Search Results

The CellSearch™ Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood.

The presence of CTC in the peripheral blood, as detected by the CellSearch™ Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring breast cancer. A CTC count of 5 or more per 7.5 mL of blood at any time during the course of the disease is predictive of shorter progression free survival and overall survival.

The CellSearch™ Circulating Tumor Cell Kit contains a ferrofluid-based capture reagent and immunofluorescent reagents. The ferrofluid reagent consists of nanoparticles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the EpCAM antigen for capturing CTC. After immunomagnetic capture and enrichment, fluorescent reagents are added for identification and cnumeration of CTC. The fluorescent reagents include the following: anti-CK-Phycoerythrin (PE) specific for the intracellular protein cytokeratin (characteristic of epithelial cells), DAPI which stains the cell nucleus, and anti-CD45-Allophycocyanin (APC) specific for leukocytes.

The reagent/sample mixture is dispensed by the CellTracks AutoPrep® System into a cartridge that is inserted into a MagNest® cell presentation device. The strong magnetic field of the MagNest® device attracts the magnetically labeled epithelial cells to the surface of the cartridge. The CellTracks® Analyzer II or CellSpotter® Analyzer automatically scans the entire surface of the cartridge, acquires images and displays any event to the user where CK-PE and DAPI fluorescence are co-located. Images are presented to the user in a gallery format for final classification. An event is classified as a tumor cell when its morphological features are consistent with that of a tumor cell and it exhibits the phenotype EpCAM+, CK+, DAPI+ and CD45-.

The CellSearch™_Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood. The presence of CTC in the peripheral blood, as detected by the CellSearch™_Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring breast cancer. A CTC count of 5 or more per 7.5 mL of blood at any time during the course of the disease is predictive of shorter progression free survival and overall survival.

ACCECPTANCE CRITERIA

STUDY DETAILS

1. Sample size used for the test set and the data provenance:

   • Recovery and Linearity: 30 samples from 5 healthy donors. Spiked with cultured breast cancer cells (SK-BR-3).
   • Reproducibility (Patient Samples): 163 duplicate samples from 47 patients.
   • Expected Values (Control Subjects): 345 total samples (145 healthy volunteers, 101 women with non-malignant breast disease, 99 women with other non-malignant diseases).
   • Clinical Study (Metastatic Breast Cancer): 177 patients with metastatic breast cancer. Follow-up analyses had varying sample sizes at different time points (e.g., 126 at 3-5 weeks, 138 for imaging comparison).
   • Data Provenance: Retrospective for recovery, linearity, and reproducibility. Prospective, multi-center clinical trial for metastatic breast cancer patients. Country of origin not specified, but the applicant is Veridex, LLC, located in Warren, NJ, USA.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • Clinical Study (Imaging Ground Truth): Two expert radiologists initially, blinded to clinical information. A third independent radiologist adjudicated disagreements. Qualifications are not specified beyond "expert radiologists."

3. Adjudication method for the test set:

   • Imaging Ground Truth:
     • If one radiologist categorized as Indeterminate (I) and the other as Stable Disease (S), Partial Response (PR), or Progressive Disease (PD), the latter radiologist's classification was used (n=11).
     • If both radiologists categorized as Indeterminate (I), the data was not used (n=3).
     • A third independent radiologist adjudicated disagreements between the two primary readers regarding PD and NPD (n=27). If the third radiologist rendered "Indeterminate (I)", the data was not used (n=2).

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • The study did not describe an MRMC comparative effectiveness study involving AI or human readers being assisted by AI. The comparison was betweenCTC measurements and radiological assessments, primarily on their prognostic value and variability. The device is not an AI-assisted diagnostic tool for human readers but rather an automated system for CTC enumeration.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes, the performance of the CellSearch™ system, which includes automated scanning and image acquisition (CellTracks® Analyzer II or CellSpotter® Analyzer) with user classification of events, was evaluated. The "user classification" aspect suggests a human-in-the-loop for final interpretation of events presented by the system, but the core processing and initial identification are automated. The recovery, linearity, limits of detection, and reproducibility studies assess the standalone performance of the system for enumerating CTCs.

6. The type of ground truth used:

   • Recovery & Linearity: Expected cell counts from spiked cultured breast cancer cells.
   • Reproducibility: Comparison of duplicate samples processed by the system.
   • Clinical Study:
     • Prognosis (PFS/OS): Clinical outcomes data (progression-free survival and overall survival) based on CT scans, clinical signs and symptoms, and time to death.
     • Imaging Comparison: Expert consensus of radiologists based on World Health Organization (WHO) bi-dimensional criteria for disease assessment (NPD vs. PD).

7. The sample size for the training set:

   • The document does not explicitly describe a separate "training set" for the device's development or a machine learning algorithm. The studies detailed are primarily validation studies of the device's technical performance and clinical utility.

8. How the ground truth for the training set was established:

   • Not applicable as no specific training set for a machine learning algorithm is described. The device operates based on immunomagnetic capture and fluorescent labeling with rule-based classification principles, followed by user classification, rather than being a trained AI model in the modern sense.

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