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New EU research: blood tests for neuroblastoma

A large international consortium has secured EU funding for research into so-called liquid biopsies for neuroblastoma, a form of childhood cancer. The researchers are testing whether a blood test can help to earlier detect the cancer coming back in children with recurrent neuroblastoma, and to increase their chances of survival. The use of blood tests marks a breakthrough in non-invasive diagnostics in children with cancer and a catch-up compared to adult oncology, according to the scientists.

Each year, around 25 children in the Netherlands are diagnosed with neuroblastoma, a tumor of the sympathetic nervous system. Half of these children have a high-risk form of the disease, which comes back after treatment in 50% of cases.

Blood or urine

‘To avoid children receiving treatment that has stopped working, it is important to keep a close eye on the possible recurrence of the cancer,’ says Dr. Lieve Tytgat, pediatric oncologist and research group leader specialized in neuroblastoma. ‘This is currently still done with scans or bone marrow biopsies. These tests are invasive for the child and we cannot do them too often. So-called liquid biopsies can offer a solution. You can learn a lot about the tumor from blood or urine samples, which we can take much more frequently and more easily from a child.’

Tytgat, together with colleagues in Vienna, leads a European research consortium of 25 collaborating institutes that conducts research into liquid biopsies in children with neuroblastoma. The project is led by the Princess Máxima Center and the Austrian St. Anna Children's Cancer Research Institute, and coordinated by SIOPE, the European Society for Pediatric Oncology.

The research that is now starting with EU funding is the first time worldwide that liquid biopsies will be used in the clinical care of children with a solid tumor. Liquid biopsies are already being used much more often in adults. Tytgat: ‘With this study we will catch up compared to research in adults; an important development for children with cancer.’

Early sign

‘Cancer cells leave traces of genetic material in blood and urine,’ Tytgat explains. ‘We will study whether we can use these traces as an early sign that the cancer is coming back after treatment in children with neuroblastoma.’ All children in the study will receive the standard tests: an MRI scan and a bone marrow biopsy every six months. In addition, half of the children are offered a blood test every month. Tytgat: ‘We will compare the results of these tests to confirm that the blood test can properly detect the return of the cancer. We are also looking at whether the blood test can detect the disease sooner than the standard tests.’

In neuroblastoma, tumor cells have many different changes in their DNA. It is one of the reasons why neuroblastoma is so difficult to treat after it has come back. ‘That is why in this new study, we also aim to look for specific DNA changes that are linked to existing targeted drugs,’ says Tytgat. ‘We hope to not only detect a recurrence earlier, but where possible also find a better treatment, tailored to the specific tumor of the individual child.’

Clinical application

Neuroblastoma cells leave various genetic traces: in DNA and mRNA. The mRNA changes in neuroblastoma are known from previous research by Tytgat, among others. In the new study, the scientists will also look for new DNA traces of neuroblastoma, or combinations of DNA and RNA changes that can even more specifically indicate the presence of tumor cells. The team also aims to develop a digital tool to ensure that the research fits in well with clinical practice. In future, they aim for this tool to help pediatric oncologists to translate the results of the liquid biopsies into the best treatment for each child.

Sabine Taschner-Mandl, PhD, Principal Investigator at St. Anna Children's Cancer Research Institute, co-leads the liquid biopsy diagnostics in the European project, named MONALISA. She says: ‘We are using liquid biopsies for children with neuroblastoma for the first time in a clinical setting; so far, we have only tested them in research. Monitoring the response to therapy and disease course is of great importance for improving the chance of survival of patients with high-risk neuroblastoma. In MONALISA we want to make liquid biopsy diagnostics available to patients across 11 European countries and plan make these innovative tests available for even more patients in the future.’

With the research, Tytgat, Taschner-Mandl and colleagues are taking an important step forward for children with cancer – starting with neuroblastoma, and aiming to expand into other tumors. Tytgat: ‘This is truly a breakthrough in the world of non-invasive diagnostics. I expect that this study will mark the start of the clinical application of liquid biopsies in childhood oncology.’

The EU grant, totaling €8 million, has been awarded to the MONALISA consortium of 25 international partners within the SIOPEN (International Society of Pediatric Oncology Europe Neuroblastoma Group). Dr. Lieve Tytgat leads the consortium in collaboration with dr. Sabine Taschner-Mandl, Principal Investigator at St. Anna Children's Cancer Research Institute in Vienna, Austria. Just over a quarter of the funding for the research has been awarded to the Princess Máxima Center.