Athens-based RTsafe combines the latest 3D printing technology to assist in the treatment of brain cancer

Radiotherapy is one of the leading techniques used to stop the growth and spread of cancer, which today is the second leading cause of death in Europe. While being effective for many types of cancers, radiotherapy treatment can be aggressive, potentially damaging healthy cells and tissues in the area where the treatment is being applied. Despite continual innovation, one of the most challenging areas to apply radiation therapy is to the brain, where it can be difficult to isolate cancer cells and the risk of collateral damage to healthy tissues is high. Despite the risks, the need for effective treatments, especially in Europe is great. Northern Europe receives the highest rates of brain cancer diagnoses worldwide, and the long term survival of those with many of these cancers can be poor and uncertain.

Despite the continual innovations in radiotherapy treatments, Dr. Evangelos Pappas from the University of West Attica noticed that the entire physics department would often endure sleepless nights before conducting brain radiosurgery.

He imagined that there must be a better way to prepare and validate treatment before the day of surgery. In 2014, Pappas joined with Dr. Thomas Maris of the University of Crete and Dr. Nikolaos Stergiopoulos of the École Polytechnique Fédérale de Lausanne in Switzerland to found RTsafe, a medical technology company that combines the founders’ scientific research with the latest 3D printing technologies. RTsafe creates anatomically accurate patient effigies that allow medical professionals to simulate treatments before application, allowing precise applications for each patient. The technology interacts with radiation in the same way as human tissue, allowing for medical professionals to fine-tune and individualise their treatments, leading to more effective therapies and reduced patient risk.

In 2014, RTsafe won the Hellenic Entrepreneurship Award, and in 2015 the company won the MIT Enterprise Forum Greece startup competition. In 2017, the company expanded to the United States in partnership with several leading hospitals and research institutes, and in 2018, RTsafe's patient-specific PseudoPatient™ head phantoms were granted FDA clearance.

I connected with RTsafe's founder and CEO Dr. Evangelos Pappas over email to learn a bit more about RTsafe's journey, as well as his advice for future founders. Alongside his work with RTsafe, Dr. Pappas is an Associate Professor of radiotherapy medical physics at the University of West Attica, Greece and a research associate at UT Health, San Antonio, TX. The interview that follows has been lightly edited for length.

What exactly is PseudoPatient? What does it do?

Radiotherapy technology is advancing at an ever-increasing pace allowing for better-targeted radiation treatments. Increasing complexity, however, challenges the accuracy of traditional Quality Assurance methods. This becomes an issue both for periodic QA and for treatment plan verification. Generic phantoms in use today do not take into consideration each patient’s individualities, limiting their scope and applicability. As a result, accidents, while rare, do occur. Patient safety needs to be enhanced especially in brain, head and neck cancers where the adjacent healthy tissue is most sensitive.

RTsafe’s PseudoPatient™ technology is an anatomically perfect replica of a patient’s head, created by 3D printing, that allows for testing of radiotherapy procedures before the actual treatment is performed. Following years of painstaking research, RTsafe has been able to produce an accurate model of the human head and brain which perfectly mimics human tissue’s reaction to radiation. RTsafe’s internationally patented process has been feasible through recent advancements in three different technologies: CT-scanning, 3D-printing and gel radiation dosimetry.

What were the initial challenges that the team had to overcome to turn this innovation into a product?

Patents and resource attraction were the main initial challenges. Additionally, a ‘product’ means that somebody has to pay for it. So, a correct evaluation of the commercialization value of the innovation and the related product, was very significant. Try to sell your version 1 to any customer. Even for testing! Would they pay even a very small amount for this? If yes, then, you are on a good track.

What advice do you have for other academics and professors considering to develop a university spinout company?

Significant European academic institutions have excellent links with the market. I admire a lot the approach of EPFL in Switzerland where in some cases offers PhDs with the obligation to the student to create a start-up company at the end of the PhD. I am sure that are many institutions in Europe, that I am not aware of, that follow similar approaches. I would for sure propose the EPFL pathway.

When it came to fundraising for the product, what strategy did you pursue, and how did you know your investment team was the right fit?

RTsafe was lucky enough to attract investors immediately after winning the 1st prize of the MIT Enterprise Competition in 2015 . Among our investors so far are friends, family, angel investors and VCs. The right investment team is the one that does not believe just in your financial vision but also, as it is in our case, in your social vision. On day one, RTsafe was not created in order to become a financially successful company and bring profits to founders and investors. RTsafe was created in order to help cancer patients to experience a much safer and more efficient treatment. This is our vision. Our true social vision that is already becoming a reality. Since this vision is the driving force for us, the following financial success is a simple outcome.

RTsafe's HQ is in Athens. What would you like others to know about the Greek tech ecosystem, and the growing medtech scene there?

Indeed, it is possible to start and grow international companies from anywhere in Europe. RTsafe started in Greece amid an economic crisis. Talking about Greece of the last ~10 years, the financial crisis and the local bureaucracy, I will refer to a lyric from Sinatra’s song and state that ‘If you can make it there (Greece), you‘ll make it anywhere……’. RTsafe’s example is a paradigm that proves that any European country can be the starting point for international business.

In Greece, in addition, there is a very valuable ‘brain’ capital. The brain-drain that the country has suffered due to the recent crisis is well-known. As more bright Greek minds return to Greece and new ones enter the workforce, the future of the Greek startup ecosystem will look much more prosperous.

RTsafe's technology is used across the world, in hospitals and clinics on five continents. When it came to building these partnerships, what advice do you have for other founders looking to develop similar pilot programs?

I would advise the following:

•  Publish your results and create a marketing plan in order to share your data globally.
• Start with a pilot in small markets. Ask for feedback, iterate and improve.
• Do not wait until you create the ‘perfect’ product. There is no such thing. Be confident in your Minimum Viable Product, even if it has disadvantages, and start sharing the solution with the world. It is THEIR feedback and needs that matters, not necessarily your plans.

What are your lessons to share with other founders beginning their journey? Do you have any key takeaways to share with the next generation of European entrepreneurs?

• Dare to share your innovative ideas. They are useless without a team and an implementation plan. Ideally, sign NDAs and/or apply for patents before that or before submitting them for publication in scientific or public journals.
• Investors invest in personalities, teams and implementation plans. Not necessarily in great ideas. They receive many amazing ideas on a daily basis. The personalities of the founders are the true differentiator.
• Try to approach VCs that are specialized in your field. This is the way to reach ‘smart money’ and harness the added value they can offer. ‘Smart money’ is much more valuable that the same amount of ‘just money’.
• Academia and entrepreneurship are well linked together in some European countries, but there is a need for the two to be linked in all European countries. The only way to pass the added value of a scientific breakthrough to the society, is via a company that commercializes these scientific results.
• As a founder, value your team as much as you value yourself. It is not necessarily the great salary that is the motivating factor, but rather the added value of going through this journey.

What should we expect next from RTsafe?

Advanced radiotherapy techniques provide treatment of cancerous tumors and a better quality of life for patients. However, the increased complexity of treatment planning, delivery workflow and quality assurance (QA) procedures have introduced clinical and technical challenges.

In response to these challenges, RTsafe is currently designing an innovative radiotherapy dedicated certification program in collaboration with major clinical, scientific, and manufacturing organizations. The expertise of RTsafe’s team in clinical and audit procedures as well as the large amount of data in SRS/SRT QA using RTsafe’s PseudoPatient™ phantoms have triggered the design of a certification program. RTsafe’s mission is to create an innovative audit process within a radiation quality management program to assure the highest levels of quality and safety. The main goals of the program include the review of procedures and protocols, evaluation of clinical and technical aspects, emphasis on continual self-assessment, improvement of clinical outcomes, and building confidence.

In parallel, RTsafe is exploring ways so that the added value that offers can be experienced by under-developed countries worldwide. There is a high demand for radiotherapy services globally. It is not only the infrastructure that is missing. Most importantly, it is the human resources that are missing such as Radiotherapy Oncologists, Medical Physicists, Radiation Therapists. We are planning to offer training tools for these professionals to help them to easily adopt high-end radiotherapy treatments in their countries in order to treat more cancer patients that they are doing today. I envisage RTsafe PseudoPatient™ phantoms to serve as training and confidence building tools in these countries, supporting and enhancing high quality radiotherapy implementation.

Finally, we are designing a significant tool for insurance companies and radiation oncologists, so that they both will have tremendous financial benefits related to medical-malpractice insurance and legal issues.

Thank you, Dr. Pappas and RTsafe!

ICYMI: Throughout May, tech.eu is focused on surfacing interesting stories, startups and people from the health/medtech industry, powered by Bayer G4A. With this program, the health industry giant aims to establish long-term partnerships with interesting digital health startups.