Prospective characterization of circulating tumor cell kinetics in patients treated with radiation therapy per definitive intent oligometastatic paradigm.
Authors: Sud Shivani , Poellmann Michael , Hall Jacob , Tan Xianming , Bu Jiyoon , Park Sin-jung , Hong Seungpyo , Wang Andrew Zhuang , Casey Dana 
Published: June 2022

3053

Background: Definitive intent oligometastatic paradigm describes a state with limited metastatic sites amenable to comprehensive radiation therapy (RT). We characterized circulating tumor cell (CTC) kinetics in response to definitive RT among patients with oligometastatic cancer and identify a CTC kinetic profile associated with progression free survival (PFS). Methods: In this single-institution prospective correlative biomarker study, we enrolled patients with any solid malignancy, ≤ 5 metastatic sites in ≤3 anatomic organ systems undergoing definitive intent RT to all disease sites. Blood specimens were collected prior to RT (baseline), during RT and at follow up visits up to 24 months post RT. Additional lines of therapy were administered per standard of care. CTCs were captured and enumerated using a previously reported nanotechnology-based assay functionalized with aEpCAM, aHER-2, and aEGFR to facilitate biomimetic cell rolling and dendrimer-mediated multivalent binding. Disease status was assessed per RECIST 1.1 criteria. On exploratory analysis disease status was correlated with CTCs as a continuous and ordinal variable (cut-point upper bound of the 3rd quartile). A favorable CTC clearance profile was defined as a decrease in CTC count between pre-treatment and end of treatment - an unfavorable CTC clearance profile was defined as the opposite. Results: We enrolled 43 patients with median follow up of 14.3 months corresponding to 255 CTC measurements. Median baseline CTC count was 28 CTCs/ml (range 0.17-1085). Thirty four patients (79%) received stereotactic body radiation therapy. On Wilcoxon signed-rank test there was no association between pre-treatment CTC count and number of disease sites (median 1 metastatic site/patient, range 1-5) nor metastases site (bone, brain, visceral), p > 0.05. Thirty one patients (72%) experienced local or systemic progression at subsequent time points. For 90% of patients, a CTC count <15/ml < 100 days post-RT corresponded to durable local control of irradiated lesions. Patients with a favorable versus unfavorable clearance profile had significantly longer PFS (median 13 vs 4 months, log rank test, p = 0.0011). During the post-RT period 24 patients (56%) went on to receive systemic therapy (cytotoxic chemotherapy, hormone therapy, immunotherapy, kinase inhibitors). On logistic regression, CTC > 15/ml at a given time point was associated with clinical disease progression within the subsequent 6 months (odds ratio 3.31, p = 0.007). An increase in CTCs to > 15/ml preceded radiographic or biochemical progression in 8 of 31 (26%) of patients experiencing disease progression. Conclusions: Our data suggests CTCs may serve as a biomarker for disease control in oligometastatic disease and may predict disease progression prior to standard assessments for patients receiving diverse therapies. Clinical trial information: NCT03161821.