Detecting circulating tumor cells by hTERT-specific replication-selective adenovirus in postoperative sarcoma patients

Aim/Background

The presence of circulating tumor cells (CTCs) in peripheral blood represents a poor prognostic factor for various carcinomas, but a clear understanding of CTCs associated with sarcoma after surgery has been lacking. We attempted to detect viable CTCs in the peripheral blood of sarcoma patients after treatment for primary tumor using a telomerase-specific replication-selective viral agent. We then investigated the correlation between number of CTCs and clinical features of sarcoma.

Methods

Nineteen blood samples were obtained from 16 patients (8 males, 8 females; mean age, 69 years) with sarcoma of the trunk or extremity after surgery. Eight patients presented with myxofibrosarcoma, 3 with liposarcoma, 2 with pleomorphic sarcoma histology and 3 others. Histological grades were assigned according to the French Federation of Cancer Centers Sarcoma Group system, with grade 2 in 5 patients and grade 3 in 11 patients. Eight patients developed distant metastasis without local recurrence after treatment. We detected viable CTCs in blood samples after incubation with telomerase-specific, replication-selective, adenoviral agent carrying the green fluorescent protein gene (OBP-401 and/or F35).

Results

The mean number of CTCs was 1.9 (range, 0-18). No significant correlations were observed between number of CTCs and clinical factors (age, sex, histology, histological grade, and metastasis). If the duration from surgery to inspection for CTCs was long, the number of CTCs decreased significantly irrespective of the presence of metastasis (p = 0.036).

Conclusions

Bone marrow disseminated tumor cells (DTCs) suggest the potential existence of specific organ niches to enhance the survival of DTCs, and may undergo a period of dormancy before growing into clinically detectable metastases. We therefore hypothesized that DTCs that form from sarcomas in the course of metastatic growth might stay in the bone marrow, and that almost all CTCs may undergo apoptosis over the long term even after the establishment of metastases. Genetic analyses aimed at harvesting viable CTCs and DTCs may help identify novel biomarkers in the future.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.