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Updated: Aug 6, 2026
Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy
Published on: June 7, 2015
First Measurement: Proactively Sparing the Immune System During SBRT to Early-Stage Lung Cancer-A Randomized Phase II
Krishni Wijesooriya1, Cam Nguyen2, Mark R Conaway3
1Department of Radiation Oncology, University of Virginia, 1300 Jefferson Park Ave, Charlottesville, VA, 22908; Department of Physics, University of Virginia, 382 McCormick Rd., Charlottesville, VA 22904.
Purpose:
Minimizing 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.
Methods:
We 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.
Results:
Average 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%(p<0.001-0.01), and 57%-92%(p<0.001-0.002), respectively. Absolute Lymphocyte Counts (ALC) changes from baseline at immediate, 4-week, and 6-month post-SBRT were: optimized: -16%, -22%, -16%; standard: -31%, -34%, -26%; overall improvement: 13.4% (95% CI, 2.8-24.0; p=0.01) with optimized-treatment. Central tumors had the largest improvement: optimized: -8%, -18%, -14%; standard: -39%, -43%, -47%; overall improvement: 29.5% (95% CI, 10.1-48.9; p=0.004). Post SBRT grade 3 or higher lymphopenia occurred in 15.4% of standard arm patients but was absent in the optimized arm (risk difference -15.4%, 95% CI: -29.2%, -1.5%; p = 0.04). Standard-arm: 11.5% (only peripheral with PTV <20 cc group) and optimized-arm: 32% (all sub-groups) patients had a post-SBRT ALC increase. Dose to immune-rich organs (heart, great vessels, thoracic spine, and lymph nodes) significantly correlated with RILK. There was no difference in grade-3+ adverse events between groups. Exploratory analysis: a trend towards increased Event-Free-Survival (two-year: 75.0% (SE = 10.8%) versus 59.8% (SE = 11.2%), p=0·10) and Overall Survival (two-year: 93.4% (SE=6.1%) versus 69.4% (SE=10.5%), p=0·14) was observed with optimized-planning compared to standard-planning in treatment naïve patients.
Conclusions:
Significant 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.
Clinicaltrials:
gov number, NCT04273893).