ctDNA-based detection of residual disease: implications for management of non-metastatic NSCLC
Abstract
Despite advancements in perioperative and consolidative immunotherapy in early-stage to locally advanced non-small cell lung cancer (NSCLC), recurrence rates remain substantial. In this context, liquid biopsy has transformed the oncological landscape by enabling the non-invasive detection of tumor-derived components, including DNA, cells, and proteins, from biological fluids. Although plasma-based circulating tumor DNA (ctDNA) analysis is routinely used in metastatic NSCLC to identify actionable genomic alterations at diagnosis and mechanisms of acquired resistance to targeted therapies, its application in non-metastatic disease represents a pivotal challenge. Leveraging minimal residual disease (MRD) detection through ctDNA offers the potential for early risk stratification, enabling the identification of patients who may benefit from treatment escalation, such as intensified adjuvant or consolidative regimens, while sparing low-risk patients from unnecessary toxicity through de-escalation strategies. This review summarizes the biological and technological foundations underlying ctDNA-based MRD detection, including tumor-informed and non-tumor-informed approaches, and examines the current evidence supporting its clinical utility in non-metastatic NSCLC. We also highlight key technical and clinical challenges and discuss future perspectives to optimize integration of ctDNA MRD assessment into routine clinical practice.
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BibTeX
@article{leclercq2026ctdnabased,
title = {{ctDNA-based detection of residual disease: implications for management of non-metastatic NSCLC}},
author = {Charline Leclercq and Mylène Wespiser and Gaëlle Tachon and Adrien Buisson and Maurice Pérol and Aurélie Swalduz},
journal = {Frontiers in Oncology},
year = {2026},
month = sep,
doi = {10.3389/fonc.2026.1951454},
url = {https://hal.science/hal-05750193v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - ctDNA-based detection of residual disease: implications for management of non-metastatic NSCLC
AU - Charline Leclercq
AU - Mylène Wespiser
AU - Gaëlle Tachon
AU - Adrien Buisson
AU - Maurice Pérol
AU - Aurélie Swalduz
PY - 2026
DA - 2026/09/04
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1951454
UR - https://hal.science/hal-05750193v1
AB - Despite advancements in perioperative and consolidative immunotherapy in early-stage to locally advanced non-small cell lung cancer (NSCLC), recurrence rates remain substantial. In this context, liquid biopsy has transformed the oncological landscape by enabling the non-invasive detection of tumor-derived components, including DNA, cells, and proteins, from biological fluids. Although plasma-based circulating tumor DNA (ctDNA) analysis is routinely used in metastatic NSCLC to identify actionable genomic alterations at diagnosis and mechanisms of acquired resistance to targeted therapies, its application in non-metastatic disease represents a pivotal challenge. Leveraging minimal residual disease (MRD) detection through ctDNA offers the potential for early risk stratification, enabling the identification of patients who may benefit from treatment escalation, such as intensified adjuvant or consolidative regimens, while sparing low-risk patients from unnecessary toxicity through de-escalation strategies. This review summarizes the biological and technological foundations underlying ctDNA-based MRD detection, including tumor-informed and non-tumor-informed approaches, and examines the current evidence supporting its clinical utility in non-metastatic NSCLC. We also highlight key technical and clinical challenges and discuss future perspectives to optimize integration of ctDNA MRD assessment into routine clinical practice.
SN - 2234-943X
ER -