(T1130-09-51) Circulating Tumor Cells as a Biomarker for Evaluating Tumor Progression and Treatment Response in Patients with Gastrointestinal Malignancies

Purpose: Cancer is still the leading cause of death worldwide, according to a report released by the World Health Organization in early 2022. Gastrointestinal (GI) malignancies are a major component of solid tumors, accounting for around 35% of all cancer mortalities. At this stage, metastasis is the primary cause of death from GI cancer. Within 5 years following curative resection, many GI patients acquire the metastatic disease, implying that metastatic-potential tumor cells have reached the circulation from the primary tumor site and produced distant metastasis. These cells are known as circulating tumor cells (CTCs), and they have been hypothesized as mediators of hematogenous metastasis of solid malignant tumors. As a result, CTC studies can provide more insight into the course of metastasis. However, CTC detection is difficult due to their low concentration in the peripheral blood, as a result restricting in-depth research into their biological characteristics. This study aims to isolate CTCs from blood samples of patients with metastatic GI cancers to determine the feasibility of including a CTC screening platform in a clinical environment and assess the relationship between CTC enumeration and various clinical variables including tumor growth and treatment response.

Methods: The study was reviewed by the institutional review board (IRB), and all patients signed a written informed consent before collecting blood samples. Participants included 59 patients with metastatic GI cancer, involving colorectal cancer, pancreatic cancer, esophageal cancer, and cholangiocarcinoma. Patients were recruited through the University of Iowa Holden Comprehensive Cancer Center. Two blood samples were collected from each patient at each time point, 1-4 blood draws were obtained from each patient at different time points, in a total of 150 draws from all the patients. The blood samples were used for detecting CTCs. The CTCs were detected/ analyzed using two different platforms. These two platforms discriminate CTCs based on different parameters: RareCyte system which relies on the density of CTCs, and ParsortixTM system which relies on the size of CTCs.

Results: The number of CTCs was influenced by cancer type, with colorectal cancer patients having the highest number of CTCs. In contrast, pancreatic and cholangiocarcinoma cancer patients had the lowest number of CTCs. In addition, the RareCyte system detected a significantly lower number of CTCs from patients receiving treatment versus patients not receiving treatment (0.7 (IQR: 0- 3.5)) versus (2.7 (IQR: 0.175- 10.98)). Also, RareCyte found a significant difference in the number of CTCs in blood samples from patients based on their response to treatment, with median CTCs significantly lower in patients who responded to treatment (0 (IQR: 0- 1.475)) and had stable tumor size (0 (IQR: 0- 1.78)) comparing to patients who did not respond to treatment (2.7 (IQR: 0.85- 8)).

Conclusion: We were able to show the feasibility of detecting CTCs across different tumor types and show there are tumor, treatment, and treatment response variables that must be considered when interpreting the results.