Faculty Bibliography

Introduction: Nevisense is a non-invasive device that measures electrical impedance spectroscopy (EIS) of individual skin lesions to aid in the diagnosis of melanoma. While EIS has demonstrated high sensitivity in diagnosing melanoma, its impact on a clinician"™s diagnostic confi dence remains unknown. Objective: To conduct a pilot study to evaluate whether clinician diagnostic confidence, sensitivity, specificity and accuracy can be increased by adding EIS measurement scores to clinical and dermoscopic images of lesions clinically suspicious for melanoma. Methods: Three pigmented lesions specialists and three 4^th year medical students completed an online survey to evaluate 34 melanocytic lesions suspicious for melanoma. For each lesion, participants provided their diagnosis, biopsy recommendation, and confidence in diagnosing a lesion as benign or malignant based on history and clinical and dermoscopic images, and again after receiving an EIS score. Results: Addition of EIS scores increased mean biopsy sensitivity for melanoma/severely dysplastic nevi from 70% to 84% (p =.014) and mean diagnostic accuracy from 74% to 86% (p =.005). Mean diagnostic confidence increased for all histopathologic categories for both students and dermatologists (all p <.05). Conclusions: In this pilot study, EIS increased novice and expert diagnosticians"™ confidence regarding dermoscopically equivocal melanocytic lesions. Further studies are needed to explore how EIS can help clinicians reassure patients regarding the management of clinically dysplastic melanocytic nevi.

BACKGROUND:MoleMap NZ is a novel New Zealand based store-and-forward telemedicine service to detect melanoma. It utilizes expert review of total body photography and close-up and dermoscopic images of skin lesions suspicious for malignancy. OBJECTIVE:The purpose of this study was to assess the effectiveness of MoleMap NZ as a melanoma early detection program. METHODS:We conducted a review of 2,108 melanocytic lesions recommended for biopsy/excision by MoleMap NZ dermoscopists from January 2015-December 2016. RESULTS:Pathologic diagnoses were available for 1,571 lesions. Of these, 1,303 (83%) lesions were benign and 260 (17%) lesions were diagnosed as melanoma, for a melanoma-specific benign-to-malignant ratio of 5.0 to 1. The number-needed-to-biopsy one melanoma was 6. Among melanomas with available tumor thickness data (n=137), 92% were <0.8mm (range: in situ - 3.1mm), with in-situ melanomas comprising 74%. LIMITATIONS/CONCLUSIONS:Only lesions recommended for excision were analyzed. Pathology results were available for 75% of these cases. Tumor thickness data was available for 53% of melanomas diagnosed. CONCLUSION/CONCLUSIONS:This real-world study of MoleMap NZ, a community-based teledermoscopy program, suggests that it has the potential to increase patients' access to specialist expertise via telemedicine. Additional studies are needed to more accurately define its efficacy.

A diagnosis of late stage melanoma is associated with significant mortality. From a public health perspective, knowledge of geographic disparities in late-stage diagnoses can inform efforts to facilitate the diagnosis of earlier stage, highly curable melanomas. We conducted a county-level analysis of melanoma in New York State to identify communities that may benefit from pilot health interventions to reduce the burden of late stage melanoma. From 1995 to 2016, late-stage melanoma incidence increased from 1.5 to 2.8 cases/100,000 in NY State. We found statistically significant associations between decreased county-level health system access (including physician density and resident educational status), and increased county incidence and proportion of late-stage disease among diagnosed cases (p<0.001 for both). Increased county-level socioeconomic status (SES), (including measures of resident wealth and medical insurance status), was positively associated with greater late-stage incidence (p<0.001). However, decreased county-level SES was positively associated with a greater proportion of late-stage disease among cases at diagnosis (p=0.009). Counties with reduced access to physician services and lower SES may be suitable for pilot interventions promoting recognition and diagnosis of early stage melanomas to reduce late stage diagnoses and associated mortality.

Nevisense is an FDA-cleared device to aid in diagnosing melanoma. Using a non-invasive probe, the device measures electrical impedance spectroscopy (EIS) of target skin lesions. While EIS has demonstrated high sensitivity in diagnosing melanoma, its impact on a clinician's diagnostic confidence remains unknown. We conducted a pilot study evaluating whether the addition of EIS scores to clinical and dermoscopic images increases diagnostic confidence, accuracy, sensitivity, and specificity for students and dermatologists when evaluating lesions clinically suspicious for melanoma. Three pigmented lesions specialists and three 4^th year medical students completed an online survey to evaluate 34 melanocytic lesions suspicious for melanoma. For each lesion, participants provided their diagnosis, biopsy recommendation, and confidence in diagnosing a lesion as benign or malignant based on history and clinical and dermoscopic images, and again after receiving an EIS score. Addition of EIS scores increased mean biopsy sensitivity for melanoma/severe dysplastic nevi (DN) from 70% to 84% (p =.014) and mean diagnostic accuracy from 74% to 86% (p =.005). Mean diagnostic confidence increased for 29/34 lesions, of which 26 were accurately diagnosed by >=4 evaluators. Increases in diagnostic confidence were significant for common melanocytic nevi, DN, and melanoma, for both students and dermatologists (all p <.05). Use of EIS may increase clinicians' confidence to provide greater reassurance regarding dermoscopically equivocal lesions such as DN. EIS thus has the potential to help clinicians better alleviate patients' anxieties during skin exams. EIS may also improve management of melanocytic lesions suspicious for melanoma among novice and expert diagnosticians, though further investigation is needed to determine if these findings translate to clinical settings. NB: All authors except for Ms. Fried are team members for a separate study utilizing a Nevisense device, loaned to NYU by Scibase.
Copyright

BACKGROUND:Melanoma lacks validated blood-based biomarkers for monitoring and predicting treatment efficacy. Cell-free circulating tumour DNA (ctDNA) is a promising biomarker; however, various detection methods have been used, and, to date, no large studies have examined the association between serial changes in ctDNA and survival after BRAF, MEK, or BRAF plus MEK inhibitor therapy. We aimed to evaluate whether baseline ctDNA concentrations and kinetics could predict survival outcomes. METHODS:mutation-positive metastatic melanoma and brain metastases. Patients in cohort A of COMBI-MB had asymptomatic brain metastases, no previous local brain-directed therapy, and an ECOG performance status of 0 or 1. Biomarker analysis was a prespecified exploratory endpoint in both trials and performed in the intention-to-treat populations in COMBI-d and COMBI-MB. We investigated the association between mutant copy number (baseline or week 4 or zero conversion status) and efficacy endpoints (progression-free survival, overall survival, and best overall response). We used Cox models, Kaplan-Meier plots, and log-rank tests to explore the association of pretreatment ctDNA concentrations with progression-free survival and overall survival. The effect of additional prognostic variables such as lactate dehydrogenase was also investigated in addition to the mutant copy number. FINDINGS/RESULTS:mutation-positive ctDNA concentration was associated with worse overall survival outcome (hazard ratio [HR] 1·13 [95% CI 1·09-1·18], p<0·0001 by univariate analysis), independent of treatment group and baseline lactate dehydrogenase concentrations (1·08 [1·03-1·13], p=0·0020), in COMBI-d. A ctDNA cutoff point of 64 copies per mL of plasma stratified patients enrolled in COMBI-d as high risk or low risk with respect to survival outcomes (HR 1·74 [95% CI 1·37-2·21], p<0·0001 for progression-free survival; 2·23 [1·73-2·87], p<0·0001 for overall survival) and was validated in the COMBI-MB cohort (3·20 [1·39-7·34], p=0·0047 for progression-free survival; 2·94 [1·18-7·32], p=0·016 for overall survival). In COMBI-d, undetectable ctDNA at week 4 was significantly associated with extended progression-free and overall survival, particularly in patients with elevated lactate dehydrogenase concentrations (HR 1·99 [95% CI 1·08-3·64], p=0·027 for progression-free survival; 2·38 [1·24-4·54], p=0·0089 for overall survival). INTERPRETATION/CONCLUSIONS:-mutant ctDNA measurements could serve as independent, predictive biomarkers of clinical outcome with targeted therapy. FUNDING/BACKGROUND:Novartis.

Importance/UNASSIGNED:Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know. Objectives/UNASSIGNED:To identify consensus-based learning constructs representing an appropriate foundational proficiency in dermoscopic image interpretation for dermatology resident physicians, including dermoscopic diagnoses, associated features, and representative teaching images. Defining these foundational proficiency learning constructs will facilitate further skill development in dermoscopic image interpretation to help residents achieve clinical proficiency. Design, Setting, and Participants/UNASSIGNED:A 2-phase modified Delphi surveying technique was used to identify resident learning constructs in 3 sequential sets of surveys-diagnoses, features, and images. Expert panelists were recruited through an email distributed to the 32 members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group. Twenty-six (81%) opted to participate. Surveys were distributed using RedCAP software. Main Outcomes and Measures/UNASSIGNED:Consensus on diagnoses, associated dermoscopic features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for US dermatology resident physicians. Results/UNASSIGNED:Twenty-six pigmented lesion and dermoscopy specialists completed 8 rounds of surveys, with 100% (26/26) response rate in all rounds. A final list of 32 diagnoses and 116 associated dermoscopic features was generated. Three hundred seventy-eight representative teaching images reached consensus with panelists. Conclusions and Relevance/UNASSIGNED:Consensus achieved in this modified Delphi process identified common dermoscopic diagnoses, associated features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for dermatology residency training. This list of validated objectives provides a consensus-based foundation of key learning points in dermoscopy to help resident physicians achieve clinical proficiency in dermoscopic image interpretation.