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

초록

Purpose: There are currently no predictive molecular biomarkers to identify patients with oligometastatic disease (OMD) who will benefit from definitive-intent radiation therapy (RT). We prospectively characterized circulating tumor cell (CTC) kinetics in patients with OMD undergoing definitive-intent RT. Methods: This prospective correlative biomarker study included patients with any solid malignancy <= 5 metastatic sites in <= 3 anatomic organ systems undergoing definitive-intent RT to all disease sites. Circulating tumor cells (CTCs) were captured and enumerated using a biomimetic cell rolling and nanotechnology-based assay functionalized with antibodies against epithelial cell adhesion molecule, against human epidermal growth factor receptor 2, and against epidermal growth factor receptor before and during RT and at follow-up visits up to 2 years post-RT. Results: We enrolled 43 patients with a median follow-up of 14.3 months. The pretreatment CTC level (cells captured/mL) was not associated with the number of disease sites (median one metastatic site/patient, range 1-5) or metastasis location (bone, brain, visceral) on Wilcoxon signed-rank test, P > .05. Post-RT, 56% of patients received systemic therapy, and 72% of patients experienced subsequent local or systemic progression. For 90% of patients, a CTC level <15 within 130 days post-RT corresponded to a durable control of irradiated lesions. Patients with a favorable versus an unfavorable clearance profile experienced significantly longer progression-free survival after RT (median 13 v 4 months, log-rank test, P = .0011). On logistic regression, CTC level >15 at a given time point was associated with clinical disease progression within the subsequent 6 months (odds ratio 3.31, P = .007). In 26% of patients with disease progression, a CTC level >15 preceded radiographic or clinical progression. Conclusion: CTCs may serve as a biomarker for disease control in OMD and may predict disease progression before standard assessments for patients receiving diverse cancer-directed therapies.

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