Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea.
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Int J Radiat Oncol Biol Phys. 2019 Dec 1;105(5):1065-1073. doi: 10.1016/j.ijrobp.2019.08.047. Epub 2019 Aug 30.
The interest in combining radiation therapy (RT) with immunotherapy is increasing. We investigated the significance of lymphopenia in patients receiving immunotherapy for non-small cell lung cancer (NSCLC), and the factors associated with treatment-related lymphopenia, with particular emphasis on RT.
In this retrospective single institution study, 268 patients with advanced NSCLC received immunotherapy, of whom 146 received RT. Lymphopenia was defined as an absolute lymphocyte count <1000 cells/mm. Patients were divided into 2 groups depending on the presence of peri-immunotherapy lymphopenia at the start of immunotherapy or during immunotherapy.
At median 6.4 months of follow-up, patients with peri-immunotherapy lymphopenia (n = 146; 54.5%) showed significantly poorer progression-free survival (PFS) (median PFS: 2.2 vs 5.9 months, P < .001) and overall survival (OS) (median OS: 5.7 vs 12.1 months, P < .001). On multivariate analysis, peri-immunotherapy lymphopenia remained a significant prognostic factor for both PFS and OS. RT significantly increased peri-immunotherapy lymphopenia with an odds ratio (OR) of 1.91 (P = .025). Factors associated with the development of RT-associated lymphopenia included multiple courses (OR, 3.78; P < .001), multiple irradiated sites (OR, 4.77; P = .018), and higher dose (≥50 Gy) (OR, 3.75; P = .004). Conversely, stereotactic body RT/radiosurgery reduced the risk (OR 0.21; P = .002).
Lymphopenia was indicative of poor prognosis in NSCLC patients receiving immunotherapy and was significantly associated with more intensive RT. Choosing appropriate RT regimens and techniques may be essential in reducing lymphopenia. Promising results are expected in the era of precision RT.
联合放疗（RT）和免疫疗法的兴趣正在增加。我们研究了接受免疫治疗的非小细胞肺癌（NSCLC）患者淋巴细胞减少的意义，以及与治疗相关的淋巴细胞减少相关的因素，特别强调了 RT。
在这项回顾性单机构研究中，268 名晚期 NSCLC 患者接受了免疫治疗，其中 146 名接受了 RT。淋巴细胞减少定义为绝对淋巴细胞计数<1000 个细胞/mm。根据免疫治疗开始时或免疫治疗期间是否存在治疗相关的淋巴细胞减少，将患者分为 2 组。
中位随访 6.4 个月时，有治疗相关淋巴细胞减少的患者（n=146；54.5%）的无进展生存期（PFS）（中位 PFS：2.2 与 5.9 个月，P<0.001）和总生存期（OS）（中位 OS：5.7 与 12.1 个月，P<0.001）明显较差。多变量分析显示，治疗相关淋巴细胞减少仍然是 PFS 和 OS 的显著预后因素。RT 显著增加了治疗相关淋巴细胞减少，优势比（OR）为 1.91（P=0.025）。与 RT 相关的淋巴细胞减少发展相关的因素包括多疗程（OR，3.78；P<0.001）、多个照射部位（OR，4.77；P=0.018）和更高剂量（≥50 Gy）（OR，3.75；P=0.004）。相反，立体定向体部 RT/放射外科降低了风险（OR 0.21；P=0.002）。
淋巴细胞减少是 NSCLC 患者接受免疫治疗预后不良的指标，与更密集的 RT 显著相关。选择适当的 RT 方案和技术可能对于减少淋巴细胞减少至关重要。在精准 RT 时代，有望取得令人鼓舞的结果。
