The immuno-inflammatory state has been shown to be associated with poor outcomes following radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from RTOG 0521. It was hypothesized the pre-treatment inflammatory state would correlate with clinical outcomes.
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 pre-treatment samples. An exploratory panel of related cytokines were also measured including: monocyte chemotactic protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), 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 (TNFα). The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT.
202 patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), 90% of patients were white. There was not an association between high sensitivity (hsCRP) and bDFS (adjusted hazard ratio [HR]=1.07 per one log increase in CRP, 95% CI: 0.83 - 1.38, p=0.60). In the exploratory, unplanned analysis, pre-treatment IL-10 was significantly associated with worse bDFS (adjusted HR=1.61 per log increase, p=0.0027) and distant metastases (HR=1.55 per log increase, p=0.028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analysis of pretreatment levels of IFN-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with g 2 or higher pollakiuria (adjusted OR=0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all p<0.05) and IL-6 was negatively associated with g 2 or higher ED (OR=0.62, p=0.027).
Pretreatment CRP is not associated with a poorer bDFS following 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.
International journal of radiation oncology, biology, physics. 2022 Jun 05 [Epub ahead of print]
William A Hall, Theodore G Karrison, Seth A Rosenthal, Mahul B Amin, Leonard G Gomella, James A Purdy, A Oliver Sartor, Jeff M Michalski, Mark G Garzotto, Carmen R Bergom, Ashesh B Jani, Colleen A F Lawton, Jeffry P Simko, Joan K Moore, Elizabeth M Gore, W Robert Lee, Paul L Nguyen, Brita L Danielson, Howard M Sandler, Felix Y Feng
Froedtert and the Medical College of Wisconsin, Department of Radiation Oncology., NRG Oncology Statistics and Data Management Center., Sutter Cancer Centers Radiation Oncology Services, Radiation Oncology Center., University of Tennessee Health Science Center, Department of Pathology., Thomas Jefferson University Hospital, Department of Urology., UC Davis Health, Radiation Oncology Department., Tulane University Health Sciences Center, Medicine and Urology Departments., Washington University School of Medicine, Department of Radiation Oncology., Oregon Health and Science University, Department of Urology., Emory University Hospital/Winship Cancer Institute, Department of Radiation Oncology., UCSF Medical Center, Department of Radiation Oncology., Wellspan Health, Oncology Research., Froedtert and the Medical College of Wisconsin, Department of Radiation Oncology; Zablocki Veterans Administration Medical Center, Department of Radiation Oncology., Duke University Medical Center, Department of Radiation Oncology., Brigham and Women's Hospital, Department of Radiation Oncology., Cross Cancer Institute, Department of Radiation Oncology., Cedars-Sinai Medical Center, Department of Radiation Oncology.