TY - JOUR
T1 - Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma
AU - Botta, Gregory P.
AU - Abdelrahim, Maen
AU - Drengler, Ronald L.
AU - Aushev, Vasily N.
AU - Esmail, Abdullah
AU - Laliotis, George
AU - Brewer, Chris M.
AU - George, Giby V.
AU - Abbate, Steven M.
AU - Chandana, Sreenivasa R.
AU - Tejani, Mohamedtaki A.
AU - Malla, Midhun
AU - Bansal, Dhruv
AU - Rivero-Hinojosa, Samuel
AU - Spickard, Erik
AU - McCormick, Nicole
AU - Cecchini, Michael
AU - Lacy, Jill
AU - Fei, Naomi
AU - Kasi, Pashtoon Murtaza
AU - Kasi, Anup
AU - Dayyani, Farshid
AU - Hanna, Diana L.
AU - Sharma, Shruti
AU - Malhotra, Meenakshi
AU - Aleshin, Alexey
AU - Liu, Minetta C.
AU - Jurdi, Adham
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/10
Y1 - 2024/10
N2 - Introduction: 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). Methods: 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 298 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. Results: 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). Conclusions: Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.
AB - Introduction: 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). Methods: 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 298 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. Results: 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). Conclusions: Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.
KW - KRAS
KW - ctDNA
KW - molecular residual disease
KW - pancreatic adenocarcinoma
UR - https://www.scopus.com/pages/publications/85204460814
U2 - 10.1093/oncolo/oyae155
DO - 10.1093/oncolo/oyae155
M3 - Article
C2 - 39022993
AN - SCOPUS:85204460814
SN - 1083-7159
VL - 29
SP - 859
EP - 869
JO - Oncologist
JF - Oncologist
IS - 10
ER -