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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 Stereotactic Body Radiation Therapy to Early-Stage
Krishni Wijesooriya1, Cam Nguyen2, Mark R Conaway3
1Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia; Department of Physics, University of Virginia, Charlottesville, Virginia.
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 And Materials:
We conducted a single-institution phase II randomized trial enrolling 51 early-stage non-small cell lung cancer patients (IA-IB/IIA), to be treated with stereotactic body radiation therapy (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 Radiation Therapy Oncology Group 0813/0915 guidelines. Peripheral blood was collected at baseline, same day, 4 weeks and 6 months posttreatment.
Results:
Average percentage reductions in integral-dose, V5, and V10 to heart, lymph-nodes, and thoracic-vertebrae in the optimized arm versus standard arm were 21%-68% (P = .04-.36), 37%-68% (P < .001-.01), and 57%-92% (P < .001-.002), respectively. Absolute lymphocyte count changes from baseline at immediate, 4 weeks, and 6 months post-SBRT were: optimized: -16%, -22%, -16%; standard: -31%, -34%, -26%; overall improvement: 13.4% (95% CI, 2.8-24.0; P = .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 = .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% to -1.5%; P = .04). Standard arm: 11.5% (only peripheral with PTV < 20 cm3 group) and optimized arm: 32% (all subgroups) 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 toward increased event-free-survival (2-year: 75.0% [SE = 10.8%] versus 59.8% [SE = 11.2%], P = .10) and overall survival (2-year: 93.4% [SE = 6.1%] versus 69.4% [SE = 10.5%], P = .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.