황수현 (성균관대학교 의과대학, 삼성서울병원) | 한빛사논문 > 한빛사

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성균관대학교 의과대학, 삼성서울병원

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J. Thorac. Oncol., Available online 9 July 2024 | https://doi.org/10.1016/j.jtho.2024.07.002 Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC

Tae Hee Hong ^1,2∗, Soohyun Hwang ^3∗, Abhijit Dasgupta ⁴, Chris Abbosh ^5†, Tiffany Hung ⁶, Jörg Bredno ⁶, Jill Walker ⁷, Xiaojin Shi ⁸, Tsveta Milenkova ⁹, Leora Horn ⁸, Joon Young Choi ¹⁰, Ho Yun Lee ¹¹, Jong Ho Cho ¹, Yong Soo Choi ¹, Young Mog Shim¹, Shoujie Chai⁶, Kate Rhodes⁶, Manami Roychowdhury-Saha⁶, Darren Hodgson ⁵, Hong Kwan Kim ¹, Myung-Ju Ahn¹²

¹Department of Thoracic Surgery, Samsung Medical Center, Seoul, Republic of Korea

²Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

³Department of Pathology and Translational Genomics, Samsung Medical Center, Seoul, Republic of Korea

⁴Early Data Science, Oncology Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA

⁵Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, UK

⁶GRAIL, LLC, Menlo Park, CA, USA

⁷Precision Medicine, Oncology R&D, AstraZeneca, Cambridge, UK

⁸Late Development Oncology, AstraZeneca, Gaithersburg, MD, USA

⁹Global Medicine Development, AstraZeneca, Cambridge, UK

¹⁰Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea

¹¹Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul, Republic of Korea

¹²Department of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea

∗Contributed equally

†Current affiliation: SAGA Diagnostics, Cambridge, UK

Corresponding author: Professor Myung-Ju Ahn

Abstract

Purpose

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).

Method

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.

Results

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.

Conclusion

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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-10)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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