Scientific Approach

Historical background and market overview

The process of accelerating protons has evolved from one primarily used to test the limits and possibilities of nuclear physics, to one which can be used to produce effective medical therapies.

The first cyclotron was built in the 1930s at the Berkeley Radiation Laboratory at the University of California, Berkeley. However the first suggestion that protons could be an effective treatment method for medical purposes was only made in 1946 in a paper published by Robert Wilson. The first treatments were performed with particle accelerators built for physics research, notably the Berkeley Radiation Laboratory in 1954 and at Uppsala in Sweden in 1957. Seven years later, Harvard University and the Massachusetts General Hospital began using protons for cancer treatment at the Harvard Cyclotron Laboratory.

For decades, proton therapy remained a cancer treatment offered at a limited number of physics laboratories. In the meantime, other advancements in the diagnosis and treatment of cancer continued to evolve. These advancements ultimately helped make proton therapy a more effective and precise treatment. These included the creation and improvement of computed tomography, 3D conformal technology, patient immobilisation devices, etc.

While proton therapy has been used to treat tumours for nearly 60 years, it has more recently become approved in the United States. In 1988, proton therapy received U.S. Food and Drug Administration (FDA) approval for the treatment of certain cancers, including brain tumours. The world's first hospital-based proton therapy centre was a low energy cyclotron centre for ocular tumours at the Clatterbridge Centre for Oncology in the UK, followed in 1990 by another centre opened at the Loma Linda University Medical Center in California. The latter had a modified cyclotron (more suitable for a hospital or medical center), called a synchrotron. Later, the Northeast Proton Therapy Center at Massachusetts General Hospital was brought online, and the HCL treatment program was transferred to it during 2001 and 2002. Since then, additional facilities have been opened but there remains a significant unmet need to cover patients’ needs, largely due to the significant cost of proton therapy systems

The majority of evidence that has been accumulated to date highlights the significant benefits in using proton as part of medical programs. By December 2013, over 120,000 patients have been treated worldwide. As of August 2013 there were 43 operational particle therapy facilities worldwide. This represents merely 0.9% of all conventional radiotherapy systems used around the world.

The proton therapy world market is anticipated to nearly triple by 2018. From 1990 to August 2013, the number of particle therapy treatment rooms in activity has experienced an annual growth rate of almost 13%.

How does proton therapy work?

Protons are positively charged particles from the nucleus of a hydrogen atom. When protons are accelerated to high speed they enter the body at a pre-set level of energy and continue in a straight line until they come to a precisely calculated depth within the body. Like regular radiotherapy treatment, proton beams will then damage and kill cancer cells. However unlike X-ray beams, they will stop once they hit their target, rather than carrying on through the body. Oncology teams can target tumour cells more precisely with protons than with x-rays by sculpting the dose to completely penetrate the volume and space of the tumour without escaping or leaking into nearby areas. This means that all the energy is delivered to the very specific physical location thereby protecting healthy tissue and vital organs.

A visual comparison of treatment with protons and x-rays

What is the Bragg Peak?

Success of proton therapy relies on the unique physical properties of protons, in particular improved energy dose distribution and less energy scatter. While moving, in the tissue, protons beams release only some of their energy. Towards the end of their trajectory, they slow down coming to a rest at the tumour site, where they release most of their energy. This is known as the Bragg-Peak effect. .

In many cancers, treatment using protons is the most accurate form of radiation available and is often used in conjunction with chemotherapy and/or surgery. Unlike X-rays, protons have specific physical properties that determine how they act when they hit something. As a result of their uniqueness, unlike photons which are X-rays, protons can be targeted more accurately to damage cancer cells and limit damage to surrounding healthy tissues.

By comparison, X-rays deliver their largest dose of radiation immediately when they enter the body. Thus this "scatter" contaminates and burns the healthy tissue. In addition, X-rays continue to emit this "scatter" as they leave the body wounding everything in its path such as organs, bone and skin. Often the dose of radiation delivered to cancerous tissue is much lower when using X-rays so as not to destroy the normal tissue and thus compromises the attempt to kill the cancerous cells.