PhD Studentship for innovative radiotherapy treatments in diffuse midline glioma (DMG)

This research project 'Exploiting the potential of protons and high-LET radiation in Diffuse Midline Glioma' aims to investigate new precision targeted therapies, such as helium ion therapy (HIT) and boron neutron capture therapy (BNCT), for the treatment of diffuse midline gliomas (DMGs), including DIPG.

High-flux accelerator-driven neutron source

Radiotherapy Treatment for DMG

Radiotherapy is the standard-of-care treatment for diffuse midline glioma (including DIPG), but radiation only achieves temporary symptom improvement, and patients eventually relapse.¹ About 70%–80% of patients respond to radiotherapy and benefit from improved neurological symptoms and quality-of-life.

The globally followed protocol of conventionally fractionated radiotherapy using X-rays involves delivering a 54 Gy radiation dose in 30 fractions, once daily for about 6 weeks.² However, X-rays can damage the healthy brain tissues surrounding the tumour, causing brain oedema and scarring. In contrast, precision targeted therapies can more accurately deliver the radiation dose to the tumour, and therefore are safer. 

Radiotherapy achieves tumour cell death by damaging the DNA. The level and complexity of DNA damage is different with different types of radiotherapy, and cells inherently try to repair any damage to their DNA which can hinder the anti-tumour effect of radiotherapy. HIT and BNCT are particularly able to cause more complex DNA damage, that the cells are less able to repair, leading to a higher degree of tumour death.^3,4.

Research and Organisation

The PhD project will be conducted in Professor Parsons’ laboratory at the University of Birmingham in association with the Cancer Research UK RadNet Birmingham Centre of Excellence, and performed in collaboration with experts in radiation physics, radiobiology, and paediatric oncology.

The Parsons group’s main research focus is on the molecular and cellular effects of different forms of radiotherapy using tumour models of head and neck cancers and adult brain cancer (glioblastoma).

Professor Jason Parsons - Professor of Radiobiology at the Department of Cancer and Genomic Sciences, University of Birmingham

Recent research into precision-targeted therapies confirmed increased tumour cell death and less damage to healthy tissues when compared to conventional, X-ray radiotherapy, offering new possibilities for treating DMGs.  HIT and BNCT particularly show promising clinical results, and clinical centres around the world are being established to harness these new radiotherapy options for the benefit of patients with cancer.^5-10 

New Potential

To our knowledge, despite the huge potential that HIT and BNCT offer, these radiotherapies have not been studied before for the treatment of DMGs. The research project’s goal is to accumulate evidence that HIT and BNCT can control DMG cells and tumours more effectively than conventional radiotherapy.

The group will also investigate the effect of radiosensitising drugs in combination with the radiotherapies. Radiosensitising drugs can increase the effects of radiotherapy by making the DMG tumour cells more vulnerable to radiation.

The HIT and BNCT radiations will be tested on 3D neurospheres that mimic the structure and function of the brain tissue better than traditional cell cultures, as well as more complex models including brain slices and a chick embryo model.

We hope that this research will open up the possibility of early phase clinical trials leading to new treatment options for DMGs. The Parsons group’s expertise in radiobiology is coupled with access to the equipment and infrastructure that are required for this research.

The University of Birmingham is the only university in the UK and Europe with MC‑40 cyclotron (for HIT), and the high-flux accelerator-driven neutron source (for BNCT).  

Expert Team

Apart from the unique research environment at the University of Birmingham, Professor Parsons has established collaborations within and outside of the university that also greatly support the project’s success.

Collaborators include Professor Stuart Green (Director of Medical Physics, University Hospitals Birmingham), Dr Ashley Vardon (NIHR Academic Clinical Lecturer, Cancer and Genomic Sciences, University of Birmingham), Professor Chris Jones (Head of the Glioma Group, The Institute of Cancer Research) and Dr Mara Vinci (Team Leader of Paediatric High-Grade Glioma Group, Bambino Gesu’ Children’s Hospital, Rome, Italy).

By funding a PhD position for this encouraging research area, we also hope to pave the way for further research and attract scientists to contribute to this area of the DMG research field.

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Stand with Us to Find a Cure for DIPG

Abbie’s Army is fighting for a future where DIPG no longer steals young lives. Your donation fuels the research needed to find a cure and helps us bring hope to families facing this tragic disease. Join our fight—donate now and make a difference.

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References

1.      Epidemiology, Diagnostic Strategies, and Therapeutic Advances in Diffuse Midline Glioma.

Miguel Llordes, G. et al.

Journal of Clinical Medicine, 2023, Volume 12, Issue 16, Page 5261

2.      Radiotherapy for Diffuse Intrinsic Pontine Glioma: Insufficient but Indispensable.

Kim, HJ. and Suh, CO. 

Brain tumor research and treatment, 2023, Volume 11, Issue 2, Pages 79-85

3.      DNA damage and repair dependencies of ionising radiation modalities.

Melia, E. and Parsons, JL.

Bioscience reports, 2023, Volume 43, Issue 10

4.      The Cellular Response to Complex DNA Damage Induced by Ionising Radiation.

Wilkinson, B, Hill, MA, and Parsons, JL.

International journal of molecular sciences, 2023, Volume 24, Issue 5

5.      Commissioning of Helium Ion Therapy and the First Patient Treatment With Active Beam Delivery.

Tessonnier, T. et al.

Internal Journal of Radiation Oncology, Biology, Physics, 2023, Volume 116, Issue 4, Pages 935-948

6.      Boron neutron capture therapy for locally recurrent head and neck squamous cell carcinoma: An analysis of dose response and survival.

Koivunoro, H. et al.

(Radiotherapy and Oncology, 2019, Volume 137, Pages 153-158

7.      Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer.

Haapaniemi, A. et al.

Internal Journal of Radiation Oncology, Biology, Physics, 2016, Volume 95, Issue 1, Pages 404-410

8.      BNCT for advanced or recurrent head and neck cancer.

Aihara, T. et al.

Applied Radiation and Isotopes, 2014, Volume 88, Pages 12-15

9.      Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial.

Hirose, K. et al.

Radiotherapy and Oncology, 2021, Volume 155, Pages 182-187

10.  Current Insights into the Radiobiology of Boron Neutron Capture Therapy and the Potential for Further Improving Biological Effectiveness.

Punshon, LD. et al.

Cells, 2024, Volume 13, Issues 24