At least on the surface, the story of carbon ion therapy counters a myth about American medicine—that while Americans pay more per capita for health care than other developed countries, the US has the world’s most advanced medical technology. But are Americans in fact missing out? The nuanced answer is that no one knows for sure, because neither carbon ion nor proton therapy has “gold standard” evidence from randomized Phase III clinical trials showing patients live longer with the treatment than with standard radiation. [(Such trials are ongoing)](https://www.cancertodaymag.org/Pages/Summer2019/Focusing-on-Proton-Therapy.aspx.

“There’s a theory it’s better treatment—theory, not proven,” says Otis Brawley, an influential oncologist at Johns Hopkins University, of particle therapy. He adds that, again in theory, carbon ions ought to be superior to protons. “We should pursue carbon ion therapy,” he says. “But we should do the clinical studies to see where it is appropriate to use it.”

The trouble is in how research has been conducted so far. The highest-quality studies require patients to be randomly assigned to particle-based or standard radiation, and in most of the existing studies—in Japan, China, or Europe—researchers made that selection; it wasn’t done randomly. Different centers use different protocols, making comparisons difficult. And the lack of carbon ion centers in the US poses a logistical challenge for American researchers.

For its part, the National Cancer Institute is funding grants to uncover the properties of ionized particles. But because the particle beams produce different biological changes at different doses, untangling their effects can be challenging, says Norman Coleman, associate director of the NCI’s Radiation Research Program. In other words, it’s not just a matter of turning up the volume.

Particle-based cancer therapy evolved almost a century ago in an atmosphere of pure scientific exploration. Ernest Lawrence created the first cyclotron in 1928 at the University of California Berkeley, a circular contraption made of glass, bronze, and sealing wax that could speed the particles until they blasted apart into high-energy particles. He won the Nobel Prize for his work.

In the ensuing decades, other scientists discovered that high-energy particles could be used as a medical therapy, and that heavy ion beams could kill tumors. In 1975, Eleanor Blakely, senior staff biophysicist at the Lawrence Berkeley National Laboratory in Berkeley, California, was part of the first team of physicians and scientists to investigate the medical uses of ions.

She studied carbon, neon, silicon, and argon. Argon, for example, caused too much tissue damage. “It became a challenge of trying to figure out which one targeted the tumor with a high enough spectrum of ionization while sparing normal tissues,” she says.

Carbon and neon had similar effectiveness, she concluded. By 1988, the lab had treated 239 cancer patients with neon in Phase I and II studies. Survival rates doubled with certain advanced cancers, such as those of the salivary gland, paranasal sinus, and bone sarcoma, compared with conventional radiation therapy.

But then this line of inquiry came to an abrupt end. When the Berkeley accelerator shut down in 1993, at the end of its lifespan, there was no financial support to build another heavy ion facility. Japan took the promising Berkeley results and built the world’s first carbon ion therapy center in 1994. Blakely would like to see carbon ion treatment return to the US, even in an experimental setting. “Carbon delivers more energy, giving it a therapeutic advantage,” she says.

Twenty-five years later, Hak Choy, chair of radiation oncology at the University of Texas Southwestern Medical Center in Dallas, hopes to be the first to fill the gap in the US. He has a detailed design and plans funded by an NCI grant.



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