Neuroblastoma is a tumor of the nervous system that can occur throughout the body. Around 25 children in the Netherlands are diagnosed with the disease each year. The cancer can come back even after intensive treatment. One reason is that standard methods—like examining bone marrow under a microscope—cannot always detect tiny amounts of remaining cancer cells.
In check-ups during and sometimes after treatment, children with neuroblastoma get scans and bone marrow tests to check the cancer goes away and stays away. In some children, the cancer comes back because tumor cells are left in the body. This makes it important to pick out those children with high-risk neuroblastoma who have residual disease, so their treatment plan can be adjusted if necessary.
Detecting ‘hidden’ cancer cells
In the Tytgat group, Lieke researched a new way to find these hidden cancer cells: the so-called ‘liquid biopsy,’ essentially a blood test. Instead of only looking at cells under a microscope, this test searches for small fragments of genetic material (DNA or RNA) from the tumor in blood or bone marrow. This approach is far more sensitive and less invasive for the child.
Her research had two parts. First, she studied children with neuroblastoma using a technique called RT-qPCR, which can measure tumor RNA in bone marrow with great precision. RNA acts as a messenger for DNA. This method proved better at predicting which children are likely to relapse compared to standard microscopic analysis.
In the second part, Lieke focused on tiny fragments of tumor DNA in the blood, known as circulating tumor DNA (ctDNA). Using advanced techniques such as digital PCR (a method to detect very small amounts of DNA) and sequencing (reading the DNA code), she showed that these fragments are a strong indicator of disease progression. These tests also look promising for other childhood cancers. The aim is for doctors to see earlier whether treatment is working or if the cancer is coming back. This could in future enable them to tailor the treatment plan to each individual child.
Better predictions
‘These new biomarkers give us a measurable signal in the blood that shows whether cancer is still present,’ says Lieke. ‘We hope this means we could better predict which children might relapse and act faster if needed. With these new blood and bone marrow tests, we expect that in future, we could monitor much more accurately whether the cancer is truly gone. That offers hope for quicker and more effective treatment if the disease comes back’
Van Zogchel is proud that her work is already being applied in a clinical trial setting. Not only at the Máxima, but also in other European countries. The blood test from her research is one of the tests that will be studied further as part of the European clinical trial, MONALISA, that will open soon.
Clinical trial
Children with high-risk neuroblastoma that came back after treatment can take part in the new trial. They will be followed up to see if the blood tests can detect the cancer coming back a second time sooner than other tests. Van Zogchel: ‘It’s wonderful to see a test that we developed in the lab now being used in a clinical trial. We’ll have to wait for the trial results, but I hope that in a few years, we can offer this simple blood test to all children with a neuroblastoma that has come back.’
Dr. Lieke van Zogchel defended her PhD thesis on October 14. Her research was supported by KWF Dutch Cancer Society, Maarten van der Weijden Foundation, Stichting aMEESing Mees, Stichting 100% Judith, and Stichting Koppie-Au.
Have you or your child had neuroblastoma, and do you have questions about this study? Check out the Question & Answer page or contact your treating physician.