Prospective Characterization of Circulating Tumor Cell Kinetics in Patients With Oligometastatic Disease Receiving Definitive Radiation Therapy

Abstract

<h3>Purpose/Objective(s)</h3> To characterize circulating tumor cell (CTC) kinetics in response to definitive radiation therapy (RT) among patients with oligometastatic cancer and identify a profile of CTC kinetics associated with subsequent disease progression. <h3>Materials/Methods</h3> Patients with oligometastatic disease, defined as any solid malignancy with ≤ 5 sites of metastatic disease, limited to 3 anatomic organ systems undergoing definitive RT to all known metastatic sites were enrolled on a prospective study. Blood specimens were collected at baseline, during RT and at routine follow up visits up to 24 months after completion of RT. Patients received additional lines of therapy per standard of care. CTCs were captured and quantified using a nanotechnology-based assay functionalized with aEpCAM, aHER-2, and aEGFR to facilitate biomimetic cell rolling and dendrimer-mediated multivalent binding. <h3>Results</h3> A total of 43 patients were enrolled with a median follow-up of 14.3 months corresponding to 255 CTC measurements. The median number of oligometastatic lesions at the time of RT was 1 per patient (range 1-5). Thirty-four patients (79%) received stereotactic body radiation therapy, and 24 patients (56%) went on to receive systemic therapy while on study (cytotoxic chemotherapy, hormone therapy, immunotherapy or targeted kinase inhibitors). All patients with available baseline specimens had detectable CTCs prior to RT, median 28 CTCs/ml (range 0.17-1085). In the post RT setting, CTC counts declined over a 100-day period, median 15 CTCs/ml (< 30 days), 7 CTCs/ml (30-99 days) and 3.5 CTCs/ml (≥100 days). For 90% of patients, a CTC count ≤ 15/ml < 100 days post-RT corresponded to local control of the irradiated lesion. On logistic regression, lack of CTC clearance to ≤ 15/ml within 100 days of RT was associated with progression of the irradiated lesion (OR 6.25, <i>P</i> = 0.16). In total, 31 patients (72%) experienced local or systemic cancer progression at subsequent time points. CTC count at the first time point post-RT was significantly associated with reduced progression free survival when evaluated as a continuous variable on Cox regression analysis (HR = 1.007, <i>P</i> = 0.007). During the follow up period, on logistic regression, CTC > 15/ml at a given time point was significantly associated with clinical disease progression within the subsequent 6 months (OR 3.31, <i>P</i> = 0.007). An increase in CTCs to > 15/ml preceded radiographic or biochemical progression in 8 of 31 (26%) of patients who progressed. <h3>Conclusion</h3> Our data suggests CTCs may serve as a biomarker for disease control in oligometastatic disease and may predict future disease progression prior to standard of care assessments for patients receiving diverse therapies.