What role can circulating tumor cell testing play in the diagnosis and treatment of gastric cancer?

Circulating tumor cells  (CTCs) were first identified in 1869, when tumor cells were shed from the primary lesion, crossed the blood vessel wall and entered the circulation to form CTCs. CTCs travel with the circulation to reach and colonize distant organs or recolonize the primary lesion, resulting in distant organ metastases or recurrence of the tumor in situ. This leads to distant metastases or recurrence in situ. So, can CTC testing be used for the diagnosis, treatment, and prognosis of gastric cancer?

Early diagnosis

Early gastric cancer mostly has no specific manifestations, and some patients are often combined with metastases or have lost the opportunity for surgical treatment when clinical symptoms appear. The key to improving the survival rate of patients with gastric cancer is early diagnosis and early treatment.

CTC can suggest potential lesions that are not detected by imaging, helping to detect metastases early and facilitating individualized treatment. In general, CTC can be detected when tumors are 1mm in size, whereas conventional imaging techniques can only detect tumors over 10mm in size, and even positron emission computed tomography (PET-CT), which is known as the “radar for early tumor detection,” can only detect tumors larger than 5mm. The CT test can detect tumors 2-6 months earlier than conventional imaging, which provides a new way to diagnose gastric cancer early.

Determining prognosis

Surgery can eradicate the primary lesion of gastric cancer, and drug therapy can kill some of the CTC, but some of the CTC remains in the bloodstream and finds new “sites” in the circulation, becoming a cause of recurrence and metastasis of gastric cancer. One study found that the progression-free survival (PFS) of CTC-positive gastric cancer patients is shorter than that of CTC-negative patients. By comparing and analyzing the type and amount of CTC in patients, doctors can detect recurrence and metastasis of gastric cancer in a timely manner, so that appropriate treatment can be given to nip it in the bud, and survival can be predicted.

Guiding individualized treatment

Individualized treatment of gastric cancer refers to treating patients with specific tumors with different treatment regimens. In recent years, targeted therapy has become a research hotspot. Targeted therapy for gastric cancer is mainly based on the results of the detection of genes such as human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) in the primary tumor, but due to the heterogeneity of tumor cells, CTCs may have genetic mutations, and relying solely on the detection and analysis of primary tumor cells is limited. However, due to the heterogeneity of tumor cells, CTCs may have genetic mutations, and relying solely on the analysis of primary tumor cells to develop a treatment plan is limited.

Physicians may choose to use CTC as a liquid biopsy sample for multiple tests, the results of which can help guide subsequent chemotherapy regimens and targeted dosing, and facilitate the action of chemotherapy to kill tumor cells and residual cancer foci in the blood.

Evaluating treatment effects

The effectiveness of surgery and chemotherapy for gastric cancer patients is still evaluated based on the time to tumor recurrence and survival, which has a long lead time. The results of the treatment can be evaluated in a timely and effective manner.

Summary

Summary

With the rapid development of CTC testing, the method is gaining recognition due to its convenient and less invasive sampling, dynamic monitoring, and better patient compliance, etc. CTC testing can be combined with other tests to help in the early diagnosis and prognosis of gastric cancer, guide the development of individualized treatment plans, and evaluate the effectiveness of treatment, which is of great importance in the diagnosis and treatment of gastric cancer. CTC testing is now being performed in large medical centers in China and is playing an increasingly important role in clinical diagnosis.

In recent years, the development of circulating nucleic acids (CNA)  assays similar to CTC has been rapid, reflecting the overall genetic variation of tumor cells and using the characteristics of the tumor cell genome to obtain tumor information at the genetic level. As a complement to CTC, the development direction of CNA is to continuously improve the sensitivity of detection and to clarify new tumor markers. (Coauthored by Songcheng Yin, Department of Gastrointestinal Oncology, The First Hospital of China Medical University)