Browsing by Author "Maher, Ian A."

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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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    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.