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Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer

Chen, Kezhong; Yang, Fan; Shen, Haifeng; Wang, Chenyang; Li, Xi; Chervova, Olga; Wu, Shuailai; ... Wang, Jun; + view all (2023) Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer. Cancer Cell , 41 (10) 1749-1762.e6. 10.1016/j.ccell.2023.08.010. Green open access

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Abstract

We report a personalized tumor-informed technology, Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) using deep sequencing of 50 patient-specific variants to detect molecular residual disease (MRD) with a limit of detection of 0.004%. PROPHET and state-of-the-art fixed-panel assays were applied to 760 plasma samples from 181 prospectively enrolled early stage non-small cell lung cancer patients. PROPHET shows higher sensitivity of 45% at baseline with circulating tumor DNA (ctDNA). It outperforms fixed-panel assays in prognostic analysis and demonstrates a median lead-time of 299 days to radiologically confirmed recurrence. Personalized non-canonical variants account for 98.2% with prognostic effects similar to canonical variants. The proposed tumor-node-metastasis-blood (TNMB) classification surpasses TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET shows potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings highlight the potential advantages of personalized cancer techniques in MRD detection.

Type: Article
Title: Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ccell.2023.08.010
Publisher version: http://dx.doi.org/10.1016/j.ccell.2023.08.010
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Non-small cell lung cancer, Circulating tumor DNA, Minimal residual disease, Liquid biopsy, Surveillance, Tumor-informed, Non-canonical variant
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: https://discovery.ucl.ac.uk/id/eprint/10201098
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