, lymphoepithelial, sarcomatoid, breslow depth 2 mm or greater. c For participant calculations, histopathologic subtype of first BCC or SCC was used. d Fisher’s exact test used in lieu of chi-2 for first-year SCC calculation p-values. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3176 Acta Derm Venereol 2019; 99: 707–708