Multi -paramEtric Imaging to Assess Treatment REsponse After Stereotactic Radiosurgery of Brain Metastases

Multi-paramEtric Imaging to Assess Treatment REsponse After Stereotactic Radiosurgery of Brain Metastases

After stereotactic radiosurgery (SRS) of brain metastases, patients undergo a standard brain magnetic resonance imaging (MRI) to assess treatment response 12 weeks after completion of treatment. The interpretation of this standard MRI can sometimes be challenging as it can be difficult to differentiate tumour getting bigger/returning (progression/recurrence) from expected radiotherapy treatment-related changes known as radionecrosis. This study is a pilot brain imaging study that is investigating if readily available forms of imaging such as contrast-clearance analysis MRI (also known as TRAMs) and/or 18 Fluoromethyl-choline positron emission tomography/computerised tomography (18F-choline PET/CT) are equivalent to multi-parametric MRI in their ability to differentiate tumour from radionecrosis. Multi-parametric MRI has the most evidence for its ability to discriminate tumour from radionecrosis but is resource intensive and not routinely available in most centres.

Differentiating tumour progression/recurrence from radionecrosis post- stereotactic radiosurgery (SRS) of brain metastases can be at times challenging on standard brain MRI. This is because radionecrosis mimics the appearances of tumour progression by appearing as contrast enhancing lesions on standard MRI.The definitive way of differentiating this is surgical excision of the area in question and histopathological evaluation. But this is not always feasible in clinical practice as not all areas of the brain are surgically accessible and an en bloc (complete) resection is needed for the result to be meaningful.

The next best option we have is the multi-parametric MRI which typically consists of three components-MR perfusion, MR diffusion and MR spectroscopy. This investigation is resource intensive, requiring considerable input form MR physics, neuroradiology reporting time , is not routinely available in all centres and hence not viable for routine clinical practice.

Therefore there is an urgent need for a reliable and viable form of imaging modality that helps differentiate tumour from radionecrosis when assessing treatment response post-SRS. It is important to be able to do this accurately as the management of both conditions are entirely different.

Currently the Royal Marsden Hospital is using contrast-clearance analysis MRI (TRAMs) to help differentiate tumour from radionecrosis if the changes seen on standard brain MRI post-SRS are deemed to be unclear. Contrast-clearance analysis MRI (TRAMs) is FDA approved and conforms to European standards (CE marked), yet has sparse evidence on its efficacy. There is some evidence for the use of 18F-choline PET/CT in primary brain tumours (gliomas) but more evidence is needed for its use in brain metastases.

Given that surgical excision is not always feasible for reasons explained above, in this study the investigators consider the muti-parametric MRI as the gold standard investigation for discriminating tumour from radionecrosis.

This pilot brain imaging study is seeking to determine if contrast-clearance analysis MRI (TRAMs) and/or 18F-choline PET/CT are equivalent to multi-parametric MRI in their ability to reliably differentiate between tumour progression/recurrence and radionecrosis. If contrast clearance analysis MRI (TRAMs) and/or 18F-choline PET/CT are found to be equivalent to multi- parametric MRI then it gives the investigators increased confidence in the findings of these readily available imaging modalities, helping treating clinicians to make rapid and reliable management plans- ultimately improving patient outcomes.

Inclusion Criteria:

• Patients with brain metastases whose primary cancer originates from the lung and whose histology is that of non-small cell lung cancer (NSCLC)
• Patient should have had SRS as their primary treatment for their brain metastases
• Follow-up standard brain MRI post-SRS has been discussed in the SRS multi-disciplinary team meeting (MDT)
• The changes seen on the post-SRS follow-up standard MRI are deemed unclear by the SRS MDT as to whether they represent tumour progression or radionecrosis.
• It is >=12 weeks since completion of SRS

Exclusion Criteria:

• Prior SRS or external beam radiotherapy to the same area
• Children (age < 18)
• Pregnant women
• Adults that lack capacity to consent
• Contraindications to intravenous gadolinium contrast and/or 18F-choline radiotracer
• Contraindications to MRI scanning (for example pacemaker )