Prognostic Value and Longitudinal Dynamics of Multigene Circulating Tumor DNA in Advanced Pancreatic Cancer Treated with 5-Fluorouracil-Based Chemotherapy.
8 affiliations
- 1Targeted Therapy Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
- 2Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
- 3Center for Liver and Pancreatobiliary Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
- 4Biostatistics Collaboration Team, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
- 5Department of Public Health & AI, National Cancer Center Graduate School of Cancer Science and Policy, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
- 6IMBdx, 38 Teheran-ro 113-gil, Gangnam-gu, Seoul 06173, Republic of Korea.
- 7Department of Laboratory Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
- 8Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
Abstract
Circulating tumor DNA (ctDNA) is a minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC), but the prognostic information added by multigene ctDNA metrics beyond KRAS and carbohydrate antigen 19-9 (CA19-9) is uncertain. In this prospective observational pilot study, 51 patients with advanced PDAC receiving 5-fluorouracil-based chemotherapy underwent 118-gene ctDNA profiling at baseline and 4 and 8 weeks after treatment initiation. ctDNA burden was summarized with variant allele frequency (VAF) metrics: Sum VAF and Top4 VAF (KRAS, TP53, CDKN2A, SMAD4). Twelve-month progression-free survival (PFS) areas under the curve were 0.816 for Top4 VAF, 0.812 for Sum VAF, 0.788 for KRAS VAF, and 0.687 for CA19-9; the Top4-KRAS difference was not statistically significant (95% confidence interval, -0.120 to 0.131). Baseline ctDNA detection and high Top4 VAF remained associated with shorter PFS and overall survival after adjustment for clinical covariates. Detectable Top4 VAF at 4 weeks was associated with shorter PFS (hazard ratio, 5.739; p < 0.001). Top4 VAF changes differed across radiologic response categories at 8 but not 4 weeks; CA19-9 showed no significant paired change. These exploratory findings suggest that baseline and early on-treatment multigene ctDNA carries prognostic information in advanced PDAC, although superiority over KRAS or CA19-9 was not established.
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BibTeX
@article{lee2026prognostic,
title = {{Prognostic Value and Longitudinal Dynamics of Multigene Circulating Tumor DNA in Advanced Pancreatic Cancer Treated with 5-Fluorouracil-Based Chemotherapy.}},
author = {Gi Yeon Lee and Jung Won Chun and Dong-Eun Lee and Jun-Ha Jang and Woo Jin Lee and Hwang-Phill Kim and Seung-Tae Lee and Sang Myung Woo and Sun-Young Kong},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198668},
url = {https://europepmc.org/article/MED/42883913},
note = {CC BY},
}
RIS
TY - JOUR
TI - Prognostic Value and Longitudinal Dynamics of Multigene Circulating Tumor DNA in Advanced Pancreatic Cancer Treated with 5-Fluorouracil-Based Chemotherapy.
AU - Gi Yeon Lee
AU - Jung Won Chun
AU - Dong-Eun Lee
AU - Jun-Ha Jang
AU - Woo Jin Lee
AU - Hwang-Phill Kim
AU - Seung-Tae Lee
AU - Sang Myung Woo
AU - Sun-Young Kong
PY - 2026
DA - 2026/09/28
JO - International journal of molecular sciences
DO - 10.3390/ijms27198668
UR - https://europepmc.org/article/MED/42883913
AB - Circulating tumor DNA (ctDNA) is a minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC), but the prognostic information added by multigene ctDNA metrics beyond KRAS and carbohydrate antigen 19-9 (CA19-9) is uncertain. In this prospective observational pilot study, 51 patients with advanced PDAC receiving 5-fluorouracil-based chemotherapy underwent 118-gene ctDNA profiling at baseline and 4 and 8 weeks after treatment initiation. ctDNA burden was summarized with variant allele frequency (VAF) metrics: Sum VAF and Top4 VAF (KRAS, TP53, CDKN2A, SMAD4). Twelve-month progression-free survival (PFS) areas under the curve were 0.816 for Top4 VAF, 0.812 for Sum VAF, 0.788 for KRAS VAF, and 0.687 for CA19-9; the Top4-KRAS difference was not statistically significant (95% confidence interval, -0.120 to 0.131). Baseline ctDNA detection and high Top4 VAF remained associated with shorter PFS and overall survival after adjustment for clinical covariates. Detectable Top4 VAF at 4 weeks was associated with shorter PFS (hazard ratio, 5.739; p < 0.001). Top4 VAF changes differed across radiologic response categories at 8 but not 4 weeks; CA19-9 showed no significant paired change. These exploratory findings suggest that baseline and early on-treatment multigene ctDNA carries prognostic information in advanced PDAC, although superiority over KRAS or CA19-9 was not established.
SN - 1422-0067
ER -