Immunotherapy for Non-melanoma Skin Cancer.
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ABSTRACT: Purpose of review
The therapeutic landscape for non-melanoma skin cancer (NMSC) has recently expanded with the development of effective and targeted immunotherapy. Here, we provide an overview of the role of immunotherapy in the management of advanced cutaneous carcinomas.Recent findings
Several agents were recently U.S. Food and Drug Administration (FDA)-approved for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma, Merkel cell carcinoma, and basal cell carcinoma. However, recent approvals in tissue-agnostic indications may also benefit other NMSCs including cutaneous adnexal solid tumors with high tumor mutation burdens or microsatellite instability. Furthermore, while FDA-approved indications will likely continue to expand, continued studies are needed to support the role of immunotherapy in the neoadjuvant, adjuvant, and refractory settings. Immunotherapy is emerging as the standard of care for several advanced NMSCs not amenable to surgery and radiation. Ongoing evaluation of the clinical trial landscape is needed to optimize enrollment and ensure continued innovation.
SUBMITTER: Shalhout SZ
PROVIDER: S-EPMC8395379 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionSeveral studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC) but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight.PurposeThe aim of this study was to examine the individual risk factors associated with the development of subsequent cancers after non melanoma skin cancer.MethodsParticipants in the population-based New Hampshire Skin Cancer Study provided detailed risk factor data, and subsequent cancers were identified via linkage with the state cancer registry. Deaths were identified via state and national death records. A Cox proportional hazard model was used to estimate risk of subsequent malignancies in NMSC patients versus controls and to assess the potential confounding effects of multiple risk factors on this risk.ResultsAmong 3584 participants, risk of a subsequent cancer (other than NMSC) was higher after basal cell carcinoma (BCC) (adjusted HR 1.40 [95% CI 1.15, 1.71]) than squamous cell carcinoma (SCC) (adjusted HR 1.18 [95% CI 0.95, 1.46]) compared to controls (adjusted for age, sex and current cigarette smoking). After SCC, risk was higher among those diagnosed before age 60 (HR 1.96 [95% CI 1.24, 3.12]). An over 3-fold risk of melanoma after SCC (HR 3.62; 95% CI 1.85, 7.11) and BCC (HR 3.28; 95% CI 1.66, 6.51) was observed, even after further adjustment for sun exposure-related factors and family history of skin cancer. In men, prostate cancer incidence was higher after BCC compared to controls (HR 1.64; 95% CI 1.10, 2.46).ConclusionsOur population-based study indicates an increased cancer risk after NMSC that cannot be fully explained by known cancer risk factors.
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Project description:BackgroundNon-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs).SummarySince immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions.Key messagesMany clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, cost-effective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts.
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Project description:Background: Mohs micrographic surgery (MMS) is the gold standard treatment for high-risk facial non-melanoma skin cancer. However, patients' access to MMS is limited by cost. The muffin technique micrographic surgery (MTMS) is an alternative micrographic technique wherein the entire excised margin is evaluated post-operatively by a pathologist using paraffin-embedded material. Herein, we describe the implementation and the preliminary results of MTMS in an academic dermatology center. Objective: To describe the MTMS and outline its efficacy and safety in a real-world clinical academic setting. Methods: A retrospective chart review was conducted of all patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) who underwent MTMS at the University of Alberta Dermatology Center from June 2016 until July 2019. Results: A total of 69 patients were included (64 BCCs and 5 SCCs). 68.1% of surgeries had clear margins following the first incision, 100% after second round re-excisions. There were no observed cases of tumor recurrence after a median 40 months of follow-up. There were no major adverse events or complications. Conclusions: MTMS is a superior alternative to simple excision of skin cancer by providing full margin control and residual tumor mapping.
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Project description:A milieu of cytokines and signaling molecules are involved in the induction of UV-induced immune suppression and thus the etiology of non-melanoma skin cancer (NMSC). Targeting the UV-induced immunosuppression pathway, and using a large population based study of NMSC, we have investigated the risk associated with functional variants in 10 genes (IL10, IL4, IL4R, TNF, TNFR2, HTR2A, HRH2, IL12B, PTGS2, and HAL). The most prominent single genetic effect was observed for IL10. There was increasing risk for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with increasing number of variant IL10 haplotypes (BCC: p(trend)?=?0.0048; SCC: p(trend)?=?0.031). Having two IL10 GC haplotypes was associated with increased odds ratios of BCC and SCC (OR(BCC)?=?1.5, 95% CI 1.1-1.9; OR(SCC)?=?1.4, 95% CI 1.0-1.9), and these associations were largely confined to women (OR(BCC)?=?2.2, 95% CI 1.4-3.4; SCC: OR(SCC)?=?1.8, 95% CI 1.1-3.0). To examine how combinations of these variants contribute to risk of BCC and SCC, we used multifactor dimensionality reduction (MDR) and classification and regression trees (CART). Results from both of these methods found that in men, a combination of skin type, burns, IL10, IL4R, and possibly TNFR2 were important in both BCC and SCC. In women, skin type, burns, and IL10 were the most critical risk factors in SCC, with risk of BCC involving these same factors plus genetic variants in HTR2A, IL12B and IL4R. These data suggest differential genetic susceptibility to UV-induced immune suppression and skin cancer risk by gender.
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Project description:BACKGROUND: Topical 5-fluorouracil 5% cream is one of the treatment modalities for non-melanoma skin cancer (NMSC). There is a lack of suitable therapies to treat patients with extensive NMSC. In this paper we report two patients with extensive NMSC treated by total body application of topical 5-fluorouracil 5% cream. OBSERVATIONS: Topical 5-fluorouracil 5% cream was applied twice daily to the total body, including normal appearing skin. During the treatment, weekly blood samples were taken for measurement of 5-fluorouracil levels. All samples showed a 5-fluorouracil level less than the detection level of 10 microg/l. Total body 5- fluorouracil 5% cream was shown to be an effective treatment in our patients; the majority of lesions cleared in both patients. CONCLUSIONS: In conclusion, total body topical 5- fluorouracil 5% cream application was successful in two patients with extensive NMSC. No detectable serum level of 5-fluorouracil could be determined. Pain and secondary infections were important side effects in our patients. However, in patients with extensive NMSC this treatment may be considered.
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