Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of advanced melanoma, but many patients do not respond to ICIs alone, and thus there is need for additional treatment options. Topical immunomodulators such as diphencyprone (DPCP) also have clinical use in advanced melanoma, particularly in the treatment of cutaneous metastases. In a previous report, we characterized the enhanced clinical response to dual agent immunotherapy with pembrolizumab and DPCP in a patient with cutaneous melanoma metastases. To improve mechanistic understanding of this response, we analyzed proteomic data using the Olink immuno-oncology panel of 96 biomarkers from tissue and serum samples of this patient throughout his treatment course. Particular attention was paid to programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3) given they are all targeted by ICIs in clinical practice. These proteins were upregulated during the period of DPCP monotherapy, then downregulated during pembrolizumab monotherapy, and then robustly upregulated again during dual therapy. Although not exclusively, the induction of checkpoint inhibitor proteins in the presence of DPCP suggests potential synergy between this agent and ICIs in the treatment of cutaneous melanoma metastases. Large-scale investigation is warranted to further evaluate this potential novel combination therapeutic approach.
Introduction: Electrical impedance spectroscopy (EIS) is a non-invasive diagnostic device that measures the electrical impedance of skin lesions to assist in the detection of melanoma. While this tool has been shown to have a high sensitivity for melanoma diagnosis, data on its impact on clinical decision-making for pigmented skin lesions (PSLs) compared to other diagnostic tools is lacking. To gain further insight into its clinical utility, we conducted a pilot study to evaluate how this technology – specifically, the effect it has on clinical decisions for PSLs – compares to traditional dermoscopy.
Methods: Dermatologists, dermatology residents, and medical students completed an online survey eliciting their biopsy decisions for 24 PSLs of varying histopathological diagnoses. Half of the lesions from each diagnosis group were presented as a clinical image with associated dermoscopic image and the other half as a clinical image with the corresponding EIS score.
Results: Decisions made with EIS demonstrated a mean sensitivity of 75% for melanomas/severely dysplastic nevi vs. 66% for decisions made with dermoscopy (p=.008). While dermatologists biopsied with similar sensitivities when using EIS or dermoscopy (81% vs. 81%), residents and medical students biopsied with significantly greater sensitivity when using EIS. Respondents who reported rarely using dermoscopy showed the greatest improvement in sensitivity and specificity when using EIS compared to dermoscopy.
Conclusion: Given that not all providers are trained in dermoscopy, and our finding that EIS particularly benefits those who infrequently use dermoscopy, EIS may complement dermoscopy by helping a broader range of providers make improved PSL diagnostic decisions.
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