Photo: In 2015, Prof. Vrba received the European Society for Hyperthermic Oncology (ESHO) Award for his research in this field. Pictured here with Prof. Ruediger Wessalowski, M.D. , head physician of the clinic where he also treats pediatric patients with hyperthermia.
Photo source.
How did you get into healthcare apps?
In 1981, I read a paper in the IEEE Trans. on Microwave Theory and Technique describing waveguide applicators for microwave hyperthermia. At that time, a completely new method for treating cancer. I was interested because I had taught the theory and technique of microwave circuits including waveguides in seminars and also used it for our research project. I was able to find and contact physicians who were knowledgeable about the method through their professional resources and literature. And they were looking for someone to build a microwave hyperthermia system so they could apply hyperthermia clinically.
Could you explain the principle of hyperthermia and its healing effect?
The most basic physical-biological principle is that we increase the temperature in the tumour area from the usual 36.5 °C to a temperature range of 41 to 45 °C. At these temperatures, there is no thermal destruction of the tumour, i.e. no necrosis. The aim is to achieve so-called apoptosis, a state in which the cell stops dividing. In essence, this is a simple physical mechanism to stop malignant growth going unchecked. By covering the area of the tumor and its surroundings with a temperature at which the patient does not experience any burns, we get the tumor cells into a state of apoptosis. We don't destroy the cells directly, after some time they die on their own and the human body can cope with them. Colleagues who are interested in the biological aspects of hyperthermia would be able to describe its other beneficial effects for cancer treatment. For example, its stimulating effect on the immunological system of patients.
It was 1981. Did you find support for your research at the faculty?
The then head of our department, Prof. Václav Tysl, supported my activity. Not financially, it was not possible, because at that time research projects were planned in 5-year cycles. And to give you an idea, there were no grants until 1993. When we wanted to make applicators, I went to Diamond on Wenceslas Square and bought aluminium bowls there, which we modified.
So you did this place on your own?
We had a well-equipped workshop at the department and the mechanic of our department, Miloslav Raab, helped me very willingly. Together we built the first hyperthermic system in Czechoslovakia (it was also one of the first in Europe). The part for temperature measurement was in charge of Mr. Ing. Jiří Bouček from the 1st Medical Faculty of Charles University.
When did you start your first clinical applications?
The first clinical applications of hyperthermia took place in the spring of 1982 at the 1st Faculty of Medicine of Charles University and were led by Prof. MUDr. Oskar Andrýsek, DrSc. In the autumn of 1982, clinical applications of hyperthermia were moved to the Institute of Radiotherapy in Prague (now the Institute of Radiation Oncology of the Faculty of Medicine), where Miroslav Lapeš, MD, began to combine hyperthermia with radiotherapy. It is important to note that in this combination better therapeutic results can be achieved than when either radiotherapy or hyperthermia is applied alone. And it was MUDr. Lapeš who proposed and introduced the timetable for combining hyperthermia and radiotherapy, which is still used by most hyperthermia clinics in the world today. The device developed by us was used from 1982 to 1985. In 1984 we were able to approach Tesla Hloubětín, which was a manufacturer of power transmitters. Of course, we at the faculty did not have the possibility to produce this type of equipment in large scale. We were able to put one together to enable the doctors to get their own experience with hyperthermia. So establishing a collaboration with Tesla Hloubětín was a logical step. Ing. Martin Borovička and Ing. Thanks to this, the second generation of the device, which was already being produced at Tesla, was created. It has been used clinically since 1986.
Have you colaborated with other medical institutions than the Institute of Radiotherapy in Prague?
Yes, it was mainly the oncology clinics of the hospitals in Hradec Králové and Brno. Oncology clinics of hospitals in České Budějovice, Olomouc and Bratislava were also interested in hyperthermia.
Do you still remember how you started with hyperthermia at Bulovka?
I remember that at first some of the doctors at the Radiotherapy Institute did not have much confidence in hyperthermia. It was logical, they knew very well how difficult it was to achieve successful treatment of cancer patients. And we came up with the hypothesis that simply raising the temperature in the treated area by 4 to 8 degrees Celsius was enough to significantly increase the success rate of treatment. However, most in the world knew about the clinical testing of hyperthermia from the foreign medical literature. Doctors prepared a group of about fifty patients for whom treatment with radiotherapy, chemotherapy, or a combination of the two methods had not led to a successful cure. Hyperthermia was thus given a chance to show what its possibilities were.
What was the result of this study?
Hyperthermia was applied in combination with radiotherapy (but the doses of ionizing radiation were halved).The doctors at the Radiotherapy Institute evaluated the results very positively. In more than half of these patients, who could not be cured by standard methods, the tumour was completely eliminated with the use of hyperthermia. In one-third of them, the tumour volume was significantly reduced and this condition was stable throughout the entire follow-up period. In the remaining patients, treatment was not successful, but in a significant proportion of them it was not possible (due to their rapidly deteriorating health) to apply the entire treatment schedule. I remember one of the very first patients - a lady of about 70 years of age. She had been treated for breast cancer, but discovered a metastasis on her forehead. It was a big complication for her, and she wore a hat even in the summer to cover it up. But the radiotherapy treatment was not effective. The patient then started a combined treatment of hyperthermia and radiotherapy and the tumour disappeared after treatment. As I mentioned earlier, the important thing about combined treatment is that the doses of radiotherapy are practically halved. An interesting aspect of this patient's treatment was that as a result of the radiotherapy, her hair in the treated area initially fell out, but within less than a year it had started to grow back, which amazed the doctors at the time.
You assisted with Ing. Boucek as technicians during the treatment itself?
We taught the doctors how to use our device. But we still preferred to be there, so we were present at every clinical application. They were twice a week at the hospital back then.
How time consuming is the treatment?
Hyperthermia is typically applied once a week, usually shortly before or after radiotherapy, and the cycle is usually scheduled for 4 to 6 weeks. The duration of exposure of the treated area to microwave power is 40 to 60 minutes. This means that you need about 60 to 90 minutes to treat one patient, including preparation for treatment. It is therefore a very time-consuming treatment method.
Interest in hyperthermia is growing. There is also room for Czech manufacturers
Let's go back to the second half of the 1980s, when you managed to get Tesla Hloubětín to cooperate...
Tesla Hloubětín produced eight hyperthermia devices that were distributed to large oncology clinics in Czechoslovakia. There was a period when this type of treatment was in relatively high demand. At the beginning of the 1990s, new possibilities opened up for oncology, both in the field of treatment and in the field of cancer diagnosis. Radiotherapy and other oncological methods improved rapidly. However, unlike abroad, interest in hyperthermia has declined in the Czech Republic. However, our group had the opportunity to start cooperating with foreign clinical departments by consulting their technical problems.
What is the interest in hyperthermia today?
Currently, the treatment of cancer patients with hyperthermia is mainly carried out at Bulovka. Nevertheless, it can be said that the interest in hyperthermia is growing again in the Czech Republic. I know of three major clinics that are considering purchasing hyperthermia equipment. They want to be able to offer comprehensive cancer treatment, like the major clinics in the EU and the USA.
Are there any manufacturers in the world?
There are two manufacturers that cover this segment globally. However, their sophisticated systems cost several million euros. Because of this, hyperthermia is most widespread in Germany, the Netherlands and some other Western European countries. And, of course, in the United States. One of these manufacturers of hyperthermia systems occasionally contacts us to consult on its partial technical problems. Particularly in the development of new applicators.
Do you see any room for Czech producers here?
We can see and have some tips, but I can't reveal more because things are under negotiation. It's not easy for someone who makes and sells such a system. But the important thing is that the know-how to build hyperthermia systems still exists here in the Czech Republic.
What is the biggest pitfall?
The manufacturer must be able to guarantee to doctors that outside the treated area the temperature will not exceed 45 degrees Celsius, this could harm the patient. Therefore, the hyperthermia applicators must be equipped with microwave technology, which makes it possible to focus the electromagnetic wave very well on the area to be treated. And supplement the treatment with so-called treatment planning, i.e. numerical spatial calculations of how the patient's body will absorb the microwave power and how the temperature in the treated area will evolve as a function of time. There is a relatively expensive way to measure the temperature inside and around the treated area using MRI. With this, you can non-invasively measure the temperature in the patient's body to within half a degree Celsius and the spatial accuracy is about half a centimeter. Another promising method for non-invasive temperature measurement is microwave differential tomography-based technologies. And these are being developed by a group of my former PhD students at the Faculty of Biomedical Engineering at CTU.
So they're a continuation of your work?
Yes. A research team has been set up there, which is actually extrapolating our activities mainly into the field of medical diagnostics based on microwave technology. In addition to microwave differential tomography, they are also researching the possibility of using UWB radar for medical diagnostics. As far as therapeutic methods are concerned, they are working on issues such as magnetic brain stimulation and electroporation (a microbiological technique in which an electric field is applied to cells - note) for the treatment of cancer.
How many PhD students have you actually educated?
16 PhD students successfully defended their doctoral theses under my supervision. Not all of them have remained in the field, but I am very pleased that several of them continue in academia. Even abroad. I am glad that I inspired them.
Are you in contact with them?
Of course.
Doctors treat patients. We engineers help them by creating technology
Did you have any comparisons in the 1980s, how unique is your research?
The inspiration for our research came through the scientific journals that were coming to Czechoslovakia at that time. So we were not the only ones who started with this healing method. I tried to follow the scientific literature so we had some information about what was happening in Western Europe or in the United States. But the possibility of establishing some kind of permanent collaboration across the Iron Curtain, to try to write a joint project, was absolutely unthinkable. You can't compare that with the conditions that young scientists have today. But the enthusiasm and initiative, I dare say, of our generation was at least equal to that of today. There was no extra financial support, we did it purely out of enthusiasm for the cause.
And to your question: our research was unique e.g. in the use of the technology of waveguides excited below the cutoff frequency (so-called evanescent vids). We were also able to ensure that there was no interaction between the electromagnetic field and the temperature sensors during hyperthermia.
Treatment based on your scientific method has been applied for more than forty years. Are there figures available on how many patients have undergone it in that time?
My estimate of the number of patients who have been treated with combined hyperthermia and radiotherapy at the Department of Radiation Oncology of the FNB since 1982 may be around 1500.
Do you have any idea how many patients you have helped to cure with your method?
I guess I could say that I contributed to the fact that some people got better, some people lived much longer. The lady I mentioned was in her seventies at the time and the main aim of the treatment was to improve her quality of life in the years she had left. By combining hyperthermia with radiotherapy, it was possible to make her tumour disappear and she then lived for about five more years with a very good quality of life. And that's no small thing either, it's not always just about healing, it's about increased quality of life. And that comes at a price.
Did the patients know to whom they owed their cure?
Most of them probably don't. They knew the doctor who treated them. The names of the technicians who helped them were not customary. I myself was personally with most of the patients until 1994, when the then rector of the CTU, Prof. Stanislav Hanzl, invited me to join his team of vice-rectors. And then I was no longer able to fulfill my duties as vice-rector and at the same time visit the clinical workplace several times a week. That was the time when the cooperation with Dr. Ladislav Opple from our department started and he started to help me. Today, he is the one who assists the doctors with the clinical applications of hyperthermia at Bulovka.
It must be satisfying for you to have played a part in saving lives...
Doctors are the ones who treat patients. As engineers, we help them by creating new technologies that they can then work with. When I talk to my physician friends about this topic and I want to stir up the discussion a little bit, I use a statement like that, that a significant part of the progress in medicine is made by engineers. And I think that is indeed the case. At the beginning, though, there's usually a doctor who says, engineer, I have such and such a problem and maybe even gives some initial hypothesis as to how it could be solved. But then it's up to the engineers to develop such a device for doctors and patients.
Professor, thank you for the interview.
I would like to add that there are certainly many people with interesting life stories at CTU FEE. I very much appreciate the invitation to this interview. I would like to mention my colleagues who helped me with advice and consultations and were interested in my work. For example, Prof. Ing. Jaroslav Vokurka, DrSc., Ing. Jiří Tichý and others. The support of colleagues from other academic departments was also important for me. Especially Mr. Ing. Jiří Pokorný, DrSc. Ing. František Jelínek, CSc., both from the Institute of the Academy of Sciences of the Czech Republic (now the Institute of the Academy of Sciences of the Czech Republic).
Interview conducted by Radovan Suk
