PowerPoint Presentation Integration of the 40-Gene Expression Profile (40-GEP) for Management and Treatment of High-risk Cutaneous Squamous Cell Carcinoma (cSCC): A Real-world Algorithm Gaurav Singh, MD, MPH, FAAD1, Stanislav N. Tolkachjov, MD2,3, Aaron S. Farberg, MD4 1Gaurav Singh MD, Milwaukee, WI; 2Epiphany Dermatology, Dallas, TX; 3University of Texas at Southwestern, Dallas, TX; 4Baylor Scott & White Health System, Dallas, TX Background › The prognostic 40-gene expression profile (40-GEP) test has established both analytical and improved clinical validity for risk stratification when compared to current staging systems. The test categorizes patients as low (Class 1), moderate (Class 2A), or high (Class 2B) risk for regional or distant metastasis within 3 years of diagnosis.1-3 › Clinical utility studies of the 40-GEP test have demonstrated its appropriate use for the intended high-risk population, and its ability to direct personalized risk-aligned patient management while also increasing clinician confidence in treatment decisions. 4-8 GS is a consultant for Castle Biosciences Inc. (CBI); ASF is an advisor for CBI and Regeneron; SNT declares no relevant conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed herein. Cases Presentations Presented at Winter Clinical Dermatology Conferences: January 13-18, 2023, Kohala Coast, Hawaii and February 17-20, 2023, Miami, FL For more information: aaron.farberg@gmail.com Conclusions Disclosures Clinical Issue and Objective For high-risk cSCC patients, the limitations of risk-stratification tools, along with broad treatment guidelines, has led to disparities in clinical practice and management, creating a diversity of patient outcomes.8 The objective of this study is to provide guidance to clinicians regarding how to incorporate the results of the 40-GEP test into common treatment modalities for their high-risk cSCC patients. Scan here for more info Clinicopathologic risk factors Case Report 1 Case Report 2 Case Report 3 • 74-year-old male • 2.2 cm diameter, moderately differentiated • Located on the left posterior scalp • >90 year-old male • 3.1cm diameter, moderately differentiated • Located on left central lateral neck • 63-year-old male • >2cm diameter, invasion beyond subcutaneous fat • located on head region Disease presentation and progression American Joint Committee on Cancer (AJCCv8) and Brigham and Women’s Hospital (BWH) Stage AJCC v8: T2 BWH: T2a AJCC v8: T2 BWH: T2a AJCC v8: T3 BWH: T2b Rationale for 40-GEP 2.2 cm diameter, multiple stages of Mohs surgery, larger defect size (4.2 x 4.2cm) multiple stages of Mohs surgery, larger defect size (4.4 x 4.1cm) Multiple stages of Mohs surgery, poor clinical margins, patient with a history of multiple cSCCs Treatment approach pre-40-GEP CT scan, RT, and follow-up every 1-month SLNB, RT, and follow-up every 6 months Imaging to evaluate for distant metastasis was considered 40-GEP Result Class 1 (Low Risk) Class 2A (Moderate Risk) Class 2A (Moderate Risk) Treatment approach post-40-GEP Forgo RT and CT scan; follow-up for monthly wound check and nodal exams every 6 months Forgo SLNB and radiation with follow-up scheduled for every 3 months Surveillance of lymph nodes with ultrasound imaging every 6 months for two years and clinical follow-up every 3 months with lymph node exam Outcomes One-year post-treatment, the wound healed with no evidence of recurrence or metastasis. 3 months post treatment, the wound has healed with no evidence of recurrence or metastasis 16 months post-treatment the wound healed with no evidence of disease Presentation Histological Diagnosis Post-procedureHistological Diagnosis Presentation Mohs Surgery Mohs Surgery Mohs Surgery Figure 1. Treatment algorithm for incorporation of 40-GEP test results into treatment decisions for a high-risk cSCC patient Patient diagnosed with primary invasive cSCC and one or more risk factors Patient qualifies for 40-GEP testing; Clinician sends primary tumor FFPE for biologic metastatic risk prediction Due to complexities in patient’s clinicopathologic risk factors, clinician decides further assessment is needed Adjuvant Radiation Therapy Nodal Assessment Class 1 Class 2A Class 2B No action if low T- stage & negative palpation Discuss and consider SLNB and/or surveillance for high and very high risk Every 6 mo for 2 yr Every 3-6 mo for 1 yr Every 2-3 mo for 1 yr **Discuss MRI, US and/or CT **Consider MRI, US and/or CT No action if extensive disease is not present Treatment* No action if high risk and negative surgical margins Consider for very high risk and high T-staged high risk Recommend for very high risk and high T- staged high risk Clinical Follow up Surveillance Imaging *multidisciplinary board should be considered; **choice of imaging technique dependent on number and type of high-risk factors; US= ultrasonography; CT= computed tomography; FFPE=Formalin-Fixed Paraffin-Embedded Surveillance suggested for high and very high risk References 1. Wysong, et al JAAD 2021 2. Ibrahim, et al Future Oncol 2021 5. Farberg, et al CMRO 2020 6. Litchman, et al CMRO 2020 3. Borman, et al Diagn Path 2022 4. Teplitz, et al JDD 2019 7. Au, et al Dermatol Ther 2022 8. Blomberg, et al Br J Derm 2017 9. NCCN v2.2022 Methods › Private practice Mohs surgeons who have utilized 40-GEP results for prognostication of high-risk SCC patients merged their risk-aligned management approaches into a singular algorithm focused on how to incorporate 40-GEP test results within the management guidelines proposed by the National Comprehensive Cancer Network (NCCN)9 (Figure 1). › Real-world cases were compiled by the authors to evaluate the following treatment modalities: surveillance imaging, sentinel lymph node biopsy (SNLB), adjuvant radiation therapy (ART), and clinical follow-up. Mohs Surgery Presentation Histological Diagnosis Post-procedure M a n a g e m e n t D e c is io n s w it h in N C C N g u id e li n e s Post-procedure › For high-risk cSCC patients, whose management is currently broad under existing guidelines, clinicians can identify risk-aligned treatment pathway improvements by use of the 40-GEP within their existing clinical practices. › One such algorithm to incorporate the 40-GEP is presented here as a mechanism to implement guideline recommendations for personalized management of patients based on their risk for poor outcomes. Conclusions https://castlebiosciences.com/research-development/publications/ Slide 1