Acute hospitalizations after proton beam therapy (PBT) versus intensity-modulated radiotherapy (IMRT) for locally advanced non–small-cell lung cancer (LA-NSCLC) in the era of immune checkpoint inhibitor (ICI) consolidation: A retrospective propensity score weighted study.
Authors: Iocolano Michelle , Yegya-Raman Nikhil , Wang Xingmei , Friedes Cole , Lee Sang Ho , Duan Lian , Li Bolin , Levin William P. , Cengel Keith A. , Langer Corey J. , Cohen Roger B. , Sun Lova , Aggarwal Charu , Doucette Abigail , Xiao Ying , Teo Kevin , O'Reilly Shannon , Zou Jennifer Wei , Simone Charles B. , Feigenberg Steven J 
Published: June 2023

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Background: Prior work found that PBT is associated with fewer acute hospitalizations compared to photons for a variety of cancers. Patients (pts) with LA-NSCLC treated with concurrent chemoradiation (cCRT) and ICI consolidation are at high risk for treatment-related toxicity and acute hospitalizations. We hypothesized that PBT is associated with fewer acute unplanned hospitalizations as compared to IMRT in the era of ICI consolidation. Methods: This single institution, multi-site retrospective study included consecutive pts with LA-NSCLC treated with definitive cCRT with either PBT or IMRT from October 2017 to December 2021. Pts were evaluated for consolidative ICI. Primary endpoint was unplanned hospitalization within 90 days of first radiation (RT) treatment. Secondary endpoints included grade 3+ pneumonitis, grade 3+ esophagitis, PFS, and OS. Logistic regression was used to assess associations with 90-day hospitalization. Competing risk regression was used for grade 3+ pneumonitis and esophagitis and Cox regression for PFS and OS. Inverse probability treatment weighting (IPTW) was applied to adjust for differences in PBT and IMRT groups. Results: 316 pts were included: 117 (37%) received PBT and 199 (63%) IMRT. Median age was 68.5 yrs; median RT dose 66.6 Gy (IQR 65.9-70.0). PBT group was older (median 71.1 vs 67.2 yrs, p < 0.005) and had a higher Charlson comorbidity index (CCI) (median 4 vs 3, p = 0.02). There was no difference in receipt of ICI consolidation (66.7% vs 68.3%, p = 0.76). PBT group had lower mean heart dose (5.9 vs 10.8 Gy, p < 0.001), LAD V15 (0 vs 6%, p = 0.001), mean lung dose (14.7 vs 15.7 Gy, p < 0.008) and effective dose to immune circulating cells (median 3.7 vs 4.9 Gy, p < 0.001) but not mean esophagus dose. PBT was associated with fewer unplanned 90-day hospitalizations (23.9% vs 34.7%; aOR 0.52, 95% CI 0.30-0.90, p = 0.02). This difference persisted on IPTW analysis (OR 0.48, 95% 0.33-0.70, p = 0.0002) after adjusting for CCI, ECOG, smoking pack yrs, T stage, N stage, target volume, concurrent chemotherapy agent and histology. Reasons for hospitalization in PBT and IMRT groups included progression (1.4% vs 1.6%), definite/probable toxicity from cCRT (11.4% vs 18.2%), possible toxicity from cCRT (7.3% vs 12.8%) or unrelated to cCRT (2.5% vs 2.3%). There was no significant difference between PBT and IMRT groups in G3+ pneumonitis (1-year 6.0% vs 9.1%, p = 0.49), G3+ esophagitis (1-year 6.0% vs 6.5%, p = 0.71), PFS (median 14.4 vs 15.1 months, p = 0.69), or OS (median 34.2 vs 29.4 months, p = 0.41); results remained unchanged in IPTW analysis. Conclusions: Among pts with LA-NSCLC treated with cCRT in the era of ICI consolidation, PBT was associated with fewer acute unplanned hospitalizations compared to IMRT.