Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Characteristic Distinctions Between Pre-/Post-COVID-19 Teledermatology Adoptees: A Cross-Sectional United States-based Analysis and the Implications for Dermatologic Healthcare Equity.

BACKGROUND: Studies suggest potential heterogeneity in telemedicine adoption with potential to exacerbate healthcare access inequity. METHODS: A pre-validated survey was electronically sent to a proprietary listserv of practicing US-based dermatologists. Results were stratified by when teledermatology was adopted. Chi-square and odds ratios (OR) with 95% confidence intervals (95%CI) were used to analyze categorical data while single-factor ANOVA with posthoc Tukey-Kramer was used for continuous data. RESULTS: 338 practicing US-based dermatologists completed the questionnaire. Academic/Government dermatologists were 4-times more likely (OR 4.08, 95%CI 2.37-7.03) to adopt teledermatology pre-COVID than private-practice dermatologists. Dermatologists with ≤10 years of experience were 1.8-times (OR 1.8, 95%CI 1.01-3.18) and 2.82-times more likely (OR 2.82, 95%CI 0.78-10.25) to adopt teledermatology pre-COVID-19 or at all, respectively, compared to dermatologists with ≥20 years of experience. Teledermatology adopters practiced more medical-dermatology (P<.0001) than non-adopters, who reported practicing more dermatologic surgery (P=.003; Tukey-Kramer α<.05) and dermatopathology (P<.0001; Tukey-Kramer α<.05). Pre-COVID-19 adopters were 4-times more likely (OR 4.69, 95%CI 1.46-15.07) to switch/incorporate live-interactive-only teledermatology (LI) post-COVID-19. Post-COVID-19 adopters were 6-times more likely (OR 6.09, 95%CI 3.36-11.06) to utilize LI than Pre-COVID-19 adopters. Pre-COVID-19 adopters use teledermatology for a larger proportion of patient visits than Post-COVID-19 adopters (19.6% v 10.4%, P<.0001), but also are 3.43-times more likely (OR 3.43, 95%CI 1.82-6.46) to report future decreases in usage. LIMITATIONS: Cross-sectional retrospective survey and potential response bias. CONCLUSION: Current teledermatology usage may be a suitable tool for medical-dermatology-focused practices. Material hurdles still exist for procedurally-oriented practices and future studies should investigate these barriers to maximize equitable access to dermatological care. J Drugs Dermatol. 2023;21(1):101-104. doi:10.36849/JDD.7169.

Electrical impedance spectroscopy significantly enhances correct biopsy choice for pigmented skin lesions beyond clinical evaluation and dermoscopy.

The purpose of this study was to investigate whether EIS technology can further improve correct biopsy choices beyond clinical and dermoscopic evaluation for melanoma (MM), severe dysplastic nevi (SDN) and benign PSLs. Images of 49 MMs, SDNs and benign PSLs were randomly selected from a prior study and were provided in a reader-type survey study to dermatologists to evaluate for biopsy. A total of 33,957 biopsy decisions were analyzed. Respondents significantly improved on the correct biopsy choice with the addition of dermoscopy versus clinical image alone for melanoma and severely dysplastic nevi. Respondents also showed a statistically significant improvement in correct biopsy choice beyond their dermoscopic evaluation when integrating the EIS score versus dermoscopy with clinical images for MM, SDN and benign lesions. Respondents also made fewer incorrect biopsy choices with the addition of the EIS score versus dermoscopy and clinical image for MM and benign lesions. Sub-analyses of biopsy choices were also conducted based on experience and practice type. The findings from this study demonstrate that the integration of EIS technology into PSL biopsy decisions has the potential to significantly improve the accuracy of lesion selection for biopsy beyond clinical and dermoscopic evaluation alone.

Dermatology Match Preference Signaling Tokens: Impact and Implications.

BACKGROUND: The dermatology residency application process implemented a new system of preference signaling tokens (PSTs) in the 2021-2022 cycle to allow applicants to express a higher level of interest in specific programs. Limited data are available on the utilization and impact of these tokens. OBJECTIVE: To determine the impact of PSTs on the application process and where in the process PSTs had the greatest influence. MATERIALS AND METHODS: A 14-question survey was sent to 62 ACGME-accredited dermatology residency programs. Primary outcomes were PST impact on 2021-2022 applications. Variables were evaluated using open-ended questions, yes/no responses, and importance ratings from 0 to 100. RESULTS: An average of 7.1% of applicants were offered interviews, but 21.1% of applicants that submitted PSTs were interviewed versus 3.7% of nonsubmitters. 22.5% of ranked applicants and 19% of matched applicants submitted a PST to that program. LIMITATIONS: Not all programs responded, and PST submission restrictions could not be assessed. CONCLUSION: The greatest PST impact was on the interview decision but had minimal subsequent impact. Given PSTs cannot be submitted to home programs or in-person away rotations, the actual impact was probably greater than found. Programs will continue to implement PSTs in future cycles.

Knowledge Gaps Among Dermatologists Regarding Immunotherapy for Non-melanoma Skin Cancer.

Background: Advanced nonmelanoma skin cancer (NMSC) is a sometimes unrecognized public health burden. The development of immune checkpoint inhibitors (ICIs), such as those affecting programmed cell death protein-1 (PD-1), have dramatically changed the management of advanced NMSC. Dermatologists need to be knowledgeable about these therapies given their key role in diagnosing, treating, and comanaging NMSC. The purpose of this study was to assess the knowledge base and identify knowledge gaps that dermatologists may have regarding ICIs and assess advanced NMSC referral patterns. Methods: A 10-question survey was emailed to United States-based dermatologists in July 2021 assessing knowledge of ICI therapy and referral patterns for metastatic cutaneous squamous cell carcinoma (mcSCC) or locally advanced basal cell carcinoma (laBCC) management. Results: At their current knowledge level, respondents averaged 40.6 out of 100 (95% CI [35.1, 46.0]) when asked how comfortable they feel counseling a patient on the risks and benefits of an ICI. Seventy-one percent reported that having more information about treatment for mcSCC or laBCC would be helpful in their practice. Being in practice for less than 10 years was not significantly associated with desiring more information about treatment. The respondents reported that the highest number of annual average referrals out for mcSCC or laBCC were made to Mohs surgeons. Fifty-four percent of respondents received referrals for mcSCC or laBCC, and of the providers receiving referrals, 40 percent of them came from general dermatology. Conclusion: These results demonstrate that a knowledge gap exists for dermatologists in treating mcSCC and laBCC with immunotherapy. There is a need among all dermatologists, regardless of years in practice, to receive this information.

Variance from published guidelines and changes in temporal trends in the management of cutaneous malignant melanoma: a 5-year update.

This study aimed to assess the current management of melanoma from relative to present guidelines and determine changes 5 years ago. An eight-question survey was sent to practicing US dermatologists using the same methodology and questions from our JAAD study. Overall, saucerization/scoop biopsy (48%) was the most commonly used method. The most commonly chosen margin for melanoma in-situ (MMIS) removal was 6-10 mm (51% of respondents). For CMM with a depth greater than 1 mm, the most commonly chosen margins were in the 1.1-1.9 cm range (55% of respondents). More respondents referred cases of MMIS and CMM out for treatment as compared to 2016. Academic dermatologists in 2021 were 8% less likely to treat MMIS as compared to all other practice types in 2021, whereas 7% more likely to treat CMM greater than 1 mm. Academic dermatologists in 2016, as compared to 2021, were 4% more likely to treat MMIS and 19% more likely to treat CMM greater than 1 mm. A total of 91% of respondents reported having some change in their management of CMM. Our study findings suggest that a knowledge gap still exists representing a continued educational opportunity to more effectively distribute and implement CMM management guidelines.

Improved cutaneous melanoma survival stratification through integration of 31-gene expression profile testing with the American Joint Committee on Cancer 8th Edition Staging.

Cutaneous melanoma (CM) survival is assessed using averaged data from the American Joint Committee on Cancer 8th edition (AJCC8). However, subsets of AJCC8 stages I-III have better or worse survival than the predicted average value. The objective of this study was to determine if the 31-gene expression profile (31-GEP) test for CM can further risk-stratify melanoma-specific mortality within each AJCC8 stage. This retrospective multicenter study of 901 archival CM samples obtained from patients with stages I-III CM assessed 31-GEP test predictions of 5-year melanoma-specific survival (MSS) using Kaplan-Meier and Cox proportional hazards. In stage I-III CM population, patients with a Class 2B result had a lower 5-year MSS (77.8%) than patients with a Class 1A result (98.7%) and log-rank testing demonstrated significant stratification of MSS [χ2 (2df, n = 901) = 99.7, P < 0.001). Within each stage, 31-GEP data provided additional risk stratification, including in stage I [χ2 (2df, n = 415) = 11.3, P = 0.004]. Cox regression multivariable analysis showed that the 31-GEP test was a significant predictor of melanoma-specific mortality (MSM) in patients with stage I-III CM [hazard ratio: 6.44 (95% confidence interval: 2.61-15.85), P < 0.001]. This retrospective study focuses on Class 1A versus Class 2B results. Intermediate results (Class 1B/2A) comprised 21.6% of cases with survival rates between Class 1A and 2B, and similar to 5-year MSS AJCC stage values. Data from the 31-GEP test significantly differentiates MSM into lower (Class 1A) and higher risk (Class 2B) groups within each AJCC8 stage. Incorporating 31-GEP results into AJCC8 survival calculations has the potential to more precisely assess survival and enhance management guidance.

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.

Advances and Considerations in the Management of Actinic Keratosis: An Expert Consensus Panel Report.

BACKGROUND: Actinic Keratosis (AK) is a potentially pre-malignant tumor with a poorly defined risk of progression to invasive squamous cell carcinoma (SCC). Because of the typical need for recurrent cycles of AK treatment, outcomes can be limited by both therapeutic efficacy and patient adherence. OBJECTIVE: To synthesize the available and most current literature into overarching principles to provide guidance on the management of AKs, improving patient experiences and treatment outcomes. METHODS: A systematic review querying epidemiology, natural history, prognosis, management of AKs as well as the mechanism of action of and adherence to current AK therapy was conducted. After reviewing the literature, an expert consensus panel consisting of 10 expert dermatologists and dermatopathologists used a modified Delphi process to develop statements regarding the pathogenesis and management of AKs. Final statements were only adopted with a supermajority vote (≥7/10). RESULTS: The panel developed 7 consensus statements regarding AKs pathogenesis and management. CONCLUSION: The poorly defined risk for AK progression into invasive SCC without universally accepted clinical-histopathological factors highlights the importance of long-term efficacious treatment. To effectively counsel and treat patients with actinic keratoses, dermatologists must understand how newer therapeutic approaches with mechanisms of action that have more rapid onset of action, shorter treatment courses, and less intense local skin reaction (LSRs) may promote adherence and improve long-term outcomes. J Drugs Dermatol. 2021;20(8):888-893. doi:10.36849/JDD.6078 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma.

BACKGROUND: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. OBJECTIVE: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management. METHODS: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n = 202) and validated in a separate, nonoverlapping, independent cohort (n = 324). RESULTS: A prognostic 40-GEP test was developed and validated, stratifying patients with high-risk cSCC into classes based on metastasis risk: class 1 (low risk), class 2A (high risk), and class 2B (highest risk). For the validation cohort, 3-year metastasis-free survival rates were 91.4%, 80.6%, and 44.0%, respectively. A positive predictive value of 60% was achieved for the highest-risk group (class 2B), an improvement over staging systems, and negative predictive value, sensitivity, and specificity were comparable to staging systems. LIMITATIONS: Potential understaging of cases could affect metastasis rate accuracy. CONCLUSION: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.

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.

Impact of Gene Expression Profile Testing on the Management of Squamous Cell Carcinoma by Dermatologists

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing likely due to improved detection and a growing elderly population. Although the prognosis of cSCC is excellent with complete surgical excision, many patients who go on to develop metastasis are initially classified as low-risk. The most commonly used staging systems, American Joint Committee on Cancer (AJCC) and Brigham Women's Hospital (BWH), have low sensitivity and low positive predictive value for predicting metastasis. A gene expression profile test (cSCC-GEP) is in development to identify patients with cSCC at high risk for metastasis and death. Objective: To determine the impact of cSCC-GEP test results on management decisions made by dermatologists for cSCC patients. Design, Setting, and Participants: 402 dermatologists attending a national dermatology conference completed an online survey designed to determine the impact of cSCC-GEP test results on management decisions in a variety of clinical situations. Participants answered a series of questions related to three cSCC patient vignettes, each featuring different patient and lesion characteristics. Main Outcomes and Measures: Proportion of dermatologists who would recommend radiation, chemotherapy/immunotherapy, or sentinel lymph node biopsy (SLNBx) for each patient vignette (without cSCC-GEP results, with a lower risk result, or with a higher risk result). The effect of the test results on the follow-up intervals recommended by dermatologists was also examined. Results: In the majority of vignettes, a lower risk cSCC-GEP test result led to a statistically significant decrease in the proportion of dermatologists who would recommend radiation, chemotherapy/immunotherapy, SLNBx, or quarterly follow-up. Conversely, a higher risk cSCC-GEP result significantly altered management toward increased intensity (more recommendations for radiation, chemotherapy/immunotherapy, SLNBx, or quarterly follow-up) in all vignettes. Conclusions and Relevance: The results of a cSCC-GEP test appear to significantly impact decisions made by dermatologists regarding subsequent management, SLNBx, and follow-up intervals for patients with cSCC. J Drugs Dermatol. 2019;18(10):980-984.