First Measurement: Proactively Sparing the Immune System During SBRT to Early-Stage Lung Cancer-A Randomized Phase II Study.

Abstract

PurposeMinimizing Radiation-Induced-Lymphocyte-Kill (RILK), a key immune-suppressive effect of Radiation Therapy (RT) to augment tumor-specific immunity is timely and important. We assessed RT dose sparing to blood/immune-rich organs beyond Radiation-Therapy-Oncology-Group (RTOG) criteria, and its effect on RILK, and adverse events.MethodsWe conducted a single-institution phase-II randomized trial enrolling 51 early-stage NSCLC patients (IA-IB/IIA), to be treated with SBRT to evaluate the effect of dose reduction to immune rich organs on RILK, focusing on lymphocytes as primary immune cells. Participants were randomized to optimized-SBRT (reducing dose to blood, bone-marrow, lymph-nodes) or standard-SBRT, both following RTOG 0813/0915 guidelines. Peripheral blood was collected at baseline, same day, 4-weeks and 6-months post-treatment.ResultsAverage percentage reductions in integral-dose, V5, and V10 to heart, lymph-nodes, and thoracic-vertebrae in the optimized-arm vs. standard-arm were 21%-68%(p=0.04 - 0.36), 37%-68%(pConclusionsSignificant RT dose reductions to immune-rich-organs in lung SBRT with comparable-safety is achievable, markedly preserving lymphocytes compared to standard-of-care. (Funded by National Cancer Institute and others.Clinicaltrialsgov number, NCT04273893).