Proton therapy is a precise, effective cancer treatment and an important resource for patients and caregivers in the Pacific Northwest. The ability to offer this type of radiation is the result of decades of work by scientists across multiple disciplines. Here’s a look at what had to happen to make proton therapy available in our region today.
No type of radiation therapy would be possible without the discovery of X-rays by Wilhelm Röntgen in 1895. This discovery was met with extreme interest in the scientific world, and a number of lines of research began. Within just a month of Röntgen's publication, the medical community was using X-rays to help surgeons. For his work, Röntgen was awarded the first Nobel Prize in Physics in 1901.
Scientists soon discovered that prolonged exposure to X-rays had noticeable effects, such as inflammation and tissue damage. Léopold Freund and Eduard Schiff, intrigued by this, suggested that X-rays could be used in the treatment of disease. As early as 1896, a physician in Chicago used X-rays to treat a woman with recurrent breast cancer. Shortly after that, journals had published many successful treatments of different types of skin issues with X-rays. However, the scientific community still didn't know what exactly it was that was helping. Was it the electrons or the ozone they created? In 1900, an Austrian radiologist named Robert Kienböck demonstrated that it was the X-rays themselves.
Soon the field of röntgenotherapy was born, mainly to treat lupus, carcinomas, leukemia, skin problems, such as eczema, and bacterial diseases such as tuberculosis.
To treat patients with X-rays, scientists used cathode tubes to accelerate electrons. When the electrons hit metal at the end of the tube, they created X-rays, which were then directed through the skin. However, when used to treat deeper-lying tumors, the X-rays deposited too much radiation in the skin, leading to unwanted side effects. Scientists experimented with cobalt and other materials to create higher-energy electrons, which, in turn, created higher-energy X-rays. To put early X-ray acceleration into perspective, the earliest tubes could create 125,000 volts. Modern machines generate 18 million volts.
Today, it’s still the case that, due to the nature of X-rays, most radiation is deposited at entry into the body, and decreases as it passes through the tissue. To counteract this, physicians now often use multiple rays that overlap only at the tumor site.
Around the turn of the 20th century, a series of discoveries helped people understand the various components of atoms. J.J. Thompson first discovered the positive and negative charges in atoms, leading to the discovery of electrons. A few years later, Ernest Rutherford discovered the atomic nucleus and the positively-charged particles they contained — protons.
William Henry Bragg found that charged particles in the atom lose energy as they travel through matter. For protons, this energy loss happens suddenly, before it comes to a stop. Bragg discovered this phenomenon in 1903, which we now call the Bragg Peak. This discovery showed great promise in reducing potential radiation side effects if used to treat conditions underneath deeper layers of healthy tissue. American physicist Robert R. Wilson was the first to suggest using protons for radiation therapy in a paper published in 1946. Berkley Radiation Laboratory, where Wilson had studied under Ernest Lawrence (see below), delivered the first proton therapy treatments for cancer in 1954. We now understand their importance in treating tumors that are close to vital organs.
A cyclotron is a type of particle accelerator that was invented by physicist Ernest Lawrence in 1930 at the University of California, Berkeley. Cyclotrons can accelerate protons to two-thirds the speed of light. Before cyclotrons, particles such as protons were accelerated in linear accelerators called linacs. Linacs cost more to operate and require more space than cyclotrons, which accelerate particles in a spiral path, resulting in both space and cost savings.
The first treatments using radiation were done without any X-ray imaging. Physicians made the margins around a tumor sufficiently large to make sure that the cancer was completely treated. External marks placed on the patient’s skin defined the area to be treated, and patients were immobilized using various accessories to ensure they were positioned properly every day. Even today, imaging is not always necessary, such as when the tumor lies on the skin.
In 1971, engineer Godfrey Hounsfield and physicist Allan Cormack invented the computerized tomography (CT) scan, which combines a series of X-ray images taken from different angles around the patient’s body and uses computer processing to create cross-sectional (slices) images of the bones, blood vessels and soft tissue. Shortly after, physicians treating patients with protons began using the scans to determine the precise location of the tumor as well as the necessary beam strength. CT scans were therefore crucial to the development of proton therapy.
Today, imaging is used in two ways for radiation therapy: CT-based imaging that physicians use to plan treatment and small amounts of X-ray imaging to position the patient precisely for treatment each day.
Treatment planning systems are essential for all types of radiation therapy. These systems are highly sophisticated computer programs developed by physicists. A proton beam coming from the cyclotron has many parameters that can make cancer treatments more accurate and effective by tweaking them to ensure maximum damage to cancer cells and minimized harm to healthy cells. A treatment planning system allows adjustments to the parameters and sends them to a proton therapy delivery system for optimum treatment.
Many of the early proton therapy centers had to create their own treatment planning software because commercial software did not yet exist. Some centers continue to use non-commercial software written by their own physicists.
Proton therapy has been used in research settings since the 1950s. Before it could become commercially available for patient treatment throughout the U.S., it had to get approval from the Food and Drug Administration.
Any new device or procedure needs an investigational device exemption that allows scientists to use the investigational device in clinical trials — first in animals and, eventually, in humans — to collect safety and effectiveness data. There must be enough evidence that a device is safe and effective. Even after FDA approval is granted, operators, manufacturers and physicians are required to track and report operational data about the facilities and their patients. FDA approval was obtained for proton therapy in 1988.
In the beginning, only large, well-established hospitals could afford to provide proton therapy because of the high cost of construction and equipment. We’re fortunate that Fred Hutchinson Cancer Center had the foresight, interest and ability to open a proton therapy center in 2013. Today, many hospitals and treatment centers are opting for a one-room proton treatment facility as an affordable way to offer all the advantages of proton therapy. In addition to the physical construction, proton therapy needs collaboration between many different professional groups, including engineers, scientists, physicists, physicians, treatment planners (dosimetrists), nurses, radiation therapists and other support staff.
Physicists and physicians are by no means done understanding all that radiation and the therapeutic effects it has to offer. Research is ongoing, including here at Fred Hutch, to see how radiation can be used more effectively and with minimal side effects. This includes finding ways to be as precise as possible in its delivery, shortening the course of treatment when possible and elevating the dose.
PBS was first introduced at the Paul Scherrer Institute in Switzerland in 1996. Using magnets to direct the proton beams, PBS “paints” the tumor with a lot of very thin, very exact beams of protons that have sharper Bragg peaks. The beams are accurate down to millimeters and do not require the apertures and compensators of the passive scattering method of proton therapy delivery. PBS sends very fast pulses of protons to the tumor until it is completely treated. The proton beam’s position and intensity can be controlled, which can lower the amount of radiation to healthy tissue even more than traditional proton therapy.
FLASH radiation therapy is another innovation currently being researched at Fred Hutch and other facilities across the globe. FLASH uses ultra-high-speed radiation (which gives radiation 100 to 1000 times faster than usual) to decrease side effects from radiation treatment. Although there have been some promising results, researchers still don’t know why or how FLASH reduces side effects, but one theory is that the ultra-high rate of radiation delivery depletes oxygen in the healthy surrounding tissue, which protects it from radiation. In 2022, a non-randomized clinical trial involving patients at Cincinnati Children’s/UC Health Proton Therapy Center found that FLASH proton therapy was safe and as effective as standard treatment.
Many events and discoveries had to fall into place to make proton therapy possible and available to a wide number of people. Thanks to these scientists’ excellent research, discovery and exploration, we can now treat many solid tumors with minimal side effects safely, effectively and with more precision than traditional radiation methods. Proton therapy has made radiation treatment safer for children, who are more sensitive to the effects of radiation; allowed physicians to treat patients who have already had radiation therapy; and minimized the chance of developing secondary cancers and other side effects.
We are proud to have treated more than 4,000 patients at the proton therapy facility and grateful to offer this treatment option in the Pacific Northwest.
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