Director of Precision Oncology & Research, Asian Institute of Oncology,
Sion, Mumbai
Dr Purvish M ParikhMD, DNB, FICP, PhD, ECMO, CPI, MBA
Circulating Tumor Cells
9th SAARC Federation of Oncologists’ Conference
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.
Circulating Tumor Cells – Liquid biopsy
Assay uses 15 ml peripheral whole blood for CTC of epithelial origin for: – detection, – enrichment and – quantification .
1. Predict progression free survival (PFS) and overall survival (OS)
2. Monitor response to therapy
CTC – Concept
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
CTC - identification
Green – cytokeratin (CK)
Red – EpCAMBlue – DAPI (Nucleus)
Composite staining showing all three features
CTC images courtesy : Datar Genetics, Mumbai, India
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
CTC – Predictive Value
Favourable CTC Unfavourable CTC
Breast CaPFS 7.0 2.7
OS 21.9 10.9
CRCPFS 7.9 4.5
OS 18.5 9.4
Prostate CaPFS 5.8 4.2
OS 21.7 11.5
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.
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.
CTC – quantitative vital cells
CTC – in vitro chemosensitivity (1)
CTC – in vitro chemosensitivity (2)
Baseline 3 hrs 6 hrs 9 hrs Baseline 3 hrs 6 hrs 9 hrsDrug
-vecontrol
Carbo-platin
Cisplatin
Adria-mycin
Cape-citabine
Drug
Paclitaxel
Docetaxel
Epirubicin
Cyclophosphamide
5 FU
Results within 9 hours
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
Remember ….. Teamwork
is everything