Blood tumor load: combining biomarkers to increase the proportion of informative patients

Background: The load of circulating tumor cells (CTC) and tumor-derived extracellular vesicles (tdEV) strongly correlates with poor clinical outcomes and can be used to evaluate treatment response and the presence of treatment targets. However, the frequency of CTC is low, making an accurate assessment impossible in most patients. Here, we introduce blood tumor load (BTL), in which CTC and tdEV are combined into one value ranging from 0 (low) to 1 (high) to simplify result interpretation and increase the percentage of patients from which a reliable assessment can be made. Patients and methods: The CTC and tdEV counts were obtained from the ACCEPT analysis of the CellSearch image datasets of 98 metastatic breast cancer patients (mBC) and 157 castration-resistant prostate cancer patients (CRPC). The BTL generated using these counts was used in human epidermal growth factor receptor 2 (HER2) expression assessment in mBC patients. The BTL scores of CRPC patients at baseline and first follow-up time points were evaluated, and a change in BTL, indicating response to therapy, was measured in the patients. Results: Using 10 CTCs as a threshold, the HER2 positivity could be determined in 34/98 (35%) breast cancer patients, whereas with BTL, the positivity increased to 76/98 (78%). The BTL showed an improved Cox hazard ratio for overall survival in 157 CRPC patients before and at first follow-up points compared with CTC and tdEV alone. A decrease in BTL indicating response to therapy was seen in 45% of CRPC patients, and an increase in BTL was seen in 9%, indicating progression on treatment. The remaining 46% of patients showed no change. Conclusions: In this study, we demonstrated the applications of BTL in improving the reliability of measuring response to therapy and increasing the proportion of patients from which the presence of a treatment target can be assessed.