Circulating tumor cell viability during and after radiotherapy mirrors treatment response in cancer patients

The response to radiotherapy (RT) is influenced by the individual DNA repair capacity of both the tumor cells and the host. In this study, we assessed whether circulating tumor cell (CTC) enumeration, kinetics, and CTC viability (i.e., the apoptotic rate) could provide a more accurate tool for monitoring and stratifying the RT response. We analyzed CTCs and tumor-derived extracellular vesicles (tdEVs) during RT in 71 lung (n = 35) and breast (n = 36) cancer patients receiving RT treatment for brain (n = 54) and bone (n = 19) metastases. The DNA repair capacity of the host was assessed by ex vivo irradiation of peripheral blood mononuclear cells (PBMCs). RT treatment did not seem, in most cases, to cause a short-term release of CTCs. We found that both the number and apoptotic rate of CTCs before and after RT treatment is a powerful indicator of poor prognosis. Additionally, the fraction of apoptotic CTCs correlated with RT response and patient outcome. This study demonstrated that the RT response is associated with tumor-specific traits, which can be accessed via easily accessible liquid biopsy approaches.