Targeting tumours with precise aim

Targeting tumours with precise aim

Yves Jongen, pioneer of proton therapy for cancer treatment

For many decades, radiation therapy for cancer posed the risk of severe damage to healthy cells. A more precise treatment, called proton therapy, was introduced into clinical practice by engineer Yves Jongen at Catholic University of Louvain, Belgium.

An entrepreneur as well as an inventor, the 65-year-old founded the global company Ion Beam Applications (IBA) in 1986 to market his proton-generating cyclotron device to treatment centres and hospitals around the world. So far, more than 21,000 patients have been treated with proton therapy.

Fighting the cancer pandemic

The number of cancer cases around the world keeps rising, with more than 13 million reported in 2012. This global pandemic increases the need for effective and - most of all - safer therapies.

In the fight against cancer, radiation therapy remains one of the strongest weapons. More than half of all cancer patients are treated with high doses of X-ray beams during the course of their illness.

X-rays trigger cell death by destroying the DNA at the core of cells. They halt the replication of cancer cells but also damage healthy tissue in their path, possibly with fatal consequences. From X-ray technology's start in the late 1800s, doctors have been forced to weigh its negatives against its positives.

Protons, a more benign alternative

In search of an alternative to the rather imprecise spread of X-rays, scientists soon zeroed in on protons. Chemically speaking, protons are hydrogen atoms stripped of their electrons.

Protons can be produced in enormous particle accelerators such as the ‘cylotron', invented and built in 1932 by Ernest Lawrence at the University of California, Berkeley. As early as 1946, American physicist Robert R. Wilson suggested using particle accelerators for radiation treatment.

Yves Jongen knew that cyclotrons needed to be constructed at a much smaller scale – and offered at a lower price tag – to make a difference in clinical practice.

Proton precision - at a high cost

As scientists discovered, protons offer a highly controlled focus on tumour sites due to a physical phenomenon known as Bragg's peak: When protons are projected into space, they concentrate their full destructive energy at the "peak" of their path, in a controlled location.

In addition, protons have a relatively large mass, making them less likely to scatter to the side when the beam is aimed at body tissue. While X-rays disperse and lose intensity on their passage through the body, proton beams can be aimed precisely to focus almost entirely on the tumour site.

Early clinical trials with protons were encouraging, especially for tumours in sensitive locations such as the brain or eye, but one problem remained: Particle accelerators cost hundreds of millions of Euros and, in the 1970s, were only available at select research laboratories in the world.

This was mainly due to the large size of accelerators, requiring a facility the size of a small gymnasium, like the Large Hadron Collider at the European Organization for Nuclear Research (CERN).

Changing the medical profession

Enter Yves Jongen, an engineer at the Catholic University of Louvain (UCL) in Belgium. Around 1975, Jongen and his colleague André Wambersie set out to build a particle accelerator designed specifically for clinical use.

Ever the realist, Jongen was aware that cyclotrons needed to be constructed at a much smaller scale - and offered at a lower price tag - to make a difference in clinical practice. As director of the Cyclotron Research Centre at Louvain, he made great strides in improving the design while successfully treating cancers such as eye melanoma and medulloblastoma, a tumour of the central nervous system that primarily affects children.

To foster scientific collaboration in the new field, Jongen became a constant presence at international meetings and symposia, including the Particle Therapy Co-Operative Group (PTCOG). Through the years, he would pen more than 200 publications on particle accelerator technology.

By 1986, Jongen had advanced the design of the new cyclotron far enough to form a company around the invention: Belgium-based Ion Beam Applications (IBA).

Transfer into clinical practice

By 1986, Jongen had advanced the design of the new cyclotron far enough to form a company around the invention: Belgium-based Ion Beam Applications (IBA). From the start, he aimed to build proton-therapy facilities specifically for clinics.

The reward came in 1994, when Massachusetts General Hospital (MGH) commissioned a cyclotron unit from IBA. By 2005, the company had received 14 more contracts as proton therapy gradually grew into a significantly safer alternative to traditional X-ray therapy.

Word of the advantages of proton therapy took the medical community by storm. Patients are exposed to 70% less radiation compared to X-rays, and studies suggest that protons pose a 50 to 80% lesser risk of causing secondary, radiation-related cancers than X-rays.

Making the technology affordable

For his efforts to bring proton therapy into the marketplace, Jongen was named 1997 Entrepreneur of the Year' by Trends-Tendances magazine. But one big challenge remained. The price for proton-treatment facilities still ranged around €100 million, with treatment costs at about €100,000 per patient - four times the cost of conventional radiation therapy.

In 2007, Jongen's team at IBA released a new, compact proton-therapy system for hospitals that could fit into a single room, came with a much lower price tag of about €24 million and had a capacity of treating 500 patients a year. It also offered tremendous energy savings, consuming only 7 kW for every 100 kW consumed by conventional cyclotrons.

Through constant innovation - securing more than 326 patents so far - IBA has grown into a market leader for proton therapy, with a 60% share of the world market and revenues of €400 million in 2012.

In September 2012, a reported 39 particle therapy centres operated around the world, more than 20 are currently under construction, and more than 21,000 patients have been treated with proton therapy so far.

With a lifetime full of achievements, Yves Jongen is far from resting on his laurels. At age 65, he continues to improve cyclotron development at IBA, where he serves as Chief Research Officer. He has been awarded the Georges Vanderlinden prize for science by the Belgium Royal Academy and remains committed to bringing the benefits of proton therapy to more patients as a powerful weapon in the global fight against cancer.

How it works

Protons are well suited for radiation therapy because their power can be focused at a controlled depth inside the body. The focal point can be determined up to the millimetre via the regulation of the beam's energy intensity.

Proton rays release most of their energy in the last few millimetres of their trajectory, allowing physicians to take precise aim at a tumour site. X-ray beams, on the contrary, decay exponentially on their way through the body and need to be fired with a higher entrance dose.

A cyclotron particle accelerator such as the one invented by Yves Jongen, accelerates charged particles up to half the speed of light through a magnetic field. It is created by a fixed-field resistive magnet and high-frequency alternating voltage from two ‘D'-shaped electrodes (called ‘dees') inside a vacuum chamber. The enormous magnet inside Jongen's cyclotron - including IBA's Proteus series - is 4.34 metres in diameter, 2.1 metres high, and weighs 220 tonnes.

Cyclotrons used for proton therapy create protons in the range of 70 to 250 MeV (mega electron Volts). By adjusting the energy level during treatment sessions, doctors can maximise the power of the proton beam right at the site of a tumour while limiting exposure of surrounding tissue.

Far from resting on his laurels, Jongen continues to improve cyclotron development at IBA, where he serves as Chief Research Officer.

The rise of proton therapy

The first proton therapy sessions for cancer patients took place at Berkeley Radiation Laboratory in 1954. In 1990, the world's first clinical proton therapy centre began treating patients at the Loma Linda University Medical Center (LLUMC) in California.

Proton therapy is especially well suited for treating tumours in delicate locations that require minimum damage to surrounding tissue, including eye tumours. As a matter of fact, some proton therapy centres solely treat ocular tumours.

For more than a decade, there were less than five centres worldwide. Thanks to Yves Jongen's efforts, there are currently 39 particle therapy centres in use and more than 20 currently under construction. Upwards of 21,000 patients have been treated with proton therapy so far.

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