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A flash of hope
A radiation oncologist’s breakthrough in delivering ultra-fast radiation may make cancer treatment more effective—and less damaging.
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Photo: National Cancer Institute, Unsplash
In 2008, Billy Loo, Jr., MD PhD, was in a gondola over Mount Taishan in China’s Shandong province, where he was attending a conference. Suspended hundreds of feet above pine-covered cliffs and winding granite stairways, Loo turned to a colleague and shared an idea that had been percolating: What if you could deliver radiation to cancer patients in an instant?
Invented in the late 19th century, radiation therapy uses beams of high-energy particles—usually X-rays—to destroy cancer cells by damaging their DNA. Today, it’s used to treat roughly two-thirds of all cancer patients. But healthy cells often become collateral damage in the process. In theory, doctors could cure nearly any cancer with high enough doses of radiation and other treatments, but the side effects would, in many cases, be devastating.
Loo’s idea suggested a new way forward. If radiation therapy could be delivered faster—so fast that patients had no time to move—it might minimize harm to healthy tissues.
In the months and then years after that trip to China, Loo and his collaborators got to work developing a groundbreaking technology known as PHASER—short for pluridirectional high-energy agile scanning electron radiotherapy—which can transmit highly targeted doses of radiation in just a fraction of a second. Early studies suggest the approach can be just as effective at eradicating tumors, while taking less of a toll on healthy cells. The technology could be available to patients within four years.
“This will have a huge impact,” says Loo, who is a professor of radiation oncology at Stanford Medicine. “We’ll see better treatment outcomes, higher rates of cure, and cures with less side effects.”
Before that gondola ride, Loo—like many in his field—had spent years working to make radiation therapy more precise to account for the fact that patients can’t remain perfectly still. As he puts it, “We’re always shooting at moving targets.”
“This will have a huge impact. We’ll see better treatment outcomes, higher rates of cure, and cures with less side effects.”Billy Loo, Jr., MD PhD
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Photo: Jess Alvarenga
He and his team implemented 4-D imaging techniques to map the way patients’ tumors shift when they breathe and technology that synchronizes radiation beams with breathing patterns. But after years of work on complex and costly innovations like these, Loo began to question his underlying assumption: Does delivering an effective dose of radiation really have to take longer than it does for the body to move?
“We started asking: What if treatment could be delivered faster than the body can move?” Loo says. “We tried to think of how to flip the equation so motion would be ‘frozen’ during treatment.”
It seemed plausible. By 2008, when Loo first floated his idea for instant radiation, the time it took to deliver a radiation dose had dropped from three hours to less than an hour in under a decade. (Today, it’s down to just two minutes.) “We’ve made a 100-fold improvement,” he says. “What if we could get another 100 or 1,000 times faster?”
Still, no one knew if such a leap would be technologically feasible—or effective. Then, in 2014, researchers at the Curie Institute in France made a remarkable discovery: When radiation was delivered to mice in a fraction of a second, it reduced harm to healthy tissue without compromising its ability to kill tumors. This new form of radiotherapy, which delivers doses of radiation in ultra-fast bursts, became known as FLASH.
“It violated a century’s worth of dogma,” Loo says. “That changed the whole ball game.”
Loo switched the focus on his lab to study the biology of ultra-fast radiation. At the same time, he doubled down on his efforts to develop the technology required to deliver it to patients. It was an ambitious pivot, but not without precedent: Stanford has a long history of breakthroughs in radiation oncology, including some of the earliest curative treatments for lymphoma and other cancers.
With seed funding from Stanford Medicine and in collaboration with SLAC National Accelerator Laboratory, Loo began putting together a world-expert team. Together they would go on to invent a new class of highly efficient linear accelerators—the machines that turn subatomic particles into radiation beams—in a device shorter than a baseball bat. They also developed a new way to power the accelerators, which will enable machines to shoot multiple beams simultaneously from different angles, eliminating the slow process of rotating the machine around a patient. Finally, the team invented a technology that can shape the intensity of each beam electronically, rather than relying on slower motorized parts. Together, these strategies can combine to deliver the same amount of radiation as current treatment machines in about a 500-fold shorter time.
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A novel patient positioning system that supports and stabilizes patients to be treated in the upright position (from seated to nearly standing), which has certain advantages compared to the traditional supine (lying down) position.
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The synchrocyclotron, a particle accelerator that accelerates protons to a high energy (equivalent to over 200 million volts) to penetrate deep into the body to reach tumors. Photos: Jess Alvarenga
Thanks to early philanthropic support—including seed grants from Stanford Biodesign and the Cancer League—Loo’s lab was able to turn bold ideas into working prototypes. With continued investment, these accelerators will be integrated with high-resolution imaging into a single PHASER unit, designed to resemble a CT scanner—streamlined, precise, and ready for clinical testing and use.
Scientists don’t understand why tumors and normal tissues seem to respond differently to ultra-fast radiation, and unlocking the underlying biology may take decades. For now, Loo’s Stanford lab is focused on optimizing FLASH today—using animal models to test how subtle differences in delivery speed affect outcomes and how the technology works in combination with drug therapies.
“After more than a century of great clinical impact, we still don’t fully understand how conventional radiotherapy works,” Loo says. “So it should not require a complete understanding to start taking advantage of the clinical benefits of FLASH.”
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“In combination with remarkable advances we’ve seen in drug therapies,FLASH radiotherapy has the potential to make a big impact in improving cures and helping patients live longer.”Billy Loo, Jr., MD PhD
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Photo: Jess Alvarenga
So far, researchers have replicated the effects of FLASH in multiple organs and tumor types. Loo believes PHASER could make it possible to cure difficult-to-treat cancers—such as those affecting the pancreas, those that have spread throughout the body, and some cancers of the lung and brain—by helping patients tolerate higher radiation doses. For diseases that are increasingly curable, such as head and neck cancers and some childhood cancers, the approach could reduce serious long-term side effects.
“In combination with remarkable advances we’ve seen in drug therapies, FLASH radiotherapy has the potential to make a big impact in improving cures and helping patients live longer,” Loo says.
The approach could also make cancer treatment more accessible. “Today, because of technology barriers, millions of patients who could benefit from radiotherapy don’t have access,” he says. “If we can make the machines compact, economical, and efficient, we can fit them in a shipping container that can travel anywhere in the world. And if treatment is faster, you can also treat more patients on the same machine.”
Loo, who specializes in treating lung cancer, has already watched survival rates rise over the course of his career.
“I’ve seen this transformation from terrible nihilism to actual hope for a lot of patients,” he says. “Being able to tell patients they have options and a shot at a cure, and especially seeing many of them doing well after treatment, is incredibly satisfying.”
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Loo is a member of the Stanford Cancer Institute, of the Molecular Imaging Program at Stanford, and of Stanford Bio-X.
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