UV biomarker genes for classification and risk stratification of cutaneous actinic keratoses and squamous cell carcinoma subtypes.

Currently, there is no sensitive molecular test for identifying transformation-prone actinic keratoses (AKs) and aggressive squamous cell carcinoma (SCC) subtypes. Biomarker-based molecular testing represents a promising tool for risk stratifying these lesions. We evaluated the utility of a panel of ultraviolet (UV) radiation-biomarker genes in distinguishing between benign and transformation-prone AKs and SCCs. The expression of the UV-biomarker genes in 31 SCC and normal skin (NS) pairs and 10 AK/NS pairs was quantified using the NanoString nCounter system. Biomarker testing models were built using logistic regression models with leave-one-out cross validation in the training set. The best model to classify AKs versus SCCs (area under curve (AUC) 0.814, precision score 0.833, recall 0.714) was constructed using a top-ranked set of 13 UV-biomarker genes. Another model based on a 15-gene panel was developed to differentiate histologically concerning from less concerning SCCs (AUC 1, precision score 1, recall 0.714). Finally, 12 of the UV-biomarker genes were differentially expressed between AKs and SCCs, while 10 genes were uniquely expressed in the more concerning SCCs. UV-biomarker gene subsets demonstrate dynamic utility as molecular tools to classify and risk stratify AK and SCC lesions, which will complement histopathologic diagnosis to guide treatment of high-risk patients.

Fall risk assessment and injury prevention in the Mohs surgery clinic: a review of the literature and recommendations for improving patient safety.

Patient falls remain a major cause of adverse events in the medical setting. Many patients receiving Mohs micrographic surgery are at high risk, both for falling and resultant injuries. Although the incidence of patient falls in dermatologic surgery is low, falls can have significant consequences for both patient and provider. Therefore, effective interventions to improve organizational safety are critical. Though there is a considerable amount of research pertaining to fall prevention strategies, the majority of studies have been confined to the inpatient setting and long-term care facilities. Implementation of fall prevention initiatives in the outpatient setting has rarely been evaluated and no studies have focused on the Mohs patient population to date. METHODS: We reviewed the literature pertaining to fall risk and prevention guidelines in the inpatient and outpatient settings as it applies to the dermatologic surgery environment. RESULTS: Herein we will discuss patient risk factors for falling relevant to the Mohs setting and review existing validated fall risk assessment tools and strategies for fall prevention. CONCLUSION: Identifying fall risk factors can improve patient safety and reduce falls in the dermatologic surgery clinic.

Treatment Outcomes of Immune-Related Cutaneous Adverse Events.

PURPOSE: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype (P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

Correction to: The Role of Oncolytic Viruses in the Treatment of Melanoma.

A correction was made to a sentence in the original article to provide additional clarification in the "Other Oncolytic Viruses" section.

Current Status of HDAC Inhibitors in Cutaneous T-cell Lymphoma.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphomas that are characterized by primary skin involvement. Mycosis fungoides (MF) and Sézary syndrome (SS), the two most common subtypes of CTCL, can be difficult to manage clinically as there are few effective treatment options available. Recently, histone deacetylase inhibitors (HDACi) have emerged as promising therapies with favorable adverse effect profiles, compared with traditional chemotherapies. In this article, we review the published literature to evaluate the role of HDACi in the treatment of CTCL. Specifically, we (1) briefly discuss the molecular rationale for the use of HDACi in CTCL; (2) compare the efficacy, tolerability, and adverse effects of HDACi; (3) review the cardiac safety data; and (4) discuss optimization of therapy with HDACi in the treatment of CTCL.

The Role of Oncolytic Viruses in the Treatment of Melanoma.

PURPOSE OF REVIEW: Oncolytic virotherapy is a new approach to the treatment of cancer and its success in the treatment of melanoma represents a breakthrough in cancer therapeutics. This paper provides a review of the current literature on the use of oncolytic viruses (OVs) in the treatment of melanoma. RECENT FINDINGS: Talimogene laherparepvec (T-VEC) is the first OV approved for the treatment of melanoma and presents new challenges as it enters the clinical setting. Several other OVs are at various stages of clinical and pre-clinical development for the treatment of melanoma. Reports from phase Ib-III clinical trials combining T-VEC with checkpoint blockade are encouraging and demonstrate potential added benefit of combination immunotherapy. OVs have recently emerged as a standard treatment option for patients with advanced melanoma. Several OVs and therapeutic combinations are in development. Immunooncolytic virotherapy combined with immune checkpoint inhibitors is promising for the treatment of advanced melanoma.

A Case of Nivolumab-Induced Bullous Pemphigoid: Review of Dermatologic Toxicity Associated with Programmed Cell Death Protein-1/Programmed Death Ligand-1 Inhibitors and Recommendations for Diagnosis and Management.

Immunotherapy has emerged as a highly effective treatment for numerous cancers. Use of checkpoint inhibitors against various molecules including programmed cell death protein-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 have become widespread in clinical practice. Compared with conventional chemotherapy, immunotherapy is associated with a unique set of immune reactions known collectively as immune-related adverse events (irAEs). Of known irAEs, cutaneous toxicity is among the most frequently observed in patients treated with immunotherapy. Although often mild, dermatologic toxicity can occasionally be high grade and potentially life-threatening. In this article, we report a case of PD-1 inhibitor-induced bullous pemphigoid-a serious adverse event that has been increasingly observed with use of PD-1/PD-L1 inhibitors. We will also review diagnosis and management of low-grade cutaneous irAEs and bullous disease with checkpoint inhibitors. KEY POINTS: PD-1/PD-L1 inhibitor-induced bullous pemphigoid (BP) is a rare but potentially serious dermatologic toxicity associated with checkpoint inhibitorsIn patients with pruritus or rash that is refractory to topical steroids, physicians should have a greater index of suspicion for higher-grade cutaneous immune-related adverse events.There is no standardized treatment algorithm for management of PD-1/PD-L1 inhibitor-induced BP, but patients frequently require topical and systemic steroids.

Secondary Prevention Strategies for Nonmelanoma Skin Cancer.

Skin cancer is the most commonly diagnosed cancer in the United States and has become a major public health problem that continues to grow. Despite numerous initiatives and increased public awareness of the dangers of skin cancer, the incidence of skin cancer continues to rise worldwide. This highlights the need for a critical review of existing skin cancer prevention strategies as a means to determine where targeted efforts may improve patient outcomes. In this article, we review the published literature and evaluate secondary prevention strategies for nonmelanoma skin cancer. Specifically, we examine the existing data on the use of chemopreventive agents for nonmelanoma skin cancer primarily in immunocompetent individuals, but also in organ transplant recipients, the best-studied immunosuppressed population. We also explore investigational therapies proposed for chemoprevention of nonmelanoma skin cancers.

A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors.

BACKGROUND: Dermatologic toxicity represents a substantial portion of all immune-related adverse events (irAEs) associated with PD-1/PD-L1 inhibitors. Bullous pemphigoid (BP) is a rare cutaneous side effect of these medications, which can initially be clinically indistinguishable from other, low-grade cutaneous toxicity. OBJECTIVE: To better characterize the clinical features of BP associated with PD-1/PD-L1 inhibitors, evaluate the efficacy of various treatment regimens, determine the frequency of prodromal pruritus, and assess whether immunological diagnostic studies for BP are warranted in patients treated with checkpoint inhibitors who develop intractable pruritus. METHODS: A comprehensive review of the English-language medical literature was performed using key terms. Papers published on any date and from all origins were considered. Fourteen publications, containing 21 patient cases, were selected independently by two reviewers and deemed relevant to the present publication. RESULTS: Pruritus was a prominent feature of the majority (12/21) of cases and preceded or occurred concurrently with BP development. Bullae developed within 6-8 months of initiation of PD-1/PD-L1 inhibitors; however, a smaller subset of patients did not develop bullae for 1-1.5 years following initiation of therapy. Mean time to pruritus was similar for pembrolizumab and nivolumab at 19 and 21 weeks, respectively. Development of BP required discontinuation of immunotherapy in 76% (16/21) of cases. CONCLUSION: Prodromal or "non-bullous" variants of BP must be considered in patients treated with checkpoint inhibitors who develop protracted or worsening pruritus. Early diagnostic immunological evaluation of the skin may lead to improved patient outcomes by facilitating timely initiation of treatment and prevent disruptions in cancer therapy.