PowerPoint Presentation › The 23-gene expression profile (GEP) and 35-GEP tests are clinically available, objective ancillary diagnostic tools that facilitate diagnosis of melanocytic lesions with ambiguous histopathology. The tests use proprietary algorithms to produce results of: suggestive of benign neoplasm; intermediate (cannot rule out malignancy); or suggestive of malignant neoplasm with high accuracy.1-6 › Communication between the diagnosing dermatopathologist/pathologist and the treating clinician is key to establishing appropriate patient management.7,8 There are circumstances when a dermatologist may find additional diagnostic information helpful in determining excision and follow-up actions.9,10 A clinical impact study of dermatologists’ use of the 23- or 35-gene expression profile tests to guide surgical excision and enhance management plan confidence Background Acknowledgments & Disclosures References › ASF has served as a consultant for Castle Biosciences, Inc. KLA, BBR, JJS, BHR, JHR, SJK, and MSG are employee shareholders of Castle Biosciences, Inc. The study was supported by Castle Biosciences, Inc. Results Aaron S Farberg, MD1, Kelli L Ahmed, PhD2, Briana B Rackley, PhD2, Jennifer J Siegel, PhD2, Brooke H Russell, PhD2, Jason H Rogers, MSc2, Sarah J Kurley, PhD2, and Matthew S Goldberg, MD2,3 1Baylor Scott & White Health System, Dallas, TX 2Castle Biosciences, Inc., Friendswood, TX 3Icahn School of Medicine at Mount Sinai, New York, NY For more information: afarberg@castlebiosciences.com Methods › Clinicians were invited for study participation based on prior use of diagnostic GEP testing (minimum 3 encounters with GEP results). 32 board certified dermatologists participated in this Institutional Review Board (IRB)-approved study. Clinicians were asked 4 questions per scenario: 1) How would you treat the patient? (No further treatment necessary, No further treatment necessary if lesion appears completely excised, Excise <5 mm margins (narrow but complete), Excise ≥5 mm margins (but <1 cm), Wide local excision (Excise ≥1 cm); 2) Which follow-up schedule would you recommend? (Every 12, 6, 3 or every month); 3) How confident are you in this management plan? (1 (not confident), 2 (slightly confident), 3 (somewhat confident), 4 (fairly confident), 5 (completely confident). › Clinical and diagnostic information for 6 uncertain patient scenarios was provided to the clinicians (Table 1). Diagnostic information was taken from real-world pathology reports of melanocytic lesions and displayed in mock form including the diagnosis and microscopic description. Clinical information was based on common clinical situations that may alter patient treatment. GEP test results were either not provided (baseline), benign, or malignant for each patient scenario. › GEP results can aid dermatologists in decision making to achieve appropriate management plans. › Management changes, including surgical excisions and follow-up frequency, were aligned with GEP results for these uncertain clinical scenarios. › Scenario-specific details demonstrate that a personalized approach can be achieved with GEP. Conclusions Table 1. Ambiguous lesion scenarios from real-world pathology reports Figure 1. Overall clinical impact across all ambiguous scenarios Presented at the 42nd Annual Fall Clinical Dermatology Conference, October 20-23, 2022, Las Vegas, NV (Encore presentation in part from ASDS 2022) Scan for more info › Clinical impact was assessed by calculating the mean percent of no change, increase in change, or decrease in change relative to no GEP results for each scenario and normalized to 100%. Figure 2. GEP results impact surgical excision planning, including margin decisions Here we present dermatologist management plans and confidence utilizing diagnostic GEP results in uncertain clinical and diagnostic scenarios. ›. Results Clinical Impression Diagnosis Included excision recommendation Cosmetic site Melanocytic neoplasm, atypical melanocytic proliferation No Cosmetic site Dysplastic nevus with features of regression Yes Personal history of melanoma Melanocytic neoplasm, atypical melanocytic proliferation No Personal history of melanoma Melanocytic neoplasm, deep penetrating Yes Comorbidities Atypical intraepidermal melanocytic proliferation (AIMP) Yes High clinical suspicion Atypical intraepidermal melanocytic proliferation (AIMP) Yes Clinical impact: The vast majority of excision decisions and follow-up changes were aligned with GEP results across the uncertain scenarios. In addition, there was an increase in overall management plan confidence with a GEP result. › Figure 3. GEP results alter follow-up frequency › Surgical margins: When a malignant GEP result is provided, there was an increase in surgical treatment for most scenarios. When a benign GEP result was received, there was a decreased in surgical management in most scenarios. › Follow-up frequency: Shown here is a representation of how GEP results can alter that cadence resulting in a tailored strategy. 1. Clarke, L. E. et al. J Cutan Pathol 2015. 42 (4) 244–252. 2. Clarke, L. E. et al. Cancer 2017. 123 (4) 617–628. 3. Clarke, L. E. et al. Personalized Medicine 2020. 17 (5) 361–371. 4. Estrada, S. et al. SKIN 2020. 4 (6) 506–522. 5. Ko, J. S. et al. Cancer Epidem Biomar Prev 2017. 26 (7) 1107–1113. 6. Ko, J. S. et al. Human Pathology 2019. 86 213–221. 7. Smith, Shane D. B., et. al. JAMA Dermatol. 2021. 157(9):1033-1034. 8. Cockerell, C. Dermatol Surg. 2018. 44(2):175-176. 9. Cockerell C, et al. Personalized Medicine. 2017. 14(2):123-130. 10. Farberg, A. et al. SKIN 2020. 4 (6) 523–533. Malignant GEP Baseline (no GEP) Benign GEP Malignant GEP Baseline (no GEP)Benign GEP Excision Follow-up Confidence GEP Result A v e ra g e % C h a n g e Benign Benign MalignantMalignant Benign Malignant -50 50 0 100 D e c re a se In c re a se Baseline https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ DD_01_035 FCD poster encore derm survey v5 to submit Slide 1