2465 - Sparing Secondary Lymphoid Organs Significantly Reduces Immune Suppression and Improves OS during Lung SBRT: Secondary Analysis of a Randomized, Phase 2 Trial
Presenter(s)
V. Rodriguez1, C. Nguyen2, and K. Wijesooriya3; 1Department of Radiation Oncology, University of Virginia Health, Charlottesville, VA, 2Department of Physics, University of Virginia, Charlottesville, VA, 3University of Virginia, Department of Radiation Oncology, Department of Physics, Charlottesville, VA
Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is shown to be equivalent to surgery with over 90% local tumor control rates for early-stage non-small cell lung cancer (NSCLC), but 5-year survival rates are poor rendering around 38% with distant failures. Radiation Therapy (RT) could lead to radiation-induced immunosuppression (RIIS). Clinical advantages of proactively sparing RT dose to secondary lymphoid organs have not previously been evaluated.
Materials/Methods: We analyzed data from a phase II randomized trial conducted from 2020 to 2023, enrolling 51 early-stage NSCLC patients treated with SBRT, to evaluate the effect of dose reduction to immune rich organs on RIIS and overall survival (OS). All treatments followed national protocol guidelines. Peripheral blood was collected at baseline, immediately, 4-weeks and 6-months post-treatment. Skin, thoracic spine thoracic lymph node (LN) stations and heart as well as all other thoracic organs were evaluated for OS and RIIS. During post hoc analysis inter-lobar and hilar lymph nodes were delineated and subtracted from thoracic LN stations to evaluate the effects of irradiating the tumor draining LN (TDLN) and the non-TDLN on OS and RIIS.
Results: For the blood-rich organs, heart and the great vessels and the lymph rich organs thoracic-spine, lymph-node-stations, and skin show statistically significant correlations (p <0.05) with post treatment RIIS. While the number of patients who received a dose >10Gy to the heart is small and heart doses did not correlate with OS, we see a significant (p =0.02) OS improvement in the low dose cohort of LN when we stratified by the median (35.4 cc) volume of LN receiving a dose of 5 Gy (V5). Two-year OS proportions are: 91.8% (SE = 5.5%) for LN V5 < 35.4 cc and 57.5% (SE=10.4%) for LN V5 = 35.4 cc. While none of the dose volumes V1 (cc) to V20 (cc) for TDLN were significantly correlated with OS, non-TDLN dose volumes from V1 to V15 had an increasing HR associated with reduced OS with V5 being the most statistically significant (HR=1.021, 95%CI: 1.008–1.035, p=0.002). While Thoracic spine dose led to significant RIIS, it did not affect OS. Skin doses V1 – V15 led to significant RIIS and skin dose volumes V1 -V10 all had an increasing HR associated with reduced OS with V2 being the most statistically significant (HR=1.039, 95% CI: 1.020–1.059, p<0.001).
Conclusion: For the first time, we have shown that irradiation of secondary lymphoid organs could lead to significant RIIS and sparing non draining lymph nodes, and skin could significantly improve the OS during SBRT to lung.