Anders Carlsson, PhD, Viswam S. Nair, MD, MS, Madelyn S

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Circulating Tumor Microemboli Diagnostics for Patients with Non–Small-Cell Lung Cancer Anders Carlsson, PhD, Viswam S. Nair, MD, MS, Madelyn S. Luttgen, BS, Khun Visith Keu, MD, George Horng, MD, Minal Vasanawala, MD, Anand Kolatkar, PhD, Mehran Jamali, MBBS, Andrei H. Iagaru, MD, Ware Kuschner, MD, Billy W. Loo, MD, PhD, Joseph B. Shrager, MD, Kelly Bethel, MD, Carl K. Hoh, MD, Lyudmila Bazhenova, MD, Jorge Nieva, MD, Peter Kuhn, PhD, Sanjiv S. Gambhir, MD, PhD Journal of Thoracic Oncology Volume 9, Issue 8, Pages 1111-1119 (August 2014) DOI: 10.1097/JTO.0000000000000235 Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Circulating tumor cells and CTM used for modeling. Panel (A) shows the composite image for an HD-CTC from a patient with stage I adenocarcinoma followed by the individual DAPI positive (Blue, B), Cytokeratin positive (Red, C), and CD45 negative (Green, D) channels defining the cell. A doublet (Panels E–H), triplet (Panels I–L), and “mega” cluster of more than 8 HD-CTCs (Panels M–P) are shown as composites and by individual channels. HD-CTM were defined as more than one HD-CTC with touching cytoplasm (see Methods) for further modeling. Journal of Thoracic Oncology 2014 9, 1111-1119DOI: (10.1097/JTO.0000000000000235) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Patient flow. This was a prospective, observational study of patients undergoing evaluation for lung cancer by FDG PET-CT that had blood drawn for CTC analysis. We excluded patients with blood processing errors, those without a definitive benign or non–small-cell lung cancer diagnosis, and those with concurrent cancers. Clinical, imaging, and CTC variables of interest were explored in a training set (n = 88) and validated in a test set (n = 41) for all patients and for the stage I subgroup only. Journal of Thoracic Oncology 2014 9, 1111-1119DOI: (10.1097/JTO.0000000000000235) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 HD-CTM integrated with clinical and imaging data improve diagnostic accuracy for NSCLC. Receiver operating characteristic (ROC) curves for diagnostic models calibrated using the training set and carried forward to the test set are shown. Models A–C were trained and tested using all comers, whereas D–F used stage I cancers only. Each plot displays the performance of two models (clinical alone and with CTM) and a p value estimating the significance of the difference between the ROC curves. The ROC AUCs and their confidence intervals are given in the bottom right corner of each plot. Journal of Thoracic Oncology 2014 9, 1111-1119DOI: (10.1097/JTO.0000000000000235) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions