Developing a technique to measure levels of tumour hypoxia during proton beam therapy through gamma-ray spectroscopy

Around 50% of patients receive radiotherapy as part of their cancer treatment. One of the most important factors influencing clinical outcome, following radiotherapy, is tumour hypoxia. Low oxygen levels (hypoxia), is a characteristic of the tumour microenvironment which drives increased metastatic potential and confers resistance to radiotherapy, decreasing overall survival. However, even with advances in radiotherapy, including a move towards proton beam therapy (PBT), hypoxia-mediated radio-resistance is a complexity that remains. This project aims to develop a technique to measure oxygen levels, and consequently hypoxia, in tumours treated with PBT in real time. During PBT, dose is deposited in tissue by both the ionisation of atomic electrons and proton interactions with the atomic nuclei. This project takes a multidisciplinary approach to harness the naturally produced radiation during PBT to measure hypoxia. Real time measurement of hypoxia during treatment will inform adaptive therapy where radiation dose can be escalated to overcome hypoxic radio-resistance during fractionated treatment planning.

A real-time, non-invasive measurement of whole tumour hypoxia has a clear clinical benefit and a simple clinical detection device could be developed. Follow-on funding would be used to further the technique to not only ascertain tumour hypoxia levels as a whole but to map the regions of differing hypoxia within a tumour. This will be achieved through a multi-detector system that can determine the gamma-ray origins using energy and time-of-flight information. This multi-detector clinical device will enable hypoxia mapping in 3 dimensions and guide dose escalation in those radiation resistant hypoxic regions in the tumour. This advancement would drive adaptive therapy whereby the treatment plan could be modified during the fractionated course of treatment to optimise the dose distribution being delivered. The proton therapy research group (of which the PI and CI's are members) currently collaborate with members of the treatment planning team at the Christie Hospital on plan optimisation and adaptive therapy.