AI for more precise radiation therapy

Artificial intelligence is changing the way radiation therapy is used to combat cancer.

A Norwegian technology, developed by the company Kongsberg Beam Technology to improve the precision of external beam radiation therapy, is being tested at Oslo University Hospital.

“There are almost half a million Norwegians living with cancer today. Many more cancer patients survive after radiation therapy, but that doesn’t necessarily mean the patients get well. What concerns us most today is to create treatment plans with less side effects,” said Karsten Rydén-Eilertsen, Head of Proton Therapy Physics at Oslo University Hospital and responsible for the test project.

Huge developments

Karsten Rydén-Eilertsen has worked with radiation therapy at Oslo University Hospital for 33 years. He remembers when the doctors had to make radiotherapy plans for cancer patients using only 2D X-ray images and palpating the tumour site with their hands. Medical physicists and radiotherapy technicians would calculate the dose using standardised charts.

“I have experienced an explosive development in the field of radiation therapy against cancer. We now only use three- and four-dimensional images that we transfer to a sophisticated treatment planning system, where we can outline the tumour and vital organs in detail. There are advanced algorithms for calculating the exact right doses for the individual patient,” Rydén-Eilertsen explained.

These developments are thanks to major advancements in imaging technology, computer power, programming and data handling.

“The big difference today is that the level of personalisation and precision is much higher. We can deposit a high dose of radiation that can destroy the tumour while sparing healthy tissue,” Rydén-Eilertsen commented.

Still many side-effects

With radiation therapy, doctors aim to eradicate the tumour, while minimizing the damage to healthy tissue and vital organs.

“It is a difficult balancing act, because sometimes the organs are so close to the tumour that you can’t avoid affecting them with radiation. Sometimes, you need to choose between destroying the tumour and keeping a vital organ,” Rydén-Eilertsen said.

This dilemma isn’t unique for radiation therapy, but is also true for other cancer treatments, such as surgery and chemotherapy.

“With radiation therapy, you will never have zero radiation dose to the surrounding tissue. There will always be some side-effects. My hope with proton therapy is that these side effects will be reduced,” added Rydén-Eilertsen.

Photons vs. protons

Traditional radiation therapy involves beaming millions of photons through the patient’s body to the tumour. The photons deposit radiation all along their way through the body before exiting. It is not possible to control the photons to only deposit radiation to cancer cells.

“Proton therapy is different. Protons are heavy particles that loose most of their energy the moment they stop. By adjusting their initial speed, you can direct them to deposit most of the radiation dose at the site of the tumour. This means that you don’t affect tissue ‘behind’ the tumour and there is minimal damage ‘in front’ of it. This opens for the possibility to greatly reduce side-effects,” explained Rydén-Eilertsen.

The challenge with protons however is that they are very sensitive to which type of tissue they pass through. The energy loss will be different in bone versus in fat.

“In proton therapy, changes in the patient’s body during treatment are critical. The anatomy of the patient may change from when we take the first CT scan for treatment planning to the day of treatment. A treatment course may take several weeks and involve 30-40 treatment sessions. The anatomy may change both between and during a session. Ideally, one may think that a new plan should be created for every session, but today we don’t have the resources for this. That is why we introduce margins to ensure that the tumour gets properly irradiated every time. Sometimes these margins need to be so large that the patient may still get side-effects,” said Rydén-Eilertsen.

First of its kind

This is where the MAMA-K technology developed by Kongsberg Beam Technology comes in. It can build a digital twin of the patient representing their anatomy as accurately as possible. The twin is created by using advanced mathematical models that allow for all image data sets to be combined into a longitudinal, virtual representation of the patient’s anatomy.

“With this mathematical modelling, we can visualize and quantify how the patient’s body, tumour and vital organs change over time, as well as, make an accurate scoring of the accumulated doses to the tumour and organs at risk,” said Rydén-Eilertsen.

This system will generate knowledge about how different cancer patients’ bodies, tumours and vital organs change while undergoing radiation therapy and the impact this may have on the delivered dose. This will be valuable when starting up proton therapy centres in Norway.

“The mathematical models may make it possible to even predict anatomical changes and the related consequences for the dosage. Artificial intelligence can tell us how the patient might look in 24 hours, so we can create a treatment plan accordingly. The next day, we can take a new CT image and compare if the AI’s prediction is correct. We can then introduce smaller margins, which will also reduce side-effects,” explained Rydén-Eilertsen.

There are 16 treatment machines that generate 3-dimensional data and 2 000 patient appointments every week at the Radium Hospital, generating a large volume of potential test data, which could map changes in cancer patients receiving radiation therapy.

“These data will be extremely valuable when we enter the era of proton therapy because they will tell us more about how patients’ bodies change. Then we can become better at adapting treatment plans and hitting the tumour directly,” explained Rydén-Eilertsen.

AI to identify organs

The next step will be to adjust the treatment plan while the patient is on the table by using real-time images. To accomplish this, the shape and location of the tumour and organs at risk must be extracted from the images. The use of AI will be crucial to realize the speed needed. AI models to identify different parts of the anatomy must be trained and tested – something Kongsberg Beam Technology hopes to have in place soon.

“One of the biggest workloads in radiation treatment today is that doctors must manually outline the tumour and organs at risk in the CT images. We have already tested AI methods to identify anatomic parts of the body, especially vital organs, and the models are very good at this. To find tumours is a different story. We have tested some models that can find breast tissue, and they work well. I think it is only a matter of technological development. A lot will happen in this area,” said Rydén-Eilertsen.

Norwegian proton therapy centres

There are two proton therapy centres being built in Norway and Rydén-Eilertsen believes the MAMA-K technology will be very useful in these centres.

“The exciting part about the establishment of proton therapy is that the number of patients eligible for treatment is quite small, perhaps between 100-200 patients every year, while the capacity of the centres is around 800 patients a year. About 70-80 per cent of patients will be recruited via clinical studies, which have the goal to document that side effects are less with protons than with photons. In this setting, it is super important to know what the patient looks like, and MAMA-K will be a useful tool to achieve this. I don’t know about anyone else that is developing this kind of technology. It is truly unique,” said Rydén-Eilertsen.

 

Kongsberg Beam Technology is a member of Oslo Cancer Cluster and participating in the Accelerator Programme at Oslo Cancer Cluster Incubator. Read more about the company at their website https://www.kongsbergbeamtech.com/

 

New targeted therapy against osteosarcoma

A new cancer treatment against osteosarcoma has been developed in the labs of Oslo Cancer Cluster Incubator.

A new target for CAR therapy against osteosarcoma has been discovered in the Translational Research Unit at the Department of Cellular Therapy (Olso University Hospital). The results of their research, which was completed in the laboratories of Oslo Cancer Cluster Incubator, were recently published in an article in Nature Communications.

“CAR is a new type of molecule. It stands for Chimeric Antigen Receptor. It is part of a bigger family of cancer treatments called immunotherapy, in which you use the immune system of the patient to fight cancer,” explained Sébastien Wälchli, who has co-led this research project with Else Marit Inderberg.

A unique molecule

Chimeric antigen receptor therapy (CAR T) is a cancer treatment in which a patient’s T cells (a type of immune cell often referred to as the “foot soldiers” of the immune system) are changed in the laboratory so they will attack cancer cells.

“In the case of the CAR, we help the immune system to recognize cancer cells by putting in a completely artificial receptor. The key part of the receptor is the recognition site, so it will guide the immune cell to the tumour. Normally, we need a molecule that can recognize a cancer marker. The molecule of choice is an antibody,” said Wälchli.

The antibody that Wälchli’s group used was first isolated by clinical researcher and sarcoma expert Prof. Øyvind Bruland in 1986.

”We designed the CAR based on this antibody by using its coding sequence. This antibody is quite unique because it recognizes the marker on the surface of lung metastasis of osteosarcoma. We created a Osteosarcoma CAR (OSCAR) molecule to see if we could use the power of this antibody in immunotherapy and the results published in Nature Communications prove that we can,” explained Wälchli.

A full preclinical validation

The preclinical development of the treatment took place in the laboratories of Oslo Cancer Cluster Incubator which are fully equipped for such a process.

“We did a full preclinical validation of OSCAR using devices installed at the incubators for the in vitro and further tested it in vivo using different animal models where we mimicked what would happen in human. Our colleagues in Barcelona tested the injection of tumour cells directly into the bone of mice and observed a lower progression of cancer in the mice treated with OSCAR T cells, than we,” said Wälchli.

Furthermore, the group did experiments to check the toxicity of OSCAR T cells.

“We tried to predict using different healthy tissues if this CAR would only recognize tumour cells and spare healthy tissues. We concluded that it was safe, but before you inject it in human, you will never know for sure,” said Wälchli.

What is osteosarcoma?

Osteosarcoma is a bone cancer and affects many children and older people. It is quite well-treated with chemotherapy, but when it metastasizes to the lungs, it becomes more difficult to treat. Surgery can slow down the progression, but the cancer can reappear.

“This is where our hearts brought us. We are not choosing cancer by patient. We always talk with the clinicians. When we first discussed with Bruland, we did not know much about osteosarcoma. He told us about patients who have absolutely no alternative,” Wälchli explained.

There are other CARs in development against osteosarcoma globally, and some have already reached clinical phase, but none cover all patients.

“In the seminal paper of Bruland in 1986, they checked the biobank and estimated that 90 per cent of all osteosarcoma patients were positive to this antigen. This was confirmed by our collaborators in Spain. According to the first estimate, it looks like this marker is the most important that has been described so far,” said Wälchli.

Cancer start-ups met investors

US healthcare and life science investors wanted to learn about Norwegian cancer companies.

Cancer entrepreneurs caught the attention of investors from the USA when they introduced their innovative ideas at a meeting in the Oslo Cancer Cluster Incubator last week.

“I was impressed by the Norwegian healthcare infrastructure and local entrepreneurial talent, which together serve as a catalyst for start-up innovation in the cancer field and wanted to learn more about how others can collaborate with this unique and world-class ecosystem,” commented Sandeep Vardhan, Managing Director at Kalpesh Ventures, one of the investors at the meeting.

The speakers were put to the test to present their companies in under five minutes. Topics ranged from novel drug targets in cancer immunotherapy and clinical decision support tools to machine-learning on colonoscopies and real-world evidence to accelerate drug development.

Taking ideas to market

“Competent investors is often key to success. That knowledgeable US investors invest time and energy in Norwegian cancer innovation and want to learn about the companies in the Oslo Cancer Cluster Incubator is a good sign. It is our job to connect start-ups with global investors and life science networks – so that they can succeed with taking their ideas to market,” commented Ketil Widerberg, CEO of Oslo Cancer Cluster Incubator.

Maria C. Lundstad Aulie was also at the meeting in her new role as Investment Manager Health and Life Sciences Oslo, Invest in Norway, Innovation Norway.

“I am excited about the interest shown in the Norwegian life science industry. An Alumina group from Colombia University, consisting of nine investors and entrepreneurs with competence and interest in health and life science, recently came to Norway to learn more about our health landscape. I am happy to work together Oslo Cancer Cluster to help follow up on every potential lead that can strengthen our health ecosystem. This visit was also a great start as I just started a new position working with the US market as well as with international investments into the health and life science industry in the bigger Oslo region,” commented Aulie.

See the presenters below:

Andreas Petlund, CEO of Augere Medical.

 

Christian Jonasson, Research Director of NordicRWE.

 

Bjarte Håvik, Project Leader at Western Norway University of Applied Sciences.

 

Ernest Aw, Research Manager and Business Developer of Thelper.

 

Mark Tyrell, Chief Medical & Executive Officer at Vitae Evidence.

 

Baked goods bringing people together

A special sweet pastry is the weekly highlight in Oslo Cancer Cluster Incubator.

Buns with a creamy vanilla centre, sugar coating and coconut sprinkles … These are the traditional Norwegian skoleboller served to the tenants of Oslo Cancer Cluster Incubator every Friday.

The buns are handmade by a group called Tilrettelagt, consisting of students with special needs who attend Ullern Upper Secondary School. Tilrettelagt arranges important training for the students to prepare them for working life.

“This is an activity that the students can enjoy and have use for in their daily lives. It also brings us out of our little bubble so we can meet with the other people in the building,” said school assistant Lisbeth Fjellstad.

Young bakers

Since the Oslo Cancer Cluster Innovation Park opened in 2015, Tilrettelagt has been baking the buns to sell to students, teachers, and companies in the building.

The students bake the buns themselves and many of the students know the recipe by heart.

“It is fantastic. My plan is to get a job at a bakery that makes gluten-free goods,” said Halvard, one of the students.

The students learn practical skills in the bakery that prepares them for worklife. Photo: Sofia Linden / Oslo Cancer Cluster

Learning practical skills

The students deliver the buns to the tenants in Oslo Cancer Cluster Incubator and sell the buns in the school hallways to other students and teachers.

“It is good for the students to learn practical skills and do meaningful work. This activity develops their skills in mathematics, Norwegian, communication, collaboration, sales, service, and hygiene. We continually work with these subjects in the bakery,” said teacher Susann Steinsvik.

In Oslo Cancer Cluster Incubator, the buns are a bonus for the hard-working cancer researchers. During the coffee breaks, they can have meaningful conversations with other tenants and develop their ideas.