Search

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. The use of proton beam therapy in locally advanced non–small cell lung cancer is associated with fewer 90‐day acute hospitalizations, lower effective dose to immune circulating cells, and less grade 3+ lymphopenia compared with intensity‐modulated radiation therapy. [ABSTRACT FROM AUTHOR]

• Higher EDIC was associated with inferior PFS and OS in a large cohort of locally advanced NSCLC treated with or without consolidative immunotherapy. • EDIC was a predictor of severe grade 4 lymphopenia. • Increased EDIC was associated with acute pneumonitis and unplanned hospitalization. • Proton therapy may be an effective tool to reduce EDIC. To explore the association of the effective dose to immune cells (EDIC) with disease control, lymphopenia, and toxicity in patients with non-small cell lung cancer (NSCLC) and identify methods to reduce EDIC. We abstracted data from all patients with locally advanced NSCLC treated with chemoradiation with or without consolidative immunotherapy over a ten-year period. Associations between EDIC and progression-free survival (PFS) and overall survival (OS) were modeled with Cox proportional hazards and Kaplan-Meier method. Logistic regression was used to model predictors of lymphopenia and higher EDIC. Analyses were performed with EDIC as a continuous and categorical variable. Lymphopenia was graded per CTCAE v5.0. Overall, 786 patients were included (228 of which received consolidative immunotherapy); median EDIC was 4.7 Gy. Patients with EDIC < 4.7 Gy had a longer median PFS (15.3 vs. 9.0 months; p < 0.001) and OS (34.2 vs. 22.4 months; p < 0.001). On multivariable modeling, EDIC correlated with inferior PFS (HR 1.08, 95 % CI 1.01–1.14, p = 0.014) and OS (HR 1.10, 95 % CI 1.04–1.18, p = 0.002). EDIC was predictive of grade 4 lymphopenia (OR 1.16, 95 % CI 1.02–1.33, p = 0.026). EDIC ≥ 4.7 Gy was associated with increased grade 2 + pneumonitis (6-month incidence: 26 % vs 20 %, p = 0.04) and unplanned hospitalizations (90-day incidence: 40 % vs 30 %, p = 0.002). Compared to protons, photon therapy was associated with EDIC ≥ 4.7 Gy (OR 5.26, 95 % CI 3.71–7.69, p < 0.001) in multivariable modeling. EDIC is associated with inferior disease outcomes, treatment-related toxicity, and the development of severe lymphopenia. Proton therapy is associated with lower EDIC. Further investigations to limit radiation dose to the immune system appear warranted. [ABSTRACT FROM AUTHOR]