182 - Association Between Circulating Immunobiomarkers and Survival In Stage III Non-Small Cell Lung Cancer (NSCLC) Treated with Chemoradiation (CRT): Longitudinal Analyses from NRG-RTOG 0617
Presenter(s)
J. A. Miccio1, C. Hu2, T. Schell1, J. D. Bradley3, W. Wang4, J. Y. Jin5, G. H. Perdew1, B. Lu6, F. Dong1,7, L. Beidler1, R. Jordan8, S. DeVries9, M. Werner-Wasik10, Y. Garces11, S. Narayan12, C. G. Robinson13, J. Lyness14, F. M. Kong15, and M. Machtay16; 1Penn State Milton S. Hershey Medical Center, Hershey, PA, 2Johns Hopkins University School of Medicine, Baltimore, MD, 3Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 4Medical College of Wisconsin, Milwaukee, WI, 5Department of Clinical Oncology, Hong Kong University Shenzhen Hospital, Shenzhen, China, 6University of Missouri School of Medicine, Columbia, MO, 7Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, 8University of California San Francisco, San Francisco, CA, 9UCSF Medical Center, San Francisco, CA, 10Department of Radiation Oncology, Sidney Kimmel Cancer Center, Philadelphia, PA, 11Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 12Michigan Cancer Research Consortium CCOP, Ypsilanti, MI, 13WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 14NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 15The University of Hong Kong, Hong Kong, China, 16Penn State Cancer Institute and College of Medicine, Hershey, PA
Purpose/Objective(s): Pre-treatment immunobiomarkers in patients enrolled on NRG-RTOG 0617 were associated with overall survival (OS) and suggested potential heterogeneity in outcomes by RT dose for selected markers. We extended these analyses to mid- and post-treatment specimens to evaluate whether prognostic signals persist during and after CRT, and to explore whether longitudinal changes modify OS or the RT dose effect.
Materials/Methods: Mid- and post-treatment blood samples were collected from consenting patients enrolled in NRG-RTOG 0617; platelet-poor plasma was analyzed in patients who received curative-intent radiotherapy (=50 Gy). Biomarkers were measured by ELISA and selected based on prior baseline association with OS (IL-6, sPD-L1) and/or suggestive heterogeneity by RT dose (IL-10, IFN?, sPD-L1). Biomarker levels were dichotomized at the median at each timepoint, and intra-patient change from baseline to mid- and post-treatment were dichotomized at the median change. Association with OS were assessed using Cox models; potential RT dose effect modification was explored using biomarker-by-RT dose interaction terms.
Results:
We analyzed n=328 baseline, n=216 baseline + mid-treatment, n=82 baseline + post-treatment samples, and n=64 with baseline, mid-, and post-treatment samples. The prognostic value of IL-6 persisted during treatment (mid-treatment HR 1.60, CI 1.17-2.19, p=0.003) and was directionally similar post- CRT (HR 1.64, CI 0.95-2.86, p=0.078). In contrast, sPD-L1 levels measured mid-treatment (HR 1.24, CI: 0.90-1.69, p=0.184) and post-CRT (HR 1.36, CI 0.80-2.33; p=0.260) were no longer associated with OS. With respect to RT dose heterogeneity at mid-treatment, IL-10 showed evidence of interaction with RT dose (interaction p=0.04); in the low mid-treatment IL-10 subgroup, the estimated dose-escalation effect was HR 0.81 (95% CI: 0.51-1.28, p=0.366). Mid-treatment sPD-L1 and IFN? showed no evidence of RT dose effect modification (interaction p>0.15). Change in IL-6 from baseline to mid-treatment demonstrated evidence of effect modification by RT dose (interaction p=0.027). In patients with larger increases in IL-6, the estimated effect of dose-escalated radiation was HR 0.78 (95% CI: 0.50–1.24, p=0.294). Finally, larger increases from baseline to post-treatment in IL-6 (HR 1.79, CI 1.04-3.08, p=0.035), IFN? (HR 1.81, CI 1.04-3.13, p=0.035) and IL-10 (HR 1.73, CI 1.01-2.97, p=0.045) were associated with worse OS.Conclusion:
Circulating immunobiomarkers showed time-dependent associations with OS after chemoradiation for stage III NSCLC. IL-6 had the most consistent prognostic signal, while sPD-L1 associations attenuated after baseline. Selected longitudinal changes showed exploratory evidence of RT dose effect modification and warrant validation in contemporary cohorts.