Physiological MRI for Precision Radiotherapy IDH-wildtype Glioblastoma

Introduction: After surgery, a key step in treatment of patients diagnosed with glioblastoma (high grade brain tumour) is radiotherapy. The ideal clinical target volume (CTV) for radiotherapy treatment planning includes all tumour cells remaining after surgery. Currently, the GTV is delineated on conventional imaging techniques that are only visualizing macroscale structural changes due to the presence of a large number of tumour cells. After delineating these visible macroscale changes, the GTV is expanded in all directions with 1.5cm into visibly healthy tissue to account for microscale tumour invasion. This standard CTV therefore also contains healthy tissue that should not be receiving radiation, causing side effects of treatment, hereby reducing quality of life for patients.

Generating a physiological CTV, in which microscale invasion of tumour cells is taken into account specifically whilst sparing healthy tissue that is not in need of radiation, is essential for reducing side effects of radiotherapy. To do so, visualisation is necessary of physiological processes of tumour cells, which are present before macroscale structural changes occur. State-of-the-art MRI techniques are now in use at the Erasmus MC that can assess these physiological processes, including oxygenation status and cell proliferation.

We aim to generate proof-of-concept of using a physiological CTV for radiotherapy treatment planning for patients with brain tumours. By extending the clinical standard MRI session used for radiotherapy planning in 10 patients diagnosed with glioblastoma with advanced MRI techniques that assess oxygenation status and cell proliferation, we will generate the physiological CTV including this information and illustrate that it is more precise in capturing microscale tumour invasion. This proof-of-principle work will be used to obtain external funding to perform the much needed, and the first of its kind globally, clinical trial to show the benefit of a physiological CTV for radiotherapy treatment planning in glioblastoma.

Rationale: Current treatment management of patients with IDH-wildtype glioblastoma is sub-optimal because of two main issues: (1) Creating an accurate target volume for radiotherapy, a key aspect of glioblastoma treatment, containing all remaining tumour cells after surgery that is impossible with the conventional CT and MRI imaging techniques currently used and (2) in the follow-up of patients after radiotherapy, conventional MRI is incapable of distinguishing tumour progression from treatment effects. The solution to these issues lies in accurate and non-invasive assessment of physiological processes of tumour cells to enable delineation of the true physiological clinical target volume (CTV) for radiotherapy planning and to allow for early detection of true tumour progression during treatment follow-up.

Objective: Generate proof-of-concept of using a physiological CTV for radiotherapy treatment planning for patients with brain tumours.