Evaluation of circulating tumor cell clusters for pan‐cancer noninvasive diagnostic triaging

Abstract

BACKGROUND: Histopathologic examination (HPE) of tumor tissue obtained by invasive biopsy is the standard for cancer diagnosis but is resource-intensive and has been associated with procedural risks. The authors demonstrate that immunocytochemistry (ICC) profiling of circulating ensembles of tumor-associated cells (C-ETACs) can noninvasively provide diagnostic guidance in solid organ cancers. METHODS: The clinical performance of this approach was tested on blood samples from 30,060 individuals, including 9416 individuals with known cancer; 6725 symptomatic individuals with suspected cancer; and 13,919 asymptomatic individuals with no prior diagnosis of cancer. C-ETACs were harvested from peripheral blood and profiled by ICC for organ-specific and subtype-specific markers relevant to the cancer type. ICC profiles were compared with HPE diagnoses to determine concordance. RESULTS: The presence of malignancy was confirmed by the detection of C-ETACs in 91.8% of the 9416 individuals with previously known cancer. Of the 6725 symptomatic individuals, 6025 were diagnosed with cancer, and 700 were diagnosed with benign conditions; C-ETACs were detected in 92.6% of samples from the 6025 individuals with cancer. In a subset of 3509 samples, ICC profiling of C-ETACs for organ-specific and subtype-specific markers was concordant with HPE findings in 93.1% of cases. C-ETACs were undetectable in 95% of samples from the 700 symptomatic individuals who had benign conditions and in 96.3% of samples from the 13,919 asymptomatic individuals. CONCLUSIONS: C-ETACs were ubiquitous (>90%) in various cancers and provided diagnostically relevant information in the majority (>90%) of cases. This is the first comprehensive report on the feasibility of ICC profiling of C-ETACs to provide pan-cancer diagnostic guidance with accuracy comparable to that of HPE. Cancer Cytopathol 2020;0:1-13.

Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells

“…The present test is based on detection of CTCs, which are ubiquitously found in the blood of patients with an underlying solid organ cancer and are undetectable in healthy individuals (18,19). We show that functionally enriched CTCs can differentiate malignant conditions from benign conditions as well as identify asymptomatic individuals with an underlying malignant condition with high specificity.…”

“…The process of ICC profiling of CTCs was as described previously (19). Comprehensive details are provided in Supplementary Materials.…”

Multi-Analyte Liquid Biopsies for Molecular Pathway Guided Personalized Treatment Selection in Advanced Refractory Cancers: A Clinical Utility Pilot Study

“…11,12,15,17 We show that in addition to gene variants (point mutations / copy number variations), MLB can provide information on upregulation of targetable pathways via ICC profiling of CTCs, akin to immunohistochemistry (IHC) on tumor tissue or cytology specimens. In a recent large (>30,000 specimens) cohort study, we have described the potential of ICC profiling of CTCs to provide diagnostically relevant information without requirement of tumor tissue 8 . In the present paper, we describe the potential application of ICC towards theranostic guidance.…”

“…All study participants provided only peripheral blood samples. The process of multi-analyte tumor profiling and generation of patient specific therapy recommendations (TR) have been described previously [4,5]. The complete details of investigations under multi-analyte tumor profiling are provided in Supplementary Methods.…”

Circulating Tumor Cell Assay to Non-Invasively Evaluate PD-L1 and Other Therapeutic Targets in Multiple Cancers

“…The process of ICC profiling of CTCs was as described previously [24]. Representative fluorescent images of Circulating Tumor Cells (CTCs) isolated from cancer patient samples immuno-stained for A) PD-L1 22C3, B) PD-L1 28.8, C) ER, D) PR, and E) HER2 are provided in Supplementary Figure S4.…”