Browsing by Author "Cook, Robert W."

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    A Gene Signature to Determine Metastatic Behavior in Thymomas
    (Public Library of Science, 2013-07-24) Gökmen-Polar, Yesim; Cook, Robert W.; Goswami, Chirayu Pankaj; Wilkinson, Jeff; Maetzold, Derek; Stone, John F.; Oelschlager, Kristen M.; Vladislav, Ioan Tudor; Shirar, Kristen L.; Kesler, Kenneth A.; Loehrer, Patrick J.; Badve, Sunil; Medicine, School of Medicine
    Purpose: Thymoma represents one of the rarest of all malignancies. Stage and completeness of resection have been used to ascertain postoperative therapeutic strategies albeit with limited prognostic accuracy. A molecular classifier would be useful to improve the assessment of metastatic behaviour and optimize patient management. Methods: qRT-PCR assay for 23 genes (19 test and four reference genes) was performed on multi-institutional archival primary thymomas (n = 36). Gene expression levels were used to compute a signature, classifying tumors into classes 1 and 2, corresponding to low or high likelihood for metastases. The signature was validated in an independent multi-institutional cohort of patients (n = 75). Results: A nine-gene signature that can predict metastatic behavior of thymomas was developed and validated. Using radial basis machine modeling in the training set, 5-year and 10-year metastasis-free survival rates were 77% and 26% for predicted low (class 1) and high (class 2) risk of metastasis (P = 0.0047, log-rank), respectively. For the validation set, 5-year metastasis-free survival rates were 97% and 30% for predicted low- and high-risk patients (P = 0.0004, log-rank), respectively. The 5-year metastasis-free survival rates for the validation set were 49% and 41% for Masaoka stages I/II and III/IV (P = 0.0537, log-rank), respectively. In univariate and multivariate Cox models evaluating common prognostic factors for thymoma metastasis, the nine-gene signature was the only independent indicator of metastases (P = 0.036). Conclusion: A nine-gene signature was established and validated which predicts the likelihood of metastasis more accurately than traditional staging. This further underscores the biologic determinants of the clinical course of thymoma and may improve patient management.
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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.