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KMID : 0939920230550041313
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대한암학회지
2023 Volume.55 No. 4 p.1313 ~ p.1320
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Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection
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Lim Dong-Hoon
Yoon Hyun-Seok
Kim Kyu-Pyo
Ryoo Baek-Yeol
Lee Sang-Soo
Park Do-Hyun
Song Tae-Jun
Hwang Dae-Wook
Lee Jae-Hoon
Song Ki-Byung
Kim Song-Cheol
Hong Seung-Mo
Hyung Jae-Won
Yoo Chang-Hoon
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Abstract
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Purpose : There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods : Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results : Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, including ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion : Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of patients with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.
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KEYWORD
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Circulating-tumor DNA, Borderline resectable pancreatic cancer, Neoadjuvant, mFOLFIRINOX, DNA damage repair, Platinum sensitivity
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