@article{8303df6a1993428da840502f94e8eb8a,
title = "Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study",
abstract = "Objectives: A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Methods: Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric diagnostic algorithms were selected and evaluated using regression modeling and receiver operating characteristic curves. Results: Seven metastasis-associated transcripts were selected from analysis in the training cohorts using 10-fold cross validation and incorporated into an MS7 classifier using platform-specific coefficients. The predictive accuracy of the MS7 classifier in Training-1 was superior to that of other clinical and molecular features, with an area under the curve (95% confidence interval) of 0.89 (0.80–0.98) for MS7 compared with 0.69 (0.59–0.80) and 0.71 (0.58–0.83) for the top evaluated clinical and molecular features, respectively. The performance of MS7 was independently validated in 245 patients using RNA sequencing and in 81 patients using microarray-based data. MS7 + MI (myometrial invasion) was preferrable to individual features and exhibited 100% sensitivity and negative predictive value. The MS7 classifier was associated with lower progression-free and overall survival (p ≤ 0.003). Conclusion: A risk assessment classifier for metastasis and prognosis in EEC patients with primary tumor derived MS7 + MI is available for further development and optimization as a companion clinical support tool.",
keywords = "endometrial cancer, metastasis, molecular classifier, prediction, risk assessment",
author = "Yovanni Casablanca and Guisong Wang and Lankes, {Heather A.} and Chunqiao Tian and Bateman, {Nicholas W.} and Miller, {Caela R.} and Chappell, {Nicole P.} and Havrilesky, {Laura J.} and Wallace, {Amy Hooks} and Ramirez, {Nilsa C.} and Miller, {David S.} and Julie Oliver and Dave Mitchell and Tracy Litzi and Blanton, {Brian E.} and Lowery, {William J.} and Risinger, {John I.} and Hamilton, {Chad A.} and Phippen, {Neil T.} and Conrads, {Thomas P.} and David Mutch and Katherine Moxley and Lee, {Roger B.} and Floor Backes and Birrer, {Michael J.} and Darcy, {Kathleen M.} and Maxwell, {George Larry}",
note = "Funding Information: This study was funded by awards from the United States Army Medical Research Acquisition Activity for the Gynecologic Disease Program (W81XWH-05-2-0005, PI: G. Larry Maxwell), the Gynecologic Cancer Center at Walter Reed Army Medical Center (W81XWH-9-2-0051, PI: G. Larry Maxwell), the Gynecologic Cancer Translational Research Center of Excellence (W81XWH-10-2-0018, PI: G. Larry Maxwell), and the Gynecologic Cancer Center of Excellence (W81XWH-11-2-0131, PI: Chad A. Hamilton, Co-PI: G. Larry Maxwell); from the Uniformed Services University of the Health Sciences from the Defense Health Program (HU0001-16-2-0006 and HU0001-21-2-0027, PI: Yovanni Casablanca, Co-PI: G. Larry Maxwell) to the Gynecologic Cancer Center of Excellence and administered by the Henry M Jackson Foundation for the Advancement of Military Medicine (HJF); and from the National Cancer Institute and the Cancer Therapy Evaluation Program (CTEP) to the Gynecologic Oncology Group Administrative Office and GOG Tissue Bank (CA114793, CA27469, PI: Philip J. DiSaia) and the Gynecologic Oncology Group Statistical and Data Center (CA37517, PI: John A. Blessing), NRG Oncology (1U10 CA180822), and NRG Operations (U10CA180868). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: Washington University School of Medicine, University of Oklahoma Health Sciences Center, Tacoma General Hospital, Ohio State University Comprehensive Cancer Center, Duke University Medical Center, University of Minnesota Medical Center–Fairview, Case Western Reserve University, University of Colorado Cancer Center—Anschutz Cancer Pavilion, the University of North Carolina at Chapel Hill, Wake Forest University Health Sciences, Yale University, Women and Infants Hospital, Abington Memorial Hospital, Wayne State University/Karmanos Cancer Institute, Penn State Milton S. Hershey Medical Center, University of Iowa Hospitals and Clinics, University of California Medical Center at Irvine–Orange Campus, Tufts-New England Medical Center, Stony Brook University Medical Center, University of Massachusetts Memorial Health Care, University of Virginia, and University of Chicago. Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = sep,
doi = "10.3390/cancers14174070",
language = "English",
volume = "14",
journal = "Cancers",
issn = "2072-6694",
number = "17",
}