VIBS 663 Biomedical Reporting: November 29, 2023

Ever since X-rays were first used to treat diseases and examine bones more than a century ago, medicine has exploited the often strange properties of matter and energy for the betterment of human health. More recently, however, doctors have tools in their anticancer arsenal more substantial, and more precise, than rays of light: beams of radiation-emitting charged particles.

Charged particle therapy, or CPT, treats cancer with beams of either alpha particles, a type of radiation made up of electron-less helium atoms; heavier atoms, like carbon, without their electrons; or singular protons, the lightest and easiest to accelerate. These beams of particles are collected and propelled through a particle accelerator before being redirected to the site where a cancer patient is being treated. As the beam enters the tissue of the patient, targeted at their tumor, the charged atoms deposit energy that destroys the cancerous cells.

Physicists first theorized about the potential for using charged particles to attack tumors in 1946, with the first tests of proton therapy on patients in 1954. CPT has been administered clinically for the past four decades. The technology to deliver this type of therapy has improved dramatically over the years, according to Jacinta Yap, a postdoctoral researcher at the University of Melbourne. As of 2019, there were 109 CPT facilities worldwide that use either beams of protons or carbon atoms, and about a quarter of a million patients have received these types of treatments.

CPT is distinct from the more common photon radiation therapy, which instead uses high-energy X-rays to target tumors.

To more precisely target tumor cells, CPT leverages the varying distribution of energy deposited along the path of charged particles as they pass through matter. This phenomenon is known as the Bragg peak. As charged particles pass through matter, the Bragg peak shows that they emit most of their energy, and thus their radiation dose, right before they stop.

The depth of a particle beam’s Bragg peak depends on the energy of the particles. In cancer treatment, the beam’s energy can be adjusted so that the particles come to rest at a certain depth in the tissue. This allows doctors to strike tumor cells with a lower risk of harming the healthy cells beyond.

In contrast, the distribution of energy for X-rays drops off gradually as it passes through living matter. In cancer treatment, this means the X-rays deposit radiation through the entire body, not just the target.

“We can shape the radiation more specifically to where the tumor is so that we can avoid side effects and improve quality of life for patients,” Yap said. “So, we know that the physics is better than what’s currently available conventionally, which is high energy X-ray photons.”

Aiming at a moving target

This increased precision also comes with its own downsides, though, Yap said. In 2021, Yap co-authored a review article published in Frontiers in Oncology examining the current shortcomings of CPT and possible solutions. 

“The reason why you can’t use it for as many tumor candidates compared to photon radiation therapy, is because it’s so precise, you need to make sure that where you’re delivering it is exactly where the tumor is,” she said in an interview.

Even the natural movement of the human body can complicate this precise treatment.

A typical session of CPT takes about 30 minutes, including patient set-up time. Since set-up procedures, and duration, can vary from clinic to clinic, the surest way to cut down this duration is improving the performance of the beam itself, Yap said.

While the beam is on, changing its energy to reach a different tissue depth takes up the most time, Yap found in her review paper. This process is called the energy layer switching time. While scanning across one layer of a tumor can take just a handful of milliseconds, adjusting the beam so that the Bragg peak targets a different layer can take anywhere from 80 milliseconds to a few seconds.

The most sluggish energy layer switching time takes place in a synchrotron, one type of particle accelerator commonly used for medical treatment. In a synchrotron, a series of magnets push and pull the charged particles around a circular particle accelerator until they speed up to the right energy. The beam is then extracted and sent to the equipment in the treatment room. To change the energy, then, the beam in the ring must be discarded and the magnets are adjusted for the next batch of charged particles.

This process can take valuable seconds, long enough for the patient’s breathing cycle to subtly shift the tumor.

A potential solution to this bottleneck, Yap proposed in her review paper, is redesigning the array of magnets in the accelerator. In a certain arrangement, the magnets can deliver a beam of particles with a range of energies, increasing the thickness of a layer that can be treated at one time. As a result, there would be less need to wait for the accelerator to change the energy of the beam, and in turn, less need to correct for potential movements.

“If you can rearrange this so that you can do a larger range, then you don’t need to wait for the bottleneck, which is waiting for the system to adjust,” Yap said. “Then, you can just send through protons of different energies without waiting, essentially removing that bottleneck.”

Importantly to busy physicians and their busy particle accelerators, a shorter treatment session with less beam time provides the capacity to treat more patients. This improvement is among the ideas that Yap identified in her review paper for making CPT more efficient and effective.

“If we can essentially treat faster, that means that we can treat more people, make it cheaper, and treat better,” she said.

So many patients, so little beam time

Despite its advantages, CPT is not nearly as prevalent today as X-ray radiotherapy because it is not as accessible.

In particular, the equipment and infrastructure to provide CPT can be prohibitively expensive, making it the main barrier to widespread CPT use, Yap said. This constraint is easing, though, as more commercial suppliers offer smaller, more affordable CPT equipment.

“Machines used to be really big and really expensive,” she said. “To put something of that size in a hospital was just not feasible, which is why a lot of facilities in the early days were built at research facilities. Now, there are a lot of commercial vendors, so that makes it much cheaper, and it standardizes the outputs you get and the performance of the machines.”

One such medical facility offering CPT is the MD Anderson Cancer Center in Houston. The massive cancer treatment provider includes a Proton Therapy Center, which has provided CPT using proton beams for decades. Next month, MD Anderson will open a new building for the Proton Therapy Center with four patient rooms to help meet growing demand, said Aubrey Bloom, an MD Anderson spokesperson.

To illustrate the complexity of building a proton therapy facility, Bloom said it has taken almost a decade to ultimately achieve this new facility.

“It’s a long process to put these things together, so they’re few and far between,” he said.

A major obstacle to building proton therapy centers is the sheer cost and size of the complex machinery, Bloom said. From the accelerator to the magnets to the mechanism that focuses the beam, the equipment for the new proton therapy building at MD Anderson costs tens of millions of dollars, weighs thousands of tons, and towers three stories tall.

Another barrier for individual patients looking for CPT is geographical location, Bloom said. Even when proton therapy may be the best option for a patient, living far away from one of the few places that offers it can negate its advantages.

“They are really selective with what kind of patients will not only benefit from it, but will benefit enough to outweigh the inconvenience, especially if they are from out of state or they don’t live near one of these centers,” he said.

The demand for proton therapy at MD Anderson is high, Bloom said; other than a few hours of calibration in the middle of each night, the beam runs day and night. The existing patient rooms for CPT at MD Anderson are usually “booked solid,” he said, and the availability of the first patient room in the new building is already full.

“The demand is very high,” Bloom said.

Right now, CPT is the most accessible in a few wealthier countries. The centers offering the treatment are concentrated in the United States, Japan, China, and Europe, with a handful elsewhere throughout the world.

“The cost is really expensive, which is the hardest part in terms of convincing governments to spend hundreds of millions of dollars on this type of technology,” Yap said.

A new CPT facility is being built in Adelaide, Australia, Yap’s home country; this facility is scheduled to start treating patients in a couple of years.

“The trajectory of the field is really into making machines cheaper and more effective,” she said. “With that, we can improve the accessibility and availability of charged particle therapy worldwide.”

Cancer is complicated, and similar people with the same cancer and the same treatment can often face different health outcomes, Yap said. Therefore, it’s important to make CPT accessible as one of many types of therapies as options for patients, including chemotherapy and traditional radiation therapy.

“The way we look at treating cancer, it’s a collective battle,” she said. “There are a lot of areas in the world that don’t even have access to X-ray radiation therapy. By increasing the number of options that we have worldwide, we can treat more people, which means a better outcome for everybody.”