Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer

• DOI: 10.1371/journal.pone.0227366
• Publication Date: 2019-12-31T13:31:26Z
• Authors: Fumiaki Watanabe; Koichi Suzuki; Sawako Tamaki; Iku Abe; Yuhei Endo; Yuji Takayama; Hideki Ishikawa; Nao Kakizawa; Masaaki Saito; Kazushige Futsuhara; Hiroshi Noda; Fumio Konishi; Toshiki Rikiyama
• Keywords: Male; 0301 basic medicine; Science; Q; R; Prognosis; Circulating Tumor DNA; 3. Good health; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras); 03 medical and health sciences; Treatment Outcome; Mutation; Biomarkers, Tumor; Medicine; Humans; Female; Longitudinal Studies; Neoplasm Recurrence, Local; Research Article; Aged; Carcinoma, Pancreatic Ductal

Background Liquid biopsies enable the detection of circulating tumor DNA (ctDNA). However, clinical significance KRAS-mutated ctDNA for pancreatic cancer has been inconsistent with respect to its prognostic and predictive potential. Methods findings A total 422 blood samples were collected from 78 patients undergoing treatments localized metastatic ductal adenocarcinoma. KRAS mutation in tissues levels plasma determined by RASKET droplet digital polymerase chain reaction. Longitudinal monitoring was performed assess predicting recurrence prognosis evaluating therapeutic responses chemotherapy compared carbohydrate antigen 19–9 (CA19-9). In 67 tissues, discrepancies point mutations rarely observed among individual patients, implying that one targeted can be prior longitudinal monitoring. One-time assessment before surgery or not clearly associated prognosis. Sequential 39 who underwent potentially resectable tumors. Increased CA19-9 significantly recurrence, but (P<0.001, P = 1.0, respectively), whereas emergence (P<0.001) regardless recurrence. Furthermore, did undergo surgery, a factor (P 0.005). Multivariate analysis revealed only independent resection (hazard ratios 54.5 10.1 surgery; P<0.001 both). Patients without within 1 year after showed better irrespective (P<0.001). No disappearance 6 months treatment correlated first-line Changes status provided critical information prediction responses. Conclusions Our study first time short period enables cancer.