Abstract 2233: Pilot study of liquid biopsy of lung cancer circulating tumor cells (CTC) captured by a novel carbon nano-tube (CNT) differential adhesion platform
Authors: Yung Rex Chin-Wei , Tyree Connor , Colbert Ashlee , Krishna Ganesh , Mehta Rakesh , Moja Jessica , Fox Daniel , Allard Jeff , Park John , Connelly Mark 
Published: June 2022

Introduction: Diagnosing and profiling lung cancers (LC) is challenging across the disease spectrum. Early-stage LC are small and hard to distinguish from benign nodules. Patients are often infirm, increasing biopsy risks. Monitoring for LC progression, recurrence or second primaries are further challenges. CTCs recovered from blood sample is non-invasive, easily repeatable across the clinical course of disease treatment and progression. Unlike cell-free nucleic acid profiles, CTC is mutation agnostic.

Aims/Methods: Pilot test of a Carbon-nanotube (CNT) platform on capturing suspected LC cells across a range of stages/cell types.51 “normal controls” recruited to balance cancer: benign cases and to test specificity. Study period 1/2020 - 8/2021Procedure details per Loeian M Lab on a Chip 2019;11:1899. 16 ml of whole blood was lysed, nucleated cells cultured for 48 hours on a CNT coated surface. Cells were fixed, stained with CK7/8/18/pancytokeratinAE1/2 epithelial markers (CTC), CD45(WBC), nuclear DAPI control. A sample is considered CTC positive if 1 or more CD45-/CK+ cells are found.

Results: 142 subjects were recruited from four clinical sites. 18 samples were non-analyzable due to shipping and preanalytical error.43 of 56 cancers had pathologic staging: 30% I, 16% II, 35% III, 19% IV.CTCs were found in 77% of LC samples (sensitivity), specificity 94%, Positive Predictive Value 92% and Negative Predictive Value 83%.Even in Stages I/II patients, 75% were found to have CTCs. The number of CTC found varied by patient, (range 0-31).

Conclusion: CNT adherence enables antigen independent capture of live, viable LC CTCs from whole blood with high specificity and PPV. Planned inclusion of additional CTC markers should improve the detection of other classes of CTCs. High specificity and PPV identify this as a useful “rule-in” test to pursue downstream testing to confirm early LC diagnosis or follow-up surveillance for recurrence.

Table 1. Performance of SS-CNT in capturing CTCs Test Result Tissue Positive Cancer Tissue Negative Cancer or Control Total CNT Test + True Pos (TP) 43 False Pos (FP) 4 47 CNT Test - False Neg (FN) 13 True Neg (TN) 64 77 56 68 124 Test Performance 1 or more CTC as positive Sensitivity TP/(TP + FN) 76.80% Specificity TN/(TN + FP) 94.10% Positive Predictive Value PPV TP/(TP + FP) Rule-in 91.50% Negative Predictive Value NPV TN/(TN + FN) Rule- out 83.10%

Citation Format: Rex Chin-Wei Yung, Connor Tyree, Ashlee Colbert, Ganesh Krishna, Rakesh Mehta, Jessica Moja, Daniel Fox, Jeff Allard, John Park, Mark Connelly. Pilot study of liquid biopsy of lung cancer circulating tumor cells (CTC) captured by a novel carbon nano-tube (CNT) differential adhesion platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2233.