白细胞去除术增加非小细胞肺癌的循环肿瘤细胞产量，与肿瘤反应和生存相关的计数。
Leukapheresis increases circulating tumour cell yield in non-small cell lung cancer, counts related to tumour response and survival.
机构信息
Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Medical Cell BioPhysics, Faculty of Sciences and Technology, University of Twente, Enschede, The Netherlands.
出版信息
Br J Cancer. 2022 Feb;126(3):409-418. doi: 10.1038/s41416-021-01634-0. Epub 2021 Nov 30.
BACKGROUND
Circulating tumour cells (CTCs) can be used to monitor cancer longitudinally, but their use in non-small cell lung cancer (NSCLC) is limited due to low numbers in the peripheral blood. Through diagnostic leukapheresis (DLA) CTCs can be obtained from larger blood volumes.
METHODS
Patients with all stages of NSCLC were selected. One total body blood volume was screened by DLA before and after treatment. Peripheral blood was drawn pre- and post DLA for CTC enumeration by CellSearch. CTCs were detected in the DLA product (volume equalling 2 × 10 leucocytes) and after leucocyte depletion (RosetteSep, 9 mL DLA product). Single-cell, whole-genome sequencing was performed on isolated CTCs.
RESULTS
Fifty-six patients were included. Before treatment, CTCs were more often detected in DLA (32/55, 58%) than in the peripheral blood (pre-DLA: 18/55, 33%; post DLA: 13/55, 23%, both at p < 0.01). CTCs per 7.5 mL DLA product were median 9.2 times (interquartile range = 5.6-24.0) higher than CTCs in 7.5 mL blood. RosetteSEP did not significantly improve CTC detection (pretreatment: 34/55, 62%, post treatment: 16/34, 47%) and CTCs per mL even decreased compared to DLA (p = 0.04).. Patients with advanced-stage disease with DLA-CTC after treatment showed fewer tumour responses and shorter progression-free survival (PFS) than those without DLA-CTC (median PFS, 2.0 vs 12.0 months, p < 0.01). DLA-CTC persistence after treatment was independent of clinical factors associated with shorter PFS (hazard ratio (HR) = 5.8, 95% confidence interval (CI), 1.4-35.5, p = 0.02). All evaluable CTCs showed aneuploidy.
CONCLUSIONS
DLA detected nine times more CTCs than in the peripheral blood. The sustained presence of CTCs in DLA after treatment was associated with therapy failure and shortened PFS.
TRIAL REGISTRATION
The study was approved by the Medical Ethical Committee (NL55754.042.15) and was registered in the Dutch trial register (NL5423).
背景
循环肿瘤细胞（CTC）可用于纵向监测癌症，但由于外周血中数量较少，其在非小细胞肺癌（NSCLC）中的应用受到限制。通过诊断性白细胞分离术（DLA），可以从更大的血液量中获得 CTC。
方法
选择所有阶段的 NSCLC 患者。在治疗前后，通过 DLA 筛选一个全身血容量。在 DLA 前和 DLA 后抽取外周血，通过 CellSearch 对 CTC 进行计数。在 DLA 产物（等于 2×10 个白细胞的体积）和白细胞耗竭后（RosetteSep，9mL DLA 产物）检测 CTC。对分离的 CTC 进行单细胞、全基因组测序。
结果
共纳入 56 例患者。治疗前，DLA 中 CTC 的检出率（32/55，58%）高于外周血（DLA 前：18/55，33%；DLA 后：13/55，23%，均 p<0.01）。DLA 产物中每 7.5ml 的 CTC 中位数是 7.5ml 血液中 CTC 的 9.2 倍（四分位距=5.6-24.0）。RosetteSEP 并不能显著提高 CTC 的检出率（治疗前：34/55，62%，治疗后：16/34，47%），而且每毫升 CTC 甚至低于 DLA（p=0.04）。治疗后有 DLA-CTC 的晚期疾病患者的肿瘤反应和无进展生存期（PFS）均较无 DLA-CTC 的患者差（中位 PFS，2.0 个月 vs 12.0 个月，p<0.01）。治疗后 DLA-CTC 的持续存在与与 PFS 缩短相关的临床因素无关（风险比（HR）=5.8，95%置信区间（CI），1.4-35.5，p=0.02）。所有可评估的 CTC 均显示非整倍性。
结论
DLA 检测到的 CTC 是外周血的 9 倍。治疗后 DLA 中 CTC 的持续存在与治疗失败和 PFS 缩短有关。
试验注册
该研究获得医学伦理委员会（NL55754.042.15）的批准，并在荷兰试验注册处（NL5423）注册。
Zotero 插件