Abstract 3485: Developing a non-invasive, diagnostic test for stage I non-small cell lung cancer using circulating tumor cells.

Introduction: Reliable, non-invasive diagnostic blood tests to assess high-risk pulmonary nodules are needed to avoid unnecessary invasive procedures and the risk of missing lung cancer. Methods: We used a prospective, observational, case-control study design of consecutively enrolled patients undergoing imaging for a lung nodule or diagnosed malignancy to investigate whether a non-EpCAM based circulating tumor cell (CTC) platform could accurately diagnose stage I non-small cell lung cancer (NSCLC). Phlebotomy was performed according to standardized protocols at all three participating medical centers and the number of CTCs was analyzed in a single blinded fashion on a continuous scale per mL of blood. For determining test characteristics, cases consisted of patients with stage I NSCLC, and controls consisted of advanced NSCLC, malignant non-NSCLC lung nodules, and benign lung nodules. Differences by disease group were compared formally by ANOVA or Chi-square analysis, and test performance for identifying stage I NSCLC compared to benign disease was assessed by sensitivity, specificity and C statistics. Results: Seventy-three of 79 samples were adequate for analysis after processing. The median age was 69 years (interquartile range [IQR] 65-76), 73% were male, 70% were Caucasian, 79% had a smoking history, and 45% had a history of cancer. Diagnoses consisted of 56 NSCLC patients, of which two-thirds were adenocarcinoma and 45 were stage I, 8 malignant non-NSCLC cases, and 9 benign nodules. There were no differences in basic clinical characteristics across diagnosis type other than plasma white blood cell count. Average nodule diameter was 2.2 cm (IQR 1.6-2.8) and this did not vary significantly by diagnosis. Median CTC/ml was 3.3, 3.0, 0.60 and 0.70 for Stage I NSCLC, Stage II-IV NSCLC, other non-NSCLCs, and benign nodules respectively. At a threshold of 1.0 CTC/mL, 2.0 CTC/mL and 5.0 CTC/mL respectively 63%, 54% and 44% of stage I NSCLCs had a detectable CTC burden. For these three thresholds sensitivity (89%, 89%, 100%) and specificity (64%, 53%, 44%) was calculated for discriminating stage I NSCLC from benign disease. The accuracy (C-statistic) for identifying stage I disease only relative to benign disease only improved from 0.84 to 0.91 when adding CTC/mL data to age, gender, smoking and cancer history, nodule size and location, and SUVmax. Discussion: CTCs may be useful for identifying stage I NSCLC from benign lung nodules. Addition of these data to non-invasive clinical and imaging parameters we currently use to risk stratify patients could improve clinical diagnosis for this group. Citation Format: Madelyn S. Luttgen, Khun Visith Keu, Viswam S. Nair, George Horng, Minal Vasanawala, Anand Kolatkar, Anders Carlsson, Mohsen Sabouri, Billy W. Loo, Joseph B. Shrager, Andrei Iagaru, Ware Kuschner, Peter Kuhn, Sanjiv S. Gambhir. Developing a non-invasive, diagnostic test for stage I non-small cell lung cancer using circulating tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3485. doi:10.1158/1538-7445.AM2013-3485