OFP01.05 Circulating Ensembles of Tumor Associated Cells Facilitate Efficient Triaging of Asymptomatic Individuals for Low Dose Computed Tomography


      Screening of Individuals for Lung cancer is presently based on radiological evaluation for presence of suspicious thoracic nodules by Low Dose Computed Tomography (LDCT). LDCT is not only associated with risks of exposure to radiation but is also not confirmatory and often necessitates an invasive biopsy in suspicious cases. We present a non-invasive approach for triaging of asymptomatic individuals prior to screening investigations such as LDCT. This approach is based on detection of Circulating Ensembles of Tumor Associated Cells (C-ETACs) which are clusters of malignant cells derived from a tumor mass.


      We collected peripheral blood from 10625 asymptomatic individuals (6627 females and 3398 males) with no prior diagnosis of cancer and no clinical symptoms indicative of cancer. All individuals underwent LDCT scans following blood collection. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and treated with an epigenetically activating medium which induces cell death in normal (non-malignant) hematolymphoid cells as well as epithelial cells in peripheral blood, but selectively confers survival privilege on apoptosis resistant tumor-derived Circulating Tumor Cells (CTCs)and their clusters (C-ETACs). Two-way association studies were performed to correlate detection of C-ETACs and LDCT findings (Lung RADS score).


      Among the 10625 individuals, samples from 467 were positive for C-ETACs while 10158 were negative for C-ETACs. Among the 10625 individuals, 8422 had no abnormal findings on LDCT (LungRADS = 1), 1833 had borderline risk of malignancy (Lung RADS = S / 2), 283 had marginally elevated risk of malignancy (Lung RADS = 2S / 3), while 78 individuals had elevated risk of malignancy (Lung RADS = 3S / 4A / 4B / 4x). Detection of C-ETACs was associated with 5-fold increase in risk of malignancy based on Lung RADS (3.2% vs 0.6%). Conversely, 19.2% of all individuals with elevated risk of malignancy were positive for C-ETACs as compared with 4.1% - 5.3% individuals with no suspicious findings or borderline risk of malignancy suggesting 4.5-fold increased risk.


      The findings suggest a positive association between detection of C-ETACs and incidence of significant findings in LDCT indicative of higher risk of malignancy. Non-invasive evaluation of asymptomatic individuals for presence of C-ETACs can facilitate efficient triaging prior to LDCT, thus significantly expediting diagnosis and treatment.