Department of Internal Medicine, Inha University Hospital, Incheon 22332, Korea.
Department of Medical Sciences, Catholic Kwandong University College of Medicine, Incheon 22711, Korea.
Int J Mol Sci. 2022 Aug 23;23(17):9527. doi: 10.3390/ijms23179527.
Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor and mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT ( = 0.039) and worse OS ( = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.
循环肿瘤 DNA（ctDNA）已被用于监测接受针对可用药突变的治疗的非小细胞肺癌（NSCLC）患者的临床病程。然而，尽管 ctDNA 提供了关于 NSCLC 如何自然进展的有价值的信息，但 ctDNA 用于无可用药突变的治疗初治 NSCLC 患者的临床病程监测和预测的临床实用性仍然未知。我们通过收集临床信息、影像学数据和血浆样本，对总共 12 名未携带 和 突变的治疗初治 NSCLC 患者进行了纵向随访。比较了 ctDNA 水平和肿瘤负担（TB）的变化。分析了 ctDNA 检测在诊断时对新发转移、体积倍增时间（VDT）和总生存期（OS）的影响。在 7 名患者（58.3%）的血浆中检测到了 ctDNA。在相当一部分患者（57.1%）中，ctDNA 水平的变化与 TB 的变化相关，并且在其他患者中还与脑转移、肿瘤坏死或肺炎相关。所有在诊断时没有转移的器官中发生新转移的患者均检测到 ctDNA。未检测到 ctDNA 的患者未发生新转移（中位随访时间：9.8 个月）。此外，与未检测到 ctDNA 的患者相比，检测到 ctDNA 的患者 VDT 更短（ = 0.039），OS 更差（ = 0.019）。通过测量 ctDNA 水平可以监测 NSCLC 进展的自然病程。在诊断时检测到 ctDNA 可以预测 NSCLC 患者新发转移、肿瘤快速生长和预后不良的发生。
