Abstract 7493: Real-time monitoring of CTC number, biomarker expression, and kinetics as prognostic and predictive markers in patients with GI malignancies
Authors: Bayer Erin G. , Bartels Brock M. , Ponting Rachel N. , Lutfi Areeb , Afghan Maaz K. , Ramirez Arturo B. , Kasi Pashtoon M. 
Published: March 2024

Background: Most of the utility in the clinic regarding liquid biopsies has been around circulating tumor DNA (ctDNA). ctDNA analysis provides valuable insight into mutational burden and therapeutic targets, but the speed and cost of analysis are prohibitive especially when it comes to serial testing. Using a cohort of patients with advanced or metastatic gastrointestinal (GI) cancers, we herein show the feasibility of using circulating tumor cell (CTC) enumeration, biomarker analysis, and kinetics as complementary to or as an alternative to ctDNA testing.

Methods: Using the RareCyte platform, nucleated cells from blood were collected, spread on slides, stained, and imaged with CyteFinder® for CTC identification (CK/EpCAM+, CD45-) and quantification of biomarkers (PD-L1/HER2 or Ki67/EGFR). CTC enumeration (CLIA-accredited CTC test) and biomarker status for each patient were tracked over time and compared with ctDNA mutational analysis and tumor burden.

Results: CTCs were detected in 60/70 samples (86%) and in 36/38 unique patients (95%). On average, more CTCs were detected in baseline samples from colorectal cancer patients compared to other subtypes (Table 1). Moreover, multiple patients showed pronounced changes in CTC number that correlated with treatment response, as well as strong correlation between CTC and tissue biomarker expression e.g. HER2. Rapid decline and/or CTC clearance was seen as early as a few days into starting effective systemic therapy. The average turnaround time for CTC testing was 5-7 days.

Table 1. CTC values in initial baseline blood draw sample Gastrointestinal cancer subtype # of patients Average # of CTCs per 7.5mL blood Median # of CTCs per 7.5mL blood Minimum # of CTCs per 7.5mL blood Maximum # of CTCs per 7.5mL blood Colorectal carcinoma 27 84 3 0 1378 Cholangiocarcinoma 3 8 3 1 23 Pancreatic cancer 3 2 2 0 3 Hepatocellular carcinoma 2 4 5 0 10 Gallbladder cancer 1 6 6 3 8 Appendix cancer 1 2 2 1 3 Anal cancer 1 0 0 0 0

Conclusions: Our study emphasizes that real-time monitoring of CTCs is complementary to traditional tumor burden monitoring via imaging and ctDNA analysis. CTCs offer multiple unique advantages vs ctDNA including early response assessment within days of initiating therapy, a substantial decrease in cost of serial testing, and the ability to assess clinically relevant cell surface protein biomarkers e.g. HER2 and PD-L1.

Citation Format: Erin G. Bayer, Brock M. Bartels, Rachel N. Ponting, Areeb Lutfi, Maaz K. Afghan, Arturo B. Ramirez, Pashtoon M. Kasi. Real-time monitoring of CTC number, biomarker expression, and kinetics as prognostic and predictive markers in patients with GI malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7493.