Radiation and Cancer Biology

SS 03 - Biology 1 - Innovative Biologic Approaches to Improve Risk Stratification and Treatment Outcomes

25 - The Influence of the Pretreatment Host Immune Inflammatory State and Response to Radiation Therapy in High Risk Adenocarcinoma of the Prostate:?A Validation Study From NRG Oncology/RTOG 0521

Sunday, October 21
1:45 PM - 1:55 PM
Location: Room 008

The Influence of the Pretreatment Host Immune Inflammatory State and Response to Radiation Therapy in High Risk Adenocarcinoma of the Prostate: A Validation Study From NRG Oncology/RTOG 0521
W. A. Hall1, T. G. Karrison2, S. A. Rosenthal3, M. Amin4, L. G. Gomella5, J. A. Purdy6, O. Sartor7, J. M. Michalski8, M. Garzotto9, C. Bergom10, A. Jani11, C. A. F. Lawton12, J. Simko13, J. Moore14, E. M. Gore1, W. R. Lee15, P. L. Nguyen16, B. Danielson17, H. M. Sandler18, and F. Y. Feng19; 1Medical College of Wisconsin and Clement J Zablocki VA Medical Center, Milwaukee, WI, 2University of Chicago, Chicago, IL, 3Sutter Medical Group and Cancer Center, Sacramento, CA, 4University of Tennessee Health Science Center, Memphis, TN, 5Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, 6UC Davis Cancer Center, Davis, CA, 7Tulane University, New Orleans, LA, 8Washington University School of Medicine, St. Louis, MO, 9Oregon Health and Science University, Portland, OR, 10Medical College of Wisconsin, Milwaukee, WI, 11Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 12Medical College of Wisconsin Department of Radiation Oncology, Milwaukee, WI, 13University of California San Francisco, San Francisco, CA, 14Wellspan Health, York, PA, 15Duke University, Durham, NC, 16Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 17Division of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada, 18Cedars Sinai Medical Center, Los Angeles, CA, 19Department of Radiation Oncology, University of California San Francisco, San Francisco, CA

Purpose/Objective(s): The host immuno-inflammatory state, as reflected by elevation in C-Reactive Protein (CRP), has been shown in several retrospective series to be associated with poor outcomes following radiation therapy (RT). We conducted a validation study using prospectively banked serum specimens from the phase III clinical trial RTOG 0521 which evaluated the addition of docetaxel to androgen suppression and RT for high risk prostate cancer.

Materials/Methods: Patients enrolled on RTOG 0521 had serum samples banked for future biomarker validation. This study was designed to validate previous findings showing an association between elevations in CRP levels and shorter biochemical failure-free survival after RT. CRP levels were measured in pre-treatment samples using a widely available, clinical grade assay. A panel of serum immuno-inflammatory 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 in this a priori designed validation study was disease-free survival (DFS), defined as the time from randomization to the development of biochemical failure, local progression, distant metastases, or death from prostate cancer, whichever occurred first. Additional endpoints included correlation with cytokine levels and toxicity events attributed to RT, namely: pollakiuria ≥ grade (g) 2, cystitis ≥ g 2, diarrhea ≥ g 2, erectile dysfunction (ed) ≥ g 2, proctitis ≥ g 2.

Results: Of 563 patients who enrolled in RTOG 0521, 202 had banked serum samples available. In the subsample, median age was 66 years (range 48-83), 90% of patients were white and 10% African-American. There was not an association between CRP and DFS ([HR]=1.06 per one log increase in CRP, 95% CI: 0.78 - 1.43, p=0.72). Pre-treatment IL-10 was significantly associated with DFS following co-variate adjustment (HR=1.59, p=0.02 per one log increase). Pretreatment levels of IFN-γ, IL-2, IL-13, IL-23 were negatively associated with g 2 or higher pollakiuria (OR=0.68, 0.75, 0.76, and 0.78, respectively, all p<0.05) and IL-12 and IL-13 were positively associated with g 2 or higher cystitis (OR=2.04 and 1.55, respectively, p<0.05).

Conclusion: Elevation in host inflammatory state, as reflected by CRP, was not associated with a poorer DFS following RT. Higher baseline levels of IL-10 were associated with lower rates of DFS. Elevated pretreatment levels of IL-12 and IL-13 were also associated with higher rates of cystitis. These data support an interaction between the host pretreatment immune inflammatory state on outcomes following RT. Anti-inflammatory medical intervention in patients with prostate cancer, in association with RT, may be worthy of future investigation. Acknowledgements: Supported by Institutional Research Grant # 14-247-29-IRG from the American Cancer Society

Author Disclosure: W.A. Hall: None. T.G. Karrison: None. S.A. Rosenthal: Chair, ACR Commission on Radiation Oncology; American College of Radiology (ACR). M. Amin: None. L.G. Gomella: Research Grant; RTOG. Honoraria; Janssen. Consultant; Dendreon, Janssen. Advisory Board; Bayer, Dendreon. Travel Expenses; RTOG. J.A. Purdy: Advisory Board; ViewRay, Inc. Travel Expenses; ViewRay, Inc. O. Sartor: Consultant; Consultant. GU Committee Medical Oncology Chair; RTOG. J.M. Michalski: Independent Contractor; Sheila Michalski and Associates. Research Grant; NCI. https://medicine.wustl.edu/news/effort-improve-radiation-therapy-veterans-receives-nearly-4-million/; Veteran's Administration. Consultant; Veteran's Administration. Stock; ViewRay Inc. Chair Radiation Oncology Committee; NRG Oncology. Radiation Oncology Practice Assessment; Veterans Affairs. Co-chair GU Steering Committee; NCI. M. Garzotto: None. A. Jani: Advisory Board; Blue Earth Diagnostics. Travel Expenses; Blue Earth Diagnostics. J. Simko: None. E.M. Gore: Partner; Stuart Wong. Co-Chair Publications Committee; NRG Oncology. W. Lee: Independent Contractor; ASTRO. P.L. Nguyen: Honoraria; Bayer. Consultant; Nanobiotix, Infinity Pharmaceuticals, GI Windows, Astellas, Augmenix. Advisory Board; Ferring, Medivation, Genome DX, Dendreon. Stock Options; Augmenix. Program Committee; Genitourinary Cancers Symposium. B. Danielson: None. H.M. Sandler: Research Grant; ACR-RTOG. Stock; Advanced Medical Isotope Corporation. Committee Chair; NRG Oncology. F.Y. Feng: Research Grant; GenomeDx. Advisory Board; GenomeDx, Dendreon, Sanofi. Travel Expenses; GenomeDx. Liaison, GU Translational Research Program; Radiation Therapy Oncology Group. President and Founder; PFS Genomics.

William Hall, MD

Medical College of Wisconsin

Medical College of Wisconsin: Assistant Professor: Employee, Assistant Professor of Radiation Oncology: Employee, Assistant Professor of Radiation Oncologyr: Employee

I am a board certified radiation oncologist with a passion for research in gastrointestinal malignancies, and radiological sciences. Thus far, in the early portion of my career, I have devoted my efforts to understanding the integration of advanced imaging modalities, including MRI, into radiation treatment planning. Moreover, I have published several peer-reviewed articles devoted to the optimal use of radiation therapy for gastrointestinal malignancies and prostate cancer. Such articles have specifically related to radiation therapy technological advances, MRI incorporation into radiation planning, and the optimal radiation therapy dosing strategy. My future research goals are focused on developing and improving our ability to identify patients that may not require surgery for rectal cancer. In addition, I hope to develop MRI strategies that would use novel and unique MRI sequences to enable precise delineation of the most malignant portions of a tumor. My aspiration is to work closely with collaborators to refine our ability to accurately identify malignant tissue and direct intensification of local radiation therapy. I see the next decade of research to be an exciting and transformative time in the management of several different malignancies and I am looking forward to making whatever contributions I can.


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25 - The Influence of the Pretreatment Host Immune Inflammatory State and Response to Radiation Therapy in High Risk Adenocarcinoma of the Prostate:?A Validation Study From NRG Oncology/RTOG 0521

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