Prognostic impact of postoperative circulating tumor <scp>DNA</scp> as a molecular minimal residual disease marker in patients with pancreatic cancer undergoing surgical resection
Tatsuo Hata, Masamichi Mizuma, Fuyuhiko Motoi, Hideo Ohtsuka, Kei Nakagawa, Takanori Morikawa, Michiaki Unno
Abstract
PURPOSE: We aimed to clarify the prognostic impact of postoperative circulating tumor DNA (ctDNA) shortly after pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Preoperative and paired postoperative blood samples were obtained from 66 patients in patients with PDAC. Cell-free DNA was extracted from the plasma, and KRAS mutations, as a benchmark of ctDNA, were examined using droplet digital PCR. Disease-free survival (DFS) and overall survival (OS) were compared between patients with presence and absence of ctDNA. RESULTS: In univariate analysis, patients with detectable postoperative ctDNA showed worse survival than those with undetectable in both DFS (P = .034) and OS (P = .022). Multivariate analysis also revealed that the presence of postoperative ctDNA was an independent risk factor for recurrence (hazard ratio: 2.677, P = .011). In contrast, preoperative ctDNA detection did not affect long-term outcomes. These trends persisted in 34 patients with resectable PDAC who underwent resection after neoadjuvant chemotherapy. Patients with detectable postoperative ctDNA were more prone to developing hepatic recurrence than those with undetectable postoperative ctDNA (P = .039). CONCLUSION: Postoperative ctDNA, as a minimal residual marker, can be useful for predicting the risk of recurrence in patients with PDAC even after curative resection.