Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms’ tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG.

10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m² daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8–10x10⁶ cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150–200 mg/m² on days 1–5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life.

The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences.

NCT04911621

In Australia, the Victorian State Government has established a number of priority primary care centres (PPCCs) across the state to address the increasing demand for emergency departments (EDs). PPCCs are general practitioner-led, free-of-charge services that aim to provide care for conditions that require urgent attention but do not require the high-acuity care of an ED. This study aims to evaluate the implementation processes, outcomes and the impact of the PPCC on reducing ED demand within Barwon, Warrnambool and Grampians Health Services in the Western region of Victoria, Australia.

This is a convergent mixed-method study. Qualitative data collection will be undertaken through semistructured interviews to understand the experiences of PPCC patients, PPCC clinical staff, PPCC managerial and administrative staff and ED clinical staff. A documentary analysis will be conducted on the materials relating to the implementation of the PPCC. The quantitative component will involve interrupted time series analysis of de-identified administrative data, comprising ED presentation records and PPCC clinical records. Implementation science frameworks will be integrated throughout the study. The RE-AIM framework is a guide used for the planning and evaluation of programmes through five outcomes: reach, effectiveness, adoption, implementation and maintenance. The Consolidated Framework for Implementation Research will be integrated.

This study has received ethical approval from Deakin University HREC (Ref No. 2023-046) and Barwon Health HREC (Ref No. 94374). Findings will be disseminated as reports, presentations and peer-reviewed journal articles.