Evaluating personalized circulating tumor DNA detection for early-stage lung cancer

Circulating tumor DNA (ctDNA) has been widely used as a minimally invasive biomarker in clinical routine. However, a number of factors such as panel design, sample quality, patients' disease stages are known to influence ctDNA detection sensitivity. In this study, we systematically evaluated common factors associated with the variability of ctDNA detection in plasma and investigated ctDNA abundance in bronchoalveolar lavage (BAL). Whole exome profiling was conducted on 61 tumor tissue samples to identify tumor-specific variants, which were then used to design personalized assay MarRyDa (R) for ctDNA detection. DNA extracted from BAL fluid and plasma were genotyped using MarRyDa (R) platform. Our analysis showed that histological subtypes and disease stages had significant differences in ctDNA detection rate. Furthermore, we found that DNA purified from BAL supernatants contains the highest levels of ctDNA compared with BAL precipitates and plasma; therefore, utilizing BAL supernatants for tumor detection might provide additional benefits. Finally, we demonstrated that tumor cellularity played significant roles in the design of personalized ctDNA panel which eventually impacts ctDNA detection sensitivity. We suggest setting a flexible criteria for sample quality control and utilization of BAL might benefit more patients in clinics.

Automated summary

In this study, we evaluated factors influencing the detection sensitivity of circulating tumor DNA (ctDNA) and found that histological subtypes and disease stages played significant roles in ctDNA detection rate. Additionally, we discovered that DNA extracted from bronchoalveolar lavage fluid had higher levels of ctDNA compared to plasma, suggesting its potential as a valuable sample source for tumor detection. Furthermore, tumor cellularity was shown to have a significant impact on the design of personalized ctDNA panels and the overall detection sensitivity.