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Ten years ago, researchers from the Faculty of Veterinary Medicine and UMC Utrecht received nearly €300,000 for an innovative cancer treatment: injecting radioactive beads into tumors for highly precise, localized radiation therapy. Ten years have passed since then, and much has changed. What progress has been made, and where will we be in another ten years? We talk to surgeon and radiation expert Bas van Nimwegen.

As early as 1991, American researcher Russell J. Mumper saw potential in the use of radioactive microspheres—holmium particles measuring around 20 micrometers in size that are injected for the internal irradiation of liver tumors. In 2001, Dutch researcher Frank Nijsen, who currently works at Radboudumc, began to focus specifically on this treatment, becoming one of the pioneers in the field of radioactive microspheres.

In 2008, Bas van Nimwegen obtained his PhD in minimally invasive surgery and laser surgery at the ľ�ϸ���Ӱ�� Clinic for Companion Animals. Around that time, he began collaborating with Frank Nijsen. They have now treated more than sixty animal patients and further developed the treatment method into a minimally invasive precision treatment.

Safe and technically feasible

Van Nimwegen: “We started with dogs and cats with tumors that could not be surgically removed. These were patients with tumors at such an advanced stage that no other treatment options were available. These animals received holmium treatment, which proved to be safe and technically feasible. The results were also promising. The holmium microspheres are suitable for local tumor treatment because tissue within 8 mm completely absorbs the radiation. Surgeons can also inject the microspheres as a liquid mixture directly into the tumor using a thin needle. This allows them to irradiate the tumor locally without affecting the surrounding tissue.

Thanks to an initial grant in 2015, the researchers were able to set up larger studies and also integrate imaging. Van Nimwegen: “We were incredibly happy with that first grant for the new treatment technique: finally, we had the resources and could translate the method, developed in companion animals, to human patients.” Two years later, another grant followed to further develop the image-guided treatment. “From that moment on, with all the imaging included, we were able to make real progress.”

Holy grail

In recent years, the focus has been on brain tumors, which are considered the “holy grail” of minimally invasive tumor treatment. Van Nimwegen explains: "Treating a brain tumor is technically complex and involves clinical risks, both in humans and animals. Swelling or inflammatory reactions can cause serious complications immediately." Nevertheless, the team managed to develop a technique that allowed them to accurately track the microspheres on CT scans. The researchers successfully applied the treatment to several dogs with brain tumors. One dog even survived for almost two years. Van Nimwegen emphasizes: “We have shown that it is possible and that it can be done safely, but we remain cautious.”

Rotating syringe

The team also developed new instruments in collaboration with Delft ľ�ϸ���Ӱ�� of Technology, including a holder for placing injection needles with millimeter precision and a steerable needle for delivering the microspheres to the tumor as accurately as possible. In addition, the researchers developed a rotating syringe to keep the microspheres moving during injection and allow them to float better in the fluid. CT proved to be more suitable than MRI for diagnostic imaging because it offers higher image resolution and because doctors in the CT room can also use regular equipment and metal instruments, such as the injection needle.

Automate and optimize

In the coming years, research will focus on further improving and automating the treatment. Van Nimwegen explains: “At present, the microspheres are still injected manually. We want to automate that process, not only to work more accurately, but also to reduce the radiation exposure for the practitioners.”

That is why the researchers are working on a system that can calculate during treatment where radioactive particles are needed and how many for the best distribution of the dose. Van Nimwegen: “I envision a smart system that makes suggestions based on previous injections and helps to irradiate a tumor effectively, with as few interventions as possible.”

Support through computing power

Ultimately, an automated needle, controlled by medical imaging data and dose calculations, could support doctors in complex treatments. According to van Nimwegen, doctors can benefit greatly from software that calculates faster and more accurately than humans. Nevertheless, he emphasizes that the doctor always remains in control. He sees no future in a system that makes decisions or performs actions independently.

Van Nimwegen is optimistic: “When we started, microspheres were first tested experimentally on pigs and later on people with liver tumors. Now it's a standard treatment. The local injection strategy is now also being tested on people with pancreatic tumors at Radboudumc. I see that interest in local treatment techniques is growing worldwide. That's why I'm optimistic about the future!”

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