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  • Perspective
  • Published:

Practical recommendations for using ctDNA in clinical decision making

Abstract

The continuous improvement in cancer care over the past decade has led to a gradual decrease in cancer-related deaths. This is largely attributed to improved treatment and disease management strategies. Early detection of recurrence using blood-based biomarkers such as circulating tumour DNA (ctDNA) is being increasingly used in clinical practice. Emerging real-world data shows the utility of ctDNA in detecting molecular residual disease and in treatment-response monitoring, helping clinicians to optimize treatment and surveillance strategies. Many studies have indicated ctDNA to be a sensitive and specific biomarker for recurrence. However, most of these studies are largely observational or anecdotal in nature, and peer-reviewed data regarding the use of ctDNA are mainly indication-specific. Here we provide general recommendations on the clinical utility of ctDNA and how to interpret ctDNA analysis in different treatment settings, especially in patients with solid tumours. Specifically, we provide an understanding around the implications, strengths and limitations of this novel biomarker and how to best apply the results in clinical practice.

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Fig. 1: Interpretation of ctDNA results in the peri-operative setting and prognostic value of ctDNA status prior to surgery for predicting survival outcomes.
Fig. 2: ctDNA detection in different clinical scenarios.

Data availability

All data generated or analysed during this study are included in this Perspective. Informed consent was obtained as part of the ordering assay. This study was approved by the corresponding Ethical and Independent Review Services (protocol no. 20-049-ALL) and was conducted in accordance with the Declaration of Helsinki. Further enquiries can be directed to the corresponding author.

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Acknowledgements

Medical writing assistance was provided by Gord Fehringer, Allyson K. Malashevich and Meenakshi Malhotra.

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S.A.C. and A.A. conceived and designed the objectives of the manuscript. All authors contributed to drafting and critically revised the manuscript for intellectual content. All authors approved the final version of the submitted report and agree to be accountable for all aspects.

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Correspondence to Stacey A. Cohen.

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Competing interests

S.A.C.: Natera (travel; local principal investigator (PI), funding to the institution (inst)), Kallyope (consultant), Istari Oncology (consultant), Pfizer (consultant; local PI, inst), Taiho (consultant), Delcath (consultant), Bayer (consultant), Merck/EMD Serono (local PI, inst), Isofol (local PI, inst), Polaris (local PI, inst), Boston Biomedical/Sumitomo Dainippon Pharma (local PI, inst), Faeth (local PI, inst) and Tempus (local PI, inst). M.C.L.: Natera (Employment and stocks), Eisai (grants and contracts to Mayo), Exact Sciences (grants and contracts to Mayo), Genentech/Roche (grants and contracts to Mayo), GRAIL (grants and contracts to Mayo; advisory board with compensation to Mayo), Merck (grants and contracts to Mayo; advisory board with compensation to Mayo), Novartis (grants and contracts to Mayo), Seattle Genetics (grants and contracts to Mayo; advisory board with compensation to Mayo), Tesaro (grants and contracts to Mayo), AstraZeneca (travel; advisory board with compensation to Mayo), Genomic Health (travel; grants and contracts to Mayo; advisory board with compensation to Mayo), Ionis (travel; advisory board with compensation to Mayo), Celgene (advisory board with compensation to Mayo), Pfizer (advisory board with compensation to Mayo) and Syndax (Advisory board with compensation to Mayo). A.A.: Natera (employment and stocks).

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Cohen, S.A., Liu, M.C. & Aleshin, A. Practical recommendations for using ctDNA in clinical decision making. Nature 619, 259–268 (2023). https://doi.org/10.1038/s41586-023-06225-y

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