scholarly journals Immune Checkpoint Inhibition in Non-Melanoma Skin Cancer: A Review of Current Evidence

2021 ◽  
Vol 11 ◽  
Author(s):  
Connor J. Stonesifer ◽  
A. Reza Djavid ◽  
Joseph M. Grimes ◽  
Alexandra E. Khaleel ◽  
Yssra S. Soliman ◽  
...  

Immuno-oncology is a rapidly evolving field with growing relevance in the treatment of numerous malignancies. The prior study of immunotherapy in dermatologic oncology has largely focused on cutaneous melanoma. However, recent focus has shifted to the use of immunotherapy to treat non-melanoma skin cancers (NMSCs), such as basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC). NMSCs represent the most ubiquitous cancers globally and, while they have a lower propensity to develop into advanced disease than cutaneous melanoma, their absolute mortality burden has recently surpassed that of melanoma. Patients with advanced NMSC are now benefiting from the successes of immunotherapy, including checkpoint inhibition with anti-CTLA-4 and anti-PD-1 monoclonal antibodies. In this review, we discuss the existing clinical evidence for immunotherapy in the treatment of NMSCs, with an emphasis on checkpoint inhibitor therapies. We highlight key studies in the field and provide up-to-date clinical evidence regarding ongoing clinical trials, as well as future study directions. Our review demonstrates that checkpoint inhibitors are positioned to provide unparalleled results in the previously challenging landscape of advanced NMSC treatment.

2021 ◽  
Vol 22 (4) ◽  
Author(s):  
Enrico Zelin ◽  
Iris Zalaudek ◽  
Marina Agozzino ◽  
Caterina Dianzani ◽  
Arianna Dri ◽  
...  

Opinion statementRecently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.


2015 ◽  
Author(s):  
Jennifer A. Wargo ◽  
Kenneth Tenabe

The prevalence of malignant skin cancers has increased significantly over the past several years. Approximately 1.2 million cases of non-melanoma skin cancer are diagnosed per year. More alarming, up to 80,000 cases of melanoma are diagnosed per year, an incidence that has been steadily increasing, with a lifetime risk of 1 in 50 for the development of melanoma. The disturbing increase in the incidence of both non-melanoma skin cancer and melanoma can largely be attributed to the social attitude toward sun exposure. The clinical assessment and management of skin lesions can be challenging. This review describes the assessment process, including thorough history and examination; the need for possible biopsy; and excision criteria. Specific types of skin cancer are distinguished and include basal cell carcinoma; squamous cell carcinoma; and melanoma; and for each type the incidence; epidemiology; histologic subtypes; diagnosis; and both surgical and non-surgical treatments are provided. Stages I-IV of melanoma are detailed, with prognostic factors described. Surgical treatment for stages I and II include description of the margins of excision and sentinel lymph node biopsy. The surgical treatment of Stage III melanoma further includes therapeutic lymph node dissection and isolated limb perfusion. Adjuvant therapies are also presented and include radiotherapy and chemotherapy. The additional treatment of metastasectomy for Stage IV melanoma is described. For both Stage III and IV melanoma, the study of vaccines to host immune cells is reported. For Stage IV melanoma, the text also describes immunotherapy treatment. Operative procedures specific to superficial and deep groin dissections are outlined. This review contains 9 figures, 3 tables, and 96 references.


Author(s):  
Rubeta Matin ◽  
Jane McGregor ◽  
Catherine Harwood

Skin cancer is very common in the UK, and its incidence is rising rapidly. There are two broad classes of primary skin cancer: non-melanoma and melanoma. Non-melanoma skin cancer is the commonest form (100 000 cases diagnosed annually in the UK), accounting for nine out of ten skin cancers and includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Cutaneous melanoma is less common (10 000 cases diagnosed in the UK annually) but confers a significantly worse prognosis and accounts for 75% of skin cancer related deaths. There are also a number of other, rarer, non-melanoma skin cancers (e.g. appendageal carcinomas, Merkel cell carcinoma, sarcomas, vascular malignancies, and cutaneous lymphomas); however, these account for less than 1% of all skin cancers in the UK and so will not be specifically discussed in this chapter. Cutaneous metastases can occur secondary to any internal cancer or, indeed, to skin cancer (e.g. melanoma). In most cases, cutaneous metastasis occurs after the diagnosis of a primary cancer and usually in late stages of the disease but, in some cases, it may be the first presentation, in which case it should prompt a thorough investigation for the primary malignancy.


2021 ◽  
pp. 69-78
Author(s):  
Barbara Jemec ◽  
Gregor B.E. Jemec

This chapter describes the diagnosis, non-surgical treatment, and surgical treatment of non-melanoma skin cancers, such as basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and others.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magdalena Ciążyńska ◽  
Grażyna Kamińska-Winciorek ◽  
Dariusz Lange ◽  
Bogumił Lewandowski ◽  
Adam Reich ◽  
...  

AbstractNon-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.


Author(s):  
Evan T. Hall ◽  
Elena Fernandez-Lopez ◽  
Ann W. Silk ◽  
Reinhard Dummer ◽  
Shailender Bhatia

In this review, we summarize the immunology of nonmelanoma skin cancers (NMSCs) and the clinical data with immunotherapy in this heterogeneous group of cancers that include basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSCC), and Merkel cell carcinoma (MCC). NMSCs are exceedingly common, and their treatment consumes substantial health care resources. Annual global mortality from NMSCs is comparable to that from malignant melanoma. Although the majority of NMSCs are localized at diagnosis and are treated effectively with surgery, metastases (nodal and distant) can sometimes arise and require systemic therapy. Given the success of immunotherapy in treating cutaneous melanoma, there has been an increasing interest in studying the immunology of NMSCs. Immunocompromised patients have a substantially higher risk of developing NMSCs (particularly CSCC and MCC), suggesting a role of the immune system in the pathogenesis of these cancers. Similar to cutaneous melanoma, the pathogenesis of BCC, CSCC, and virus-negative MCC is related to DNA damage from ultraviolet radiation exposure, and these cancers have a very high tumor mutational burden, which likely results in higher levels of tumor neoantigens that may be targets for the immune system. Viral antigens in virus-positive MCC are also strongly immunogenic. Emerging data from clinical trials of immune checkpoint inhibitors in NMSCs look very promising and are rapidly changing the treatment landscape of these cancers. Specifically, pembrolizumab and avelumab are U.S. Food and Drug Administration–approved for treatment of metastatic MCC and cemiplimab for metastatic CSCC. Several ongoing trials are investigating novel immunotherapies (monotherapies as well as combination) for treatment of NMSCs.


2018 ◽  
Vol 10 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Khalel Imanbayev ◽  
Abay Makishev ◽  
Murat Zhagiparov ◽  
Pauline McLoone

The association between ultraviolet radiation exposure and skin cancer is well established. Limited studies have reported an association between frostbite and the development of non-melanoma skin cancer but evidence for a proven link is insufficient and possible carcinogenic mechanisms have not been fully explored. In this report, 3 cases of non-melanoma skin cancer (1 case of basal cell carcinoma and 2 cases of squamous cell carcinoma of the skin) which developed at a site of previous frostbite caused by exposure to extremely cold temperatures in Astana, the capital city of Kazakhstan, are described.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1268-1268
Author(s):  
Timothy G Call ◽  
Kari G Rabe ◽  
Brewer D Jerry ◽  
Neil E. Kay ◽  
Clive S. Zent ◽  
...  

Abstract Abstract 1268 Poster Board I-290 Purpose There are reports of an increased risk of skin cancers in patients with B-Chronic Lymphocytic Leukemia (CLL). These skin cancers include basal cell and squamous cell carcinoma. This analysis was performed to more completely define the prevalence of skin cancers in patients in the Mayo Clinic Rochester CLL database and to look for contributing factors. Methods The Mayo Clinic Rochester CLL Database includes all patients with a diagnosis of CLL since January 1995 seen in the Division of Hematology and who have signed institutional review board approved consents for research. For this study, 2240 patients were analyzed to compare differences in characteristics between CLL patients with and without skin cancer. Chi-square statistics were used to compare qualitative variables (age categories, gender, referral status, ALC categories, CD38, ZAP-70, IgVH gene mutation status, FISH categories, Rai stage), and t-tests were used for quantitative variables (age at diagnosis, ALC values). Overall survival (OS) and time to first treatment (TFT) analyses were performed with results being displayed using Kaplan-Meier curves and p-values calculated using a log-rank test. Prevalence of melanoma among CLL patients was compared to the age-adjusted prevalence of melanoma in individuals in the Iowa SEER registry. Results Median follow-up for the 2240 patients diagnosed between 1/1/1995 and 8/11/2009 was 4.6 years. In aggregate, 293 (13.1%) patients were found to have non-melanoma skin cancer (squamous cell carcinoma or basal cell carcinoma) cancer. The diagnosis of non-melanoma skin cancer occurred before the CLL diagnosis in 39% and at or after the diagnosis of CLL in 61%. There were 57 (2.5%) cases of melanoma in association with CLL. The diagnosis of melanoma occurred before the CLL diagnosis in 38% and at or after the diagnosis of CLL in 62%.The prevalence of non-melanoma skin cancer and melanoma skin cancer were both higher in non-referred (geographically regional) CLL patients than referred CLL patients (16.6% vs. 11.4%, p<0.001 for non melanoma; 2.0% vs. 3.6%, p=0.03 for melanoma). The prevalence of melanoma in CLL patients was higher than that of age-adjusted prevalence for individuals in the Iowa SEER registry (2.5% vs. 0.03%; p<0.001). We next evaluated the relationship between CLL patients with skin cancer and demographic characteristics, prognostic parameters, and CLL related treatment. The risk of non-melanoma skin cancer in CLL was found to be associated with age (median age at diagnosis with skin cancer 67.6 vs. without skin cancer 63.3, p<0.001) and with sex (males 15.1% vs females 8.9%, p <0.001). There was no statistical significant difference in frequency of non-melanoma skin cancer associated with absolute lymphocyte count (ALC), Rai stage, CD 38, Zap 70, IgVH gene mutation status, FISH, or treatment history. The risk of melanoma in CLL was found to be associated with age at diagnosis (median age with melanoma 69.9 vs. without melanoma 63.8, p=0.002) and CD38 (positive 1.3% vs negative 3.1%, p=0.03). There was no statistically significant difference associated with gender, ALC, Rai stage, Zap 70, IgVH gene mutation status, FISH, or treatment history. Since the presence of skin cancer could be a marker of immune dysregulation we hypothesized skin cancer may be associated with clinical outcome of CLL. Accordingly, we evaluated the relationship between non-melanoma skin cancer and melanoma skin cancer and TFT and OS. Contrary to our hypothesis, TFT (median 6.0 years vs. 4.9; p=0.04) and OS (median 10.8 years vs. 9.7; p=0.02) of patients with non-melanoma skin cancer were both longer than those without non-melanoma skin cancer. No differences in TFT (p=0.06) or OS (p=0.66) were observed among patients with melanoma compared to those without melanoma. Conclusions We find in our cohort of CLL patients a higher prevalence of melanoma than the general population. Risk of melanoma and non-melanoma skin cancer among patients with CLL does not appear to be related to CLL characteristics, with the exception of CD 38, or CLL outcome. The diagnosis of melanoma and non-melanoma skin cancer in patients with CLL does not appear to be a risk factor for either CLL specific outcomes (TFT) or shorter survival. Disclosures Kay: Biogenc-Idec, Celgene, Genentech, genmab: Membership on an entity's Board of Directors or advisory committees; Genentech, Celgene, Hospira, Polyphenon Pharma, Sanofi-Aventis: Research Funding. Zent:Genentech, Bayer, Genzyme, Novartis: Research Funding. Shanafelt:Genentech: Research Funding; Hospira: Membership on an entity's Board of Directors or advisory committees, Research Funding; Polyphenon E International: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Bayer Health Care Pharmaceuticals: Research Funding.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21559-e21559
Author(s):  
Xi Yang ◽  
Lilit Karapetyan ◽  
Na Bo ◽  
Hong Wang ◽  
Cindy Sander ◽  
...  

e21559 Background: Patients (PTs) with cutaneous melanoma are at increased risk of developing second primary melanoma and non-melanoma skin cancers. The primary aim of this study was to define the association between MPM and personal history of non-melanoma skin cancers and other non-skin cancers. The secondary aim was to evaluate the association between MPM and the presence of other cancers among first-degree relatives (FDRs). Methods: We performed a retrospective case-control study including cases with MPM and controls with single primary melanoma (SPM) from the University of Pittsburgh Cancer Institute Melanoma Center Biological Sample and Nevus Bank. The proportions and percentages of non-melanoma skin cancer, other non-skin cancer, 1st degree family history of melanoma, and 1st degree family history of other non-melanoma cancers were calculated separately for MPM and SPM groups. Fisher’s exact tests were performed to test whether MPM was associated with these variables. For each significant variable, a multivariable logistic regression model was used to test its association with MPM after adjusting for age, gender, melanoma staging, and smoking status. Results: In total, 311 PTs (39.2% men; median age at initial diagnosis 51years) were enrolled, including 194 with SPM (38.6%; 51) and 117 with MPM (39.8%; 48). 28 (9%) of PTs had squamous cell carcinoma (SCC), and 63 (20%) had basal cell carcinoma (BCC). The most common non-skin cancers in the whole cohort were prostate (4.8%), breast (3.8%), hematological (1.9%), colorectal (1.3%), and cervical cancers (1.3%). FDR history of melanoma, non-melanoma skin cancer, and other cancers were positive in 15.4%, 7.1% and 46.3% PTs, respectively. The most common non-skin cancers in FDRs were breast, prostate, lung, colorectal and hematological malignancies. In comparison to PTs with SPM, PTs with MPM were more likely to have SCC (14.5% vs 5.7%, p=0.013) but not BCC and other non-skin cancers. FDRs of PTs with MPM had higher prevalence of melanoma (23.1% vs 10.8%, p=0.005), prostate cancer (31.9% vs 5.3%, p=0.0002) but not other non-melanoma skin and non-skin cancers. In multivariate analysis the association remained significant between MPM and SCC (OR 2.7, 95% CI 1.1-6.6, p=0.032), FDR history of melanoma (OR 2.0, 95% CI 1.03-4.1, p=0.042), and FDR history of prostate cancer (OR 5.6, 95% CI 1.6-20.3, p=0.008). Conclusions: MPM is associated with higher prevalence of SCC and FDR history of melanoma and prostate cancer, but not BCC and other non-melanoma cancers in comparison to SPM.


2018 ◽  
Vol 6 (1) ◽  
pp. 120-122
Author(s):  
Georgi Tchernev ◽  
Stanislav Philipov ◽  
Anastasiya Atanasova Chokoeva ◽  
Uwe Wollina ◽  
Torello Lotti ◽  
...  

Keratinocyte skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common cancer occurring in people with fair skin, worldwide. Despite all known triggers, several suggested contributors are still investigated. We will focus our attention on the personal history of previous cancers and radiation exposure as occupational risk factors, as in the presented case. We report a patient, with multiple BCCs, and subsequent occurrence of a SCC on photo-exposed area of the face, as we want to emphasize the importance of strict following up of these patients, regarding the risk for developing new tumors in short periods of time, no matter if the triggering exposure factor is known from the history, or not.  Although keratinocytes tumours are associated with the low mortality rate, we focus the attention on the fact, that the history of non-melanoma skin cancer is associated with increased mortality.


Sign in / Sign up

Export Citation Format

Share Document