Supplementary Table 1 from Association of Molecular Subtypes with Pathologic Response, PFS, and OS in a Phase II Study of COXEN with Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

Lerner, Seth P.; McConkey, David J.; Tangen, Catherine M.; Meeks, Joshua J.; Flaig, Thomas W.; Hua, Xing; Daneshmand, Siamak; Alva, Ajjai Shivaram; Lucia, M. Scott; Theodorescu, Dan; Goldkorn, Amir; Milowsky, Matthew I.; Choi, Woonyoung; Bangs, Rick; Gustafson, Daniel L.; Plets, Melissa; Thompson, Ian M.

doi:10.1158/1078-0432.25011423.v1

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Supplementary Table 1 from Association of Molecular Subtypes with Pathologic Response, PFS, and OS in a Phase II Study of COXEN with Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

journal contribution

posted on 2024-01-17, 08:21 authored by Seth P. Lerner, David J. McConkey, Catherine M. Tangen, Joshua J. Meeks, Thomas W. Flaig, Xing Hua, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Woonyoung Choi, Rick Bangs, Daniel L. Gustafson, Melissa Plets, Ian M. Thompson

Three-way classifier comparison for n=155 patients

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

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ARTICLE ABSTRACT

The Coexpression Extrapolation (COXEN) gene expression model with chemotherapy-specific scores [for methotrexate, vinblastine, adriamycin, cisplatin (ddMVAC) and gemcitabine/cisplatin (GC)] was developed to identify responders to neoadjuvant chemotherapy (NAC). We investigated RNA-based molecular subtypes as additional predictive biomarkers for NAC response, progression-free survival (PFS), and overall survival (OS) in patients treated in S1314. A total of 237 patients were randomized between four cycles of ddMVAC (51%) and GC (49%). On the basis of Affymetrix transcriptomic data, we determined subtypes using three classifiers: TCGA (k = 5), Consensus (k = 6), and MD Anderson (MDA; k = 3) and assessed subtype association with path response to NAC and determined associations with COXEN. We also tested whether each classifier contributed additional predictive power when added to a model based on predefined stratification (strat) factors (PS 0 vs. 1; T2 vs. T3, T4a). A total of 155 patients had gene expression results, received at least three of four cycles of NAC, and had pT-N response based on radical cystectomy. TCGA three-group classifier basal-squamous (BS)/neuronal, luminal (Lum), Lum infiltrated, and GC COXEN score yielded the largest AUCs for pT0 (0.59, P = 0.28; 0.60, P = 0.18, respectively). For downstaging (