MRI-guided treatment of brain tumors

Case

MRI-guided treatment of brain tumors

Researchers from Radboudumc have taken a crucial step in making a treatment for liver cancer, which uses radioactive microspheres, suitable for brain tumours too.

It is a precision bombardment against cancer: microscopically small radioactive spheres, which irradiate a tumour from the inside. This treatment has been used for patients with liver cancer since 2009. Tens of millions of these spheres (with a diameter of about 30 micrometres) containing the radioactive element holmium-166 are inserted into the common hepatic artery at once via a catheter. They become trapped in the smallest blood vessels of the tumour where the radiation kills the tumour cells. The benefit of this treatment is that mainly the sick tissue is irradiated. Healthy cells suffer less because the radiation only has a range of several millimetres. Also, because holmium is visible on an MRI scan, the outcome can be seen.

Invention

Frank Nijsen is a medical biologist at Radboudumc and co-inventor of the treatment. He has worked on the spheres since 1994, and started to develop the liver cancer therapy together with oncologist Bernard Zonnenberg and radiochemist Fred van het Schip. The production of the spheres was transferred from UMC Utrecht to the spin-off Quirem Medical, where Nijsen is a part-time scientific director.

In 2015, they acquired the CE certification, the safety certificate needed to be able to treat patients in European hospitals. The treatment is currently used in nine European countries, and good results are often seen. Various studies funded by Technology Foundation STW (the predecessor of NWO Domain Applied and Engineering Sciences) contributed to the development of the new technology. These included research into improved irradiation conditions in the nuclear reactor of TU Delft.

Treating brain tumours

In a new study, funded within the Open Technology Programme of NWO Domain AES, Nijsen is focusing on the treatment of brain tumours using this technology. In a so-called phantom study, in which the tumour tissue is simulated, the researchers recently demonstrated that they can inject the microspheres to the desired position in the tumour. Nijsen: ‘We have now demonstrated that we can exert control over where exactly the spheres end up.’

This could be a turning point in the way we treat

For this, the researchers designed a special needle with a steerable point that can controllably bend in all directions. This will allow the researchers to inject the spheres at various locations in the tumour. During the study, it was demonstrated for the first time that this idea works. Being able to reach different locations is important to ensure that the microspheres are properly distributed across the tumour: ‘Otherwise, it could be the case that the tumour is reached but that no spheres with radiation end up in the tumour edges. Then, after the treatment, a piece of cancerous tissue would remain that could then simply grow into a new tumour.’

Phantom study of MRI-guided treatment with holmium microspheres in brain tumorsPhantom study of MRI-guided treatment with holmium microspheres in brain tumors

MRI-guided treatment

The distribution of the microspheres across the tumour is related to a second important development in Nijsen’s research. This centres on the visibility of the spheres on MRI scans. In the past, it could only be seen after the treatment whether the spheres had ended up in the right place, says Nijsen. ‘So, in effect, the spheres were blindly injected. Afterwards, we could determine whether radioactivity was present in the tumours by making a PET or SPECT scan. However, due to the low resolution of those images, we could say little about the exact distribution of the spheres in the tumour. We clearly saw that many patients benefited from the treatment, but it could still be the case that some parts of the tumours had not been reached. Later we could use high-resolution MRI to see the exact distribution of the spheres, but again only in retrospect.’

Targeted dosage

Now it is possible to treat during an MRI scan, which means we can see where the spheres end up as they are administered. Therefore, the researchers can now introduce the microspheres in separate doses as well. After each dose, it can be decided whether a new dose is needed, for example because not all parts of the tumour have been reached. However, if these parts have been reached, the administration can be stopped earlier to prevent healthy tissue from becoming damaged. Nijsen: ‘By adjusting the position of the catheter, you can inject specific quantities of spheres to parts of the tumour where no radioactivity is present yet. This will now be investigated further and applied in patients.’

An important aspect of real-time observations with MRI is the high resolution of the images, down to an accuracy of two millimetres. That is vitally important for seeing the distribution of the spheres, says Nijsen. ‘The resolution of six to eight millimetres obtained with a PET or a SPECT scan is too rough to observe a good distribution in a tumour several centimetres in size. Then the image frequently gave the erroneous impression of a good distribution even though sometimes a part of the tumour scarcely received a dose.’

Click on the image to watch a videoClick on the image to watch a video about the treatment (Radboudumc)

‘Turning point’

Nijsen is excited about the new possibilities: ‘We have created an MRI-guided treatment as a result of which we can see what we are doing. This could be a turning point in the way we treat. We will be able to match treatments far better to the patient’s individual situation.’ That will hopefully mean that the treatment will become more effective and have fewer side effects, says Nijsen. ‘We might soon know for certain that a given quantity of radiation will kill the tumour instead of parts of it surviving. The treatment will now be investigated further. Based on the first groups of patients, we expect that it will eventually be possible to personalise the treatment far more.’

Considerable medical need

After the development of the first treatment, it was a logical step to study the possibilities for other types of cancer. Nijsen focussed, for example, on pancreatic cancer and brain tumours: ‘I looked at the medical need. For example, four million people worldwide suffer from brain cancer. The chances of survival are limited. A major step forward is needed.’ The poor survival figures are related to the limited treatment possibilities, explains Nijsen. Surgery, for example, is often too drastic: you cannot simply remove the entire tumour tissue from the vulnerable brain. The alternative of placing medicines in the tumour is difficult because the blood-brain barrier stops substances from getting in.

With the treatment, Nijsen hopes ‘to achieve at least the same effect as with surgical intervention’. The advantage: ‘This treatment is far less invasive. Furthermore, we are thinking about the combination of different treatments, for example immunotherapy or standard chemotherapy. The latter attacks a tumour from the outside. That means you can treat the tumour from both the inside and the outside.’

Treating animals

The next step in the research is the treatment of animal patients; dogs or cats with a brain tumour. This takes place in collaboration with the Faculty of Veterinary Medicine at Utrecht University under the leadership of Dr Bas van Nimwegen. The main advantage of using dogs and cats is that they are more similar to people in terms of physiology than mice, as a result of which the research provides better information. Furthermore, it offers the animals the prospect of an extended life: ‘The owners of animals with a brain tumour often hear from the vet that the only option is to euthanise the animal. Hopefully, the animals will benefit from the treatment and, at the same time, our knowledge and treatment technique will be improved.’

Based on the outcomes of these studies, the medical biologist thinks the step to tests with human patients can be made faster. ‘The knowledge transfer is considerable. We can make rapid progress,’ says Nijsen. ‘If we see that there is some effect, then I already expect to be able to test the technique on people for the first time within a few years.’

Text: Dirk-Jan Zom

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