Changes in numbers of circulating tumour cells as a biomarker for treatment response.
Joachim Fluhrer, Svenja Frister, Ulrich Pachmann, Katharina Pachmann
Transfusionsmedizinisches Labor Pachmann, Bayreuth Germany
Background: Solid malignant tumours are known to release cells into the circulation during growth. After removal of the primary tumour such cells must be able to survive because metastases frequently develop even after years of relapse free survival. It is, however not known, how long such cells survive in the blood. We have developed a test, maintrac®, to detect these cells and have shown that changes in the number of these cells can be used as a biomarker to monitor cancer treatment.
Methods: Whole uncoagulated blood was submitted to red blood cell lysis and the white blood cell sediment containing the tumour cells incubated with antibody staining epithelial cells (anti-EpCAM). Positively staining cells were measured by a scanning microscope and assessed for viable cells which were counted and recorded.
Results: Epithelial antigen positive cells, presumably cells derived from the patient’s cancer, were eliminated from blood by effective treatment but reseeding from remote niches into blood frequently occurred as well as survival of resistant cells with an increase in circulating tumour cell numbers preceding relapse. Effective endocrine treatment of breast and prostate cancer preferentially resulted in silencing tumor cells leading to constant cell numbers over years. Stopping endocrine treatment often allowed regrowth of tumour cells with increasing cell numbers in blood preceding relapse. Stable or decreasing circulating tumor cell numbers highly significantly correlated with improved relapse free survival (p<0.001, hazard ratio > 8) during different treatments and in different cancer entities.
Conclusion: Changes in the numbers of circulating tumour cells (CTCs) provide a reliable biomarker for monitoring cancer treatment. This has now been confirmed in analyses during 15 years of observation.