Karsten Rydén-Eilertsen, Head of Proton Therapy Physics at Oslo University Hospital, is testing the new technology from Kongsberg Beam Technology in a clinical environment, and hopes to improve the precision of radiation therapy.

AI for more precise radiation therapy

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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/

 

The post AI for more precise radiation therapy first appeared on Oslo Cancer Cluster.

Pascal van Peborgh, Senior Director Medical Affairs for Gilead Nordics.

Gilead joins Oslo Cancer Cluster

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Gilead

The newest member of Oslo Cancer Cluster is Gilead, a biopharmaceutical company advancing innovative medicines to prevent and treat life-threatening diseases.

Pascal van Peborgh, Senior Director Medical Affairs for Gilead Nordics answered some questions on why Gilead joins Oslo Cancer Cluster, how they are involved in the cancer field and why the Nordics is an important area for the company.

What is Gilead’s motivation to join Oslo Cancer Cluster (OCC)?

“Gilead’s ambition is to build strong partnerships with cancer research centers and oncology-focused organizations to accelerate research and ultimately provide Norwegian patients with novel therapeutic options. We want to work together with other OCC members on basic research topics and in finding ways to provide better access for patients who suffer from cancer. Part of this ambition was why we partnered in the CONNECT public-private partnership.”

Tell us more about Gilead’s investment in cancer and the company’s oncology pipeline.

“Gilead has a long history of bringing innovation to patients in improving patients’ outcomes and at times provided a cure for people facing specific life-threatening infectious diseases such as HIV and Hepatitis C. Gilead is now applying the same approach and commitment to cancer. We have purposefully built a deep and broad oncology portfolio with a focus on trying to address critical unmet needs in oncology care.

“This framework defines our portfolio, with assets that have complementary MOAs and strong scientific rationale for treatment combination opportunities. From antibody-drug conjugates and small molecules to cell therapy-based approaches, our research and development programs are providing new hope for people with overlooked, underserved, and difficult-to-treat cancers.

“This includes many of the most exciting and most promising targets in oncology today, with strong potential across tumor types, lines of treatment, and multiple opportunities for unique combination therapies. We have investigational agents in trials across varied solid tumors: breast, lung, GI, GU, including bladder, among many others. And in blood cancers: MDS, AML, LBCL, adult lymphoblastic leukemia and more. We are well positioned to establish Gilead as a leading Oncology company.”

What do you think about opportunities in Norway, and the Nordics, for the development of new cancer treatments? How do you view the milieus here for cancer research and health industry?

“We see Norway as a pioneer in Precision Medicine, e.g., the CONNECT and IMPRESS initiatives. It has also a strong history of registry data utilization, e.g., and building further new additions to cancer registry like INSPIRE BC and LC. Norway is also highly ranked for cancer research in Europe, with a government and policies supporting the development of precision medicines and clinical trials, with Inven2 and NorTrial being established as examples.

“In addition, the systematization of care in Norway and especially around Oslo University Hospital provides a central node with adequate infrastructure, expertise, and innovation in the cancer research eco-system and more specifically for translational research and clinical trials. Finally, the Oslo University Hospital being an accredited Comprehensive Cancer Center with an extensive international network provides us with further confidence to invest in cancer research in Norway.“

Do you have an ambition to launch cancer clinical trials in the Nordics?

“Our ambition is to continue to initiate new clinical trials within oncology in the Nordics in greater scope, and more specifically in Norway. We at Gilead, view the Nordic countries as having high-quality infrastructure that supports clinical research and studies. The countries have national support functions that provides information and services to researchers that are interested in clinical research – both for observational studies and for clinical interventional studies.

“Gilead, with its own R&D portfolio or through opt-in agreements has currently more than 70 ongoing oncology R&D programs focusing on three therapeutic strategies: triggering tumor intrinsic cell death, promoting immune-mediated tumor killing, and remodeling of the tumor microenvironment. To be able to fully deliver on this pipeline we will need close collaboration with clinical and academic research.”

 

Learn more about the members of Oslo Cancer Cluster by visiting our Member Overview page.

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Krista Kruuv-Käo, project manager of AnteNOR, presented how polygenic risk scores can be used to prevent breast cancer at a recent meeting organised by the Norwegian Cancer Mission Hub. Photo: Sofia Linden / Oslo Cancer Cluster

Polygenic risk scores: a European cancer priority 

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The EU is looking to polygenic risk scores to improve prevention and early detection of cancer

Polygenic risk scores (PRS) have become one of the focus areas for prevention and early detection of cancer in the European Union’s Mission on Cancer. 

“PRS tests can provide a measure of your personal risk of developing a specific disease due to your genes,” explained Krista Kruuv-Käo, project manager of AnteNOR, a project that investigates how PRS can be implemented for prevention and early detection of breast cancer in Norway. 

Europe’s Beating Cancer Plan outlines 10 flagship initiatives and number 7 focuses on how cancers develop: 

“Alongside the ‘Genomic for Public Health’ project, the European Initiative to Understand Cancer (UNCAN.eu), planned to be launched under the foreseen Mission on Cancer to increase the understanding of how cancers develop, will also help identify individuals at high risk from common cancers using the polygenic risk scores technique. This should facilitate personalised approaches to cancer prevention and care, allowing for actions to be taken to decrease risk or to detect cancer as early as possible.”

What about Norway?

There are about 4 200 new cases and almost 600 deaths due to breast cancer in Norway each year, according to reports from the Norwegian Cancer Registry.  

“Early detection of breast cancer can save lives, but approximately 40 per cent of breast cancer cases in Norway are not detected at an early stage. For breast cancer, 31 per cent of all diagnoses are due to genetic predisposition and many women develop cancer before they reach the screening age of 50,” Kruuv-Käo commented. 

There are already genetic tests in the Norwegian specialist healthcare service for monogenic pathogenic variants, such as BRCA1 and BRCA2, but not on a population-wide basis. PRS tests have not been implemented yet, although they are both cheaper and can identify more women with a moderate to high risk of developing breast cancer. 

Improving cancer screening

The results of the AnteNOR project were recently presented at a meeting organized by the Norwegian Cancer Mission Hub. 

“The project shows that PRS tests can be used for effective risk stratification for population-wide breast screening. By introducing genetic risk testing with PRS tests and monogenic testing, the women with moderate to high risk of developing breast cancer can be identified before the screening age of 50 years. With a personalised screening programme, some women may need to screen earlier and more often, while others can go to screenings less frequently in the future,” Kruuv-Käo explained. 

Estonia is already preparing for the introduction of a personalized breast cancer screening program, and the plan is to launch it this year. Will Norway follow? 

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The research group OSCAR (short for Osteosarcoma and CAR) consists of Nadia Mensali, PhD; Sany Joaquina, MSc; Sébastien Wälchli, PhD, and Else Marit Inderberg, PhD.

New targeted therapy against osteosarcoma

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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.

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