Personalized analysis of minimal residual cancer cells in peritoneal lavage fluid predicts peritoneal dissemination of gastric cancer
Abstract Peritoneal dissemination (PD) is the major type of gastric cancer (GC) recurrence and leads to rapid death. Current approach cannot precisely determine which patients are at high risk of PD. In this study, we developed a technology to detect minimal residual cancer cells in peritoneal lavage fluid (PLF) samples by parallel profiling tumor-specific mutations. We applied the technology to a prospective cohort of 110 GC patients. The technology showed ultra-high sensitivity by successfully detecting all the 27 cases that developed PD. The minimal residual cancer cells in PLF was associated with an increased risk of PD (HR = 145.13; 95%CI = 20.20-18435.79; p < 0.001) and significantly shorter overall survival. In pathologically high-risk (T4) patients, the PLF mutation profiling model exhibited even greater specificity of 91% and positive predictive value of 88%, while retaining sensitivity of 100%. PLF cancer cell fraction remained the strongest independent predictor of PD and recurrence-free survival over pathologic diagnosis and cytological diagnosis in GC patients. This approach may help in the postsurgical management of GC patients by detecting PD far before the metastatic lesions grow to significant size detectable by conventional methods such as MRI and CT scanning.