The Breur Award is the highest honour given by the European Society for Radiotherapy and Oncology (ESTRO), in recognition of the major contribution made by the winner to radiotherapy. At this year’s ESTRO meeting in Copenhagen, the award was presented to Jan Lagendijk from UMC Utrecht.
Lagendijk led the development of the MR-Linac, accomplishing the complex task of combining a linear accelerator with an MRI scanner to enable MR-guided radiotherapy. In his award lecture, Lagendijk described the evolution of the MR-Linac from idea to commercial reality, and the challenges that he and his team faced along the way.
Lagendijk first began investigating the potential of image-guided radiotherapy back in 1998. He soon realized that the key to optimizing radiotherapy lies in knowing the exact location of the tumour and being able to paint the radiation dose accordingly. “Because most tumours are soft tissue, you can clearly see the tumour location in MR images,” he explained. “So in 1999, we decided to start a project on MRI-guided radiotherapy; not just simulations, but also trying to make an MR-Linac.”
Lagendijk pointed out that when he first presented this concept, at an ESTRO meeting the following year, he was cautioned that the idea was so extreme it could ruin his career. He also noted that in the project’s early years, funding was limited as referees did not believe that it could work, and the number of PhD students in the group plummeted.
Salvation came from an unexpected source. Around that time, with the increasing prevalence of the mobile phone, people were starting to worry that mobile phones may overheat the brain. Using its hyperthermia experience, the UMC Utrecht group developed a model to calculate the temperature rise in the brain due to mobile phone exposure, and performed a study to assess this effect. The study was funded by Nokia and Motorola who, said Lagendijk, paid so well that the team could take on five additional PhD students to work on MRI-guided radiotherapy. “So the start of the MR-Linac project was financed by Nokia and Motorola, not by the radiotherapy industry,” he said.
The MR-Linac design was completed in 2004, with the group opting to use a high-end 1.5 T MRI scanner. “The big breakthrough was that we were able to modify the MRI’s active shielding to make a toroid around the MRI with almost no magnetic field,” Lagendijk explained. “And in that way, we can decouple the MRI and the linac and can run them both at the same time.”
In 2009 the team built the first prototype system and performed the celebrated MR imaging of a pork chop with the accelerator beam on and off. “With that pork chop image we were able to prove there is no difference between beam-on and beam-off images,” said Lagendijk. “That was a proof-of-concept that MRI guidance will work with a real-time beam.”
Then Philips and Elekta came on board, and the rest is history. In 2014 the team built the first clinical-grade prototype and in the summer of 2018, the Unity MR-Linac was installed at UMC Utrecht. Following its receipt of the CE mark, the Unity treated the first patient in August of that year.
Today there are numerous Unity MR-Linacs installed worldwide, being used to treat a wide range of tumour sites. UMC Utrecht has treated more than 1000 patients to date on its two Unity MR-Linacs, and is now installing a third Unity system. The largest application is prostate cancer, which comprise about half of all cases. The centre also treats a lot of oligometastases and rectal cancers, with pancreas, lung and head-and-neck cancers growing in number.
And the technology continues to evolve. “At Utrecht, we are working extremely hard with a lot of PhD students to develop real-time imaging,” Lagendijk told the ESTRO delegates. “We can now go to about 30, 40 or 50 Hz, looking at deformation fields. We can use that information to target the beam, but also to really see how the dose is accumulated in the patient.”
The impact of MR guidance for radiotherapy patients is clear: less normal tissue involvement and smaller margins means less toxicity, while the ability to deliver higher dose to the tumour may provide better tumour control. Lagendijk emphasizes, however, that what’s really important is the concept of “seeing what you treat”. “The moment you see what you treat, you start to optimize, as you see what you are doing is not optimal,” he explained. “We see, especially with the prostate, that it’s like surgery without the knife – we start to replace surgery.”
First report of clinical MRI-Linac treatments wins journal citations prize
Lagendijk rounded off his presentation by introducing a potential breakthrough technology – the use of the MR-Linac to treat metastatic disease, guided by PET. “We are trying to create a new treatment pipeline, making an MRI/PET with the same MRI technology as the Unity,” he said. “We can use that MRI/PET radiotherapy simulator to find those small tumours, motion corrected with intrinsic registration, and use that information in the Unity pipeline. In that way, we will be able to boost 20 lymph nodes, say, or 20 small metastases.”
“At UMC Utrecht, it’s our philosophy that real-time MR-guided radiotherapy will be the next-generation standard in radiotherapy,” Lagendijk concluded. “And when you see what you treat, you want to optimize.”