Standard radiation techniques have evolved over the years, now allowing more precision and targeting to avoid unnecessary side effects. Proton therapy is an invisible and highly controlled beam that works by using pencil point precision to target a tumour. When it releases radiation, the radiation beam slows down, which allows the protons to interact with electrons allowing a release of high-energy. This high-energy is then released into its designated location (the tumour). As the beam is controlled by a physician the beam only targets the shape and depth of a tumour to allow healthy tissue to remain undamaged.
When it comes to getting rid of cancer, the sharpest scalpel may be a proton beam.
Although many people believe proton therapy is relatively new, it’s been around as early as 1946 with treatments on patients starting around 1954. From there proton therapy has evolved and expanded to other locations around the world, with the first UK proton centre for ocular tumours opening in 1989.
Below we outline the history of protons, from the development of the cyclotron, through to the latest advancements made possible through the power of ‘pencil-beam’ proton scanning nozzles and ‘Intensity Modulated Proton Therapy’ (IMPT).
Attacking Cancer with Protons
Proton radiation therapy is considered a better way to treat cancer because it has fewer side effects, but the technology is expensive. An American Proton Therapy Institute for example required eight years and $125 million to build, and can serve up to 150 patients a day.
The majority of proton centres throughout the world currently use ‘scattered beam’ nozzles to deliver the protons to cancerous tumours, as in the picture above (using the brass aperture and lucite compensator).
While scattered beams are extremely effective, a newer generation of beam, known as ‘pencil-beam’, now allows oncologists to treat cancer patients with a higher degree of precision.
Pencil-beam technology is more precise and has sub-millimetre accuracy. Proton therapy centres around the world are now upgrading to this newer style of proton delivery, and new facilities are being built from scratch with pencil-beam nozzles.
Proton therapy is based on the use of positively charged elementary particles of hydrogen atom nuclei – namely protons that have a weight much higher than that of electrons.
Protons are accelerated in a cyclotron to a speed equal to approximately half the speed of light. This also determines their energy, which reaches up to 230 MeV (mega-electron volts) and enables them to damage tumours up to a depth of approximately 30 cm. The protons are then targeted with a strong magnetic field into a very narrow beam (a “pencil beam”) and transferred with a high degree of accuracy via a 3D image to the malignant tumour. Energy is released during deceleration in the tumour tissue with subsequent ionisation and damage to the DNA of the affected cell. If the damage is sufficient, the cell stops dividing (and growing) or dies immediately.
The main benefit of the proton beam is the fact that the absolute greatest part of its energy is transferred to the area of the so-called ‘Bragg peak’, i.e. directly to the tumour, where it has maximum destructive effect. The beam of accelerated particles has a high energy level and is very accurately targeted. Most of the energy is transferred solely to tumour tissue. In comparison with current irradiation procedures, it preserves healthy tissue in front of the tumour and does not damage healthy tissue behind the tumour at all. Since the patient is irradiated in an isocentric system from all directions and the intensity of beams can be well modulated (IMPT), this method provides further reduction of adverse effects.
These physical properties of the proton beam – low entry dose, maximal dose of energy at the required depth and a zero exit dose – enable extremely precise modulation of dose distribution inside the patient’s body and represent the main advantage of proton radiotherapy. Due to this feature it is possible to increase the dose directed at the tumour to a level above that which could be achieved using common, conventional X-ray radiotherapy techniques – and at the same time reduces the dose to surrounding tissues that are sensitive to the harmful effects of radiation.
Proton therapy is made possible through the technology of a ‘cyclotron’.
A cyclotron is a type of particle accelerator in which charged particles accelerate outwards from the centre along a spiral path. The particles are held to a spiral trajectory by a static magnetic field and accelerated by a rapidly varying (radio frequency) electric field.
Cyclotrons can be used in particle therapy to treat cancer. Ion beams from cyclotrons can be used, as in protons therapy, to penetrate the body and kill tumours by radiation damage, while minimising damage to healthy tissue along their path. Cyclotron beams can be used to bombard other atoms to produce short-lived positron-emitting isotopes suitable for PET imaging.
The cyclotron was invented and patented by Ernest Lawrence of the University of California, Berkeley, where it was first operated in 1932.
The first European cyclotron was constructed in Leningrad in the physics department of the Radium Institute, headed by Vitaly Khlopin. This instrument was first proposed in 1932 by George Gamow and Lev Mysovskii and was installed and became operative by 1937.
The world’s largest cyclotron is located at the RIKEN laboratory in Japan. Called the SRC, for Superconducting Ring Cyclotron, it has 6 separate superconducting sectors, and is 19 m in diameter and 8 m high. Built to accelerate heavy ions, its maximum magnetic field is 3.8 tesla, yielding a bending ability of 8 tesla-metres. The total weight of the cyclotron is 8,300 tonnes. It has accelerated uranium ions to 345 MeV per atomic mass unit.
In addition TRIUMF, Canada’s national laboratory for nuclear and particle physics, houses one of the world’s largest cyclotrons. The 18 m diameter, 4,000 tonne main magnet produces a field of 0.46 T while a 23 MHz 94 kV electric field is used to accelerate the 300 μA beam.
Dr. Robert Wilson first proposed the use of protons for cancer treatment in 1946.
The Father of Proton Therapy
Robert Rathbun Wilson, PhD, has been described as ‘the father of proton therapy’. He learned high-energy physics at the Radiation Laboratory of Ernest O. Lawrence at the University of California, Berkeley.
He was also a member of one of the Manhattan Project groups that developed the atomic bomb, and headed an immense team of physicists that conceived, developed, built, and operated the Fermi National Accelerator Laboratory (Fermilab) outside of Chicago. Dr. Wilson understood and practiced teamwork and collaboration.
He was a serious sculptor of international renown, whose works are displayed at many universities and research institutions, including Fermilab; he was a firmly committed advocate of human rights, and he championed unceasingly for the peaceful use of atomic energy that he helped to unleash.
Robert Wilson’s contribution to proton radiation therapy was made in a paper he published more than a half-century ago entitled “Radiological Use of Fast Protons” (Radiology 1946:47:487-91). This article established the fundamental tenets and techniques that are being followed today at other proton therapy institutions around the world.
It was at a Fermilab conference in 1985 that James M. Slater, MD, FACR, chairman of Loma Linda’s department of radiation medicine, approached Fermilab’s director, Leon Lederman, PhD, and deputy director, Philip V. Livdahl, about the feasibility of building a hospital-based proton cyclotron. Mr. Livdahl has long shared Dr. Wilson’s interest in the medical use of protons and opined that Fermilab could do so. Also at the 1985 meeting, Dr. Wilson became an avid supporter of the evolving Loma Linda facility and followed its construction to completion and on through to the treatment of its first patient.
Dr. Wilson died on January 16, 2000, at his home in Ithaca, New York.