PD01.10 Diagnostic Non-Invasive Biopsy Can Substitute Conventional Tissue Dependent Procedures in Suspected Cases of Lung Cancer

Obtaining tissue from lung lesions for histopathological analysis is conventionally the only method of definitive diagnosis of lung cancer. However, there are considerable risks associated with invasive procedures including Pneumothorax, Haemothorax, Empyema, Pulmonary Embolism besides bleeding and pain. Additionally, the tissue is oftentimes necrotic and may not cover tumor heterogeneity. Liquid biopsies for detection of ctDNA are now approved for considering treatments with Tyrosine Kinase Inhibitors (TKI) but wholesome, substitutive non-invasive biopsy for diagnosis is presently unavailable. We present here a breakthrough, non-invasive biopsy based on a Circulating Tumor Associated Cell (C-TAC) Assay that enables efficient immunofluorescent interrogation coupled with molecular characterization in a single blood draw. We obtained 15 ml of venous blood draw from 498 known patients of lung cancer, [327 (65.7 %) male, 171 (34.3 %) female]. C-TACs were enriched by paradoxical cytotoxic processing and characterised for cancer (EPCAM, PanCK) and lung specific antigens (TTF1 and Napsin) besides EMA, P40, CK7, Synaptophysin, Chromogranin A, CD56, Calretinin, PD-L1, ALK (D5F3) by immunocytochemistry (ICC). EGFR mutations, ALK, RET and ROS1 fusions were evaluated from plasma by NGS. C-TACs (EPCAM and CK positive) could be obtained from 458 samples out of 498 (92.0 %). Among the 95 samples that were characterised by staining for organ specific antigens, 100 % samples were positive for Napsin whilst 67.0 % samples were TTF1 positive. Classification of lung cancer subtypes of adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma and neuroendocrine tumors was possible in 94 out of 95 samples (98.9 %). ctDNA was obtained from 332 samples. EGFR mutations were detected in 110 (33.1 %) samples, which had concordance with tissue EGFR status in 89 % of 124 EGFR positive samples. ALK fusion was detected in 2 (0.6 %) samples which had concordance of 100 % with tissue ALK status. None of the tissue evaluated carried RET or ROS1 fusion and none were detected in any plasma sample. Our results show that ICC based characterization of C-TACs can provide necessary diagnostic information non-invasively to substitute conventional procedures dependent on tissue extraction. Additionally, ctDNA based detection of molecular characteristics completes most clinical decision-making requirements in lung cancer.