Accelerator physicists have been striving to discover ever more powerful ways to generate and steer particle beams for research into the physics, materials, and matter, including practical uses in medicine, such as tackling cancer, the second leading cause of death in the US today, affecting one in two men and one in three women.

Fig. 1 – Different types of radiation treatment cause different kinds of damage to the DNA in a tumor cell. X-ray photons (top arrow) cause fairly simple damage (purple area) that cancer cells can sometimes repair between treatments. Charged particles—particularly ions heavier than protons (bottom arrow)—cause more and more complex forms of damage, resulting in less repair and a more lethal effect on the tumor. (Credit: NASA)

Using beams of accelerated protons or heavier ions such as carbon, oncologists can deliver cell-killing energy to precisely targeted tumors—and do so without causing extensive damage to surrounding healthy tissue, eliminating the major drawback of conventional radiation therapy using x-rays.

A symposium exploring the latest advances and challenges in this field was held during the 2014 meeting of the American Association for the Advancement of Science in Chicago in February. The session called “Targeting Tumors: Ion Beam Accelerators Take Aim at Cancer,” was organized by the U.S. Department of Energy’s Brookhaven National Lab - oratory. Brookhaven Lab is the only place in the US where scientists can conduct fundamental radiobiological studies of how beams of ions heavier than protons, such as carbon ions, affect cells and DNA.

“We could cure a very high percentage of tumors if we could give sufficiently high doses of radiation, but we can’t because of the damage to healthy tissue,” said radiation biologist Kathryn Held of Harvard Medical School and Massachusetts General Hospital during her presentation. “That’s the advantage of particles. We can tailor the dose to the tumor and limit the amount of damage in the critical surrounding normal tissues.”

Yet, despite the promise of this approach and the emergence of encouraging clinical results from carbon treatment facilities in Asia and Europe, there are currently no carbon therapy centers operating in the US.

Participants in the session agreed that the situation has to change, especially since the concept of particle therapy began in the US. Much of the initial radiation biology and clinical work was done at DOE’s Lawrence Berkeley National Laboratory.

Stephen Peggs, an accelerator physicist at Brookhaven Lab and adjunct professor at Stony Brook University, explained that unlike conventional x-rays, which deposit energy—and cause damage—all along their path as they travel through healthy tissue en route to a tumor, protons and other ions deposit most of their energy where the beam stops. Using magnets, accelerators can steer these charged particles left, right, up, and down, and vary the energy of the beam to precisely place the cell-killing energy right where it’s needed: directly in the tumor.

The first implementation of particle therapy used helium and other ions generated by a machine built for fundamental physics research, the Bevatron accelerator at Berkeley Lab. Those pioneering spin-off studies “established a foundation for all subsequent ion therapy,” Peggs said. “It was also a ground-breaking and serendipitous demonstration of the transfer of emerging technology from DOE to medicine.”

As accelerators for physics research grew in size, pioneering experiments in particle therapy continued, operating at physics research facilities until the very first accelerator built for hospital-based proton therapy was completed with the help of DOE scientists at Fermilab in 1990. But even before that machine left Illinois for Loma Linda University Medical Center in California, said Peggs, who was at Fermilab at the time, physicists were thinking about how it could be made better. The mantra of making machines smaller, faster, cheaper—and capable of accelerating more kinds of ions—has driven the field since then.

Advances in magnet technology, including compact superconducting magnets and beam-delivery systems developed at Brookhaven Lab, hold great promise for new machines. As a principal investigator in a Cooperative Research and Development Agreement contract between Brookhaven Lab and Best Medical International, Peggs is working to incorporate these technologies in a prototype “ion Rapid Cycling Medical Synchrotron” capable of delivering protons and/or carbon ions for radiobiology research and for treating patients.

The benefits of using charged particles heavier than protons (e.g., carbon ions) stem not only from their physical properties— they stop and deposit their energy over an even smaller and better targeted tumor volume than protons—but also a range of biological advantages they have over x-rays. Compared with x-ray photons, carbon ions are much more effective at killing tumor cells, putting a “huge hole” through DNA compared to a pinprick caused by x-rays, which causes clustered or complex DNA damage that is less accurately repaired between treatments. (See Figure 1)

It is still important to conduct further research to explore, for example, which heavy ions are best and how treatment fractions should be delivered. Studies suggest that use of a smaller number of very high dose fractions, called hypofractionation, might be more effective, which would be an advantage to patients. More studies are needed, but there are very few places to conduct this research. One is a facility built by NASA at Brookhaven Lab to explore the effects of space radiation on cells and DNA. The goal of the NASA Space Radiation Laboratory is to fully understand risks and design protections for future astronauts. But much of the research is relevant to understanding the mechanisms and basic radiobiological responses that can apply to the treatment of cancer.

They explained that when you can target the tumor and spare critical tissue, you get fewer side effects. For example, when treating brain tumors with protons, doctors can spare the nerve going to the eye or the cochlea to preserve vision and hearing. Data also show that children with brain tumors treated with protons have better scores on math and spelling tests than children treated with x-rays.

Eric Colby, program manager for the Accelerator Stewardship program in DOE’s Office of High Energy Physics, says he joined DOE because he saw a lot of interest and tech transfer opportunities to make this kind of cancer treatment cheaper, better, and faster. “The goal of accelerator stewardship,” he said, “is to look at technologies developed over the years for basic physics research to see how they can be used in other fields—to transfer technologies from basic science to new practical uses.”


Medical Design Briefs Magazine

This article first appeared in the May, 2014 issue of Medical Design Briefs Magazine.

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