Impact of Tumor-Derived DNA Testing in Peritoneal Lavage of Pancreatic Cancer Patients with and Without Occult Intra-Abdominal Metastases

• Published in: Annals of surgical oncology Vol. 29; no. 4; pp. 2685 - 2697
• Main Authors: Chiba, Kazuharu, Hata, Tatsuo, Mizuma, Masamichi, Masuda, Kunihiro, Aoki, Shuichi, Takadate, Tatsuyuki, Kawaguchi, Kei, Nakagawa, Kei, Morikawa, Takanori, Motoi, Fuyuhiko, Furukawa, Toru, Unno, Michiaki
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2022; Springer Nature B.V
• Subjects: Ascites; Body fluids; Cytology; Deoxyribonucleic acid; DNA; Humans; Medicine; Medicine & Public Health; Metastases; Minimal residual disease; Multivariate analysis; Neoplasm Staging; Next-generation sequencing; Oncology; Pancreatic cancer; Pancreatic Neoplasms - surgery; Patients; Peritoneal Lavage; Peritoneum; Peritoneum - pathology; Prognosis; Surgery; Surgical Oncology; Translational Research; Tumor cells; Staging laparoscopy; Droplet digital PCR; Next-generation sequencing; Occult metastasis; Peritoneal lavage cytology; Pancreatic cancer
• ISSN: 1068-9265; 1534-4681; 1534-4681
• DOI: 10.1245/s10434-021-10997-w

Background The fractional abundance of tumor-derived DNA in body fluids depends on the metastatic sites and the degree of expansion. We aimed to assess the clinical significance of tumor-derived DNA testing in the peritoneal lavage of patients with pancreatic cancer. Methods The prevalence and abundance of tumor-derived DNA was assessed in 204 subjects with ascites by peritoneal lavage (AS) and the evaluable paired plasma (PL) from 149 pancreatic cancer patients undergoing abdominal exploration. Genetic profiles were evaluated by next-generation sequencing, and prognostic impact was assessed using Cox proportional hazard models. Results Of 204 subjects, AS samples from patients with peritoneal dissemination (PER+) and positive cytology (CY+) showed significantly higher prevalence and abundance of tumor-derived DNA than those with negative counterparts. Tumor-derived DNA prevalence and abundance in AS were more likely to be higher than in paired PL in a subgroup of patients with PER+ and CY+, respectively. Next-generation sequencing revealed concordant or discrepant mutational patterns between the AS and PL samples. Multivariate analysis showed that both tumor-derived DNA in AS (hazard ratio [HR] 3.940, p  = 0.009) and PL (HR 2.936, p  = 0.026) were independently associated with poor survival in treatment-naïve patients. In patients who underwent resection, tumor-derived DNA positivity in the AS was more predictive of early recurrence than in PL. Conclusions Tumor-derived DNA in AS can serve as characterizing the genetic profiles of tumor cells attributable to the development of PER+ and predicting the minimal residual disease and early recurrence in patients with pancreatic cancer.