From the Guidelines
Circulating tumor DNA (ctDNA) is a valuable tool for non-invasive cancer detection, monitoring, and management, allowing for early detection, treatment monitoring, and identification of specific mutations to guide targeted therapy selection. The use of ctDNA has been supported by recent studies, including a 2022 study published in Modern Pathology, which highlights the importance of ctDNA analysis in monitoring tumor biology in patients with cancer 1. Another study published in Annals of Oncology in 2022 also recommends the use of ctDNA testing to identify EGFR alterations and some resistance mechanisms in patients with non-small-cell lung cancer 1.
The benefits of ctDNA include:
- Early cancer detection, allowing physicians to identify malignancies before they become symptomatic or visible on imaging
- Treatment monitoring, as changes in ctDNA levels can indicate whether a therapy is working or if the cancer is developing resistance
- Recurrence monitoring, as ctDNA can detect cancer return months before conventional methods
- Tumor genotyping to identify specific mutations that may guide targeted therapy selection, such as EGFR mutations in lung cancer that respond to drugs like osimertinib or erlotinib
The technology works because dying tumor cells release DNA fragments with cancer-specific mutations into the bloodstream, which can be detected using highly sensitive next-generation sequencing techniques, providing real-time insights into cancer biology without requiring tissue biopsies. As stated in a 2022 study published in Annals of Oncology, ctDNA testing is of value and recommended, if no tissue is available, to identify the EGFR alterations and some resistance mechanisms, both in primary diagnostic and resistance setting 1.
It's worth noting that while ctDNA has many benefits, it's not without limitations. For example, a 2018 study published in the Journal of Thoracic Oncology notes that the sensitivity of ctDNA analysis is lower (60%–70%), such that the absence of mutation finding does not exclude the possibility of a mutation 1. However, the use of ctDNA remains a valuable tool in the management of cancer, and its benefits outweigh its limitations.
From the Research
Uses of Circulating Tumor DNA (ctDNA)
- ctDNA is used as a biomarker for lung cancer, allowing for early detection, monitoring, and therapy prediction 2
- It is used to detect EGFR mutations in non-small cell lung cancer (NSCLC) patients, which can inform treatment decisions 2, 3
- ctDNA analysis can be used to monitor response to therapy in metastatic disease, particularly in patients receiving targeted therapies or immunotherapy 2, 3
- It can be used to detect minimal residual disease (MRD) in patients with NSCLC after curative-intent treatment, which may serve as a prognostic and predictive biomarker for recurrence and response to therapy 4
- ctDNA has potential applications in early lung cancer detection, although its sensitivity and specificity for detecting early-stage tumors are still being researched 5
- It can be used as a prognostic indicator, with positive detection of ctDNA associated with worse overall survival (OS) rates 5
- ctDNA analysis can provide real-time genetic data, allowing for the monitoring of tumor development, therapeutic response, and tumor outcomes 6
Clinical Applications of ctDNA
- ctDNA testing can be used to guide clinical management of advanced NSCLC, including detecting clinically-actionable EGFR mutations and monitoring response to therapy 3, 4
- It can be used to investigate cancer, from bench to bedside, and has potential applications in precision medicine 6
- ctDNA analysis can be used to identify the fundamental processes that cause cancer, allowing for the development of novel therapies to target these genetic-driving processes 6
- Liquid biopsies, which depend on the identification of ctDNA, can provide rich reservoirs of crucial and real-time genetic data, allowing for non-invasive monitoring of cancer 6