William A Hall1, Theodore G Karrison2, Seth A Rosenthal3, Mahul B Amin4, Leonard G Gomella5, James A Purdy6, A Oliver Sartor7, Jeff M Michalski8, Mark G Garzotto9, Carmen Bergom8, Ashesh B Jani10, Colleen A F Lawton11, Jeffry P Simko12, Joan K Moore13, Elizabeth M Gore14, W Robert Lee15, Paul L Nguyen16, Brita L Danielson17, Howard M Sandler18, Felix Y Feng19. 1. Department of Radiation Oncology, Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: whall@mcw.edu. 2. NRG Oncology Statistics and Data Management Center. 3. Radiation Oncology Center, Sutter Cancer Centers Radiation Oncology Services. 4. Department of Pathology, University of Tennessee Health Science Center. 5. Department of Urology, Thomas Jefferson University Hospital. 6. Radiation Oncology Department, UC Davis Health. 7. Medicine and Urology Departments, Tulane University Health Sciences Center. 8. Department of Radiation Oncology, Washington University School of Medicine. 9. Department of Urology, Oregon Health and Science University. 10. Department of Radiation Oncology, Emory University Hospital/Winship Cancer Institute. 11. Department of Radiation Oncology, Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin. 12. Department of Pathology, UC San Francisco Medical Center. 13. Oncology Research, Wellspan Health. 14. Department of Radiation Oncology, Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Radiation Oncology, Zablocki Veterans Administration Medical Center. 15. Department of Radiation Oncology, Duke University Medical Center. 16. Department of Radiation Oncology, Brigham and Women's Hospital. 17. Department of Radiation Oncology, Cross Cancer Institute. 18. Department of Radiation Oncology, Cedars-Sinai Medical Center. 19. Department of Radiation Oncology, UC San Francisco Medical Center.
Abstract
PURPOSE: The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes. METHODS AND MATERIALS: Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT. RESULTS: Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027). CONCLUSIONS: Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.
PURPOSE: The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes. METHODS AND MATERIALS: Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT. RESULTS: Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027). CONCLUSIONS: Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.
Authors: Jennifer J Hu; James J Urbanic; L Doug Case; Cristiane Takita; Jean L Wright; Doris R Brown; Carl D Langefeld; Mark O Lively; Sandra E Mitchell; Anu Thakrar; David Bryant; Kathy Baglan; Jon Strasser; Luis Baez-Diaz; Glenn J Lesser; Edward G Shaw Journal: J Clin Oncol Date: 2018-07-10 Impact factor: 44.544
Authors: John Danesh; Jeremy G Wheeler; Gideon M Hirschfield; Shinichi Eda; Gudny Eiriksdottir; Ann Rumley; Gordon D O Lowe; Mark B Pepys; Vilmundur Gudnason Journal: N Engl J Med Date: 2004-04-01 Impact factor: 91.245
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