Circulating Tumor Cell Assessment in Presumed Early Stage Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy: A Prospective Pilot Study

Purpose: In patients treated with stereotactic body radiation therapy (SBRT) for presumed early stage non-small cell lung cancer (NSCLC), detection and monitoring of circulating tumor cells (CTCs) may be useful for assessing treatment response safely and noninvasively. No published reports of CTC trends in this patient population exist to date. Methods and Materials: Patients with clinically diagnosed stage I NSCLC treated with SBRT were eligible for this institutional review board–approved prospective clinical trial. Peripheral blood samples were assayed for CTCs via a green fluorescent protein-expressing adenoviral probe. CTC positivity was defined as 1.3 green fluorescent protein-positive cells/mL of collected blood. Samples were obtained before (pre–radiation therapy [RT]), during, and after SBRT (post-RT; months 1, 3, 6, 12, 18, and 24). SBRT was delivered in ≤5 fractions (median dose of 50 Gy in 12.5 Gy fractions) to a biological equivalent dose of ≥100 Gy in all cases. Results: Forty-eight consecutive patients (T1a [73%], T1b [21%], and T2a [6%]) were enrolled. Median follow-up was 14.2 months. Twenty patients (42%) had a positive CTC level pre-RT, with a median CTC count of 4.2 CTCs per mL (interquartile range [IQR], 2.2-18.7). Of these 20 patients, 17 had evaluable post-RT CTC evaluations showing reduced CTC counts at 1 month (median, 0.2; IQR, 0.1-0.8) and 3 months (median, 0.6; IQR, 0-1.1). Three of these 17 patients experienced disease progression at a median of 19.9 months; all 3 experienced ≥1 positive post-RT CTC test predating clinical progression by a median of 16 months (range, 2-17 months). In contrast, among patients presenting with CTC-detectable disease and for whom all post-RT CTC tests were negative, none experienced recurrence or progression. Conclusions: CTC monitoring after SBRT for presumed early stage NSCLC may give lead-time notice of disease recurrence or progression. Conversely, negative CTC counts after treatment may provide reassurance of disease control. CTC analysis is thus potentially useful in enhancing clinical diagnosis and follow-up in this population.