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

Malkawi W, Lutfi A, Afghan MK, Shah LM, Costandy L, Ramirez AB, et al.

Frontiers in Oncology. 2023;13. DOI 10.3389/fonc.2023.1305181. PMID 38044994. PMCID PMC10693413.

How to cite

AMA

Malkawi W, Lutfi A, Afghan MK, Shah LM, Costandy L, Ramirez AB, et al. Circulating tumor cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies. Front Oncol. 2023;13:1305181. doi:10.3389/fonc.2023.1305181

APA

Malkawi, W., Lutfi, A., Afghan, M. K., Shah, L. M., Costandy, L., Ramirez, A. B., et al. (2023). Circulating tumor cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies. Frontiers in Oncology, 13, 1305181. https://doi.org/10.3389/fonc.2023.1305181

BibTeX

@article{malkawi2023circulating,
  title   = {Circulating tumor cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies},
  author  = {Malkawi, W. and Lutfi, A. and Afghan, M. K. and Shah, L. M. and Costandy, L. and Ramirez, A. B. and others},
  journal = {Frontiers in Oncology},
  volume  = {13},
  pages   = {1305181},
  year    = {2023},
  doi     = {10.3389/fonc.2023.1305181}
}

Circulating tumor cells offer a way to read a cancer from a tube of blood, but most liquid-biopsy work has centered on circulating tumor DNA rather than the cells themselves. This study asked whether counting and characterizing whole circulating tumor cells is practical in the clinic, following 59 patients with advanced gastrointestinal cancers across repeated blood draws timed to their regular treatment visits. Using a density-based approach that does not select cells by surface marker, the team enumerated circulating tumor cells, profiled them for four clinically relevant biomarkers, sequenced individually retrieved cells to confirm their tumor origin, and watched the counts shift as disease responded or progressed — a real-time, complementary readout alongside DNA-based tests.

Key findings

  • Across 59 GI-cancer patients and 150 blood draws, CTC burden was highest in colorectal cancer. Colorectal cancer, just over half the cohort (54%), carried the most circulating tumor cells (mean 15.8 per 7.5 mL), compared with a mean of 4.2 per 7.5 mL in pancreatic cancer.
  • Serial sampling tied CTC counts to treatment and response. Across the 150 draws, patients receiving treatment had significantly fewer circulating tumor cells than untreated patients, and counts differed between responding or stable disease and progressive disease.
  • When circulating tumor cells were present, they could be phenotyped and sequenced. Dual-biomarker assays profiled four markers — HER2, PD-L1, Ki-67, and EGFR — and targeted sequencing with a 65-gene panel of individually retrieved cells confirmed the tumor of origin in five patients.

AccuCyte in the 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.”

— Malkawi et al., Frontiers in Oncology (2023), Abstract, “Methods”

Disclosure: RareCyte is listed as an author affiliation on the publication cited above.

Disclosure: RareCyte is named in the competing-interests statement of the publication cited above.

Why it matters for AccuCyte users

If you are weighing AccuCyte for circulating tumor cell work, look at where it sits in this study: at the very front, before any cell is counted or characterized. Blood was drawn into AccuCyte collection tubes at routine treatment visits, and each sample was processed by separation based on cell density rather than an antigen-capture step. That distinction is why the rest of the workflow was possible. A method built around a surface marker such as EpCAM retains only cells that still display it, so a circulating tumor cell that has shifted phenotype and lost that marker is gone before you can see it. Because AccuCyte separates on density and stays agnostic to surface markers, those cells remain on the slide — available to be enumerated, phenotyped for HER2, PD-L1, Ki-67, and EGFR, and picked for targeted sequencing. For serial monitoring across a treatment course, that antigen-agnostic first step is what keeps the population you are tracking intact.