X-ray showing comparison of dose distributions between proton therapy and radiation therapy
X-ray showing comparison of dose distributions between proton therapy and radiation therapy
Taheri-Kadkhoda et al. Radiation Oncology 2008 3:4 doi:10.1186/1748-717X-3-4

Particle accelerators are famously large machines. The largest and most famous one even has it in the name: the Large Hadron Collider (LHC). When you stand in the 27km long LHC tunnel deep underground it looks as if the chain of blue magnets simply stretches off to infinity.

So when people talk about putting particle accelerators in hospital basements to treat cancer, there is understandably some reticence as to their size and cost.

Despite this, proton therapy is big business. According to the Particle Therapy Co-Operative Group, at the end of 2012 over 100,000 patients had been treated with charged particles worldwide. Of those, roughly 94,000 were treated with protons.

To understand why hospitals are using this treatment at all, we need to ask: what happens when you fire a beam of protons into the human body?

It’s a question that physicist R R Wilson must have been pretty excited about in 1944 when he published a paper in a medical journal simply called ‘Radiological use of fast protons’ (Radiology, 1946:47:487-91). The paper described how new ‘high energy’ particle accelerators could provide protons or other light ions which would penetrate deep enough into the body to be therapeutically useful.

When treating any cancer with radiation the aim is to increase the dose deposited in cancerous cells while sparing as much of the healthy tissue as possible. For tumours deep inside the body or in the brain this can become particularly difficult. It’s also crucial in many cases of childhood cancer where the child is still developing.

Protons deposit only a low dose at high energy, gradually decreasing their speed until they reach a kind of sweet spot where they rapidly lose all of their energy and stop, depositing a high radiation dose. This is called the ‘Bragg peak’. The depth of the Bragg peak depends on the initial energy of the protons. Because they come to a complete stop, there is no dose deposited past that point. This becomes a real advantage if there is a brain or an eye directly behind the target tumour.

Contrast this with typical X-ray radiotherapy, where the dose is actually greatest just under the skin and then drops off with depth, and it becomes clear why proton therapy is so popular.

Dose deposition of a proton beam showing the Bragg peak (red) compared to the dose deposition of a typical X-ray beam (pink). In reality the Bragg peak is actually remarkably fine, so it is usually spread out or scanned creating the so-called ‘Spread-out Bragg Peak” shown as the ‘modified’ proton beam (blue). Credit: Wikipedia/Dr A A Miller

If you were trying to treat something deep inside the body, it looks like a no-brainer: you’d choose protons. If you wanted an even greater effect you could choose to use slightly heavier ions like Helium or Carbon where there is an even higher and sharper peak in the dose distribution.

Surprisingly, there are no Phase III randomised clinical trials that ‘prove’ proton therapy is superior to X-ray radiotherapy. In fact, ethical considerations may rule them out. If we already know the difference in the physics, it could be considered unethical to offer patients conventional radiotherapy when proton therapy is available.

Previous developments in conventional radiotherapy, such as the move from analog X-rays to digital, or from hand-calculated treatment plans to simulation codes were simply approved and adopted immediately. Many centers offering this treatment consider protons simply another type of radiation to be used in radiotherapy, not an entirely new treatment.

In practice it turns out to be a little more challenging than the basic physics leads us to believe. But then nothing is simple when you’re dealing with the human body and something as messy as cancer. This is one reason why the Particle Therapy Cancer Research Institute in Oxford was created, co-directed by Prof Ken Peach, which brings together physicists, IT experts, biologists and oncologists to try and address some outstanding questions in the field.

As Prof Peach’s colleagues in the Gray Institute know well, every cancer is different. For any given cancer we need to be able to determine the most effective combination of therapies which are needed to achieve a cure including surgery, conventional radiotherapy, chemotherapy, gene therapies and methods like proton or ion therapy.

When it comes to proton and ion therapy Prof Peach says we still need greater understanding of the biological response of tissue along the particle path:

“We already know there is a smaller biological effect on the plateau [or low-dose] region and a higher effect in the Bragg peak. Further understanding of biological effects is key to achieving a lower uncertainty in the actual delivered dose to the patient and having a more effective treatment.”

With the current trend toward using heavier ions, such as carbon, more research is needed to understand whether they provide a real clinical benefit and also to ascertain which ion is the best compromise once all the complexities are taken into account.

In physics, I often hear people say that when a concept is simple and elegant it ‘must be right’. Proton and ion therapy certainly seemed that way to begin with, but now it’s practitioners are learning that reaping the full benefit of the Bragg peak is a lot more complex when human biology is involved. The idea may have started in the particle physics lab, but without the ingenuity of engineers, doctors and radiation biologists, this therapy would not be the success story it is today.

In the meantime, physicists are contributing to proton and ion therapy through the development of new accelerators and new imaging technologies to help oncologists deliver the best treatment possible. For more on that, keep an eye out for my next post.

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