Nano-Based Quantification of Circulating Tumor Cells as a Biomarker of Disease Status in Oligometastatic Patients Following Metastases-Directed Radiation Therapy

Circulating tumor cells (CTCs) have been demonstrated as a biomarker in certain advanced cancers. Additionally, there has been increasing recognition that definitive treatment, including radiotherapy (RT), may lead to cure or significantly increased time to progression in oligometastatic solid malignancies. However, differentiating between patients with truly oligometastatic disease and those who will develop systemic disease is difficult. In most cases, secondary to a lack of reliable biomarker, surveillance often relies heavily on imaging. We hypothesized that CTCs are a sensitive biomarker in post-treatment surveillance after metastasis-directed definitive RT in oligometastatic patients. Patients with oligometastatic solid-tumor malignancies with up to 3 metastases undergoing definitive RT to all known metastatic sites were enrolled on a prospective study. Peripheral blood (7 mL) was drawn prior to initiation of RT, 1-3 time points during RT, and at subsequent follow up appointments. CTCs were quantified using CapioCyte, a nanotechnology based CTC capture system that takes advantage of biomimetic cell rolling and dendrimer-mediated strong multivalent binding. A total of 33 patients were enrolled with a median follow-up of 12.4 months. All patients had detectable CTCs on enrollment with a median of 24 CTCs/mL (range 3-120). Pre-treatment CTCs did not predict subsequent recurrence (p=0.94). 20 patients (67%) subsequently had progression of disease, with an overall median PFS of 4.6 months. Of those who recurred, 10 patients had CTCs quantified at or near the time of progression, with 8 of these patients showing a corresponding increase in CTCs (2.5-28.7 fold increase). Out of 6 patients who were started on systemic therapy after progression, CTCs declined or were stable in all 5 patients with a partial response or stable disease, and increased in 1 patient who progressed. Our data suggests CTCs as quantified by the CapioCyte technology correspond with disease status and are a reliable biomarker for post-treatment surveillance in oligometastatic solid-tumor malignancies.