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.
方法:我们提取了10年期间内所有局部晚期非小细胞肺癌患者的数据,这些患者接受或不接受综合免疫治疗的放化疗。使用Cox比例风险和Kaplan-Meier方法对EDIC与无进展生存期(PFS)和总生存期(OS)之间的关联进行建模。使用Logistic回归对淋巴细胞减少和较高EDIC的预测因子进行建模。使用EDIC作为连续和分类变量进行分析。根据CTCAEv5.0对淋巴细胞减少症进行分级。
结果:总体而言,纳入786例患者(其中228例接受了综合免疫治疗);EDIC中位数为4.7G。EDIC<4.7Gy的患者中位PFS较长(15.3vs.9.0个月;p<0.001)和OS(34.2与22.4个月;p<0.001)。在多变量建模中,EDIC与较差的PFS(HR1.08,95CI1.01-1.14,p=0.014)和OS(HR1.10,95CI1.04-1.18,p=0.002)相关。EDIC可预测4级淋巴细胞减少(OR1.16,95CI1.02-1.33,p=0.026)。EDIC≥4.7Gy与2级肺炎增加相关(6个月发病率:26%vs20%,p=0.04)和计划外住院(90天发病率:40%vs30%,p=0.002)。与质子相比,在多变量建模中,光子治疗与EDIC≥4.7Gy(OR5.26,95CI3.71-7.69,p<0.001)相关.
结论:EDIC与较差的疾病结局和严重淋巴细胞减少的发展相关。质子治疗与较低的EDIC相关。似乎有必要进行进一步的研究以限制对免疫系统的辐射剂量。