Acute hospitalizations after proton therapy versus intensity‐modulated radiotherapy for locally advanced non–small cell lung cancer in the durvalumab era

Abstract Introduction It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non–small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity‐modulated radiotherapy (IMRT). Methods Patients with locally advanced non–small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90‐day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan–Meier method was used for progression‐free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. Results Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older ( p < .001) and had higher Charlson Comorbidity Index scores ( p = .02). The PBT group received a lower mean heart dose ( p < .0001), left anterior descending artery V15 Gy ( p = .001), mean lung dose ( p = .008), and effective dose to immune circulating cells ( p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38–0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37–0.81; p = .003). There was no difference in other G3+ toxicities, progression‐free survival, or overall survival. Conclusions PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.