2061 - Unplanned Hospitalizations and Lymphopenia after Proton Beam Therapy (PBT) vs. Intensity-Modulated Radiation Therapy (IMRT) in Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC): An Analysis of 74

M. Iocolano¹, N. Yegya-Raman¹, X. Wang², C. Friedes¹, S. H. Lee¹, L. Duan^3,4, B. Li³, W. P. Levin¹, K. A. Cengel¹, C. Langer⁵, R. Cohen⁵, L. Sun⁵, C. Aggarwal⁵, A. Douchette⁶, Y. Xiao³, B. K. K. Teo³, S. E. OReilly³, W. Zou³, J. D. Bradley¹, and S. J. Feigenberg¹; ¹Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, ²University of Pennsylvania, Department of Biostatistics and Epidemiology, Philadelphia, PA, ³Department of Radiation Oncology, Division of Physics, University of Pennsylvania, Philadelphia, PA, ⁴Department of Radiation Physics, MD Anderson Cancer Center, Houston, TX, ⁵Department of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, ⁶Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA

Purpose/Objective(s): We previously reported an association between PBT and fewer unplanned hospitalizations, lower effective dose to immune circulating cells (EDIC) and less G3+ lymphopenia compared to IMRT among pts with LA-NSCLC treated with concurrent chemoradiation (cCRT) in the era of ICI consolidation. We seek to corroborate these results in a larger cohort. Materials/

Methods: This single-institution, multi-site retrospective study evaluated consecutive pts with unresectable LA-NSCLC treated with cCRT using IMRT or PBT from 01/2011 to 12/2021. The primary endpoint was 90-day unplanned hospitalization from first RT fraction. Secondary endpoints included G3+ lymphopenia, G3+ pneumonitis, G3+ esophagitis, G3+ cardiac events, PFS and OS. Logistic regression was used to evaluate 90-day hospitalization and G3+ lymphopenia. Competing risk regression was used to evaluate G3+ pneumonitis, esophagitis and cardiac events. Kaplan-Meier analysis was used for PFS and OS. Inverse-probability treatment weighting (IPTW) was used to account for imbalances between treatment groups.
Results: Of 746 pts included, 295 (39.5%) were treated with PBT and 451 (60.5%) with IMRT. The PBT group was older (median 70.3 vs 65.6 yrs, p<0.0001), had a higher Charlson Comorbidity Index (CCI) (median 4 vs 3, p<0.0001) and received a slightly higher RT dose (median 6664 vs 6660 cGy, p=0.04). There was no difference in the use of ICI post cCRT (26.8% vs 30.6%, p=0.26) or duration of therapy (median 32 vs 38 weeks, p=0.99). The PBT group received a lower mean heart dose (median 6.4 vs 12.4 Gy, p<0.0001), LAD V15Gy (median 0 vs 10.2%, p<0.0001), lung V20Gy (median 26.8 vs 28.5%, p=0.04) and EDIC (median 4 vs 5.4, p<0.0001) but a higher esophagus V50Gy (median 23.8 vs 18.9%, p=0.005). After IPTW-analysis adjusting for age, race, COPD, CCI, ECOG performance status, smoking pack years, histology, GTV, N stage, concurrent chemotherapy agent and ICI receipt, PBT was associated with fewer acute hospitalizations (aOR 0.64, 95% CI 0.51-0.80, p=0.0001) and less G3+ lymphopenia (aOR 0.52, 95% CI 0.40-0.68, p<0.001) compared with IMRT. After IPTW-adjustment, PBT was associated with an improved OS compared to IMRT (median OS 31.2 vs 23.6 mo, p=0.02) but no difference in PFS (median PFS 14.2 vs 11.5 mo, p=0.23). Presence of an unplanned hospitalization (median OS 17.8 vs 33.5 mo, p<0.0001) or G3+ lymphopenia (median OS 28.0 vs 37.3 mo, p=0.03) was associated with worse OS. There was no difference in incidence of G3+ pneumonitis, G3+ esophagitis or G3+ cardiac events.
Conclusion: An acute, unplanned hospitalization or G3+ lymphopenia during or immediately after definitive treatment for LA-NSCLC is associated with worse OS. Our data suggests that PBT may be associated with fewer hospitalizations and improved patient outcomes due to lower RT dose to circulating lymphocytes, but prospective data are needed.