Gastric cancer is one of the most common malignant tumors in China, with the second highest incidence and the third highest mortality.Adenocarcinoma accounts for 95% of gastric malignancies and is the most common malignancy of the digestive tract. Seventy percent of the patients with early gastric cancer had no obvious symptoms, and a few had nausea, vomiting or ulcer-like upper gastrointestinal symptoms.
Surgical treatment is the first choice for the treatment of early gastric cancer, but postoperative recurrence and metastasis are prone to occur. At the same time, there are relatively few chemotherapy drugs for gastric cancer, only a few chemotherapy drugs of Paclitaxel and platinum drugs are selected, and the chemotherapy regimen is relatively single. Meanwhile, the prognosis of gastric cancer in different parts is significantly different, and its molecular heterogeneity is strong. Studies have shown that about 13% of gastric cancer has HER2 gene variation, and there is no other specific driver gene mutation except HER2. Currently, only two targeted drugs, trastuzumab and apatinib, are approved for the treatment of gastric cancer in China.
CtDNA is the body's endogenous tumor DNA free of cells in circulating blood. It is generally believed that ctDNA in the blood of tumor patients is mainly derived from tumor cell necrosis and proliferation after apoptosis, as well as the release of proliferative and active tumor cells. At present, most studies have proved that the DNA of tumor cells has consistent genetic changes with ctDNA, and the same genetic changes may be detected in the plasma free DNA of patients with driver gene mutations in the primary or metastatic lesions. Therefore, ctDNA is a characteristic tumor biomarker and can be qualitatively, quantitatively and dynamically tracked.
Immunoassay point inhibitors, including pd-1 inhibitors, pd-l1 inhibitors and ctla-4 inhibitors, have achieved significant efficacy in a variety of tumors and are expected to change the treatment status of tumors. In the case of gastric cancer, recently the Lancet Oncology published the final results and review of the KEYNOTE 012 study that investigated the efficacy of Pembrolizumab in patients with advanced pd-l1 positive gastric cancer. Results showed that 53% of patients had tumor regression, 22% had partial imaging remission, and the median duration of remission was 40 weeks. Pembrolizumab is also superior to standard second-line chemotherapy. However, currently there is no recognized indicator that can predict the efficacy of immunotherapy for gastric cancer, and relevant research is urgently needed.
The purpose of this study was to investigate the correlation between the dynamic changes of ctDNA during surgery and the effect of immunotherapy on gastric cancer patients and its effect as a hematological index for the prognosis of advanced gastric cancer. Meanwhile, molecular markers related to the prognosis of advanced gastric cancer were screened out by comparing the differences in the molecular characteristics of gastric cancer tissues among patients with different prognosis.
