01

Tae Hee Hong1, Soohyun Hwang2, Abhijit Dasgupta3, Chris Abbosh4, Tiffany Hung5, Jörg Bredno5, Jill Walker6, Xiaojin Shi7, Tsveta Milenkova8, Leora Horn7, Joon Young Choi 9, Ho Yun Lee10, Jong Ho Cho11, Yong Soo Choi11, Young Mog Shim11, Shoujie Chai5, Kate Rhodes5, Manami Roychowdhury-Saha5, Darren Hodgson4, Hong Kwan Kim11, Myung-Ju Ahn12

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

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

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

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

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

6 GRAIL, LLC, Menlo Park, CA, USA

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

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

9 Global Medicine Development, AstraZeneca, Cambridge, UK

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

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

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

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.

[CITATION]: Hong TH, Hwang S, Dasgupta A, et al. Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC. J Thorac Oncol. 2024 Jul 9:S1556-0864(24)00666-X. 

[DOI]: 10.1016/j.jtho.2024.07.002.

[IF]:21.0

02

Norifumi Tsubokawa MD/PhD1; Takahiro Mimae MD/PhD1; Akira Saeki MD1; Yoshihiro Miyata MD/PhD1; Chiaki Kanno MD2; Yujin Kudo MD/PhD2; Takuya Nagashima MD/PhD3; Hiroyuki Ito MD/PhD3; Norihiko Ikeda MD/PhD2; Morihito Okada MD/PhD1

1 Department of Surgical Oncology, Hiroshima University.

2 Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan.

3 Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.

Objectives: 

This study aimed to determine the feasibility of segmentectomy in patients with central, whole tumor size ≤ 2 cm and radiologically solid-dominant cN0 non-small cell lung cancer (NSCLC).

Methods: 

We retrospectively reviewed 1240 patients who underwent lobectomy or segmentectomy for small and radiologically solid-dominant cN0 NSCLC between January 2010 and December 2022. The inclusion criteria encompassed centrally located tumors defined as tumors located in the inner two-thirds of the pulmonary parenchyma. Propensity score matching was applied to balance the baseline characteristics.

Results:

Among the 299 eligible patients, no significant differences in recurrence-free survival (RFS) and overall survival (OS) were observed between the segmentectomy (n= 121) and lobectomy (n = 178) groups (P = 0.794 and 0.577, respectively). After propensity score matching, no significant differences in hilar and mediastinal lymph node upstaging were found among the 93 matched patients (P = 1.00) and locoregional recurrence was comparable between those who underwent segmentectomy (n = 4) and lobectomy (n = 4). RFS and OS did not significantly differ between the two groups (P = 0.700 and 0.870, respectively). Propensity score-adjusted multivariable Cox analysis for RFS and OS indicated that segmentectomy was not an independent prognostic factor (RFS: hazard ratio, 0.89; 95% confidence interval, 0.43-1.85; P = 0.755; OS: hazard ratio, 1.09; 95% confidence interval, 0.38-3.14; P = 0.860).

Conclusions: 

Segmentectomy may be a viable treatment option with local control and prognosis comparable to that of lobectomy in appropriately selected patients with central, small (≤2 cm), and radiologically solid-dominant NSCLC.

[CITATION]: Tsubokawa N, Mimae T, Saeki A, et al. Feasibility and Comparative Prognosis of Segmentectomy vs. Lobectomy in Centrally Located Small and Solid Dominant cN0 Non-Small Cell Lung Cancer. J Thorac Cardiovasc Surg. 2024 Jul 3:S0022-5223(24)00538-5. 

[DOI]: 10.1016/j.jtcvs.2024.06.016

[IF]: 4.9