Impact of ccfDNA on clinical decision making in NEN patients

Neuroendocrine neoplasms (NENs) require regular assessment of tumor growth and treatment response. However, adequate, non-invasive tumor markers are currently lacking. Recently, we demonstrated that sequential genome-wide copy number alteration (CNA) profiling of circulating cell-free DNA (ccfDNA) could serve as novel, non-invasive biomarker in NEN patients. Expanding upon these findings, we will explore and benchmark a new analytical approach, GIPXplore, against the current gold standard for ccfDNA CNA analysis (ichorCNA). Moreover, aberrant methylation in ccfDNA will be analyzed using the novel, highly sensitive MSRE-smMIP-seq technology. Both methods for detection and quantification of tumoral DNA will be correlated to clinical outcomes in an extensive prospectively collected cohort of 250 NEN patients. This cohort will be established through the international collaboration between the Belgian ENETS CoEs and Dutch FORCE initiative. In doing so, we will validate the potential added value of ccfDNA analysis for clinical decision-making in NEN patients and facilitate clinical implementation.