Improving Immune Preservation for Lung Cancer Patients with Ultra-Fast Proton Therapy Using Pin Ridge Filters
Abstract
Purpose
Radiation-induced lymphopenia (RIL) is a prevalent and clinically significant toxicity in lung cancer radiotherapy. Circulating lymphocyte exposure is inherently time-dependent due to blood flow through irradiated volumes during beam delivery. Intensity-modulated proton therapy (IMPT) relies on energy switching that extends delivery times, potentially increasing low-dose irradiation of blood. We recently developed a patient-specific pin ridge filter (pRF) technique within our clinical treatment planning system (TPS), enabling ultra-fast proton delivery using a single beam energy. This work investigates whether pRF-based delivery mitigates blood dose relative to IMPT using time-resolved blood dose accumulation synchronized with temporal simulations of pencil beam scanning (PBS).
Methods
pRF plans were generated within our TPS for six lung SBRT patients previously treated with IMPT (5x10Gy RBE). Temporal PBS delivery simulations were performed for IMPT and pRF plans, explicitly modeling spot delivery, scanning times and energy switching. To calculate blood dose–volume histograms (bDVHs), blood dose accumulation was performed using the hematological dose (HEDOS) framework by discretizing delivery into 50 ms timesteps and accumulating partial doses to blood particles (BPs) within the lung volume at each timestep. BPs underwent random-walk motion to approximate intrapulmonary circulation.
Results
pRF-based delivery shortened delivery time relative to IMPT (median reduction: 80.8%, range: [69.3-90.7]%), which reduced circulating blood exposure. pRF plans decreased the volume of irradiated blood (median reduction: 52.4%, range: [40.2, 58.2]%). Blood dose reductions were dominated by the low-dose region: median blood volumes receiving 5–35 cGy were reduced by 13.8% to 0.1%, respectively. Small increases were observed at higher doses (40–50 cGy: +1.7% to +1.1%).
Conclusion
pRF-based delivery significantly reduced delivery time and the volume of irradiated blood compared with IMPT, with the largest differences occurring in the low-dose range. These findings indicate that delivery-time optimization can meaningfully alter blood dose distributions and may provide a pathway towards immune-sparing proton therapy.