PURPOSE To test the hypothesis that effective dose to circulating immune cells (EDIC) impacts the severity of radiation-induced lymphopenia and clinical outcomes of esophageal cancer patients treated with concurrent chemoradiotherapy (CCRT). MATERIAL AND METHODS 488 esophageal cancer patients treated with CCRT with and without surgery were analyzed. The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose (MLD), mean heart dose (MHD), mean liver dose (MlD), and integral dose (ITD) of the body region scanned, calculated as: EDIC=0.12∗MLD+0.08∗MHD+0.15∗0.85∗MlD∗n451/2+0.45+0.35∗0.85∗nk1/2∗ITD62∗103 Where n is the fraction number. Correlations of EDIC with overall survival (OS), progression free survival (PFS), distant metastasis free survival (DMFS), and locoregional control (LRC) rates were analyzed using both univariable and multivariable Cox models. Lymphopenia during CCRT was graded according to Common Terminology Criteria for Adverse Events version 4.0. RESULTS Grade 4 lymphopenia resulted in inferior clinical outcomes, including OS, PFS, and DMFS. The median EDIC was 3.6 Gy (range, 0.8-6.0 Gy). Higher EDIC was strongly associated with severe lymphopenia, particularly when EDIC was above 4 Gy. Patients with EDIC > 4.0 Gy had more G4 lymphopenia than those with EDIC ≤ 4.0 Gy (67.3% vs. 40.8%; P < 0.001). On multivariate analysis, increasing EDIC was independently and inversely associated with worse OS, PFS, and DMFS. CONCLUSION EDIC can be recommended as a useful tool to predict lymphopenia and inferior clinical outcomes, and it should be minimized below 4 Gy.

中文翻译：

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免疫细胞有效剂量对放化疗后食管癌淋巴细胞减少及存活率的影响

目的 检验循环免疫细胞的有效剂量 (EDIC) 会影响放射诱导的淋巴细胞减少的严重程度和接受同步放化疗 (CCRT) 治疗的食管癌患者的临床结果的假设。材料与方法 对 488 名接受 CCRT 手术和未手术治疗的食管癌患者进行了分析。EDIC模型以平均肺剂量（MLD）、平均心脏剂量（MHD）为基础，将循环免疫细胞的暴露量视为流向肺、心脏、肝脏的血流量与身体暴露区域体积的比例)，扫描的身体区域的平均肝脏剂量 (MlD) 和积分剂量 (ITD)，计算公式为： EDIC=0.12∗MLD+0.08∗MHD+0.15∗0.85∗MlD∗n451/2+0.45+0.35∗0.85∗ nk1/2∗ITD62∗103 其中 n 是分数。EDIC 与总生存期 (OS) 的相关性，使用单变量和多变量 Cox 模型分析无进展生存 (PFS)、无远处转移生存 (DMFS) 和局部区域控制 (LRC) 率。CCRT 期间的淋巴细胞减少症根据不良事件通用术语标准 4.0 版进行分级。结果 4 级淋巴细胞减少导致较差的临床结果，包括 OS、PFS 和 DMFS。中位 EDIC 为 3.6 Gy（范围，0.8-6.0 Gy）。较高的 EDIC 与严重的淋巴细胞减少密切相关，尤其是当 EDIC 高于 4 Gy 时。与 EDIC ≤ 4.0 Gy 的患者相比，EDIC > 4.0 Gy 患者的 G4 淋巴细胞减少症更多（67.3% 对 40.8%；P < 0.001）。在多变量分析中，增加 EDIC 与较差的 OS、PFS 和 DMFS 独立且呈负相关。