The Influence of the Pretreatment Immune State on Response to Radiation Therapy in High-Risk Prostate Cancer: A Validation Study From NRG/RTOG 0521. Int J Radiat Oncol Biol Phys 2022 Oct 01;114(2):266-274
Date
06/09/2022Pubmed ID
35675855Pubmed Central ID
PMC9444930DOI
10.1016/j.ijrobp.2022.05.048Scopus ID
2-s2.0-85136601546 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
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.
Author List
Hall WA, Karrison TG, Rosenthal SA, Amin MB, Gomella LG, Purdy JA, Sartor AO, Michalski JM, Garzotto MG, Bergom C, Jani AB, Lawton CAF, Simko JP, Moore JK, Gore EM, Lee WR, Nguyen PL, Danielson BL, Sandler HM, Feng FYAuthors
Elizabeth M. Gore MD Professor in the Radiation Oncology department at Medical College of WisconsinWilliam Adrian Hall MD Professor in the Radiation Oncology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Biomarkers
C-Reactive Protein
Cytokines
Disease-Free Survival
Humans
Immunity
Inflammation
Male
Middle Aged
Prostatic Neoplasms
