Monitoring of Circulating Tumor Cells (CTCs) during the Course of Disease in Patients with Solid Tumors

Purpose: It is well known that tumor cells can be released form solid tumors during growth and that these cells can be the source of metastases during the later course of disease. It seems therefore essential to monitor these cells in order to determine at what stages of disease the cells are released and how they behave during and after therapy in order to early detect renewed tumor activity which might require action for prevention of disease progression. Methods: Tumor suspect cells from blood are detected using a non-dissipative approach including only red blood cell lysis and subsequent staining with an antibody that detects a epithelial specific antigen on the cells expressed exclusively by cells derived from epithelial tissues since cancers are epithelial tumors. Subsequently these cells can be quantified using a highly sophisticated microscopic approach with a special semiautomated microscope. Cells can additionally be characterized for special markers expressed on the cells which may be essential for targeted therapy. Results: Up to now more than 23 000 analyses have been performed, monitoring patients with different cnacers during treatment and the further course of disease. I can be shown that in a considerable fraction of patients additinal cells are releeased from the tumor during surgery. The response of these cells to conventional chemotherapeutic treatment can be faithfully followed and a good response to treatment has been shown to correlate with a long disease free survival. The same is true for maintenance treatment for e.g. breast or prostate cancer. In contrast, during neoadjuvant chemotherapy or during chemotherapy of metastatic disease when manisfest tumor is still present, cells can be released during the short high dose treatment. These cells can then resettle and lead to tumor progression a reason why metastatic disease is virtually not curable. Conclusion: Using the maintrac®appoach it is possible to supervise the development of systemic disease in solid tumors, the source of metastatic disease at any time of the course of disease and to timely adapt therapy. In metastatic disease it is not advisable to use high dose treatment with spectacular shrinkage of the tumors which, however, leads to cell release and relapse. Our results rather suggest that long term low dose therapy or alternative therapies that can be continued for long periods would be preferable.