Jenny Adamski, John R Apps, Sarita Depani, Rebecca M Hill, Barry Pizer, Thankamma Ajithkumar, Simon Bailey, Kim S Bull, Fernando Carceller, Julia V Cockle, Robert A Dineen, Jessica A Douglas-Pugh, Jenny Gains, Debbie Hicks, Mette Jorgensen, John-Paul Kilday, Juan-Pedro Martinez-Barbera, Timothy A Ritzmann, Emma Thompson, Simon Gates, Darren Hargrave, Allan Hackshaw, G A Amos Burke, Steven C Clifford
Rare paediatric central nervous system (CNS) tumours comprise a biologically-heterogeneous group of low-incidence diseases that present significant challenges to both therapeutic development and clinical research, limiting the availability of high-quality evidence to guide clinical care. The UK3CR Children's Cancer Research Group (CRG) CNS Tumours Subgroup convened a multidisciplinary workshop to identify research priorities and establish a strategic framework for advancing clinical trials in this setting. Four high-priority tumour groups-craniopharyngioma, choroid plexus carcinoma (CPC), very high-risk medulloblastoma (VHR-MB), and rare embryonal and sarcomatous tumours (REST), including embryonal tumour with multilayered rosettes (ETMR)-were evaluated. Key outcomes included the feasibility of a UK-led craniopharyngioma trial, the need for enhanced national CPC data collection, and support for European early-phase platform trials in VHR-MB. REST highlighted transnational regulatory complexity requiring coordinated registries and parallel trial models. Cross-cutting barriers included regulatory discordance, contracting delays, fragmented funding, pharmacovigilance differences, data-sharing constraints, and interoperable infrastructures. The workshop emphasised innovative methodologies, including Bayesian/adaptive designs, platform trials, and external control arms, to maximise efficiency in small populations, alongside strengthened patient involvement and international collaboration. Collectively, these findings define a collaborative and internationally-aligned strategic roadmap to accelerate clinical research and improve outcomes in rare paediatric CNS tumours.