A simple score can identify an "ultra-high risk" (UHR) cohort (score = 5) comprising 8% of patients with 5-year EFS <10%. These patients appear not to benefit from induction therapy and could potentially be directed earlier to alternative experimental therapies in future trials.

The authors provide an update on most issues related to biology, diagnosis, and treatment of children with ependymoma based on a literature review. Ependymoma is the third most common brain tumor in children and overall survival ranges from 24% to 75% at 5 years. The extent of surgical resection remains the principal risk factor that clearly influences outcome. The influence of age, location, grade, or stage has proved to be more controversial. Current standard therapy includes surgical resection and radiotherapy. Chemotherapy has a role in infants to avoid/delay radiotherapy and can be helpful to improve resectability. About half of patients will experience relapse, and outcome is dismal. New radiation modalities, reirradiation, chemotherapy, or targeted agents have been tested with promising results. Results of multi-institutional clinical trials are awaited to determine the best first-line treatment, while results of early phase I/ II trials will explore directed therapies based on new biologic factors.

BackgroundFor children with cancer, the clinical integration of precision medicine to enable predictive biomarker–based therapeutic stratification is urgently needed.MethodsWe have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours. Furthermore, for a cohort of 12 patients, we used a circulating tumour DNA (ctDNA)–specific panel to sequence ctDNA from matched plasma samples and compared plasma and tumour findings.ResultsA total of 255 samples were submitted from 223 patients for the NGS panel. Using FFPE tissue, 82% of all submitted samples passed quality control for clinical reporting. At least one genetic alteration was detected in 70% of sequenced samples. The overall detection rate of clinically actionable alterations, defined by modified OncoKB criteria, for all sequenced samples was 51%. A total of 8 patients were sequenced at different stages of treatment. In 6 of these, there were differences in the genetic alterations detected between time points. Sequencing of matched ctDNA in a cohort of extracranial paediatric solid tumours also identified a high detection rate of somatic alterations in plasma.ConclusionWe demonstrate that tailored clinical molecular profiling of both tumour DNA and plasma-derived ctDNA is feasible for children with solid tumours. Furthermore, we show that a targeted NGS panel–based approach can identify actionable genetic alterations in a high proportion of patients.