Circulating tumor cells (CTCs) have significant potential to become an important tool for monitoring the effects of treatment in solid tumors. The present study reports the occurance of CTCs in cervical cancer (CC) patients during radical chemoradiotherapy (CRT), including brachytherapy (BRT), and during the follow-up period. Patients diagnosed with CC treated with radical CRT were included in the study (n=30). A total of 167 CTC-tests (MetaCell®) were provided at predefined testing time points during the study follow-up (e.g., before CRT, after CRT, every three months of follow-up). In parallel with CTC-testing, SCC-Ag were measured to compare their predictive values during treatment. CTCs were present in 96% (25/26) of patients at the time of diagnosis and in 61% (14/23) after treatment. Patients who relapsed during the 36-month follow-up (n=10) showed an elevation in pre-treatment CTC- numbers, similarly there was a significant increase in pre-treatment SCC-Ag. As next, an increased number of CTCs was observed approximately 12 weeks before relapse was diagnosed by standard imaging modalities (MRI, US, PET-CT) in 3 of 4 patients. In addition to standardized vital cytomorphology of enriched CTCs, quantitative PCR (qPCR) was used to inform the nature of CTCs before treatment. Analysis revealed increased SOX2 and POUSF expression in CTCs in the group of patients with recurrence (P < 0.02). Disease aggressiveness may be related to increased expression of stem cell markers, as found in samples from relapsed patients. CTCs may be an aid to assess tumor burden and disease aggressiveness. An increase in CTCs precedes an increase in SCC-Ag and confirmation of relapse by imaging, as shown in our study.

3rd Department of Surgery 1st Faculty of Medicine Charles University 5 Uvalu 84 150 06 Prague 5 Czech Republic

Department of Gynaecology Military University Hospital and The 3rd Faculty of Medicine U Vojenske Nemocnice 1200 169 02 Prague 6 Czech Republic

Department of Oncology The 3rd Faculty of Medicine Charles University Prague and Faculty Hospital Kralovske Vinohrady Srobarova 50 100 34 Prague 10 Czech Republic

Department of Thoracic Surgery Krajská zdravotní a s Hospital 41100 Ústí nad Labem Czech Republic

Department of Thoracic Surgery Lower Silesian Oncology Pulmonology and Hematology Center and Technical University Wroclaw Plac Ludwika Hirszfelda 12 534 13 Wrocław Poland

Laboratory of Personalized Medicine Oncology Clinic Faculty Hospital Kralovske Vinohrady Srobarova 50 100 34 Prague 10 Czech Republic

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