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Brookhaven | Long Island, NY | USA

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Particle Beam Cancer Therapy: The Promise and Challenges

Advances in accelerators built for fundamental physics research have inspired improved cancer treatment facilities. But will one of the most promising—a carbon ion treatment facility—be built in the U.S.? Participants at a symposium organized by Brookhaven Lab for the 2014 AAAS meeting explored the science and surrounding issues.

by Karen McNulty Walsh

Accelerator physicists are natural-born problem solvers, finding ever more powerful ways to generate and steer particle beams for research into the mysteries of physics, materials, and matter. And from the very beginning, this field born at the dawn of the atomic age has actively sought ways to apply advanced technologies to tackle more practical problems. At the top of the list—even in those early days— was taking aim at cancer, the second leading cause of death in the U.S. today, affecting one in two men and one in three women.

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.

“This is cancer care aimed at curing cancer, not just treating it,” said Ken Peach, a physicist and professor at the Particle Therapy Cancer Research Institute at Oxford University.

Peach was one of six participants in a symposium exploring the latest advances and challenges in this field—and a related press briefing attended by more than 30 science journalists—at the 2014 meeting of the American Association for the Advancement of Science in Chicago on February 16. The session, “Targeting Tumors: Ion Beam Accelerators Take Aim at Cancer,” was organized by the U.S. Department of Energy’s (DOE’s) Brookhaven National Laboratory, an active partner in an effort to build a prototype carbon-ion accelerator for medical research and therapy. Brookhaven Lab is also currently the only place in the U.S. where scientists can conduct fundamental radiobiological studies of how beams of ions heavier than protons, such as carbon ions, affect cells and DNA.

Participants in a symposium and press briefing exploring the latest advances and challenges in particle therapy for cancer at the 2014 AAAS meeting: Eric Colby (U.S. Department of Energy), Jim Deye (National Cancer Institute), Hak Choy (University of Texas Southwestern Medical Center), Kathryn Held (Harvard Medical School and Massachusetts General Hospital), Stephen Peggs (Brookhaven National Laboratory and Stony Brook University), and Ken Peach (Oxford University). (Credit: AAAS)

Participants in a symposium and press briefing exploring the latest advances and challenges in particle therapy for cancer at the 2014 AAAS meeting: Eric Colby (U.S. Department of Energy), Jim Deye (National Cancer Institute), Hak Choy (University of Texas Southwestern Medical Center), Kathryn Held (Harvard Medical School and Massachusetts General Hospital), Stephen Peggs (Brookhaven National Laboratory and Stony Brook University), and Ken Peach (Oxford University). (Credit: AAAS)

“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 U.S.

Participants in the Brookhaven-organized session agreed: That situation has to change—especially since the very idea of particle therapy was born in the U.S.

Physicists as pioneers

“When Harvard physicist Robert Wilson, who later became the first director of Fermilab, was asked to explore the potential dangers of proton particle radiation [just after World War II], he flipped the problem on its head and described how proton beams might be extremely useful—as effective killers of cancer cells,” said Stephen Peggs, an accelerator physicist at Brookhaven Lab and adjunct professor at Stony Brook University.

As Peggs explained, the reason is simple: 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 (and beyond it), 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: in the tumor.

The first implementation of particle therapy used helium and other ions generated by the Bevatron at Berkeley Lab. Those spin-off studies “established a foundation for all subsequent ion therapy,” Peggs said. And as accelerators for physics research grew in size, pioneering experiments in particle therapy continued, operating “parasitically” 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, 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. Peggs is working to incorporate these technologies in a prototype ‘ion Rapid Cycling Medical Synchrotron’ (iRCMS) capable of delivering protons and/or carbon ions for radiobiology research and for treating patients.

Brookhaven Lab accelerator physicist Stephen Peggs with magnet technology that could reduce the size of particle accelerators needed to steer heavy ion beams and deliver cell-killing energy to precisely targeted tumors while sparing surrounding healthy tissue.

Brookhaven Lab accelerator physicist Stephen Peggs with magnet technology that could reduce the size of particle accelerators needed to steer heavy ion beams and deliver cell-killing energy to precisely targeted tumors while sparing surrounding healthy tissue.

Small machine, big particle impact

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.

As Kathryn Held elaborated in her talk, compared with x-ray photons, “carbon ions are much more effective at killing tumor cells. They put a huge hole through DNA compared to the small pinprick caused by x-rays, which causes clustered or complex DNA damage that is less accurately repaired between treatments—less repaired, period—and thus more lethal [to the tumor].” Carbon ions also appear to be more effective than x-rays at killing oxygen-deprived tumor cells, and might be most effective in fewer higher doses, “but we need more basic biological studies to really understand these effects,” Held said.

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)

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)

Held conducts research at the NASA Space Radiation Laboratory (NSRL) at Brookhaven Lab, an accelerator-based facility designed to fully understand risks and design protections for future astronauts exposed to radiation. But much of that research is relevant to understanding the mechanisms and basic radiobiological responses that can apply to the treatment of cancer. But additional facilities and funding are needed for research specifically aimed at understanding the radiobiological effects of heavier ions for potential cancer therapies, Held emphasized.

Hak Choy, a radiation oncologist and chair in the Department of Radiation Oncology at the University of Texas Southwestern Medical Center, presented compelling clinical data on the benefits of proton particle therapy, including improved outcomes and reduced side effects when compared with conventional radiation, particularly for treating tumors in sensitive areas such as the brain and spine and in children. “When you can target the tumor and spare critical tissue you get fewer side effects,” he said.

Data from Japan and Europe suggest that carbon ions could be three or four times more biologically potent than protons, Choy said, backing that claim with impressive survival statistics for certain types of cancers where carbon therapy surpassed protons, and was even better than surgery for one type of salivary gland cancer. “And carbon therapy is noninvasive,” he emphasized.

To learn more about this promising technology and the challenges of building a carbon ion treatment/research facility in the U.S., including perspectives from the National Cancer Institute, DOE and a discussion about economics, read the full summary of the AAAS symposium here: http://www.bnl.gov/newsroom/news.php?a=24672.

Karen McNulty Walsh is a science writer in the Media & Communications Office at Brookhaven National Laboratory.

 

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  • Uncle Al

    How is that better and less expensive than intruding a thin triple-walled cannula and repeatedly freezing (gas expansion below its Joule-Thomson inversion temperature) the tumor to death by cell rupture? Dead is dead, and the cells lyse either way.