Expert Consensus on the Use of Prognostic Gene Expression Profiling Tests for the Management of Cutaneous Melanoma: Consensus from the Skin Cancer Prevention Working Group.

BACKGROUND: Prognostic assessment of cutaneous melanoma relies on historical, clinicopathological, and phenotypic risk factors according to American Joint Committee on Cancer(AJCC) and National Comprehensive Cancer Network (NCCN) guidelines but may not account for a patient's individual additional genetic risk factors. OBJECTIVE: To review the available literature regarding commercially available gene expression profile (GEP) tests and their use in the management of cutaneous melanoma. METHODS: A literature search was conducted for original, English-language studies or meta-analyses published between 2010 and 2021 on commercially available GEP tests in cutaneous melanoma prognosis, clinical decision-making regarding sentinel lymph node biopsy, and real-world efficacy. After the literature review, the Skin Cancer Prevention Working Group, an expert panel of dermatologists with specialized training in melanoma and non-melanoma skin cancer diagnosis and management, utilized a modified Delphi technique to develop consensus statements regarding prognostic gene expression profile tests. Statements were only adopted with a supermajority vote of > 80%. RESULTS: The initial search identified 1064 studies/meta-analyses that met the search criteria. Of these, we included 21 original articles and meta-analyses that studied the 31-GEP test (DecisionDx-Melanoma; Castle Biosciences, Inc.), five original articles that studied the 11-GEP test (Melagenix; NeraCare GmbH), and four original articles that studied the 8-GEP test with clinicopathological factors (Merlin; 8-GEP + CP; SkylineDx B.V.) in this review. Six statements received supermajority approval and were adopted by the panel. CONCLUSION: GEP tests provide additional, reproducible information for dermatologists to consider within the larger framework of the eighth edition of the AJCC and NCCN cutaneous melanoma guidelines when counseling regarding prognosis and when considering a sentinel lymph node biopsy.

Photoprotection for all: Current gaps and opportunities.

The effects of solar radiation on human skin differ based on the skin phototype, presence or absence of photodermatoses, biologic capacity to repair DNA damage, wavelength, intensity of sun exposure, geographic latitude, and other factors, underscoring the need for a more tailored approach to photoprotection. To date, the focus of photoprotection guidelines has been to prevent sunburn and DNA damage induced by UV radiation, both UVB and UVA; however, several recent studies have shown that visible light also generates reactive oxygen and nitrogen species that can contribute to skin damage and pigmentation on the skin, particularly in people with skin of color. Therefore, individuals with dark skin, while naturally better protected against UVB radiation by virtue of the high eumelanin content in melanocytes, may need additional protection from visible light-induced skin damage. The current options for photoprotection products need to expand, and potential strategies against visible light include the addition of iron oxide, titanium dioxide, and biologically relevant antioxidants to sunscreen formulations as well as supplementation with orally active antioxidants.

Impact of a prognostic 40-gene expression profiling test on clinical management decisions for high-risk cutaneous squamous cell carcinoma.

Objective: To determine how results from a prognostic 40-gene expression profiling (40-GEP) test would impact clinician management decisions and how their choices would align with a National Comprehensive Cancer Network (NCCN) compliant, risk-directed management plan for high-risk cutaneous squamous cell carcinoma (cSCC).Methods: Clinicians attending a national dermatology conference were presented with 40-GEP test validation data. They were asked to rate clinicopathological features and molecular test results to assess their opinion of how concerning each is to cSCC prognosis. When presented with vignettes describing patients with NCCN-defined high-risk features, clinicians were asked to select a treatment plan using pre-test (no 40-GEP results), then, post-test (40-GEP Class 1, 2A, or 2B results) methodology along with corresponding metastasis rates for each test group.Results: Risk factors deemed of highest concern for metastatic outcomes were a Class 2B 40-GEP result, perineural invasion, immunosuppression, invasion beyond subcutaneous fat, and tumor diameter >1 cm on the scalp. When presented with a 40-GEP result that indicated reduced risk of metastasis (Class 1), clinicians altered their treatment management plan accordingly. Specifically, there was significant reduction in the recommendations for sentinel lymph node biopsy, adjuvant radiation or chemotherapy, follow-up time, and nodal imaging. By comparison, when a 40-GEP result indicated an increased risk of metastasis (Class 2B), significant risk-appropriate increases in management intensity was observed for the aforementioned clinical decisions.Conclusion: Integration of 40-GEP results impacted management decisions in a significant and risk-appropriate manner for high-risk cSCC patient scenarios, while remaining aligned with national guidelines for patient management.

What's New in Melanoma.

Melanoma is rapidly evolving because of advances in noninvasive diagnosis, targeted therapies, and improved prognostic methods. This article discusses what is new in melanoma risk factors, prevention, clinical management, and targeted treatment. The incidence continues to increase worldwide, whereas mortality is steadily improving. This trend reinforces the importance of dermatologists comprehensively understanding all aspects of melanoma. Further research is needed to continue making a material impact on outcomes for patients.

Successful Treatment of Generalized Essential Telangiectasia With 6-Mercaptopurine.

Generalized essential telangiectasia (GET) is a notoriously difficult to treat disorder with no current satisfactory treatments. This case and discussion report the use of 6-mercaptopurine (6-MP) as a successful treatment for GET. Moreover, we show that GET may represent a state of increased angiogenesis, a paradigm shift from the current understanding that these telangiectasias represent dilatations of only pre-existing vessels. This new view of GET may drive others to look at novel agents for treatment.

J Drugs Dermatol. 2017;16(3):280-282.

Polypodium leucotomos extract: a status report on clinical efficacy and safety.

Various extracts of polypodium leucotomos (PLE) applied topically or taken orally have been shown to have several beneficial antioxidant, photoprotectant, antimutagenic, and immunoregulatory effects. Modern studies have evaluated the efficacy of PLE orally as a photoprotective agent and for use in several photo-aggravated dermatologic disorders such as polymorphous light eruption, other photodermatoses, and melasma. No articles have been published evaluating the safety of PLE. We performed a PUBMED search for any randomized clinical trials related to PLE, or anapsos, a synonym. The primary safety endpoint of the review was any mention of an adverse event, side effect, or toxicity. Overall, 19 human and 6 basic science studies were included spanning over 40 years of research. Oral PLE was administered at daily doses ranging from 120 mg to 1080 mg. No adverse effects were reported in laboratory studies. In humans, side effects (gastrointestinal complaints and pruritus) were mild to moderate and found only in very small numbers of patients overall (16/1016 [2%]). This review concludes PLE is well tolerated at all doses administered and associated with a negligible risk of side effects.

Epidemiology of melanoma.

Malignant melanoma represents a significant and growing public health burden in the US and worldwide. It is estimated that 68, 130 cases of invasive malignant melanoma and at least 48,000 cases of melanoma in-situ will be diagnosed in the US this year. Melanoma is also one of the few remaining cancers with increasing US incidence. In the 1930s, the lifetime risk of an American developing invasive malignant melanoma was 1 in 1,500. Currently, that risk is 1 in 59. Deaths from malignant melanoma are also increasing. The mortality rate from malignant melanoma has risen about 2% annually since 1960. This year, it is estimated that 8,700 Americans will die from this cancer. The identification of individuals at high risk for malignant melanoma is important for the development of focused and efficient prevention efforts. Acute sun exposure resulting in sunburn remains a significant risk factor for the development of melanoma, but numerous other potential risk factors have been cited. Included among these are atypical mole syndrome/dysplastic nevus syndrome, blistering sunburns, immunosuppression, prior therapy with psoralen with ultraviolet A light (UVA) light, UV exposure at tanning salons, elevated socioeconomic status, and history of melanoma in a first-degree relative. With a better understanding of the reasons for the increasing rate of this cancer, and with enhanced early detection approaches, we may be able to decrease the incidence and mortality of malignant melanoma.

Natural advances in eczema care.

Atopic dermatitis (AD) is a chronic relapsing dermatitis characterized by increased transepidermal water loss (TEWL) and subjective symptoms of pruritus, inflammation, skin sensitivity, and dryness. AD is a frequent issue for individuals of color, though it may be underrecognized. Therapy for AD is based on reducing pruritus and inflammation, and normalizing skin surface lipids, particularly ceramides. Topical corticosteroids are the gold-standard treatment for controlling disease flares, but a variety of active natural ingredients can be used adjunctively to help control itch, inflammation, and dryness. Oatmeal, particularly avenanthramides, a newly discovered oat fraction, may be of particular value in restoring the cutaneous barrier and reducing symptoms of AD. Feverfew, licorice, and dexpanthenol also have been shown to be effective in the management of inflammation. Licorice, which has some skin-lightening activity, may be helpful in patients with postinflammatory hyperpigmentation (PIH). The compromised skin barrier in AD is especially vulnerable to UV radiation exposure. Several new long-lasting photostable sunscreen ingredients provide longer durations of protection with improved cosmetic attributes.