Abstract：
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.
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.
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.
摘要：
目的：探讨免疫细胞有效剂量（EDIC）与疾病控制的关系，淋巴细胞减少,非小细胞肺癌（NSCLC）患者的毒性和确定减少EDIC的方法。
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。
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。
