TY - JOUR
T1 - The Influence of the Pretreatment Immune State on Response to Radiation Therapy in High-Risk Prostate Cancer
T2 - A Validation Study From NRG/RTOG 0521
AU - Hall, William A.
AU - Karrison, Theodore G.
AU - Rosenthal, Seth A.
AU - Amin, Mahul B.
AU - Gomella, Leonard G.
AU - Purdy, James A.
AU - Sartor, A. Oliver
AU - Michalski, Jeff M.
AU - Garzotto, Mark G.
AU - Bergom, Carmen
AU - Jani, Ashesh B.
AU - Lawton, Colleen A.F.
AU - Simko, Jeffry P.
AU - Moore, Joan K.
AU - Gore, Elizabeth M.
AU - Lee, W. Robert
AU - Nguyen, Paul L.
AU - Danielson, Brita L.
AU - Sandler, Howard M.
AU - Feng, Felix Y.
N1 - Funding Information:
This project was supported by grants UG1CA189867 (NRG Oncology NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), and U24CA196067 (NRG Specimen Bank) from the National Cancer Institute (NCI) and Sanofi Aventis, Inc, along with research grant number 14 to 247-29-IRG from the American Cancer Society. The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), award number KL2TR001438. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
This project was supported by grants UG1CA189867 (NRG Oncology NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), and U24CA196067 (NRG Specimen Bank) from the National Cancer Institute (NCI) and Sanofi Aventis, Inc, along with research grant number 14 to 247-29-IRG from the American Cancer Society. The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), award number KL2TR001438. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Disclosures: M.B.A. reports other from Precipio Diagnostics, other from Cell Max, Urogen, Advanced Diagnostics, and Core Diagnostics, and personal fees from Genomic Health outside the submitted work. F.Y.F. reports personal fees from Dendreon, EMD Serono, Janssen Oncology, Ferring, Sanofi, Bayer, Blue Earth Diagnostics, Celgene, Medivation/Astellas, Clovis Oncology, and Genentech, and other from PFS Genomics and Nutcracker Therapeutics, outside the submitted work. F.Y.F. has a patent (EP3047037 A4) issued. M.G.G. reports grants from Merck, Astellas, Candel Therapeutics, Sesen Bio, and an advisory board position for Lantheus, outside the submitted work. W.A.H. reports grants from American Cancer Society during the conduct of the study and other from Elekta AB, Stockholm, Sweden, outside the submitted work. P.L.N. reports grants and personal fees from Astellas; personal fees from COTA, Bayer, Janssen, Genome DX, Ferring, Astellas, Dendreon, Boston Scientific, and Blue Earth Diagnostics; and personal fees and other from Augmenix, outside the submitted work. H.M.S. reports personal fees from Janssen and RadioGel outside the submitted work. A.O.S. reports personal fees from AAA, Astellas, EMD Serono, Hinova, Myovant, and Pfizer; grants and personal fees from AstraZeneca, Bayer, Blue Earth Diagnostics, Constellation, Dendreon, Endocyte, Johnson & Johnson, Progenics, and Sanofi; and grants from Innocrin, Invitae, Merck, Roche, and SOTIO, during the conduct of the study. J.P.S. acknowledges reception of National Cancer Institute (USA) grant number 5 U24 CA196067-03 during the conduct of the study. All other authors have no disclosures to declare.
Funding Information:
Disclosures: M.B.A. reports other from Precipio Diagnostics, other from Cell Max, Urogen, Advanced Diagnostics, and Core Diagnostics, and personal fees from Genomic Health outside the submitted work. F.Y.F. reports personal fees from Dendreon, EMD Serono, Janssen Oncology, Ferring, Sanofi, Bayer, Blue Earth Diagnostics, Celgene, Medivation/Astellas, Clovis Oncology, and Genentech, and other from PFS Genomics and Nutcracker Therapeutics, outside the submitted work. F.Y.F. has a patent (EP3047037 A4) issued. M.G.G. reports grants from Merck, Astellas, Candel Therapeutics, Sesen Bio, and an advisory board position for Lantheus, outside the submitted work. W.A.H. reports grants from American Cancer Society during the conduct of the study and other from Elekta AB, Stockholm, Sweden, outside the submitted work. P.L.N. reports grants and personal fees from Astellas; personal fees from COTA, Bayer, Janssen, Genome DX, Ferring, Astellas, Dendreon, Boston Scientific, and Blue Earth Diagnostics; and personal fees and other from Augmenix, outside the submitted work. H.M.S. reports personal fees from Janssen and RadioGel outside the submitted work. A.O.S. reports personal fees from AAA, Astellas, EMD Serono, Hinova, Myovant, and Pfizer; grants and personal fees from AstraZeneca, Bayer, Blue Earth Diagnostics, Constellation, Dendreon, Endocyte, Johnson & Johnson, Progenics, and Sanofi; and grants from Innocrin, Invitae, Merck, Roche, and SOTIO, during the conduct of the study. J.P.S. acknowledges reception of National Cancer Institute (USA) grant number 5 U24 CA196067-03 during the conduct of the study. All other authors have no disclosures to declare.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ijrobp.2022.05.048
DO - 10.1016/j.ijrobp.2022.05.048
M3 - Article
C2 - 35675855
AN - SCOPUS:85136601546
SN - 0360-3016
VL - 114
SP - 266
EP - 274
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -