Proton therapy up close: Yves Jongen, chief research officer of IBA

Since founding IBA in 1986, Jongen has seen the particle-accelerator manufacturer grow to world-leader status. The firm currently boasts more than a 60% market share in sales of proton-therapy systems, giving Jongen a unique viewpoint on the development of this burgeoning industry. There are currently 22 proton-therapy centres worldwide and, with the number of patients treated now approaching the 50 000 mark, it's certainly a technology that's moving in the right direction.

Yves Jongen

To meet the growing demand for proton-therapy systems, IBA is investing over €3 million this year to fund an extensive expansion programme. Plans include ramping production capacity and hiring 250 new staff. Tami Freeman visited the company headquarters in Louvain-la-Neuve to talk with Jongen about his plans for the company.

TF: What do you see as the key selling points of proton therapy?
YJ: If you look at the competing radiation used today, X-rays, the beams decay exponentially throughout the body so they give a higher entrance dose. X-rays also exit the body on the other side, so you irradiate tissue both upstream and downstream of the tumour.

With protons, their energy loss is inversely proportional to their energy, so most energy is deposited in the last millimetres of their trajectory. The protons will stop at a particular depth, dependent on their initial energy, and you can adjust this to within tenths of millimetres. Actually, the position peak is so sharp that it's generally smaller than the tumour, so you need to modulate the energy of the proton to give a uniform dose in the tumour. The big thing is that there's no dose downstream.

Why is that so important?
In a number of radiation therapies - for example, when treating the brain - there's a maximum dose that can be given to healthy tissue in order to avoid loss of function. With the radiation level to healthy tissue constrained, you generally won't give as much radiation to the tumour as is ideal. The highly targeted delivery is proton therapy's selling point.

Another example is medulloblastoma, a paediatric tumour that extends throughout the central nervous system. It's particularly important with children to minimize the dose given to healthy tissue, because when you irradiate tissue there's always the possibility of a secondary cancer arising many years later. If you irradiate with photons, you give a pretty high dose to all the organs in the way of the beam - that's something you really want to avoid. That's really why people are using protons instead.

How is the proton-therapy market developing?
It's really taking up. Today there are 22 proton-therapy centres treating patients worldwide. If you look at the evolution of the industry, from 1994 to 2005 there were 14 industrial contracts signed in those 11 years. Last year, four contracts were signed with IBA, and this year we expect eight deals to be signed. We are at the point where it goes from being a marginal technology to moving into the mainstream.

And how is IBA addressing this growth?
At present, IBA has one test cell that can accommodate two accelerators. Typically, a proton-therapy cyclotron spends six months in such a cell, which limits our basic production capacity to four systems per year - and we sold four last year. So we're extending to build two additional test cells (which will house one cyclotron each), doubling our yearly capacity to eight cyclotrons. To meet our objectives for 2007, we also need to hire more than 250 people worldwide. It's a challenging time, but it's an interesting challenge.

What do you think is fuelling this growth?
One factor is the snowballing of publications on proton therapy at international conferences - as more hospitals get proton-therapy systems they start publishing papers. Proton therapy started with relatively rare cases, the most common of which was eye melanoma, a tumour on the back of the eye that must be irradiated without irradiating the brain. But now it's really expanded into mainstream tumours, such as prostate, lung and breast.

Treatment centre

Cancer is unlike other disease - the level of self-referral of patients is very large. I saw the statistics from the proton-therapy centre that we opened in Florida last year and more than 80% of patients were self-referred. There's nothing like a deadly disease to get patients going on the Internet and collecting information. The power of the Internet has helped the growth of proton therapy.

Are more equipment vendors showing an interest in offering proton-therapy systems?
Siemens is in this market, Varian has moved into it, and I think that people at Elekta will certainly be thinking about it. Every big company in the field of radiation therapy is doing [some] soul-searching at the moment.

Do you see cost as a hurdle for hospitals considering proton therapy?
The total equipment cost for a typical proton-therapy system is around €45 million for an average configuration. Add to that the cost of the building and the associated medical imaging equipment, and the total investment for a proton-therapy facility comes out at around €100 million - it's a sizeable investment. But it can be a profitable option. A multiroom facility typically treats 2000 patients per year and generates a revenue of about €20,000 per patient. So despite the heavy investment, a proton-therapy system can create significant revenues for the hospital.

Is there a way to lower the start-up costs?
IBA recently released its compact proton-therapy system, designed for hospitals that cannot afford a €100 million project. The idea here was to make a system with only one treatment room and also to decrease the cost by making the system reproducible. This brings the equipment costs down to €18 million. Adding the building costs and you're looking at a total investment of €23 or 24 million. The system is limited in throughput, but one treatment room can treat around 500 patients per year, which is still a very acceptable rate for a number of hospitals.

Do you see this as a step forward for proton therapy?
I think so. I think the market is right for it. At first, proton therapy was only considered for big teaching hospitals, research institutions or university hospitals. These have such a large number of patients that a big multiroom facility makes sense. But now, patients at second-tier community hospitals are putting pressure on these smaller hospitals to offer proton therapy as well.

IBA recently launched a particle therapy system that can accelerate carbon ions. What's the benefit of carbon?
As Gray famously demonstrated, it takes more dose to kill cells that are irradiated in oxygen-depleted regions. This is the case for photons or protons and it's pretty bad news for cancer treatment as many tumours tend to have an anoxic core. Heavier particles like carbon ions have a much higher linear energy transfer than photons or protons. This means that when the ions travel close to the cell's DNA, the resulting ionization directly breaks the bonds in the DNA, whether oxygen is present or not. This is great news because it means you can treat radioresistant tumours that resist classical photons and protons.

So why doesn’t everyone use carbon beams?
A carbon system costs twice that of a proton-therapy system, so there won't be a lot of them and they'll tend to be national projects. Another issue is their size. Typically, 27 cm is considered an appropriate depth to treat deep tumours. To reach this in the body you need an energy of 400 MeV per nucleon, which for carbon ions is 4.8 GeV. This means that the accelerator size has to be bigger. A synchrotron solution is pretty large, about 35 m diameter. IBA has come up with a different technology - a superconducting cyclotron - which is smaller in cost and size.

Many of our customers were asking to buy a proton-therapy system that could upgrade to a carbon-ion system, so we have developed a two-step approach based on two cyclotrons. Carbon therapy is the next step in complexity in radiotherapy - anyone sensible starts with proton therapy first - and this approach seems popular with potential users.

Has IBA sold a carbon-beam system yet?
One carbon-beam system was sold in Japan by Mitsubishi a few years ago, but there hasn't been a private sale of a carbon-therapy system by any company in the rest of the world. However, there are a number of tenders in Europe at the moment in which IBA is in competition. The other big competitor in this area is Siemens.

How does the future look for IBA?
It's extremely exciting and in a way a bit frightening because this field is really exploding. With the development of any new technology, you have early adopters and then all of a sudden the volume of sales increases enormously. We seem to be at that point in particle therapy today.

IBA has certainly been one of the forerunners in this field, with more than half of the world market. Now I think that we have to keep moving extremely rapidly. We have to continue developing the system, continue keeping the customers happy and realize that, with the arrival of Varian, it's likely our market share will decrease. But the size of the market is expanding rapidly, so it will still mean bigger numbers in terms of systems sold.

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