A Multi-Center Clinical Study to Harvest and Characterize Circulating Tumor Cells from Patients with Metastatic Breast Cancer Using the Parsortix® PC1 System

Abstract

Circulating tumor cells (CTCs) captured from the blood of cancer patients may serve as a surrogate source of tumor material that can be obtained via a venipuncture (also known as a liquid biopsy) and used to better understand tumor characteristics. However, the only FDA-cleared CTC assay has been limited to the enumeration of surface marker–defined cells and not further characterization of the CTCs. In this study, we tested the ability of a semi-automated device capable of capturing and harvesting CTCs from peripheral blood based on cell size and deformability, agnostic of cell-surface markers (the Parsortix® PC1 System), to yield CTCs for evaluation by downstream techniques commonly available in clinical laboratories. The data generated from this study were used to support a De Novo request (DEN200062) for the classification of this device, which the FDA recently granted. As part of a multicenter clinical trial, peripheral blood samples from 216 patients with metastatic breast cancer (MBC) and 205 healthy volunteers were subjected to CTC enrichment. A board-certified pathologist enumerated the CTCs from each participant by cytologic evaluation of Wright-Giemsa-stained slides. As proof of principle, cells harvested from a concurrent parallel sample provided by each participant were evaluated using one of three additional evaluation techniques: molecular profiling by qRT-PCR, RNA sequencing, or cytogenetic analysis of HER2 amplification by FISH. The study demonstrated that the Parsortix® PC1 System can effectively capture and harvest CTCs from the peripheral blood of MBC patients and that the harvested cells can be evaluated using orthogonal methodologies such as gene expression and/or Fluorescence In Situ Hybridization (FISH).

Circulating Tumor Cells in Cancer Diagnostics and Prognostics by Single-Molecule and Single-Cell Characterization

“…Microfluidics can also harness the lower deformability of CTCs compared to other blood components. The FDA approved Parsortix as the first medical device for the capture and harvest of CTCs from mBRCA patients for subsequent analysis (ClinicalTrials.gov identifier: NCT03427450) . CTCs are captured in a disposable filtration cassette and can be fixed and stained for identification and enumeration, or recovered for external staining and/or downstream analyses.…”

“…The FDA approved Parsortix as the first medical device for the capture and harvest of CTCs from mBRCA patients for subsequent analysis (ClinicalTrials.gov identifier: NCT03427450). 9 CTCs are captured in a disposable filtration cassette and can be fixed and stained for identification and enumeration, or recovered for external staining and/or downstream analyses. This approach has led to some remarkable discoveries such as single-cell RNA sequencing of CTCs isolated with Parsortix, revealing that CTCs in BrCa patients are actively and preferentially shed during sleep rather than being constantly shed over time, as previously believed.…”

“…Fortunately, there have been significant technological advances in the isolation, analysis, and characterization of CTCs, at both the single-cell and single-molecule levels, which can aid the identification of new molecular and biophysical markers. For example, the Parsortix PC1 Clinical System (ANGLE plc., Surrey, England), a 3D microfiltration device for the capture and harvest of CTCs, has recently received US FDA approval for use as a diagnostic tool in metastatic breast cancer …”

“…For example, the Parsortix PC1 Clinical System (ANGLE plc., Surrey, England), a 3D microfiltration device for the capture and harvest of CTCs, has recently received US FDA approval for use as a diagnostic tool in metastatic breast cancer. 9 The limitations imposed by the scarcity of CTCs can also be addressed by cell culture, with efforts being made to establish CTC-derived cell lines for downstream analyses, such as drug testing. 10 The current conventional and commercially available in vitro cell culture approaches, 2D and 2.5D, respectively, seem increasingly inadequate to convey the necessary cues for the preservation and expansion of patient-derived CTCs.…”

Extracellular Vesicles as Biomarkers in Head and Neck Squamous Cell Carcinoma: From Diagnosis to Disease-Free Survival

“…The CellSearch system, an immunomagnetic assay with magnetic nanoparticle-based separating technology, is the cleared U.S. Food and Drug Administration (FDA) biological methodology for CTC enumeration [ 101 ]. Physical methods generally capture CTCs by various size filtrations, and as the representative, the Parsortix ® PC1 system was cleared by the FDA in May 2022 [ 102 ]. However, these technologies have their own drawbacks that may have some biases, for instance, the biological extraction of CTCs requires a sufficient expression of the known and selected marker on the cell surface, and physical filtration would probably overlook the other blood components whose diameters and properties are close to those of CTCs [ 92 , 100 ].…”