Background Oral nicotinamide has been proposed as a chemoprevention strategy to reduce new keratinocyte carcinomas in people with a history of skin cancer, but its effect may differ between immunocompetent patients and transplant recipients. Objective To evaluate the effectiveness and safety of oral nicotinamide for the secondary prevention of cutaneous squamous cell carcinoma and other keratinocyte carcinoma–related outcomes in adults with a history of skin cancer. Methods We conducted a systematic review following PRISMA 2020. We searched PubMed/MEDLINE, Embase, and LILACS through the Virtual Health Library from inception to May 30, 2026. We included comparative studies (randomized clinical trials and controlled nonrandomized studies) evaluating oral nicotinamide versus placebo, no treatment, usual care, or another preventive strategy. Risk of bias was assessed with RoB 2 for randomized trials and ROBINS‐I for nonrandomized studies, and the certainty of evidence was assessed with GRADE. We performed a narrative synthesis and an exploratory random‐effects meta‐analysis of randomized trials when clinically appropriate; effect measures were rate ratios for randomized trials and hazard ratios for the observational cohort. Randomized and nonrandomized designs were not statistically pooled together. Results We identified 1076 records; after removing 151 duplicates, 925 records were screened, 17 full texts were assessed, and 5 studies were included: 4 randomized clinical trials and 1 large retrospective cohort. In high‐risk immunocompetent adults, the benefit signal was driven by a single pivotal randomized trial (ONTRAC; n = 386), in which nicotinamide reduced new nonmelanoma skin cancers (rate ratio, 0.77; 95% CI, 0.62–0.96). In transplant recipients, the main exploratory meta‐analysis of two randomized trials ( n = 180) showed no significant reduction in total keratinocyte carcinoma/nonmelanoma skin cancer (pooled rate ratio, 0.97; 95% CI, 0.77–1.22; I 2 = 0.0%), cSCC/SCC (0.90; 95% CI, 0.65–1.25; 2 trials), or basal cell carcinoma (0.80; 95% CI, 0.20–3.18; 2 trials). A large retrospective cohort (Breglio et al.; 33,822 patients) reported an overall 14% reduction in skin cancer (hazard ratio, 0.86; 95% CI, 0.83–0.89) that was greatest for cSCC and greatest when nicotinamide was started after the first skin cancer, but there was no overall benefit in transplant recipients (hazard ratio, 1.02; 95% CI, 0.84–1.25). Certainty was low or very low for the transplant–recipient outcomes. Conclusions In high‐risk immunocompetent adults, oral nicotinamide may reduce new nonmelanoma skin cancers during active treatment, but this conclusion rests predominantly on one large randomized trial and should be regarded as provisional. In transplant recipients, the randomized evidence does not demonstrate a significant benefit, a finding concordant with the overall null result in the large observational cohort. An observational signal favoring early initiation is hypothesis‐generating and requires prospective confirmation. Limitations Evidence was limited by the very small number of randomized trials (only two contributed to the main meta‐analysis), imprecision, follow‐up of 12 months or less in all randomized trials, the observational nature of the largest study, and low or very low certainty for the transplant–recipient outcomes.
Background:Postoperative management of close or positive margins after conventional excision of facial nonmelanoma skin cancer is challenging, especially in elderly patients and anatomically constrained sites where re-excision may impose functional or aesthetic morbidity. Methods:We retrospectively analysed 238 facial carcinoma cases treated by conventional excision at a peripheral ENT unit, including 172 basal cell carcinomas (BCC) and 66 squamous cell carcinomas (SCC). Margins were classified as clear, close or positive. Outcomes were analysed descriptively; two-sided Fisher exact tests were used as exploratory descriptors of distributional imbalance under sparse-event conditions, not as tests of treatment superiority or equivalence. Results:In BCC, no recurrence occurred after clear margins (0/90). Among non-clear-margin BCCs, recurrence remained uncommon after structured surveillance (5/65) and early re-excision (1/17). In SCC, recurrence occurred only after positive margins (3/15), with none after clear or close margins. Conclusion:The findings support histotype-specific postoperative interpretation of margin status after conventional facial skin cancer excision. In this cohort, selected lower-risk BCC cases were managed through structured surveillance, whereas SCC recurrence was confined to positive-margin cases, supporting a lower threshold for timely re-excision or equivalent oncologic management when clinically feasible.
Introduction:Cemiplimab has been licensed for use in the United Kingdom as the sole immunotherapy agent for first-line use in advanced cutaneous squamous cell carcinoma (a-cSCC). Given that previous clinical trials leading to the approval of cemiplimab had relatively small patient cohorts with relatively short follow-up periods, with a large proportion of patients who had received prior systemic treatment, this retrospective real-world study sought to add further insight into survival and toxicity in patients who exclusively had received first-line use of cemiplimab, as well as comparing response rates (RRs) based on primary site location. Methods:This retrospective study identified patients diagnosed with a-cSCC between 01/08/2019 and 31/03/2024 who received cemiplimab as first-line treatment at our institution. Data to enable response assessment and toxicity were collected and analyzed. Results:50 patients were identified with a mean age of 75 years (range: 44-94). 78% (n = 39) of the patients' primary lesion originated from the head and neck (H&N) region, whilst the remaining 22% (n = 11) had a primary lesion from other areas. No patients had received prior systemic treatment for a-cSCC. Overall, the disease control rate (DCR) was 74%, and the RR was 55.8% with complete response in 35% (n = 15), partial response in 21% (n = 9), and stable disease in 19% (n = 8). In patients with H&N primary site of disease, RR was 58.9% versus 27.2% in patients with non-H&N primary site of disease, with a p value of 0.027. The overall mean PFS for the study population was 27.3 months (95% CI: 21.2-33.5 months), with the median PFS not reached for the study duration. The median PFS for patients with H&N primary site of disease was not reached as compared to the median PFS of 4 months (95% CI: 2.2-5.7 months) for patients with non-H&N primary site of disease, with a p value of 0.049. The median OS for the study population was 34 months (95% CI: 15.4-52.5 months). Grade 3 toxicities were reported in 22% (n = 11) with no Grade 4 toxicites. Discussion:The use of cemiplimab as first-line treatment in a-cSCC demonstrates high efficacy and low rates of serious toxicity, which is especially reassuring in a patient cohort comprising of more elderly patients. The high complete RR seen in our patient cohort may reflect the exclusive first-line use of cemiplimab in our study, as per now established real-world practice in a-cSCC. Higher RRs and PFS are seen in patients with head/neck primary site of disease vs. non head/neck primary site, which should be evaluated further in future clinical trials.
Background:Basal cell carcinomas (BCCs) with aggressive histology are infiltrative, destructive, aggressive, and metastatic tumors. Aggressive variants include morpheaform, infiltrative, metatypical or basosquamous, micronodular, and mixed subtypes. Selecting the appropriate treatment is crucial to eliminate this type of tumor and avoid complications such as mutilation and deformities when located in the facial region, as well as tumor recurrence. Interferons may represent a therapeutic option because of their curative potential and long-term cosmetic effects. Material and Methods:A descriptive, longitudinal, observational case-series study was conducted, including patients with a histopathological diagnosis of aggressive BCC. Perilesional HeberFERON was administered for three weeks, and patients were then followed for 5 years. The main outcome variables were cure at 16 weeks and recurrence at 5 years. Results:Twenty-three patients were included, and one discontinued treatment. After therapy, 14 (63.6%) patients achieved cure (complete response [CR]). Those who did not achieve a CR underwent surgery and were declared cured. All 22 patients were followed for five years; two (9.0%) were lost to follow-up. Survival analysis showed that 86.4% (95% CI, 74%-99%) had the probability of remaining recurrence-free at five years. Conclusions:HeberFERON can be considered a first-line treatment for BCC with aggressive histology and as a therapy prior to subsequent surgery.
Background:Cutaneous lymphomas (CLs) are rare neoplastic skin disorders, primarily of T-cell origin. Since the widespread rollout of SARS-CoV-2 vaccines, several cases of CLs and non-neoplastic lymphoproliferative disorders (nn-LPDs) temporally associated with vaccination have been reported, raising concerns about a potential immunologic link. Objective:To systematically review the literature on cases of CLs and related nn-LPDs occurring after COVID-19 vaccination, focusing on clinical features, subtype distribution, latency to onset, and proposed pathophysiological mechanisms. Methods:A systematic review was conducted according to PRISMA guidelines. Case reports and series describing new-onset or relapsed CLs or nn-LPDs temporally following SARS-CoV-2 vaccination were included. Demographic, clinical, histological, therapeutic and temporal data were extracted and analysed. Results:Fifteen manuscripts encompassing 35 cases met the inclusion criteria. Eighteen (51.4%) were histologically confirmed CLs, most commonly lymphomatoid papulosis (n = 9), followed by Sézary syndrome (n = 3) and mycosis fungoides (n = 2). The remaining 17 cases (48.6%) were classified as nn-LPDs, including cutaneous lymphoid hyperplasia, lymphomatoid reactions and CD4+ small/medium T-cell lymphoproliferative disorders. CD30 positivity was noted in 76.2% of the cases with available immunophenotyping. Most patients (80%) received the BNT162b2 (Pfizer-BioNTech) vaccine. In the 17 new-onset CLs, time to onset ranged from 3 to 42 days, with most cases clustering within 14 days. Conclusions:Most of the cases were low-grade T-cell CLs and nn-LPDs. Although a causal relationship cannot be established, the short latency observed in many new-onset cases raises the possibility that some patients may have harboured an undiagnosed disease, with vaccination acting as a trigger for clinical manifestation or for raised awareness. These findings support indeed the need for continued pharmacovigilance among clinicians, especially in patients with prior or latent lymphoproliferative conditions. Nevertheless, these extremely rare and indolent events should not alter the overall favourable risk-benefit profile of COVID-19 vaccination.
