SCI

24 July 2024

Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC

(Journal of Thoracic Oncology, IF: 21.0)

  • Tae Hee Hong, Soohyun Hwang, Abhijit Dasgupta, Chris Abbosh, Tiffany Hung, Jörg Bredno, Jill Walker, Xiaojin Shi, Tsveta Milenkova, Leora Horn, Joon Young Choi, Ho Yun Lee, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Shoujie Chai, Kate Rhodes, Manami Roychowdhury-Saha, Darren Hodgson, Hong Kwan Kim, Myung-Ju Ahn

  • CORRESPONDENCE TO: silkahn@skku.edu

Purpose 目的

The use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC).

在手术前对早期肺癌患者进行肿瘤循环肿瘤DNA（ctDNA）检测受到限制，主要是因为组织获取受限和周转时间延长。本研究旨在评估肿瘤幼稚、基于甲基化的无细胞DNA检测在肺癌（NSCLC）手术患者中的临床价值。

 

Method 方法

We analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging.

我们分析了895名EGFR和ALK野生型、临床I期或II期NSCLC患者的术前血浆样本。评估ctDNA状态与肿瘤体积、代谢活性、组织学、组织学亚型和临床TNM分期至病理TNM分期升期的预后意义。

 

Results 结果

Pre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies.

414例临床I期肺腺癌（LUAD）患者中有55例（13%）在术前检测到ctDNA，且与较低的无复发生存率（RFS）相关（2年RFS 69%对91%；对数秩P<0.001），接近临床II期LUAD。对于临床II期LUAD或非LUAD患者，术前ctDNA检测无法预测预患者后。在LUAD中，肿瘤体积和正电子发射断层扫描结果可预测术前ctDNA检测。此外，术前ctDNA检测可预测术后发现IASLC G3肿瘤（P<0.001）和病理TNM分期升期（P<0.001）。值得注意的是，术前ctDNA检测与肿瘤中较高的PD-L1表达密切相关（阳性率28%对55%，P<0.001），因而确定了一个可能受益于抗PD-（L）-1疗法的亚组。

 

Conclusion 结论

These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

这些发现俊支持将ctDNA检测整合到早期NSCLC的常规诊断工作中，而无需肿瘤组织分析。此外，它在临床上可用于识别可能受益于创新治疗的高危患者，包括新辅助免疫检查点抑制剂。