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The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC

医学 内科学 入射(几何) 肺癌 肿瘤科 比例危险模型 免疫疗法 逻辑回归 胃肠病学 癌症 光学 物理
作者
Cole Friedes,Michelle Iocolano,Sang Ho Lee,Lian Duan,Bolin Li,Abigail Doucette,Roger B. Cohen,Charu Aggarwal,Lova Sun,William P. Levin,Keith A. Cengel,Gary D. Kao,Boon‐Keng Teo,Corey J. Langer,Ying Xiao,Jeffrey D. Bradley,Steven J. Feigenberg,Nikhil Yegya‐Raman
出处
期刊:Radiotherapy and Oncology [Elsevier BV]
卷期号:190: 110030-110030 被引量:11
标识
DOI:10.1016/j.radonc.2023.110030
摘要

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
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