
In a series of vast underground caverns on the outskirts of Geneva, Switzerland, experiments are taking place which may one day lead to new generation of radiotherapy machines. The hope is that these devices could make it possible to cure complex brain tumours, eliminate cancers that have metastasised to distant organs, and generally limit the toll which cancer treatment exerts on the human body.
The home of these experiments is the European Laboratory for Particle Physics (Cern), best known to the world as the particle physics hub that developed the Large Hadron Collider, a 27 kilometre (16.7 mile)-long ring of superconducting magnets capable of accelerating particles to near the speed of light.
Arguably Cern’s crowning achievement was the 2012 discovery of the Higgs boson, the so-called “God Particle” which gives other particles their mass and in doing so lays the foundation for everything that exists in the universe. But in recent years, the centre’s unique expertise in accelerating high-energy particles has found a new niche – the world of cancer radiotherapy.
Eleven years ago, Marie-Catherine Vozenin, a radiobiologist now working at Geneva University Hospitals (Hug), and others published a paper outlining a paradigm-shifting approach to traditional radiotherapy treatment which they called Flash. By delivering radiation at ultra-high dose rates, with exposures of less than a second, they showed that it was possible to destroy tumours in rodents while sparing healthy tissue.
Its impact was immediate. International experts described it as a seminal breakthrough, and it galvanised fellow radiobiologists around the world to conduct their own experiments using the Flash approach to treat a wide variety of tumours in rodents, household pets, and now humans.
The Flash concept resonated as it addressed some of the long-standing limitations of radiotherapy, one of the most common cancer therapies, which two-thirds of all cancer patients will receive at some point in their treatment journey. Typically delivered through administering a beam of X-rays or other particles over the course of two to five minutes, the total dose is usually spread across dozens of individual treatment sessions over up to eight weeks, to make it more tolerable for the patient.
Over the past three decades, advanced imaging scans and state-of-the-art radiotherapy machines have made it possible to target an individual tumour with increasing precision. But the risk of damaging or deadly side effects is still present.
Vozenin cites the example of paediatric brain tumours, which can often be cured by blasting the brain with radiotherapy, but at a great cost. “The survivors are often left with lifelong anxiety and depression, while the impact of the radiation affects brain development, causing significant loss of IQ,” she says. “We’re [sometimes] able to cure these kids but the price they pay is high.”
Billy Loo, a professor of radiation oncology who runs the Flash sciences lab at Stanford University School of Medicine in the US, explains that tumours, especially those of larger volume, are rarely neatly segregated from the surrounding tissue. This means it’s often next to impossible to avoid harming healthy cells, so oncologists are often unable to use as high a dose as they would like, says Loo.
Cancer specialists have long believed that being able to boost the radiation dose would greatly enhance their ability to cure patients with difficult-to-treat cancers, according to Vozenin. For example, research has previously indicated that being able to increase the radiation dose in lung cancer patients with tumours that have metastasised to the brain could improve survival.
In recent years, animal studies have repeatedly shown that Flash makes it possible to markedly increase the amount of radiation delivered to the body while minimising the impact that it has on surrounding healthy tissue. In one experiment, healthy lab mice which were given two rounds of radiation via Flash did not develop the typical side effects which would be expected during the second round. In another study, animals treated with Flash for head and neck cancers experienced fewer side effects, such as reduced saliva production or difficulty swallowing.
Loo is cautiously optimistic that going forwards, such benefits may also translate to human patients. “Flash produces less normal tissue injury than conventional irradiation, without compromising anti-tumour efficacy – which could be game-changing,” he says. An additional hope is that this could then reduce the risk of secondary cancers, resulting from radiation-induced damage later in life, although it is still too early to know if that will be the case.
Now, increasing numbers of human trials are beginning to take place around the world. Cincinnati Children’s Hospital in Ohio, US, is planning an early stage trial in children with metastatic cancer that has spread to their chest bones. Meanwhile, oncologists at Lausanne University Hospital in Switzerland are conducting a Phase 2 trial – where the details are finessed, including the optimum dose, how effective the treatment is and if there are any side effects – for patients with localised skin cancer.
But the next phase of research is not only about testing whether Flash works in people. It’s also about identifying which kind of radiation is the best one to use.
From carbon ions to protons and electrons, there are many ways of delivering radiotherapy, each with different applications and challenges. One of the most precise forms of radiotherapy is hadron therapy, delivered with carbon ions. But there are only 14 facilities which can deliver this in the entire world, each one costing an estimated $150m (£122m). Currently this therapy is delivered using a conventional dosing regime, in which the radiation is delivered over several minutes. However, with the Flash protocol the ions would be delivered in less than a second.
“High energy electrons can be used to treat superficial tumours in the skin,” says André-Dante Durham Faivre, a radiation oncologist at Hug. “Photons, i.e. 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 very specialised cases, as it’s only very, very big clinical centres that can offer that type of treatment. The particle accelerator needed to administer carbon ion radiotherapy is the size of a building.”