Jin Jian-Yue, Hu Chen, Xiao Ying, Zhang Hong, Paulus Rebecca, Ellsworth Susannah G, Schild Steven E, Bogart Jeffrey A, Dobelbower Michael Chris, Kavadi Vivek S, Narayan Samir, Iyengar Puneeth, Robinson Cliff, Greenberger Joel S, Koprowski Christopher, Machtay Mitchell, Curran Walter, Choy Hak, Bradley Jeffrey D, Kong Feng-Ming Spring
Department of Radiation Oncology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
NRG Oncology Statistics and Data Management Center, Philadelphia, PA 19103, USA.
Cancers (Basel). 2021 Dec 8;13(24):6193. doi: 10.3390/cancers13246193.
: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). : This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC-survival relationship was analyzed with consideration of clinical significant factors. : A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1-12.2 Gy) and 6.3 Gy (2.1-11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, = 0.005) and LPFS (HR = 1.09, = 0.02) but PFS (HR = 1.05, = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6-8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. : The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.
我们假设循环血液中免疫细胞的有效辐射剂量（EDIC）是局部晚期非小细胞肺癌（NSCLC）患者治疗结果的一个重要因素。这是一项对III期试验NRG/RTOG 0617的二次研究，该试验针对接受放射治疗的III期NSCLC患者。EDIC是根据所有含血器官的辐射剂量，并考虑血流和分次照射效应，计算得出的全血等效均匀剂量。主要终点是总生存期（OS），次要终点是无进展生存期（PFS）和局部无进展生存期（LPFS）。在考虑临床显著因素的情况下分析EDIC与生存期的关系。共有456名患者符合条件。低剂量组和高剂量组的EDIC中位数分别为5.6 Gy（范围2.1 - 12.2 Gy）和6.3 Gy（2.1 - 11.6 Gy）。在调整肿瘤剂量、大体肿瘤体积和其他因素后，EDIC与OS（风险比[HR] = 1.12，P = 0.005）和LPFS（HR = 1.09，P = 0.02）显著相关，但与PFS（HR = 1.05，P = 0.17）无关。OS随着EDIC的增加呈非线性下降：当EDIC < 6 Gy时，两年OS首先以8%/Gy的斜率下降，当EDIC为6 - 8 Gy时相对保持不变，当EDIC > 8 Gy时随后以12%/Gy的斜率进一步下降。EDIC是RTOG 0617中III期NSCLC患者OS和LPFS不良的一个重要独立危险因素，表明对循环免疫细胞的辐射剂量对肿瘤控制至关重要。在放疗计划制定过程中应考虑免疫系统的危险器官。
