Immune system dose with proton vs photon radiotherapy for treatment of locally advanced NSCLC

Purpose Emerging data have illuminated the impact of effective radiation dose to immune cells (EDIC) on outcomes in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT). Hypothesizing that intensity modulated proton therapy (IMPT) may reduce EDIC versus IMRT, we conducted a dosimetric analysis of patients treated at our institution. Methods Data were retrospectively collected for 12 patients with locally advanced, unresectable NSCLC diagnosed between 2019 and 2021 who had physician-approved IMRT and IMPT plans. Data to calculate EDIC from both Jin et. al. (PMID: 34944813) and Ladbury et. al’s (PMID: 31175902) models were abstracted. Paired t-tests were utilized to compare the difference in mean EDIC between IMPT and IMRT plans. Results IMPT decreased EDIC for 11 of 12 patients (91.7%). The mean EDIC per the Jin model was significantly lower with IMPT than IMRT (3.04 GyE versus 4.99 Gy, p<0.001). Similarly, the mean EDIC per the Ladbury model was significantly lower with IMPT than IMRT (4.50 GyE versus 7.60 Gy, p<0.002). Modeled 2-year-overall-survival was significantly longer with IMPT than IMRT (median 71% vs. 63%; p = 0.03). Conclusion IMPT offers a statistically significant reduction in EDIC compared to IMRT. Given the emergence of EDIC as a modifiable prognostic factor in treatment planning, our dosimetric study highlights a potential role for IMPT to address an unmet need in improving oncologic outcomes in patients with locoregionally advanced NSCLC.