Investigating the radiobiology of protons, helium ions and BNCT in head and neck tumour treatment

About the Project

Background

Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer worldwide with an annual incidence of ~890,000 cases/year and deaths of ~450,000 cases/year. There has been a particularly rapid rise in the incidence of human papillomavirus type 16 (HPV)-associated tumours of the oropharynx. However interestingly, HPV-positive patients respond better to radiotherapy and chemotherapy in comparison to patients with HPV-negative disease whose outcome is very poor. Despite this, acute and long-term side adverse effects of radiotherapy treatment in HNSCC patients are common. Therefore, more targeted and effective treatments for HNSCC, particularly radioresistant HPV-negative disease, are actively being sought.

Proton beam therapy (PBT) is capable of delivering radiation of a higher biological effectiveness direct to the tumour. Furthermore, the delivery of PBT at ultra-high dose rates (>40 Gy/s; FLASH) has been shown to promote significant normal tissue sparing whilst still maintaining tumour control. Helium ion therapy (HIT) is significantly more effective than X-rays and PBT in tumour cell killing. Additionally, boron neutron capture therapy (BNCT) is an alternative targeted treatment in which specific uptake of boronated compounds by the tumour cells and irradiation with thermal neutron beams generates highly reactive particle ions causing cell death. However, there is significant biological and clinical uncertainty in the utilisation of these novel radiotherapy techniques, although they have huge translational potential for patient benefit.

Objectives

This exciting PhD studentship will develop novel research investigating the comparative effect of PBT (at both conventional and FLASH dose rates), HIT and BNCT, versus conventional X-ray radiation, at the molecular and cellular level, using normal and tumour cell models of HNSCC. This will be achieved through the use of established 2D cell lines, 3D spheroids, patient-derived organoids and the in vivo chick embryo model. The project will involve an examination of end-points such as cell survival, DNA damage and repair, cell death mechanisms and tumour growth. The long-term goal of the project is to enhance our biological understanding of PBT (including at FLASH dose rates), as well as HIT and BNCT, particularly using tumour models of HNSCC and to contribute to determining the optimal radiotherapy treatment for HNSCC patients.

Impact and training

This molecular and cellular biology-focussed research project will utilise the unique resources present at the University of Birmingham, including the MC40 cyclotron for proton and helium ion irradiations at both conventional and FLASH dose rates, and the high flux accelerator-driven neutron facility for BNCT. This novel work is at the interface of clinical and translational medicine, and which has high translational potential in the establishment of more effective and safer treatments for HNSCC using radiotherapy, particularly PBT, HIT and BNCT.

How to apply

Applications should be directed to Professor Jason Parsons at j.parsons.3@bham.ac.uk. To apply, please send:

• A Detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree transcripts;
• Evidence of your proficiency in the English language, if applicable.

Funding Notes

Applications are invited from self-funded students. Candidates are expected to hold (or about to obtain) a minimum second-class honours degree (or equivalent) in a related area/subject.