Liquid biopsy in neuroblastoma: cfDNA analysis for sensitive follow-up monitoring and early relapse detection

Background:

In the current SIOPEN high-risk neuroblastoma (NB) study, MRD detection methods are based on bone marrow (BM) samples. When, however, relapses occur outside the BM, disease detection may fail. Due to their minimal invasive nature, peripheral blood (PB) plasma based liquid biopsy samples can be taken repeatedly, enabling a close follow-up of disease evolution. We investigated the feasibility of MYCN copy number detection for MRD monitoring in PB cfDNA of NB patients with proven MYCN amplification.

Results:

MYCN levels, analyzed by ddPCR, correlated with treatment response and the clinical course of 10 NB patients. Further, MYCN copy detection in plasma was compared to the highly sensitive detection of GD2pos/CD56pos/DAPIpos DTCs in BM aspirates. Remarkably, in one case, despite absence of tumor cells in the BM, elevated MYCN copies (10 copies/reference) were detected in two plasma samples already six weeks before the clinical manifestation of a local relapse.

Conclusion:

cfDNA from blood plasma can be used for sensitive disease monitoring and early relapse detection also in cases when no BM disease can be measured as exemplified by a patient with a local disease relapse.