PPROSPERITIT is a prospective clinical study assessing the use of comprehensive molecular profiling to define the best matching targeted and immune treatment for relapsed, refractory or very high risk pediatric CNS tumors.

PPROSPERITIT will identify specific molecular changes by using genomic sequencing technologies in refractory/recurrent or very high-risk pediatric CNS tumors. The study will employ an analytically validated comparison of a selection of targeted agents/immune therapies on the basis of commercially available comprehensive genomic profiling FoundationOneHeme panel (F1Heme, comprising DNA and RNA analysis) vs selection of agents based on more complex DNA/RNA/Protein based analyses. This will be coupled to a computer algorithm that uses preexisting definitions and prioritization of target-agent pairs to assign patients by actionable mutation results to a targeted treatment. The selection of targeted agents will be performed by a multidisciplinary molecular tumor board, but the recommended treatment will not be a part of the PPROSPERTIT study.

Inclusion Criteria:

1. Patient Informed consent form must be appropriately obtained under the applicable local and regulatory requirements. Each patient must sign a consent form prior the enrollment to document their willingness to participate.
2. The subject is male or female, aged 1 - 19 years
3. The subject must have a histologically proven recurrent/ refractory or very high-risk CNS tumors
4. Patients must be in good overall physical condition, which allows tumor biopsy
5. Patients must have a life expectancy of at least 3 months.
6. Patients must have a tumor amenable to image-guided or direct vision biopsy and be willing and able to undergo a tumor biopsy and/or blood taking for molecular profiling.
7. Patients must be accessible for follow-up.

Exclusion Criteria:

1. Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
2. Pregnant and/or breastfeeding women, if applicable
3. No intention to treat the patient.