Circulating Tumor Cells Are Associated with Recurrent Disease in Patients with Early-Stage Non–Small Cell Lung Cancer Treated with Stereotactic Body Radiotherapy

Purpose: Although stereotactic body radiotherapy (SBRT) is effective in early-stage non–small cell lung cancer (NSCLC), approximately 10%–15% of patients will fail regionally and 20%–25% distantly. We evaluate a novel circulating tumor cell (CTC) assay as a prognostic marker for increased risk of recurrence following SBRT. Experimental Design: Ninety-two subjects (median age, 71 years) with T1a (64%), T1b (23%), or T2a (13%) stage I NSCLC treated with SBRT were prospectively enrolled. CTCs were enumerated by utilizing a GFP-expressing adenoviral probe that detects elevated telomerase activity in cancer cells. Samples were obtained before, during, and serially up to 24 months after treatment. SBRT was delivered to a median dose of 50 Gy (range, 40–60 Gy), mostly commonly in four to five fractions (92%). Results: Thirty-eight of 92 subjects (41%) had a positive CTC test prior to SBRT. A cutoff of ≥5 CTCs/mL before treatment defined favorable (n ¼ 78) and unfavorable (n ¼ 14) prognostic groups. Increased risk of nodal (P ¼ 0.04) and distant (P ¼ 0.03) failure was observed in the unfavorable group. Within 3 months following SBRT, CTCs continued to be detected in 10 of 35 (29%) subjects. Persistent detection of CTCs was associated with increased risk of distant failure (P ¼ 0.04) and trended toward increased regional (P ¼ 0.08) and local failure (P ¼ 0.16). Conclusions: Higher pretreatment CTCs and persistence of CTCs posttreatment is significantly associated with increased risk of recurrence outside the targeted treatment site. This suggests that CTC analysis may potentially identify patients at higher risk for regional or distant recurrences and who may benefit from either systemic therapy and/or timely locoregional salvage treatment.