Brain metastases occur when cancer cells spread from their original site to the brain. Any cancer can spread to the brain, but some of the most common types to cause brain metastases are lung, breast and skin (melanoma). Brain metastases occur in 10-30% of adults with cancer.
The NCRI Groups bring together experts across a range of disciplines to coordinate development of a strategic portfolio of trials within their field. However, the NCRI Brain Group identified that to develop trials for brain metastases, they needed to establish links with other NCRI Groups.
The NCRI Brain Group hosted its first Brain Metastases Workshop in March 2018. The workshop brought together members of the NCRI Lung, Breast and Skin Groups, along with the Brain Meningioma & Metastasis Sub Group, patients and charities.
In the room where it happens
The workshop allowed experts with diverse skills sets and distinct areas of expertise to develop study ideas. Two trials developed at the workshop were subsequently fully worked up for funding submission and hope to recruit over 200 patients: the BRITEMET trial has now been funded, whilst the RADIANT BC trial hopes to secure funding in the coming months.
The workshop was a great success. We had two very powerful talks from patients that really set the scene for how brain metastases impact people and the real lack of available studies. I was delighted that so many experienced clinicians and researchers worked together to develop two new studies for patients with brain metastases. It was a great example of cross-discipline working and knowledge exchange. I hope the 2020 workshop will be even more successful and lead to further studies for patients.Michael Jenkinson, Professor of Neurosurgery, University of Liverpool and NCRI Brain Group chair
The BRITEMET trial: Predicting immunotherapy response in metastatic melanoma
Brain metastases is a frequent problem in patients with advanced skin cancer. Nearly 40% of patients with metastatic melanoma have brain metastases at diagnosis. Immunotherapy is a potentially transformative treatment but in melanoma, only half of patients respond.
Dr Rasheed Zakaria is a Specialist Trainee in Neurosurgery at The Walton Centre NHS Foundation Trust and member of the brain metastasis and meningioma clinical subgroup. He wanted to improve treatment for these patients by identifying patients who will benefit from immunotherapy, using biomarkers to predict the patient response.
The BRITEMET trial will look at whether reduced fractional anisotropy (found to be associated with immune cell infiltration around brain metastases) can identify if people will respond to immunotherapy.
At the Brain Metastasis Workshop Dr Zakaria was able to discuss his idea with multi-disciplinary teams including oncologists and radiographers, who provided feedback on the set up and timings of the trial. The group also clarified to Dr Zakaria that melanoma is currently treated using immunotherapy, so was the correct cancer type to focus on, as initially he had focussed on all cancer types.
The trial is being funded by a Postdoctoral Research Bursary from Cancer Research UK and hopes to recruit 20 people as pilot study, to generate data for future research.
The RADIANT BC trial: Combining radiosurgery with immunotherapy and systemic therapies in breast cancer patients with brain metastases
Brain metastasis is an increasing problem for women living with secondary breast cancer. For patients that have limited brain metastases, most receive high dose radiotherapy called radiosurgery and subsequently systemic medications, which treat cancer throughout the entire body. Whole brain radiotherapy has been shown to reduce recurrences in localised regions in patients with limited brain metastasis, but does not improve overall survival and can cause cognitive problems.
In collaboration with the University of Birmingham Cancer Research UK Clinical Trials Unit, Professor Carlo Palmieri, University of Liverpool and Clatterbridge Cancer Centre and Dr Anthony Kong, King’s College London and Guy’s Cancer Centre, wanted to test combining radiosurgery with immunotherapy without whole brain radiotherapy, followed by the combination of immunotherapy with subsequent systemic treatments in patients with limited brain metastases.
The researchers designed a multi-arm, multi-stage trial, taking into account the feedback that was obtained at the workshop. The trial design allows the researchers to test multiple combinations simultaneously, also allowing combinations to be dropped or added. There are currently 10 different treatment combinations being tested in the trial which is being run by University of Birmingham.
Developing future brain metastasis trials
Following the success of this workshop, the NCRI Brain Group are hosting a second workshop in February 2020. In an evolution of the workshop design, groups attending will be asked to present ideas to the group of experts in different cancer types, in order to develop ideas that are both cross cutting and primary cancer specific.