Thesis Lieke van Zogchel

Abstract 

Cancer remains a leading cause of childhood death in the Netherlands and other high-income countries, especially solid tumors. Despite intensive multi-modal therapies, survival rates remain low, mainly due to high relapse rates. One of the reasons is that current diagnostics are not sensitive enough to detect minimal residual disease (MRD). My thesis explores the potential of liquid biopsies – innovative techniques that detect tumor-derived material, such as circulating tumor DNA or cells, in body fluids like blood, cerebrospinal fluid, and bone marrow. These methods may allow earlier, more accurate, and less invasive detection of cancer.
The thesis is divided into two parts. Part I focuses on MRD in children with neuroblastoma, the most common extracranial solid tumor in childhood. Using highly sensitive molecular analyses (RT-qPCR for RNA markers) of bone marrow, we identified patient subgroups at very high risk of relapse. We also developed new marker panels to capture tumor cells that undergo phenotypic changes making them invisible to current methods, thus improving detection of hidden disease.
Part II investigates circulating tumor DNA (ctDNA) as a biomarker in several pediatric solid tumors, including neuroblastoma, nephroblastoma, rhabdomyosarcoma, and Ewing sarcoma. With advanced technologies such as droplet digital PCR and sequencing, we demonstrated that ctDNA can serve as a minimally invasive tool to monitor tumor burden, assess treatment response, and detect relapse earlier than conventional diagnostics.
Together, these studies show that liquid biopsies hold great promise for improving risk stratification and clinical care of children with solid tumors, ultimately aiming to increase survival.