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Circulating Tumor Cells

Describes the importance of liquid biopsy and circulating tumor cells enumeration as a marker of predictive and prognostic value in cancer treatment

purvish
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Circulating Tumor Cells

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  1. Circulating Tumor Cells Dr Purvish M ParikhMD, DNB, FICP, PhD, ECMO, CPI, MBApurvish1@gmail.com 9th SAARC Federation of Oncologists’ Conference Director of Precision Oncology & Research, Asian Institute of Oncology, Sion, Mumbai

  2. Circulating Tumor Cells (CTC) • Cristofanilli M et al: CTC, disease progression, and survival in MBC. NEJM 2004; 351: 781-791 • Google search - 9,11,000 hits • Medline Search – 15,272 publications 706 so far in 2014 • Kim H et al: Development of On-Chip Multi-Imaging Flow Cytometry for Identification of Imaging Biomarkers of Clustered CTC. PLoS One. 2014 Aug 20;9(8):e104372.

  3. Circulating Tumor Cells – Liquid biopsy Assay uses 15 ml peripheral whole blood for CTC of epithelial origin for: • detection, • enrichment and • quantification . • Predict progression free survival (PFS) and overall survival (OS) 2. Monitor response to therapy

  4. CTC – Concept

  5. CTC - identification • Nucleated cells (DAPI+) • Expressing CK (cytokeratin) in cytoplasm, and EpCAM (epithelial cell adhesion molecule) on cell surface • Using immunofluorescent reagents. CTC images courtesy : Datar Genetics, Mumbai, India

  6. CTC - identification CTC images courtesy : Datar Genetics, Mumbai, India Green – cytokeratin (CK) Composite staining showing all three features Blue – DAPI (Nucleus) Red – EpCAM

  7. CTC – cut off levels 5 CTCs/7.5 mL blood: • Metastatic breast cancer • Metastatic prostate cancer 3 CTCs/7.5 mL blood: • Metastatic colorectal cancer

  8. CTC – Predictive Value

  9. CTC – Monitoring Rx efficacy • Predict treatment response earlier (3-4 weeks) than imaging (8-12 weeks) after initiation of therapy. • Accurate indicator of rapid disease progression and shorter survival.

  10. CTC – additional application • Captured CTCs can be used for molecular profiling studies (DNA, RNA) including FISH, array based methodologies, and cellular phenotyping (PSA, HER-2/neu or EGFR ) • Also has application in cancers of urinary bladder, biliary duct, liver, pancreas and lung.

  11. CTC – quantitative vital cells

  12. CTC – in vitro chemosensitivity (1)

  13. CTC – in vitro chemosensitivity (2) Results within 9 hours

  14. Role of Molecular Testing Exists at every stage of the cancer • Correct diagnosis • Prognostic and predictive value • Selecting • Most effective drug / combination • High risk patients for additional Rx • Early detection of recurrence • Preventing unwanted drug toxicity • Screening - family history of cancer

  15. Remember …..Teamwork is everything

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