From:  Liquid biopsy for minimal residual disease and monitoring in early-stage non-small cell lung cancer: current clinical utility and implementation challenges

 Overview of clinical trials assessing ctDNA-based MRD detection for recurrence and treatment guidance in NSCLC

StudiesStudy designTrial registrationStageTreatment methodsDefinition of MRDMost informative landmark timepoint for recurrence/progression prediction
Chaudhuri 2017 [7]Prospective cohortNCT01385722, NCT00349830IB–III NSCLCSurgery ± CRTPresence of at least one tumor-specific SNV in plasmaFirst ctDNA sample collected within 4 months after treatment completion
Chen 2019 DYNAMIC [18]Prospective observationalNCT02965391I–IIIA NSCLCSurgery ± CRT/targeted therapycSMART-based detection of tumor-specific mutationsPostoperative day 3 (Time P2)
Isaksson 2019 [23]Retrospective observationalNAI–IIIA NSCLCSurgery ± CRTddPCR-detected mutations3-month postoperative MRD assessment
Ohara 2020 [26]Prospective observationalNAIIA–IIIA LCSurgery ± ICIPresence of at least one tumor-specific mutation detected by CAPP-SeqCtDNA + at Pre-operative or Post-operative timepoint
Kuang 2020 [24]Prospective observationalNCT03465241IB–III NSCLCSurgery ± chemoDetection of at least one shared somatic mutation in plasma and tumor tissue samples using NGSPost-chemotherapy ctDNA detection
Peng 2020 [28]Prospective observationalNAI–IV LCSurgery ± chemo/targeted therapyDetection of tumor-specific mutations in plasma using cSMART (circulating single-molecule amplification and resequencing technology)Postoperative ctDNA detection
Moding 2020 [20]Prospective observationalNCT00349830, MDACC LAB09-0983, NCT02525757IIB–III NSCLCCRT consolidation immune checkpoint inhibition (ICI)Presence of at least one tumor-specific mutation detected in plasma using CAPP-SeqPost-CRT and early during consolidation ICI
Qiu 2021 [16]Prospective observationalChiCTR19000–24656II–III NSCLCSurgery ± chemoNGS-based detection of tumor mutationsPostoperative and post-ACT ctDNA detection
Waldeck 2021 [29]Prospective observationalDRKS00009521IA-IIB NSCLCSurgery ± chemoDetection of at least one tumor-specific mutation in plasma using a tumor-informed NGS panel1–2 weeks postoperative ctDNA detection
Xia 2022 LUNGCA-1 [17]Multicenter prospectiveNCT03317080I–III NSCLCSurgery ± ADTDetection of tumor-specific mutations in ctDNA at postoperative day 3 and/or 1 month1 month postoperative ctDNA detection
Zhang 2022 [30]Prospective observationalNAI–IIIA NSCLCSurgery ± chemo/targeted therapyDetection of tumor-specific mutations in ctDNA using NGSLongitudinal ctDNA monitoring during postoperative follow-up
Li 2022 [25]Prospective observationalNCT03465241I–IIIA NSCLCSurgery ± chemoDetection of at least one tumor-specific mutation in plasma using a 425-gene NGS panelLongitudinal ctDNA monitoring during postoperative follow-up
Abbosh 2023 TRACERx [21]Prospective observationalNCT01888601IA–IIIB NSCLCSurgery chemotherapy/radiotherapyDetection of tumor-specific mutations in ctDNA using a tumor-informed approachPostoperative ctDNA detection within 120 days
Chen 2023 PROPHET [15]Prospective observationalNCT03634826I–III NSCLCSurgery ± ADTDetection of at least one tumor-specific mutation using the PROPHET algorithmLandmark: 1 month postoperation time point C. Longitudinal: ctDNA monitoring during postoperative follow-up
Gale 2022 LUCID [19]Prospective observationalNAI–II NSCLCSurgery ± chemoDetection of at least one tumor-specific mutation using RaDaR assayPostoperative ctDNA detection within 2 weeks to 4 months after treatment
Pan 2023 [27]Prospective observationalNCT04841811IIB–IIIC NSCLCChemoradiotherapy +/– ICI/TKIDetection of at least one tumor-specific mutation using ER-seq assayLandmark: after-RT time point, Longitudinal: ctDNA monitoring during and after treatment
Zhang 2023 [31]Retrospective observationalNAIA–IIIB NSCLCSurgery ± chemoDetection of at least one tumor-specific mutation using NGSctDNA detection at postoperative timepoints
Bossé 2024 MCED [22]ObservationalNAIA–IBSurgeryDetection of ctDNA via a plasma-only targeted methylation-based MCED testNA
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NA: information not available; CRT: chemoradiation therapy; NSCLC: non-small cell lung cancer; ctDNA: circulating tumour DNA; ICI: immune checkpoint inhibitor; NGS: next-generation sequencing; TKI: tyrosine kinase inhibitor