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- Title
Short-term serial circulating tumor DNA assessment predicts therapeutic efficacy for patients with advanced pancreatic cancer.
- Authors
Motobayashi, Hideki; Kitahata, Yuji; Okada, Ken-ichi; Miyazawa, Motoki; Ueno, Masaki; Hayami, Shinya; Miyamoto, Atsushi; Shimizu, Atsushi; Sato, Masatoshi; Yoshimura, Tomohiro; Nakamura, Yuki; Takemoto, Norio; Nakai, Tomoki; Hyo, Takahiko; Matsumoto, Kyohei; Yamaue, Hiroki; Kawai, Manabu
- Abstract
Purpose: We investigated the potential clinical utility of short-term serial KRAS-mutated circulating cell-free tumor DNA (ctDNA) assessment for predicting therapeutic response in patients undergoing first-line chemotherapy for advanced pancreatic cancer. Methods: We collected 144 blood samples from 18 patients with locally advanced or metastatic cancer that were undergoing initial first-line chemotherapy of gemcitabine plus nab-paclitaxel (GEM plus nab-PTX). Analysis of KRAS-mutated ctDNA was quantified by digital droplet polymerase chain reaction (ddPCR) as mutant allele frequency (MAF). This study investigated pretreatment KRAS-mutated ctDNA status and ctDNA kinetics every few days (days 1, 3, 5 and 7) after initiation of chemotherapy and their potential as predictive indicators. Results: Of the 18 enrolled patients, an increase in KRAS-mutated ctDNA MAF values from day 0–7 after initiation of chemotherapy was significantly associated with disease progression (P < 0.001). Meanwhile, positive pretreatment ctDNA status (MAF ≥ 0.02%) (P = 0.585) and carbohydrate antigen 19-9 (CA19-9) values above the median (P = 0.266) were not associated with disease progression. In univariate analysis, this short-term increase in ctDNA MAF values (day 0–7) was found to be associated with significantly shorter progression free survival (PFS) (hazard ration [HR], 24.234; range, (2.761–212.686); P = 0.0002). Conclusion: This short-term ctDNA kinetics assessment may provide predictive information to reflect real-time therapeutic response and lead to effective refinement of regimen in patients with advanced pancreatic cancer undergoing systemic chemotherapy.
- Subjects
CIRCULATING tumor DNA; CANCER patients; PANCREATIC tumors; TREATMENT effectiveness; PROGRESSION-free survival; CANCER chemotherapy; POLYMERASE chain reaction
- Publication
Journal of Cancer Research & Clinical Oncology, 2024, Vol 150, Issue 2, p1
- ISSN
0171-5216
- Publication type
Article
- DOI
10.1007/s00432-023-05594-1