Brain tumours are the leading cause of paediatric cancer-associated death worldwide. High-grade glioma (HGG) represents a main cause of paediatric brain tumours and is associated with poor prognosis despite surgical and chemoradiotherapeutic advances. The molecular genetics of paediatric HGG (pHGG) are distinct from those in adults, and therefore, adult clinical trial data cannot be extrapolated to children. Compared to adult HGG, pHGG is characterised by more frequent mutations in PDGFRA, TP53 and recurrent K27M and G34R/V mutations on histone H3. Ongoing trials are investigating novel targeted therapies in pHGG. Promising results have been achieved with BRAF/MEK and PI3K/mTOR inhibitors. Combination of PI3K/mTOR, EGFR, CDK4/6, and HDAC inhibitors are potentially viable options. Inhibitors targeting the UPS proteosome, ADAM10/17, IDO, and XPO1 are more novel and are being investigated in early-phase trials. Despite preclinical and clinical trials holding promise for the discovery of effective pHGG treatments, several issues persist. Inadequate blood-brain barrier penetration, unfavourable pharmacokinetics, dose-limiting toxicities, long-term adverse effects in the developing child, and short-lived duration of response due to relapse and resistance highlight the need for further improvement. Future pHGG management will largely depend on selecting combination therapies which work synergistically based on a sound knowledge of the underlying molecular target pathways. A systematic investigation of multimodal therapy with chemoradiotherapy, surgery, target agents and immunotherapy is paramount. This review provides a comprehensive overview of pHGG focusing on molecular genetics and novel targeted therapies. The diagnostics, genetic discrepancies with adults and their clinical implications, as well as conventional treatment approaches are discussed.Intracranial and intraspinal tumours are the most common solid tumours in paediatrics (1). They are the second leading cause of cancer-associated death in children and adolescents under the age of 19 in the USA and Canada (1), with an average annual age-adjusted incidence of 6.06 per 100,000 in the USA between 2012 and 2016 (2). Brain tumours are now the leading cause of paediatric-cancer-associated death worldwide, surpassing deaths from childhood leukaemia (3). Gliomas represent the highest proportion of childhood brain tumours (4, 5) accounting for 60% of paediatric brain tumour cases (5, 6), of which approximately half are classified as high grade (6, 7).

e16066 Background: The increased incidence of cancer after renal transplantation is well recognised. Differences in cancer risk depend on the type of cancer but overall the incidence of solid cancer in kidney transplant recipient is at least twofold. Long term immunosuppression, oncogenic viruses and changes in immune surveillance are contributing factors. The incidence of renal cell carcinoma (RCC) is approximately six-fold greater than in the general population. Screening for RCC in the post-transplantation setting is not routine. Methods: Retrospective case series of kidney transplant recipients who underwent transplantation between 1987 and 2018 at Guy’s Hospital (London, UK). Collected data on patients who developed RCC post-transplant included: baseline demographics, renal disease, transplant survival, tumour characteristics, cancer treatment and survival. Results: 2968 patients underwent kidney transplantation between 1987 and 2018 at our Centre. 52 patients (1.8%) developed RCC. 40 (74%) were male with a median age of 51 years. 37% (71%) were white and 12 (23%) were black. The causes of end stage kidney disease included IgA nephropathy, hypertension and polycystic kidney disease. Median time to RCC diagnosis after transplant was 9 years (range 0-27). 86% of patients presented with stage 1/2 tumours, with the majority (72%) occurring in native kidneys. Most underwent radical nephrectomy although 5 patients were managed with radiofrequency-ablation (RFA) or surveillance (donor kidneys). Of 6 patients with metastatic disease, 5 received pazopanib and 1 everolimus. 4 patients continued systemic therapy for over 3 months and all derived clinical benefit with a median drug exposure of 19 months .15 patients required further kidney transplant or dialysis. Overall only 2 patients died from RCC. Conclusions: This retrospective study is the largest single-centre UK study to our knowledge. Kidney transplant recipients experience a marked increased risk of developing RCC. Most diagnosed RCCs are small and disease-specific mortality is low. With a third of tumours arising in donor organs, questions around optimum loco-regional approach and screening of high-risk population remain unanswered.