Local radiotherapy reduces circulating tumor cells and metastatic progression: role of circulating cell detection in response to vascular damaging therapies

Noninvasive biological readouts of tumor metastatic risk and therapeutic efficacy are needed as healthcare costs rise. Conventional imaging modalities are expensive; require significant periods of time to see appreciable change and repetitive use increases risk of hazardous side effects. Utilizing circulating tumor cells (CTCs) as a minimally invasive biological readout of tumor progression or therapeutic response is increasingly being studied. While focus has primarily been on the predictive value of naturally occurring CTCs, a more recent effort has emerged regarding the potential consequence of therapy induced CTCs. Here we report an investigation on the acute and long-term effect of vascular disrupting therapies (high-dose radiotherapy and tumor necrosis factor-alpha (TNF)) on CTCs monitored with a non-invasive real-time system. Acute mobilization of CTCs into the blood following both radiation and TNF treatment was observed. There was no increase in metastasis frequency or extent between control and TNF-treated mice; however, a significant reduction in lung metastasis was noted in the radiotherapy alone group. Mice treated with both TNF and radiotherapy had a slightly elevated metastatic profile between that of radiation alone and control (untreated) tumors. Possible mechanisms based on therapy specific vessel disruption and cell death are discussed. Overall, CTCs correlated with tumor progression and suggest CTC enumeration described herein may be useful in clinical management of solid tumor malignancies.