Journal article
Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma
The oncologist (Dayton, Ohio), Vol.29(10), pp.859-869
10/03/2024
DOI: 10.1093/oncolo/oyae155
PMCID: PMC11449101
PMID: 39022993
Abstract
Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC).INTRODUCTIONPersonalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC).In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 299 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023.METHODSIn this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 299 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023.Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001).RESULTSOf the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001).Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.CONCLUSIONSPerioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.
Details
- Title: Subtitle
- Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma
- Creators
- Gregory P Botta - University of California San DiegoMaen Abdelrahim - Houston MethodistRonald L Drengler - South Texas Accelerated Research TherapeuticsVasily N Aushev - NateraAbdullah Esmail - Houston MethodistGeorge Laliotis - NateraChris M Brewer - NateraGiby V George - NateraSteven M Abbate - South Texas Accelerated Research TherapeuticsSreenivasa R Chandana - Hematology Oncology ConsultantsMohamedtaki A Tejani - Florida Hospital Cancer InstituteMidhun Malla - University of Alabama at BirminghamDhruv Bansal - Saint Luke's HospitalSamuel Rivero-Hinojosa - NateraErik Spickard - NateraNicole McCormick - NateraMichael Cecchini - Yale UniversityJill Lacy - Yale UniversityNaomi Fei - University of IowaPashtoon Murtaza Kasi - Cornell CollegeAnup Kasi - The University of Kansas Cancer CenterFarshid Dayyani - University of California, IrvineDiana L Hanna - USC Norris Comprehensive Cancer CenterShruti Sharma - NateraMeenakshi Malhotra - NateraAlexey Aleshin - NateraMinetta C Liu - NateraAdham Jurdi - Natera
- Resource Type
- Journal article
- Publication Details
- The oncologist (Dayton, Ohio), Vol.29(10), pp.859-869
- DOI
- 10.1093/oncolo/oyae155
- PMID
- 39022993
- PMCID
- PMC11449101
- NLM abbreviation
- Oncologist
- ISSN
- 1549-490X
- eISSN
- 1549-490X
- Language
- English
- Electronic publication date
- 07/17/2024
- Date published
- 10/03/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984658255302771
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