2025
Identifying the optimal post-surgical timing of molecular residual disease (MRD) detection in colorectal cancer (CRC) using an ultra-sensitive assay: Interim results from the VICTORI study.
Solar Vasconcelos J, Titmuss E, Navarro F, Abbott C, Chia B, Topham J, Ladua G, Krishnan T, Hegebarth D, Lim H, Gill K, Gill S, Brown C, Ghuman A, Meneghetti A, Renouf D, Schaeffer D, Chen R, Boyle S, Loree J. Identifying the optimal post-surgical timing of molecular residual disease (MRD) detection in colorectal cancer (CRC) using an ultra-sensitive assay: Interim results from the VICTORI study. Journal Of Clinical Oncology 2025, 43: 275-275. DOI: 10.1200/jco.2025.43.4_suppl.275.Peer-Reviewed Original ResearchMolecular residual diseaseColorectal cancerCtDNA detectionDetection of molecular residual diseaseWeek 8Week 4Resectable colorectal cancerYear of surgeryTime of surgerySingle nucleotide variantsYear follow-upPost-surgical timesNeoadjuvant therapyResidual diseaseCurative intentMRD assaysResidual cancerClinical relapseDisease recurrenceCtDNA concentrationRecurrent cancerClinical outcomesCfDNA concentrationFollow-upRecurrence
2024
Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction
Li X, Liu T, Bacchiocchi A, Li M, Cheng W, Wittkop T, Mendez F, Wang Y, Tang P, Yao Q, Bosenberg M, Sznol M, Yan Q, Faham M, Weng L, Halaban R, Jin H, Hu Z. Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction. EMBO Molecular Medicine 2024, 16: 2188-2209. PMID: 39164471, PMCID: PMC11393307, DOI: 10.1038/s44321-024-00115-0.Peer-Reviewed Original ResearchMolecular residual diseaseCirculating tumor DNAWhole-genome sequencingCell-free DNAGenome sequenceDetection of molecular residual diseaseCirculating tumor DNA detectionResidual disease detectionConsistent with clinical outcomesVariant allele frequencyResidual diseaseMelanoma patientsMonitoring immunotherapyTumor DNAEsophageal cancerClinical outcomesColorectal cancerWGS technologiesAllele frequenciesCancerDNAAnalytical sensitivitySequenceImmunotherapyRelapseAssociation of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma
Botta G, Abdelrahim M, Drengler R, Aushev V, Esmail A, Laliotis G, Brewer C, George G, Abbate S, Chandana S, Tejani M, Malla M, Bansal D, Rivero-Hinojosa S, Spickard E, McCormick N, Cecchini M, Lacy J, Fei N, Kasi P, Kasi A, Dayyani F, Hanna D, Sharma S, Malhotra M, Aleshin A, Liu M, Jurdi A. Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma. The Oncologist 2024, 29: 859-869. PMID: 39022993, PMCID: PMC11449101, DOI: 10.1093/oncolo/oyae155.Peer-Reviewed Original ResearchMolecular residual diseasePancreatic ductal adenocarcinomaPatient survival outcomesCtDNA detectionSurvival outcomesStage I–III pancreatic ductal adenocarcinomaAssociated with shorter DFSMedian follow-up timeFollow-up timeCtDNA levelsResidual diseaseShorter DFSPrognostic factorsPancreatic adenocarcinomaAssociated with patient survival outcomesDuctal adenocarcinomaRetrospective analysisDiagnosed patientsMultivariate analysisSurveillance periodPatientsPlasma samplesTumor informationWhole exomeSurveillance windowCirculating tumor DNA (ctDNA) kinetics in colorectal cancer (CRC) treated with curative intent in the VICTORI study with an ultrasensitive MRD assay.
Solar Vasconcelos J, Titmuss E, Navarro F, Abbott C, Chia B, Topham J, Ladua G, Krishnan T, Hegebarth D, Lim H, Gill K, Gill S, Brown C, Ghuman A, Meneghetti A, Renouf D, Schaeffer D, Chen R, Boyle S, Loree J. Circulating tumor DNA (ctDNA) kinetics in colorectal cancer (CRC) treated with curative intent in the VICTORI study with an ultrasensitive MRD assay. Journal Of Clinical Oncology 2024, 42: e15625-e15625. DOI: 10.1200/jco.2024.42.16_suppl.e15625.Peer-Reviewed Original ResearchMolecular residual diseaseCirculating tumor DNARecurrence-free survivalColorectal cancerMRD assaysDetection of molecular residual diseaseLevels of circulating tumor DNAPoor recurrence-free survivalTreated with curative intentDetect circulating tumor DNAProspective cohort of patientsCurative interventionsCurative-intent treatmentCohort of patientsSingle nucleotide variantsStage I-IIISeparation of patientsMRD- patientsMRD testingNeoadjuvant treatmentResidual diseaseClinical recurrenceCurative intentRectal cancerTumor DNAPrognostic and predictive value of ultrasensitive ctDNA monitoring in a metastatic pan-cancer cohort treated with immune checkpoint inhibitors in the context of phase 1 clinical trials.
Toledo R, Calahorro García A, Mirallas O, Moreno A, Galvao V, Alonso G, Vieito M, Brana I, Oberoi A, Lostes-Bardaji M, Jimenez J, Sanz M, Viaplana C, Perez-Lopez R, Nuciforo P, Abbott C, Pugh J, Chen R, Boyle S, Garralda E. Prognostic and predictive value of ultrasensitive ctDNA monitoring in a metastatic pan-cancer cohort treated with immune checkpoint inhibitors in the context of phase 1 clinical trials. Journal Of Clinical Oncology 2024, 42: 2510-2510. DOI: 10.1200/jco.2024.42.16_suppl.2510.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsPhase 1 clinical trialMolecular residual diseaseCheckpoint inhibitorsCtDNA levelsICI responseDetection of molecular residual diseaseDynamics of circulating tumor DNATreated with immune checkpoint inhibitorsDuration of PFSRefractory metastatic tumorsImmune checkpoint inhibitionAccurate patient managementLiquid biopsy testingTreatment cycle 3Levels of ctDNAStage IV cancer patientsLiquid biopsy platformPan-cancer cohortAssociated with significant increasesSequencing of tumorsWhole-genome sequencing of tumoursCtDNA clearanceCtDNA dynamicsCtDNA monitoringUltra-sensitive ctDNA dynamics to capture therapy response in pembrolizumab-treated gastroesophageal cancer.
Nixon A, Navarro F, Zhou K, Abbott C, Howard L, Brady J, Liu Y, Jia J, Niedzwiecki D, Chen R, Strickler J, Boyle S, Uronis H. Ultra-sensitive ctDNA dynamics to capture therapy response in pembrolizumab-treated gastroesophageal cancer. Journal Of Clinical Oncology 2024, 42: 4025-4025. DOI: 10.1200/jco.2024.42.16_suppl.4025.Peer-Reviewed Original ResearchMetastatic esophagogastric cancerMolecular residual diseaseImmune checkpoint blockadeProgression-free survivalCtDNA dynamicsCtDNA levelsHigher hazard ratioOverall survivalDetection of molecular residual diseasePhase II study of pembrolizumabSingle-arm phase II studyWhole-genome sequencingSingle nucleotide variantsMolecular progressionResponse rateStudy of pembrolizumabBaseline prior to treatmentUnivariate Cox regression analysisCox regression analysisFFPE tumor samplesOverall response rateMedian lead timeImprove treatment decision-makingLong-term survivalLiquid biopsy platformMolecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).
John T, Grohe C, Goldman J, Kato T, Laktionov K, Bonanno L, Tiseo M, Majem M, Domine M, Ahn M, Perol M, Hartmaier R, Robichaux J, Bhetariya P, Markovets A, Rukazenkov Y, Muldoon C, Herbst R, Tsuboi M, Wu Y. Molecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2024, 42: 8005-8005. DOI: 10.1200/jco.2024.42.16_suppl.8005.Peer-Reviewed Original ResearchDisease-free survivalMolecular residual diseaseNon-small cell lung cancerDisease-free survival eventsDisease recurrenceEGFR-mutantOverall survivalStage IB-IIIA non-small cell lung cancerEGFR T790M resistance mutationT790M resistance mutationMedian follow-up timeEGFR-TKI sensitivityResected tumor tissueCell lung cancerTumor-specific variantsMedian lead timeWhole-exome sequencingDetection of ctDNAADAURA studyADAURA trialInvestigator-assessedMolecular recurrenceEGFR-TKIsResidual diseaseEligible ptsUltra-sensitive ctDNA mutation tracking to identify molecular residual disease and predict relapse in patients with early breast cancer.
Garcia-Murillas I, Cutts R, Abbott C, Boyle S, Pugh J, Chen R, Dunne K, Bunce C, Johnston S, Ring A, Russell S, Evans A, Skene A, Wheatley D, Smith I, Turner N. Ultra-sensitive ctDNA mutation tracking to identify molecular residual disease and predict relapse in patients with early breast cancer. Journal Of Clinical Oncology 2024, 42: 1010-1010. DOI: 10.1200/jco.2024.42.16_suppl.1010.Peer-Reviewed Original ResearchMolecular residual diseaseCirculating tumor DNAEarly breast cancerBreast cancer patientsFollow-upNeoadjuvant chemotherapyResidual diseaseClinical relapseCtDNA detectionClinical outcomesBreast cancerAssociated with relapse free survivalDetection of molecular residual diseaseCancer patientsCirculating tumor DNA levelsLevels of circulating tumor DNAHigh risk of relapseHigh riskCirculating tumor DNA detectionMedian lead-timeRelapse free survivalDe-escalation studiesBreast cancer relapseShortened overall survivalBaseline prior to treatment
2022
Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors
Kasi PM, Fehringer G, Taniguchi H, Starling N, Nakamura Y, Kotani D, Powles T, Li BT, Pusztai L, Aushev VN, Kalashnikova E, Sharma S, Malhotra M, Demko ZP, Aleshin A, Rodriguez A, Billings PR, Grothey A, Taieb J, Cunningham D, Yoshino T, Kopetz S. Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors. JCO Precision Oncology 2022, 6: e2100181. PMID: 35263168, PMCID: PMC8926064, DOI: 10.1200/po.21.00181.Peer-Reviewed Original ResearchConceptsMolecular residual diseaseSurrogate end pointsCtDNA testingMRD detectionResidual diseaseClinical trialsCancer recurrenceTumor DNAEnd pointMRD-positive patientsUse of ctDNAHigh-risk categoryCtDNA dynamicsTrial enrichmentAccelerated approvalDifferent cancer typesCancer managementClinical utilityHigh riskClinical practiceSmall cohortSolid tumorsRecurrenceTrial durationTreatment assignment
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