Circulating tumour cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies

Walla Malkawi; Areeb Lutfi; Maaz Khan Afghan; Lamisha Mashiyat Shah; Lillian Costandy; Arturo B Ramirez; Thaddeus C George; Fatima Toor; Aliasger K Salem; Pashtoon Murtaza Kasi

doi:10.3389/fonc.2023.1305181

Circulating tumour cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies

Front Oncol. 2023 Nov 17:13:1305181. doi: 10.3389/fonc.2023.1305181. eCollection 2023.

Authors

Affiliations

¹ Division of Pharmaceutics and Translational Therapeutics, University of Iowa, Iowa, IA, United States.
² Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY, United States.
³ RareCyte, Inc., Seattle, WA, United States.
⁴ Experimental Therapeutics Program, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa, IA, United States.
⁵ Department of Electrical and Computer Engineering, University of Iowa, Iowa, IA, United States.

Abstract

Objective: Most of the work in terms of liquid biopsies in patients with solid tumors is focused on circulating tumor DNA (ctDNA). Our aim was to evaluate the feasibility of using circulating tumor cells (CTCs) in peripheral blood samples from patients with advanced or metastatic gastrointestinal (GI) cancers.

Methods: In this prospective study, blood samples were collected from each patient in 2 AccuCyte^® blood collection tubes and each tube underwent CTC analysis performed utilizing the RareCyte^® platform. The results from both tubes were averaged and a total of 150 draws were done, with 281 unique reported results. The cadence of sampling was based on convenience sampling and piggybacked onto days of actual clinical follow-ups and treatment visits. The CTC results were correlated with patient- and tumor-related variables.

Results: Data from a total of 59 unique patients were included in this study. Patients had a median age of 58 years, with males representing 69% of the study population. More than 57% had received treatment prior to taking blood samples. The type of GI malignancy varied, with more than half the patients having colorectal cancer (CRC, 54%) followed by esophageal/gastric cancer (17%). The least common cancer was cholangiocarcinoma (9%). The greatest number of CTCs were found in patients with colorectal cancer (Mean: 15.8 per 7.5 ml; Median: 7.5 per 7.5 ml). In comparison, patients with pancreatic cancer (PC) had considerably fewer CTCs (Mean: 4.2 per 7.5 ml; Median: 3 per 7.5 ml). Additionally, we found that patients receiving treatment had significantly fewer CTCs than patients who were not receiving treatment (Median 2.7 versus 0.7). CTC numbers showed noteworthy disparities between patients with responding/stable disease in comparison to those with untreated/progressive disease (Median of 2.7 versus 0). When CTCs were present, biomarker analyses of the four markers human epidermal growth factor receptor 2 (HER2)/programmed death-ligand 1 (PD-L1)/Kiel 67 (Ki-67)/epidermal growth factor receptor (EGFR) was feasible. Single cell sequencing confirmed the tumor of origin.

Conclusion: Our study is one of the first prospective real-time studies evaluating CTCs in patients with GI malignancies. While ctDNA-based analyses are more common in clinical trials and practice, CTC analysis provides complementary information from a liquid biopsy perspective that is of value and worthy of continued research.

Keywords: biomarker; circulating tumor (ctDNA); circulating tumor cell (CTC); feasibility; gastrointestinal malignancies; kinetics.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The ctDNA and tumor next-generation sequencing-based testing was done as part of the routine standard of care. Principal Investigator -author PMK’s own discretionary, departmental and center of advancement funds from University of Iowa were utilized to supplement the salary/time of the PhD student, as well as testing that was performed through the RareCyte’s platform.