Browsing by Author "Brodland, David G."

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    Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test
    (Future Medicine, 2022-03) Ibrahim, Sherrif F.; Kasprzak, Julia M.; Hall, Mary A.; Fitzgerald, Alison L.; Siegel, Jennifer J.; Kurley, Sarah J.; Covington, Kyle R.; Goldberg, Matthew S.; Farberg, Aaron S.; Trotter, Shannon C.; Reed, Kenneth; Brodland, David G.; Koyfman, Shlomo A.; Somani, Ally-Khan; Arron, Sarah T.; Wysong, Ashley; Dermatology, School of Medicine
    Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan–Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for Class 1 and ≥50% for Class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies.
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    Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma
    (Wiley, 2022-01-06) Arron, Sarah T.; Wysong, Ashley; Hall, Mary A.; Bailey, Christine N.; Covington, Kyle R.; Kurley, Sarah J.; Goldberg, Matthew S.; Kasprzak, Julia M.; Somani, Ally-Khan; Ibrahim, Sherrif F.; Brodland, David G.; Cleaver, Nathan J.; Maher, Ian A.; Xia, Yang; Koyfman, Shlomo A.; Newman, Jason G.; Dermatology, School of Medicine
    Objective: Over 50% of newly diagnosed cutaneous squamous cell carcinoma (cSCC) lesions occur in the head and neck (cSCC-HN), and metastasis to nodal basins in this region further complicates surgical and adjuvant treatment. The current study addressed whether the 40-gene expression profile (40-GEP) test can predict metastatic risk in cSCC-HN with improved accuracy and provide independent prognostic value to complement current risk assessment methods. Study design: Multicenter, retrospective cohort study. Methods: Formalin-fixed paraffin-embedded primary tumor tissue and associated clinical data from patients with cSCC-HN (n = 278) were collected from 33 independent centers. Samples were analyzed via the 40-GEP test. Cases were staged per American Joint Committee on Cancer, Eighth Edition (AJCC8) and Brigham and Women's Hospital (BWH) criteria after comprehensive medical record and pathology report review. Metastasis-free survival (MFS) rates were determined, and risk factors were analyzed via Cox regression. Results: The 40-GEP test classified the cohort into low (Class 1, n = 126; 45.3%), moderate (Class 2A, n = 134; 48.2%), and high (Class 2B, n = 18; 6.5%) metastatic risk at 3 years postdiagnosis. Regional/distant metastasis occurred in 54 patients (19.4%). MFS rates were 92.1% (Class 1), 76.1% (Class 2A), and 44.4% (Class 2B; p < .0001). Multivariate analysis of 40-GEP results with AJCC8 or BWH tumor stage, or clinicopathologic risk factors, demonstrated independent prognostic value of the 40-GEP test (p < .03). Accuracy of predicting metastatic risk was also improved using 40-GEP classification (p < .02). Conclusions: Improved metastatic risk stratification through the 40-GEP test could complement cSCC-HN risk assessment for better-informed decision-making for treatment and surveillance and ultimately improve patient outcomes.
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    Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients
    (Springer, 2024) Wysong, Ashley; Somani, Ally-Khan; Ibrahim, Sherrif F.; Cañueto, Javier; Fitzgerald, Alison L.; Siegel, Jennifer J.; Prasai, Anesh; Goldberg, Matthew S.; Farberg, Aaron S.; Regula, Christie; Bar, Anna; Kasprzak, Julia; Brodland, David G.; Koyfman, Shlomo A.; Arron, Sarah T.; Dermatology, School of Medicine
    Introduction: The validated 40-gene expression profile (40-GEP) test independently stratifies risk of regional or distant metastasis for cutaneous squamous cell carcinoma (cSCC) tumors with high-risk clinicopathologic features. This study evaluated the stratification of risk by the 40-GEP test in a large cohort of tumors with one or more high-risk factors and in clinically relevant subgroups, including tumors within National Comprehensive Cancer Network (NCCN) high- and very-high-risk groups, lower-stage BWH T1 and T2a tumors, and patients > 65 years old. Methods: This multicenter (n = 58) performance study of the 40-GEP included 897 patients. Kaplan-Meier analyses were performed to assess risk stratification profiles for 40-GEP Class 1 (low), Class 2A (higher) and Class 2B (highest) risk groups, while nested Cox regression models were used to compare risk prediction of clinicopathologic risk classification systems versus risk classification systems in combination with 40-GEP. Results: Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models). Conclusion: The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions.
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    Validation of a 40-Gene Expression Profile Test to Predict Metastatic Risk in Localized High-Risk Cutaneous Squamous Cell Carcinoma
    (Elsevier, 2020) Wysong, Ashley; Newman, Jason G.; Covington, Kyle R.; Kurley, Sarah J.; Ibrahim, Sherrif F.; Farberg, Aaron S.; Bar, Anna; Cleaver, Nathan J.; Somani, Ally-Khan; Panther, David; Brodland, David G.; Zitelli, John; Toyohara, Jennifer; Maher, Ian A.; Xia, Yang; Bibee, Kristin; Griego, Robert; Rigel, Darrell S.; Plasseraud, Kristen Meldi; Estrada, Sarah; Sholl, Lauren Meldi; Johnson, Clare; Cook, Robert W.; Schmults, Chrysalyne D.; Arron, Sarah T.; Dermatology, School of Medicine
    Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value (PPV) 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, non-overlaping, independent cohort (n=324). Results: A prognostic, 40-gene expression profile (40-GEP) test was developed and validated, stratifying high-risk cSCC patients 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 (MFS) rates were 91.4%, 80.6%, and 44.0%, respectively. A PPV of 60% was achieved for the highest-risk group (Class 2B), an improvement over staging systems; while 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.