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 Cohort Study

Abstract

Patients (pts) with LA-NSCLC treated with concurrent chemoradiation (cCRT) and ICI consolidation are at high risk for treatment-related toxicities and subsequent hospitalization. We hypothesized that PBT is associated with a reduction in acute unplanned hospitalizations as compared to IMRT in the era of ICI consolidation. 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 treatment-related 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. A total of 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 significant difference in ECOG, smoking pack-years, T stage, N stage, target volume size, or 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%); which persisted on multivariable analysis (OR 0.52, 95% CI 0.30-0.90, p = 0.02) after adjusting for CCI, smoking pack-years, T4 tumors and target volume. Reasons for hospitalization in PBT and IMRT groups included progression (1.7% vs 1.5%), definite/probable toxicity from cCRT (11.1% vs 18.6%), possible toxicity from cCRT (7.7% vs 12.6%) or unrelated to cCRT (3.4% vs 2.0%). There was no significant difference between PBT or 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). 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. There was no difference in G3+ pneumonitis, G3+ esophagitis, PFS or OS.