Cell Surface Vimentin Positive Circulating Tumor Cell-Based Relapse Prediction in a Long-Term Longitudinal Study of Post-Remission Neuroblastoma Patients

Neuroblastoma (NB) is a deadly childhood disease that carries a 50% chance of relapse for anyone in remission and similar level of 5-year survival. We investigated the value of our proprietary approach – cell surface vimentin (CSV) positive circulating tumor cells (CTC) to monitor treatment response and predict relapse in NB patients under remission in a Phase II long-term preventative clinical trial. We longitudinally analyzed peripheral blood samples from 93 patients for 27 cycles (~25 months) and discovered that presence of CSV + CTCs in the first two sequential samples (baseline, cycle 4 [month 3–4]) was a significant indicator of earlier relapse. We observed strong correlation between relapse-free survival (RFS) and lack of CSV + CTCs in first 4 cycles of therapy (95%). There was sensitivity reaching 100% in predicting RFS in patients who had neither CSV + CTCs nor MycN amplification. Of note, the low number of CSV + CTCs seems equivalent to low tumor load because the prevention therapy difluoromethylornithine yields faster reduction of relapse risk when none or only 1–2 CSV + CTCs (every 6 ml) are present in the blood samples compared to > 3 CSV + CTCs. To the best of our knowledge, this is the first study that directly observes CTCs in under remission NB patients for relapse prediction and the first to gather sequential CSV + CTC data in any study in a long-term longitudinal manner.