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When can we be confident of surgical cure with ctDNA?

Tracking circulating tumour DNA (ctDNA) after surgery holds promise for patient management and therapeutic intervention in non-small-cell lung cancer (NSCLC). A study published by Zhang and colleagues tracks ctDNA from 261 patients with stages I–III NSCLC and suggests that the likelihood of disease relapse decreases for high-risk stage II/III patients after 18 months without ctDNA detection.

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  1. Wan, J. C. M. et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat. Rev. Cancer 17, 223–238 (2017).

    Article  CAS  Google Scholar 

  2. Sun, K., Jiang, P., Chan, K. C. A. & Lo, Y. M. D. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments. Proc. Natl Acad. Sci. USA 112, E5503–E5512 (2015).

    Article  CAS  Google Scholar 

  3. Moding, E. J., Nabet, B. Y., Alizadeh, A. A. & Diehn, M. Detecting liquid remnants of solid tumors: circulating tumor DNA minimal residual disease. Cancer Discov. 11, 2968–2986 (2021).

    Article  CAS  Google Scholar 

  4. Abbosh, C., Birkbak, N. J. & Swanton, C. Early stage NSCLC — challenges to implementing ctDNA-based screening and MRD detection. Nat. Rev. Clin. Oncol. 15, 577–586 (2018).

    Article  CAS  Google Scholar 

  5. Zhang, J.-T. et al. Longitudinal undetectable molecular residual disease defines potentially cured population in localized non-small cell lung cancer. Cancer Discov. (2022).

    Article  PubMed  Google Scholar 

  6. De Mattos-Arruda, L. et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat. Commun. 6, 8839 (2015).

    Article  Google Scholar 

  7. Wakelee, H. A. et al. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 18, 1610–1623 (2017).

    Article  CAS  Google Scholar 

  8. Kurtz, D. M. et al. Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nat. Biotechnol. 39, 1537–1547 (2021).

    Article  CAS  Google Scholar 

  9. Wan, J. C. M. et al. ctDNA monitoring using patient-specific sequencing and integration of variant reads. Sci. Transl. Med. 12, eaaz8084 (2020).

    Article  CAS  Google Scholar 

  10. Powles, T. et al. ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature 595, 432–437 (2021).

    Article  CAS  Google Scholar 

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M.J.-H. is a CRUK Career Establishment Awardee and has received funding from CRUK, IASLC International Lung Cancer Foundation, Lung Cancer Research Foundation, Rosetrees Trust, UKI NETs, NIHR and the NIHR UCLH Biomedical Research Centre.

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Correspondence to Alexander Frankell or Mariam Jamal-Hanjani.

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Competing interests

A.M.F. is a co-inventor on a patent application to determine methods and systems for tumour monitoring (GB2114434.0). M.J.-H. has consulted for, and is a member of the Scientific Advisory Board and Steering Committee of, Achilles Therapeutics, has received speaker honoraria from Astex Pharmaceuticals and the Oslo Cancer Cluster, and holds a patent, as co-inventor, (PCT/US2017/028013) relating to methods for lung cancer detection.

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Frankell, A., Jamal-Hanjani, M. When can we be confident of surgical cure with ctDNA?. Nat Rev Clin Oncol 19, 571–572 (2022).

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