학술논문

Prognostic Significance of Immune Cell Infiltration in Muscle-invasive Bladder Cancer Treated with Definitive Chemoradiation: A Secondary Analysis of RTOG 0524 and RTOG 0712.
Document Type
Academic Journal
Author
Rana Z; University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA.; Kamran SC; Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Shetty AC; University of Maryland School of Medicine, Baltimore, MD, USA.; Sutera P; Johns Hopkins University, Baltimore, MD, USA.; Song Y; University of Maryland School of Medicine, Baltimore, MD, USA.; Bazyar S; University of Maryland, Baltimore, MD, USA.; Solanki AA; Loyola University Medical Center, Maywood, IL, USA.; Simko JP; UCSF Medical Center-Mount Zion, San Francisco, CA, USA.; Pollack A; University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, FL, USA.; McConkey D; Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Cancer Center, Baltimore, MD, USA.; Kates M; Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Cancer Center, Baltimore, MD, USA.; Siddiqui MM; University of Maryland, Baltimore, MD, USA.; Hiken J; CoFactor Genomics, San Francisco, CA, USA.; Earls J; CoFactor Genomics, San Francisco, CA, USA.; Messina D; CoFactor Genomics, San Francisco, CA, USA.; Mouw KW; Dana-Farber/Harvard Cancer Center, Boston, MA, USA.; Miyamoto D; Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Shipley WU; Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Michaelson MD; Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Zietman A; Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Coen JJ; Department of Radiation Oncology, GenesisCare USA-Warwick, Warwick, RI, USA.; Dahl DM; Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Jani AB; Emory University Hospital/Winship Cancer Institute, Atlanta, GA, USA.; Souhami L; McGill University Health Centre Research Institute, Montreal, Canada.; Chang BK; Parkview Regional Medical Center, Fort Wayne, IN, USA.; Lee RJ; Intermountain Medical Center, Murray, UT, USA.; Pham H; Virginia Mason Medical Center, Seattle, WA, USA.; Marshall DT; Medical University of South Carolina, Charleston, SC, USA.; Shen X; University of Kansas Cancer Center, Kansas City, KS, USA.; Pugh SL; NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA.; Feng FY; UCSF Medical Center-Mission Bay, San Francisco, CA, USA.; Efstathiou JA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Tran PT; University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA. Electronic address: phuoc.tran@som.umaryland.edu.; Deek MP; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address: matthewdeek@gmail.com.
Source
Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101724904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2588-9311 (Electronic) Linking ISSN: 25889311 NLM ISO Abbreviation: Eur Urol Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26-1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24-0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40, 95% CI 0.21-0.75; p = 0.005) and OS (HR 0.49, 95% CI 0.25-0.94; p = 0.033). Higher IDO1 expression (IFNγ signature) was also associated with longer DFS (HR 0.44, 95% CI 0.24-0.88; p = 0.021) and OS (HR 0.49, 95% CI 0.24-0.99; p = 0.048). These findings should be validated in prospective CRT trials that include biomarkers, particularly for trials incorporating immunotherapy for MIBC. PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation.
(Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)