With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5‐year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5‐year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.

Mutations in PI3K/AKT pathway genes and amplifications of PIK3CA are associated with patterns of recurrence in gastric cancers

Background: To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). Methods: Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). Results: Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). Conclusions: In patients with pre-CRT serum CEA ≥6 ng/ml, those with “normalized” CEA levels after CRT may have similar DFS to those with “normal” (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml.