Quadrant of co-occurrence of circulating tumor DNA and PD-L1 expression on circulating tumor cells in monitoring disease aggressiveness and metastasis in lung cancer.

Abstract

e15040 Background: Liquid biopsies analyzing circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) allow minimally invasive monitoring and testing of lung cancer at different stages. It is known that 90% of patients succumb due to metastasis. However, accounting for patients with early metastatic signatures is extremely challenging. In addition, monitoring minimal residual disease (MRD) and identifying patients for recurrence is very prudent. While the role of CTCs in % prediction of survival has been established in several cancers. However, CTC's co-occurrence role with CtDNA and vice versa is not implored in monitoring the aggressiveness of the disease, response to therapies, and therapy decisions. In this study, we investigated ctDNA and CTC's combined roles in monitoring disease aggressiveness and metastasis in lung cancer patients. Methods: A cohort of 265 lung cancer patients with late-stage cancer were retrospectively analyzed for co-occurrence of dual biomarker ctDNA and CTC. The results were correlated as quadrant to assess clinical disease states, obtained from PET scans and HPE findings. Next Generation Sequencing (NGS) test was performed using OncoMonitor dual biomarker assay having CTC enumeration with PD-L1 expression. CTC count was performed using the OncoDiscover Liquid Biopsy Test, approved by CDSCO-India, in 1.5 ml of blood. Results: CTC distribution in this study ranged from 1-8 CTCs with a mean CTC distribution of 1.22. Amongst these patients, 75.47% (n = 200) showed the presence of CTCs and amongst these 200, 91.50% (n = 183) showed PD-L1 expression on their CTCs with a mean value of 0.99. While both biomarkers were positive for ctDNA and CTC (ctDNA+/CTC+) in 135 (50.94%) patients. Interestingly, only 19 (7.17%) patients were negative for both ctDNA and CTC (ctDNA-/CTC-). Similarly, 43 patients (16.23) were positive for ctDNA and negative for CTC (ctDNA+/CTC-), while 68 (25.66%) patients were negative for ctDNA and positive for CTC (ctDNA-/CTC+). The ctDNA+/CTC- cohort had the highest metastatic rate of 62.8%, with ctDNA+/CTC+ at 57.0%. Noteworthy, the ctDNA+ cohort showed the highest % of progressive disease patients with 20.2% and 18.6% along with CTC+ and CTC- status, respectively. The mutations, EGFR, TP53, and KRAS were observed in 62.64% (166/265) of patients. Only stable disease was observed in 29.4% of patients when both biomarkers ctDNA-/CTC- were absent. Conclusions: Overall, the ctDNA+ cohort showed a higher rate of MRD, progression, and metastasis with no stable disease. The quadrant that combined clinical results of the CTC-PD-L1 cells and CtDNA manifest the non-invasive monitoring of disease progression, treatment response, complete remission, and utility of early metastatic detection in lung cancer patients.