A groundbreaking new treatment promises to tackle more types of cancer with fewer side effects than traditional radiotherapy. It also takes less than a second.
In a vast network of underground caves on the outskirts of Geneva, Switzerland, experiments are taking place that could one day lead to a new generation of radiation therapy machines. The hope is that these devices could cure complex brain tumors , eliminate cancer that has spread to distant organs, and generally limit the impact of cancer treatment on the human body. People.
The site of these experiments is the European Laboratory of Nuclear Physics (CERN), best known in the world as a centre for particle physics, having developed the Large Hadron Collider, a 27 km (16.7 mi) long ring of superconducting magnets capable of accelerating particles to nearly the speed of light.
Perhaps CERN’s greatest achievement was the 2012 discovery of the Higgs boson , the so-called “God particle” that gives mass to other particles and thus underlies everything in the universe. But in recent years, the center’s unique expertise in accelerating high-energy particles has found a new niche: the world of cancer radiation therapy.
Eleven years ago, Marie-Catherine Vozenin, a radiobiologist now at the University Hospitals of Geneva (Hug), and others published a paper describing a tissue-altering, imaging approach to traditional radiotherapy that they call Flash. Using extremely high doses of radiation with exposure times of less than a second, they showed that they could destroy tumors in rodents while sparing healthy tissue.
Its effects are felt immediately. International experts have described it as a fundamental breakthrough, and it has prompted radiobiologists around the world to conduct their own experiments using Flash to treat a variety of tumors in rodents, pets, and now humans.
The Flash concept has resonated because it addresses some long-standing limitations of radiation therapy, one of the most common cancer treatments, with two-thirds of cancer patients receiving it at some point during treatment . Typically delivered through a beam of X-rays or other particles over two to five minutes, the total dose is often spread over dozens of separate treatments over eight weeks to ensure the patient can tolerate it.
Over the past three decades, improved imaging scanners and modern radiation therapy machines have helped target individual tumors with greater precision . However, the risk of harmful or fatal side effects still exists.
Vozenin cites the example of childhood brain tumors, which can often be cured with radiation to the brain, but at great expense. “Survivors often suffer from lifelong anxiety and depression, and the radiation impacts brain development, causing significant IQ loss,” she said. “We can [sometimes] cure these children, but the price they pay is very high.”
Billy Lu, professor of radiation oncology and director of the Flash Science Lab at Stanford University School of Medicine in the US, explains that tumours, especially large ones, are rarely clearly delineated from surrounding tissue. This means that it is often impossible to avoid damaging healthy cells, so oncologists often cannot use as high a dose as they would like, Lu says.
Oncology experts have long believed that the ability to increase radiation doses would significantly improve the chances of curing patients with hard-to-treat cancers, Vozenin said. For example, previous studies have shown that increasing radiation doses in lung cancer patients whose tumors have spread to the brain could improve survival.
In recent years, animal studies have repeatedly shown that Flash can significantly increase the amount of radiation delivered to the body while minimizing the effects on surrounding healthy tissue. In one experiment, healthy lab mice given two rounds of pulsed radiation did not show the typical side effects expected in a second round. In another study, animals treated with the drug Flash for head and neck cancer showed fewer side effects, such as decreased saliva production or difficulty swallowing.
Lu is cautiously optimistic that similar benefits could trickle down to patients in the future. “The flash causes less damage to healthy tissue than traditional radiation, without compromising the anti-tumor effectiveness. That could be a game changer,” he said. Another hope is that it could reduce the risk of secondary cancers caused by radiation damage later in life, though it’s too early to say whether that will happen.
More human trials are now underway around the world. Cincinnati Children’s Hospital in Ohio, USA, plans to conduct an early study in children with metastatic cancer that has spread to the breastbone. Meanwhile, oncologists at the University Hospital of Lausanne in Switzerland are conducting a phase 2 study to clarify details, including the optimal dose, effectiveness, and side effects, for patients with localized skin cancer.
However, the next stage of research will not only be about testing Flash’s effectiveness in humans, but also about determining what type of radiation is best to use.
Selecting Seeds
From carbon ions to protons and electrons, there are many ways to deliver radiotherapy, each with its own uses and challenges. One of the most precise forms of radiotherapy is hadron therapy, which uses carbon ions. However, there are only 14 institutions in the world that can offer this procedure, each costing an estimated $150 million (£122 million) . Currently, this therapy is delivered using a conventional dosing regimen, which delivers radiation over a period of minutes . However, with the Flash protocol, the ions will be delivered in less than a second.
“High-energy electrons can be used to treat superficial tumours on the skin,” says André-Dante Durham Faivre, a radiation oncologist at Hug. “Photons, which are X-rays, or protons [a type of subatomic particle], can be used to treat deeper tumours, while we save carbon ions and helium particles for the fields. “This is a very special case because only very, very large clinical centres can provide this treatment. The particle accelerator needed to perform carbon ion radiotherapy is the size of a building.”
This is the dilemma associated with flash therapy. Because it requires extremely sophisticated particle accelerators to produce subatomic particles , the treatment can currently only be performed using large equipment in specialized centers, which are very expensive. This means that patients will likely have to travel long distances to receive the treatment, and while researchers hope that Flash will eventually be available to everyone who needs it, for now, treatments like proton therapy are only available to a small group of patients .
Protons are currently the particle of choice for human Flash trials because they can penetrate up to 30 cm (12 inches) into the body, allowing them to reach relatively deep internal organs, and because existing proton therapy machines can be relatively easily adapted to deliver Flash doses.
In 2020, the University of Cincinnati Medical Center began the first clinical trial of flash-beam proton beam therapy in patients with primary cancer that has metastasized to bone. Early results showed that the treatment was as effective as traditional radiation therapy and had similar rates of side effects. Now, radiation oncologists at the Perelman School of Medicine at the University of Pennsylvania hope to begin their own trial later this year in patients with recurrent head and neck cancer.
“These patients have few other options because their tumors cannot be removed surgically,” said Alexander Lin, a professor of radiation oncology at the University of Pennsylvania, who will lead the proposed study. “Undergoing another course of standard radiation therapy could potentially lead to dangerous side effects, such as jaw fractures, oral injuries, and even potential damage to the carotid artery. We believe that flash proton therapy will be less toxic.”
A real challenge
However, if flash proton therapy is approved by regulators in the future, one drawback is that the machines required for it are still relatively large, meaning the treatment can only be performed in certain centers, limiting patient access.
CERN is currently collaborating with researchers at the University Hospital of Lausanne and the French company TheryQ to test and develop a new type of accelerator that delivers even more radiation — called energetic electrons. Very high — at the level of a flash dose. The Hug researchers are currently in talks with commercial partners to develop a pulsed X-ray imaging machine, according to Durham Faivre.
Durham Faivre says the accelerators will allow Flash to be used to treat deep tumors without the need for a giant machine. The ultimate goal is to allow any hospital with radiotherapy equipment to offer Flash. “We believe that over time, flash X-ray machines will be able to replace existing traditional X-ray machines,” he says.
In particular, Durham Favre is optimistic that the new accelerators will allow oncologists to tackle more complex tumors such as glioblastoma, the most common form of brain cancer and one of the deadliest forms of cancer, with a five-year survival rate of just 5% .
Following the University of Cincinnati study, oncologists also hope that the Flash machine could improve treatment for many forms of metastatic disease (when cancer has spread beyond its original site) and actually cure diseases in patients previously thought incurable. Lu predicts that Flash could be used to destroy primary and secondary tumors, then use chemotherapy or immunotherapy to eliminate the microscopic cancer cells that allow the disease to spread.
“Metastatic cancers affect a large part of the body because they spread diffusely,” says Durham Favre. This means they are often difficult to treat, he explains, because it is impossible to deliver enough radiation to the body’s tissues to kill all the cancer cells. Otherwise, the patient may not survive the radiation that hits previously healthy tissue. However, he says new treatments are changing that, especially for people with a limited number of metastases. “Flash opens up the prospect of safely treating a much larger number of metastases,” he says.
Another hope is that Flash could make radiation therapy more accessible to everyone.
Radiotherapy distance
At the UICC World Cancer Congress last September — a conference that brings together cancer experts from around the world — Kathy Graef, vice president of the nonprofit Bio Ventures for Global Health, highlighted a major global health problem sometimes called the ” radiation gap . ”
Using data compiled by the Lancet Commission on Cancer , Graef describes how there are only 195 radiotherapy machines in all of sub-Saharan Africa, compared to 4,172 in the United States and Canada. She explained that annual cancer incidence and death rates on the African continent are projected to double by 2040 , and the region is projected to need more than 5,000 additional machines over the next two decades, a demand many countries will struggle to meet.
In December, a new review of national cancer plans worldwide found that the radiotherapy gap extends beyond Africa to many low- and middle-income countries. “Only about 10% of cancer patients in low-income countries have access to radiotherapy, compared with 90% in high-income countries,” said Lisa Stevens, director of the Action on Cancer Therapy program at the International Atomic Energy Agency and one of the paper’s authors. “Integrating radiotherapy into cancer control strategies is more important than ever.”
The problems behind these statistics go beyond the cost of the machines. In hot and humid conditions, particle accelerators for radiotherapy often fail, and without enough trained technicians, they can take a long time to repair. As a result, the International Cancer Expert Corps (ICEC), in partnership with CERN and several UK universities, has launched an initiative called Project Stella to develop next-generation accelerators, as well as integrated software that can predict failures in advance and optimise maintenance, allowing countries to get the most out of their existing machines while minimising downtime.
But Durham Faivre is optimistic that the Flash machine could also play a role in ultimately making it easier for cancer patients in low- and middle-income countries to get the treatment they need. Instead of traveling long distances over days and weeks to get multiple radiation treatments, the Flash could help them get everything they need in just one or a few sessions. Because each treatment takes less than a second, it also allows doctors to treat more patients in a day.
“If we had a machine that was a standard size that could fit into every hospital bunker in the world and could administer Flash, that would allow countries to treat more patients,” Durham Faivre said. “If instead of treating 50 patients a day, you can treat 150 patients a day, you’ll dramatically increase your capacity and your ability to meet public health needs.”
Many experts believe it will also bring significant cost savings to high-income countries and potentially significantly improve the quality of life of patients.
“It would be a more cost-effective treatment after the initial investment because it requires far fewer procedures,” said Constantinos Koumenis, a professor of radiation oncology at the Perelman School of Medicine at the University of Pennsylvania in the US. He added that the health system could also save money by reducing hospitalizations due to complications.
The first step, Koumenis explains, is to find out how effective Flash is and whether it is truly better than standard radiation therapy.
