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Updated: Jun 27, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted
Weijia Huang1,2, Kai Xu1,2, Zhenkun Liu1,2
1Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Background:
Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing.
Methods:
Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS.
Results:
A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS.
Conclusion:
ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Insights
Next-generation sequencing (NGS) using circulating tumor DNA (ctDNA) shows comparable results to tissue-based NGS for non-small cell lung cancer (NSCLC) mutations. This ctDNA approach is suitable for advanced or metastatic NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Molecular subtyping is crucial for targeted therapy in non-small cell lung cancer (NSCLC).
- Next-generation sequencing (NGS) is a key tool for molecular subtyping.
- Assessing concordance between circulating tumor DNA (ctDNA) and tissue-based NGS is vital for clinical application.
Purpose of the Study:
- To investigate the concordance of NGS results between ctDNA and tissue in NSCLC patients.
- To identify patient characteristics that predict high concordance for ctDNA testing.
- To evaluate ctDNA-based NGS as a complementary diagnostic tool.
Main Methods:
- Enrolled 85 NSCLC patients who underwent both ctDNA- and tissue-based NGS.
- Utilized a 425-cancer gene panel on a HiSeq 4000 NGS platform.
- Employed Cohen's kappa coefficient and machine learning models to assess concordance and identify predictors.
Main Results:
- 44 patients (51.8%) showed consistent gene mutation types between ctDNA and tissue NGS.
- Advanced disease stages (T stage, M stage) and tumor mutation burden were critical discriminators for concordance.
- ctDNA-based NGS is suitable for patients with advanced disease and distant metastases.
Conclusions:
- ctDNA-based NGS demonstrates comparable performance to tissue-based NGS for detecting target gene mutations in NSCLC.
- ctDNA-based NGS can be considered as a viable option for advanced or metastatic NSCLC.
- This approach offers a less invasive alternative for molecular profiling in specific patient populations.
