Only 10% of patients in low-income countries have access to radiation therapy. Manjit Dosanjh and Steinar Stapnes tell the Courier about the need to disrupt the market for a technology that is indispensable when treating cancer.
How important is radiation therapy to clinical outcomes today?
Manjit Fifty to 60% of cancer patients can benefit from radiation therapy for cure or palliation. Pain relief is also critical in low- and middle-income countries (LMICs) because by the time tumours are discovered it is often too late to cure them. Radiation therapy typically accounts for 10% of the cost of cancer treatment, but more than half of the cure, so it’s relatively inexpensive compared to chemotherapy, surgery or immunotherapy. Radiation therapy will be tremendously important for the foreseeable future.
What is the state of the art?
Manjit The most precise thing we have at the moment is hadron therapy with carbon ions, because the Bragg peak is very sharp. But there are only 14 facilities in the whole world. It’s also hugely expensive, with each machine costing around $150 million (M). Proton therapy is also attractive, with each proton delivering about a third of the radiobiological effect of a carbon ion. The first proton patient was treated at Berkeley in September 1954, in the same month CERN was founded. Seventy years later, we have about 130 machines and we’ve treated 350,000 patients. But the reality is that we have to make the machines more affordable and more widely available. Particle therapy with protons and hadrons probably accounts for less than 1% of radiation-therapy treatments whereas roughly 90 to 95% of patients are treated using electron linacs. These machines are much less expensive, costing between $1M and $5M, depending on the model and how good you are at negotiating.
Most radiation therapy in the developing world is delivered by cobalt-60 machines. How do they work?
Manjit A cobalt-60 machine treats patients using a radioactive source. Cobalt has a half-life of just over five years, so patients have to be treated longer and longer to be given the same dose as the cobalt-60 gets older, which is a hardship for them, and slows the number of patients who can be treated. Linacs are superior because you can take advantage of advanced treatment options that target the tumour using focusing, multi-beams and imaging. You come in from different directions and energies, and you can paint the tumour with precision. To the best extent possible, you can avoid damaging healthy tissue. And the other thing about linacs is that once you turn it off there’s no radiation anymore, whereas cobalt machines present a security risk. One reason we’ve got funding from the US Department of Energy (DOE) is because our work supports their goal of reducing global reliance on high-activity radioactive sources through the promotion of non-radioisotopic technologies. The problem was highlighted by the ART (access to radiotherapy technologies) study I led for International Cancer Expert Corps (ICEC) on the state of radiation therapy in former Soviet Union countries. There, the legacy has always been cobalt. Only three of the 11 countries we studied have had the resources and knowledge to be able to go totally to linacs. Most still have more than 50% cobalt radiation therapy.
The kick-off meeting for STELLA took place at CERN from 29 to 30 May. How will the project work?
Manjit STELLA stands for Smart Technology to Extend Lives with Linear Accelerators. We are an international collaboration working to increase access to radiation therapy in LMICs, and in rural regions in high-income countries. We’re working to develop a linac that is less expensive, more robust and, in time, less costly to operate, service and maintain than currently available options.
Steinar $1.75M funding from the DOE has launched an 18 month “pre-design” study. ICEC and CERN will collaborate with the universities of Oxford, Cambridge and Lancaster, and a network of 28 LMICs who advise and guide us, providing vital input on their needs. We’re not going to build a radiation-therapy machine, but we will specify it to such a level that we can have informed discussions with industry partners, foundations, NGOs and governments who are interested in investing in developing lower cost and more robust solutions. The next steps, including prototype construction, will require a lot more funding.
What motivates the project?
Steinar The basic problem is that access to radiation therapy in LMICs is embarrassingly limited. Most technical developments are directed towards high-income countries, ultimately profiting the rich people in the world – in other words, ourselves. At present, only 10% of patients in LMICs have access to radiation therapy.
We’re working to develop a linac that is less expensive, more robust and less costly to operate, service and maintain than currently available options
Manjit The basic design of the linac hasn’t changed much in 70 years. Despite that, prices are going up, and the cost of service contracts and software upgrades is very high. Currently, we have around 420 machines in Africa, many of which are down for long intervals, which often impacts treatment outcomes. Often, a hospital can buy the linac but they can’t afford the service contract or repairs, or they don’t have staff with the skills to maintain them. I was born in a small village with no gas, electricity or water. I wasn’t supposed to go to school because girls didn’t. I was fortunate to have got an education that enabled me to have a better life with access to the healthcare treatments that I need. I look at this question from the perspective of how we can make radiation therapy available around the world in places such as where I’m originally from.
What’s your vision for the STELLA machine?
Steinar We want to get rid of the cobalt machines because they are not as effective as linacs for cancer treatment and they are a security risk. Hadron-therapy machines are more costly, but they are more precise, so we need to make them more affordable in the future. As Manjit said, globally 90 or 95% of radiation treatments are given by an electron linac, most often running at 6 MeV. In a modern radiation therapy facility today, such linacs are not developing so fast. Our challenge is to make them more reliable and serviceable. We want to develop a workhorse radiation therapy system that can do high-quality treatment. The other, perhaps more important, key parts are imaging and software. CERN has valuable experience here because we build and integrate a lot of detector systems including readout and data-analysis. From a certain perspective, STELLA will be an advanced detector system with an integrated linac.
Are any technical challenges common to both STELLA and to projects in fundamental physics?
Steinar The early and remote prediction of faults is one. This area is developing rapidly, and it would be very interesting for us to deploy this on a number of accelerators. On the detector and sensor side, we would like to make STELLA easily upgradeable, and some of these upgrades could be very much linked to what we want to do for our future detectors. This can increase the industrial base for developing these types of detectors as the medical market is very large. Software can also be interesting, for example for distributed monitoring and learning.
Where are the biggest challenges in bringing STELLA to market?
Steinar We must make medical linacs open in terms of hardware. Hospitals with local experts must be able to improve and repair the system. It must have a long lifetime. It needs to be upgradeable, particularly with regard to imaging, because detector R&D and imaging software are moving quickly. We want it to be open in terms of software, so that we can monitor the performance of the system, predict faults, and do treatment planning off site using artificial intelligence. Our biggest contribution will be to write a specification for a system where we “enforce” this type of open hardware and open software. Everything we do in our field relies on that open approach, which allows us to integrate the expertise of the community. That’s something we’re good at at CERN and in our community. A challenge for STELLA is to build in openness while ensuring that the machines can remain medically qualified and operational at all times.
How will STELLA disrupt the model of expensive service contracts and lower the cost of linacs?
Steinar This is quite a complex area, and we don’t know the solution yet. We need to develop a radically different service model so that developing countries can afford to maintain their machines. Deployment might also need a different approach. One of the work packages of this project is to look at different models and bring in expertise on new ideas. The challenges are not unique to radiation therapy. In the next 18 months we’ll get input from people who’ve done similar things.
Manjit Gavi, the global alliance for vaccines, was set up 24 years ago to save millions of children who died every year from vaccine-preventable diseases such as measles, TB, tetanus and rubella using vaccinations that were not available to millions of children in poorer parts of the world, especially Africa. Before, people were dying of these diseases, but now they get a vaccination and live. Vaccines and radiation therapy are totally different technologies, but we may need to think that way to really make a critical difference.
Steinar There are differences with respect to vaccine development. A vaccine is relatively cheap, whereas a linac costs millions of dollars. The diseases addressed by vaccines affect a lot of children, more so than cancer, so the patients have a different demographic. But nonetheless, the fact is that there was a group of countries and organisations who took this on as a challenge, and we can learn from their experiences.
Manjit We would like to work with the UN on their efforts to get rid of the disparities and focus on making radiation therapy available to the 70% of the world that doesn’t have access. To accomplish that, we need global buy-in, especially from the countries who are really suffering, and we need governmental, private and philanthropic support to do so.
What’s your message to policymakers reading this who say that they don’t have the resources to increase global access to radiation therapy?
Steinar Our message is that this is a solvable problem. The world needs roughly 5000 machines at $5M or less each. On a global scale this is absolutely solvable. We have to find a way to spread out the technology and make it available for the whole world. The problem is very concrete. And the solution is clear from a technical standpoint.
Manjit The International Atomic Energy Agency (IAEA) have said that the world needs one of these machines for every 200 to 250 thousand people. Globally, we have a population of 8 billion. This is therefore a huge opportunity for businesses and a huge opportunity for governments to improve the productivity of their workforces. If patients are sick they are not productive. Particularly in developing countries, patients are often of a working economic age. If you don’t have good machines and early treatment options for these people, not only are they not producing, but they’re going to have to be taken care of. That’s an economic burden on the health service and there is a knock-on effect on agriculture, food, the economy and the welfare of children. One example is cervical cancer. Nine out of 10 deaths from cervical cancer are in developing countries. For every 100 women affected, 20 to 30 children die because they don’t have family support.
How can you make STELLA attractive to investors?
Steinar Our goal is to be able to discuss the project with potential investor partners – and not only in industry but also governments and NGOs, because the next natural step will be to actually build a prototype. Ultimately, this has to be done by industry partners. We likely cannot rely on them to completely fund this out of their own pockets, because it’s a high-risk project from a business point of view. So we need to develop a good business model and find government and private partners who are willing to invest. The dream is to go into a five-year project after that.
We need to develop a good business model and find government and private partners who are willing to invest
Manjit It’s important to remember that this opportunity is not only linked to low-income countries. One in two UK citizens will get cancer in their lifetime, but according to a study that came out in February, only 25 to 28% of UK citizens have adequate access to radiation therapy. This is also an opportunity for young people to join an industrial system that could actually solve this problem. Radiation therapy is one of the most multidisciplinary fields there is, all the way from accelerators to radio-oncology and everything in between. The young generation is altruistic. This will capture their spirit and imagination.
Can STELLA help close the radiation-therapy gap?
Manjit When the IAEA first visualised radiation-therapy inequalities in 2012, it raised awareness, but it didn’t move the needle. That’s because it’s not enough to just train people. We also need more affordable and robust machines. If in 10 or 20 years people start getting treatment because they are sick, not because they’re dying, that would be a major achievement. We need to give people hope that they can recover from cancer.
