Fig. 6: Proposed strategy to improve the clinical management of paediatric patients with MB using liquid biopsies.

At the time of patient hospitalisation, MRI allows the detection of hydrocephalus and the brain tumour. CSF drainage is required for patients with hydrocephalus and the CSF sample can be used for WES of ctDNA. The analysis of CSF ctDNA identifies mutations, CNVs, arm-level and chromosome gain/loss and the frequency of somatic mutations. The genomic characterisation of the cancer provides information about MB-subgroup and the risk stratification, that is critical for the diagnosis and prognosis. In addition, therapeutic targets can be identified from the analysis of CSF ctDNA. The information obtained from the CSF ctDNA can guide the surgical resection, identifying those patients for which residual disease is a risk modifier and confers worse prognosis. Analysis of follow-up CSF samples could complement the MRI to identify minimal residual disease or early detection of relapse. Improving the monitoring of tumour progression and identifying response or resistance to therapeutic targets. Importantly, if disease progression is identified, analysis of CSF ctDNA can characterise the relapsed tumour, providing information about the diagnosis, prognosis and potential therapeutic targets. This will be extremely critical for patients with disseminated disease so the therapeutic strategy can be adjusted. Moreover, the comparison of CSF ctDNA from primary with refractory disease would provide information about the emergence of secondary tumours. The study of tumour heterogeneity and cancer evolution would reveal mechanisms of resistance and aid in the discovery of therapeutic targets for MB. Altogether, the analysis of CSF ctDNA can aid in the clinical management of patients and provide information about relapse to advance research towards precision medicine.