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Prof.. Dr. Assen Dudov, dm, is the head of the Clinic of Medical Oncology at “Acibadem City Clinic UMBAL Mladost”, medical director of the medical institution and chairman of the Bulgarian Oncological Scientific Society. He specializes in Saint John’s College, University of Oxford, Great Britain; Institut Jules Bordet, Belgium; Thorax Clinic Heidelberg, Germany; Gustave Rossy Institute, France; San Francisco Comprehensive Cancer Center, USA; Harvard Medical School, USA; Massachussetts General Hospital, USA; MD Anderson Cancer Center, USA. Prof.. Dudov is a member of the European Organization for Research and Treatment of Cancer (EORTC); European Medical Oncology Association (ESMO); European Organization for Research and Treatment of Neuroendocrine Tumors (ENETS); American Cancer Research Association (AACR). His interests are focused on the treatment of solid tumors and in particular approaches to overcoming drug resistance.. He is also a specialist in the field of targeted therapy for breast cancer, neuroendocrine tumors of the colon and rectum, kidney and prostate. The interview is dedicated to World Cancer Day – 4 February.
How COVID-19 affects your patients?
To the sick, which we treat in our medical institution in “Acibadem City Clinic-Mladost”, COVID-19 is also affected, as in patients not only with cancer, and with everyone else across the country. There is no way we can be cut off from the world, because anyway, this disease has found the entire healthcare system in the world unexpectedly unprepared. This, of course, is quite understandable. Bulgaria is no exception to the confusion, which was created in the overall healthcare process last year.
Of course, there was a period, in which after the great fright and the first lockdown, which was really too dramatic, there was a release, including among patients, but it seems that this is constant talking, Continuous flooding of information regarding the COVID pandemic to some extent leads to discomfort among cancer patients. I am personally amazed at how many professionals it turned out, that there is on the control of infectious diseases in our country.
Let's put it mildly – I listen with interest to how these processes are explained, including treatment, including monitoring and control of the disease by a variety of representatives of the medical and other fields. I hear quite specific details in the field of virology from surgeons, by healthcare administrators, by mathematicians, by political scientists. I understand, that everyone wants their own 15 minutes of glory, to be shown on television, to appear on the net, to see his, to say it, turbulent thoughts, in various editions. But anyway, this leads to a confusion of patients.
It also causes confusion among healthy people, because the flooding with diverse information and the desire of everyone to shine at least for a while, Unfortunately, somehow blurs the really sensible voices of professionals, which cannot take their rightful place in the general noise and be heard adequately enough, in order for this to have some beneficial effect on cancer patients as well, and on the entire patient population, and I would say on the whole human population, because you know, that patients are not a function of their decisions alone, they are also a function of the decisions of their loved ones, to their relatives. And when they are not convinced enough of one action or another, as a result of all this confusion and abundance of speech, unreasonable decisions can be made, which have a direct impact on health.
Did the diagnosis and treatment of cancer patients slow down last year??
In continuation of what has been shared so far, I want to say, that there were delays in diagnosis last year. Fortunately, a lot, much less in the treatment of our patients. The nature of the disease is as follows, that the reasonable man understands, that he may not get COVID-19, but unfortunately the cancer cannot wait for its cure.
However, this did not happen with the diagnosis. Many people, who had been diagnosed with the disease or were in the process of being diagnosed with clear information, that it is most likely a cancer, however, they left things for a while. And these bad results from the delay, unfortunately, are now a part of our daily lives. There were many sick in very good, in excellent general condition and perhaps because of that, that they felt enough discomfort, decided, that one can wait for the beginning, then the middle of the epidemic wave, took all this crazy advice for various supplements, etc., which probably gave some of them security, that it helps them to wait until the diagnosis is completed and the cancer treatment is started.
This led to a group of patients, who appeared with advanced disease, much more advanced than the time of diagnosis, which greatly reduces the possibilities of subsequent treatment. Something more, this is not just my opinion, and I would say, that my opinion doesn't matter, because in modern medicine, evidence-based, early diagnosis and treatment have been proven in world practice.
In this regard, I want to share one thing I would say unique, a very important and very instructively reliable clinical study, which was conducted in the past 2020 r. of Hannah and associates. This is a clinical study, started on 10 April 2020 r. and after its completion the results were published on 4 November in the British Medical Journal. The results are so important and revealing, that access to this publication is available to all, as it provides very important data on how treatment delays are affected and what risks and adverse consequences it has for the life and health of cancer patients.
This unique test shows health systems around the world, not only in our country, and all over the world, on giant populations what is the adverse effect of delaying treatment with the main methods. In oncology, these are the operative method, radiotherapy and chemotherapy, which is a term, used traditionally, otherwise it involves immunotherapy, targeting treatment, various other drug classes. It could also be called systemic drug therapy, like it is, of course, much more correctly. The delay of these three methods is very accurately estimated on the basis of an extremely precise and in-depth study of accurate and clear indicators through mathematical models..
One of them converts, converts the risk reduction in treatment into a certain number, which shows the increase in mortality for everyone 4 weeks of delayed treatment at seven major sites, which were followed in the clinical trial. These are bladder cancers, breast cancer, colon cancer, rectal cancer, the rectum, which is given due to the specifics of treatment there, lung cancer, cervical cancer and tumors of the head and neck.
These three main methods of treatment are considered. For example, the delay in surgical treatment at these seven sites varies in increasing mortality each 4 weeks with about 6%. When delaying radiation therapy with 4 weeks in tumors of the head and neck and in other mentioned localizations reaches 9%. AND, notice, delay in systemic drug therapy, of chemobiological treatment is associated with about 14% risk of death for everyone 4 weeks delay.
I think, that these numbers, which are draconianly accurate and calculated by a huge team with no emotions, since we are talking about scientific research, are indicative enough, to explain what COVID-19 did, stirring the world's health systems. This is not just about patients' fear of visiting a hospital during the COVID epidemic.. This is about the overall confusion of any healthcare system, which had to allocate and continue to allocate resources to COVID patients, which reduces resources for other diseases. On the one hand, reduces the purely technical organizational and equipment capabilities in a hospital, which are occupied by COVID patients, for the treatment of other diseases.
In this case, we are talking in particular about cancer patients. These are some results, which have greatly shaken the oncology community, as well as health administrations around the world, as this huge multinational team, led by Hannah, which uses a number of information databases, to sift over 2000 tested and select those of them, who have a definite clear degree of reliability and make this retrospective analysis through specific mathematical models with the inclusion of leading computer and software centers, such as the one in Vienna, and in a number of other countries, so that we can have clarity, accuracy and certainty and there is no possibility for unclear interpretation of the results. The message is one and it is clear.
The difficulties facing cancer patients in the world and the challenges facing any health care system are enormous. These challenges must be actively sought to be optimally addressed, so much so, of course, as far as reality allows us. And in no case be underestimated in these difficult times of pandemic and other diseases, especially cancer in all its varieties and localizations, for all this is carried like a boomerang back to humanity by chance, which will be very advanced and extremely difficult to treat.
The more avant-garde, the more complicated and long a treatment, the more expensive it is. So do these, who in a health care system realize their money, need to know, that in the next period additional funding should be provided for these patients who are delayed in their diagnosis and treatment. This puts our country next to everyone else.
We must also pay sufficient and timely attention to cancer patients, so that there cannot be this severe imbalance, which occurs especially in some countries. And not to face him in a few months, after a year or as long as the continuing non-pink situation takes, for which there is still a vaccine, there is hope among all reasonable people, that the current bad trend could be reversed. Then we will witness everything, which is now accumulating on the side, smoldering. AND, of course, in particular a huge group of cancer patients, which will require much more care, much more teamwork and, of course, more funding.
In our practice in the medical institution I think, that in late autumn and early winter on 2020 r. we will see these negative results from some delayed patients, directed, but decided to postpone it or just couldn't handle it, that they have to take certain directions, to go through certain units, before they came to us and were late.
I thought, that by the end of the year this will be cleared up, but it did not turn out that way. right now, at the beginning of 2021 g., are patients, who have very advanced diseases, whose diagnosis was made in March-April-May last year. Of course, so long untreated cancers are already at an advanced stage, which significantly changes the life perspective of patients and, of course, it also reduces our ability to adequately, successful and long-lasting treatment of the disease. There is, Unfortunately, and young patients, in which it has reached somewhere in the diagnosis, in the pandemic so in full swing. There was doubt in some of them, clearly described and explained for cancer, but this became a fact in the diagnosis much later.
Otherwise in relation to the sick, who conduct treatment, dare I say, that our patients in particular have not stopped and postponed their treatment. Even in these difficult moments of the first lockdown, when documents were required to pass through the checkpoints, we still have patients from all over the country, including we have patients, who are from abroad. So that, despite these difficulties, common sense, and I'm proud, that Bulgarians have common sense in difficult times, did not allow patients to procrastinate, cancel or stop their treatment.
Of course, units always exist on various other subjective factors. However, treatment is a two-way process. One of them is the doctor, the medical team, on the other hand is the patient, who has his free will and can decide when and whether to choose to be treated. The patients were strict. We have not returned absolutely no one.
We have combined everything adequately and with accurate instrumental tracking, with conventional visual diagnostics, with the most modern nuclear methods, which we have, with a five-scanner, with various other studies, associated with isotopes, state-of-the-art computed tomography examinations, magnetic resonance, complex clinical and laboratory tests. We succeeded despite the difficulties and despite that, that it was necessary to open such a COVID unit with us as well, which significantly took away from our resource, as doctors, who are on duty in it, there is no way they can go back to medical oncology, in other units. They must be quarantined after they leave, to be tested.
This, of course, loads everyone a lot and physically, and not least mentally, which is really a challenge for doctors. And I would like to say one huge thing “thanks to” to my colleagues – doctors, nurses, laboratory technicians, all, who are on this team, which despite the difficulties, despite total exhaustion, despite all the inconveniences, everything they cause to their families with their absence, with their fatigue and inability to be adequate in a family setting.
I want to say once again a huge thank you to all of them. and of course, I wish as a believer, as a Christian – God bless them – and he guards them, because they deserved it, they really do their best and are placed in extremely difficult working conditions, who really can not only emotionally, but also to actually compare it to the conditions during a war.
In connection with the controversy over vaccines, what is your opinion about their use in cancer patients and are there any risks for them??
As I already mentioned, I'm amazed at how many connoisseurs there are on COVID-19, and of immunology, of virology in Bulgaria, including far from the medical community, from various other spheres of society, leaving aside the galaxy of mathematicians, who joined, there are also politicians, who have a statement, which is rather suitable for a doctor.
As I said, everyone wants their few minutes of glory, but disagreement also confuses patients, and their loved ones, and interferes with sane voices, who are heard to send real information. There has been a lot of talk about vaccines. Many RNA connoisseurs also flocked there, vector, adenoviral vaccines, etc.. I want to say something very brief.
In any case, we already have a huge number of vaccinations, we have clarity about the toxicological profile, side effects of vaccines. Especially when experts say, that there can be no genetic changes due to the vaccine, which is generally clear to doctors, but experts say, which is much more important. When we have the brief characteristics of the products, of the vaccines themselves, these are their files, describing absolutely everything.
And when we already have a lot of experience, I think it is madness to deprive patients of vaccination activity, as this is against their interests – and their, and society. The second million people are approaching Israel, vaccinated and are one of the leading countries in immuno-oncological treatment, in scientific activity, in practical application.
In fact, the carriers, ie. the basis of these first vaccines is precisely based on such models, used for other treatments and no wonder, that as someone says “they were created very quickly”. It's not fast at all, just quickly hung on these carriers the relevant elements, so that the body can build immunity against COVID-19.
And Israel, this country, which is famous for the best immunooncological centers, put oncology patients in the second vaccination group. They are now being vaccinated with Pfizer-BioNTech, will soon start with Moderna, ie. – with RNA vaccines. And that, in my opinion, gives enough clarity and certainty for sober patients. A delay in treatment, as I shared in connection though for other reasons, postponement only with 4 weeks increases the likelihood of death, from 8 weeks – even more.
The results of the detailed results of the clinical trial on the fatal consequences of delaying treatment for a longer period of time are nightmarish.. In this logical connection it is quite clear, that patients should be protected. There is no time and place during their chemotherapy treatment, with radiation therapy, combination of chemo- and radiation therapy or surgery to stop them, postpone, because the patient is currently suffering from COVID-19, which you know sometimes lasts longer, which can delay cancer treatment with 1, 2 or 3 months.
For me, there is absolutely no doubt, that common sense and the evidence obtained so far in medicine speak in favor of the vaccination of cancer patients, as this is the way they can continue to treat their oncological suffering without worrying, so that it is as effective as possible and not to their detriment.
What is your balance sheet for the past 2020 r. on the frequency of oncological diseases and the most common localizations and stages, treated at your hospital?
If we go back to the past 2020 g., the frequency of patients, passed through our medical institution, increased, maybe because of that, that there were logistical difficulties in some places in the treatment, of the trip, of a number of other subjective factors with medical establishments, which were to provide resources for COVID-19, which, by the way, we have done and we know how difficult our work is. Of course, this probably complicates the work of some other medical institutions even more. T
So that, without thinking, that there is some drastic increase in cancer patients, the relative proportion of patients, passed through the Medical Oncology Clinic of “Acibadem City Clinic-Mladost” it was quite large. The most common localizations were largely the usual ones, namely colon and rectal cancer, breast cancer, of the lungs.
It is interesting, that in the last about 2 years we have an extremely large number of patients with stomach cancer and despite the 32nd year, in which I work in medical oncology, I work exclusively with cancer patients and their anti-tumor treatment, so far I have no explanation for their increased number. Of course, I hope the big centers, who conduct sufficient research, to give some results, which explain the significantly increased incidence of stomach cancer.
Many years ago this was one of the localizations, which worldwide we, oncologists, we were proud, that decreases, that the probable reasons for this are the avoidance of certain species, considered extremely carcinogenic foods – smoked fish, some also specifically prepared delicacies, the large presence of nitrate, etc., but apparently not only eating habits lead to some change in this disease. Patients appear exclusively at a young age.
I only had at least last year 6-7 patients with stomach cancer, which are between 30 and 40 years, patient, which was on 27 years. Since the beginning of the year, in the first two weeks alone, we already have 3 patients with newly diagnosed stomach cancer. I hope there is a quicker explanation. We have the most modern treatment options for this localization.
I participated as a principal investigator about 10 years ago in an extremely important one, prestigious international clinical trial, in which the clinic I ran at the time was the only center in Europe. Aspects of this clinical trial are already with additional biological therapies. There are many citations in the literature, including our team and I am proud, that Bulgaria is present on the map of this location with dignity.
From this point of view, this localization is an additional challenge for me, because I see some change in her and I want us to do our best, so that we can exercise the best control. This is reflected in the standards for antitumor drug treatment of the Bulgarian Oncological Scientific Society, which we adapted to the latest requirements of the American Oncology Association and the European Society of Medical Oncology and issued at the end of December despite the difficult situation.
Colleagues from the country have received them, but with us everything changes so quickly, that a new update is forthcoming. It will probably be around May, so that by the beginning of June the new indications, authorized by the European Medicines Agency, by regulatory authorities, from the NHIF, which also takes on new innovative methods of treatment by reimbursing them, to be reflected in these updated guidelines.
Of course, I'm not just talking about stomach cancer, and for each localization. Believe me, has unique technologies, which enter the treatment of cancer. I am happy to say – and in our country too.
Are there new approaches and methods worldwide, which have started to be applied or are to be applied in the world and respectively in Bulgaria?
Despite all the difficulties, there have been many innovative therapies over the past year, which take an increasing volume in the work of oncologists, I mean biological therapies, biological approaches to cancer treatment, other targeted therapies, which have entered and which show extremely fantastic results even in very advanced tumors.
After so many years of work when I said to myself after a great success and a long lull, after a second great success and a long lull whether there will be another big breakthrough, be happy, that are obtained. There was a real boom, qualitative breakthrough in the treatment of cancer with the introduction of biological therapies and in proving their effectiveness, with more and more localizations of this suffering.
Of course, in no case should the unique possibilities be underestimated, which is also provided by modern robotic surgery, unique opportunities, which are obtained in radiotherapy with modern sophisticated devices, who perform radiosurgery in a unique way, perform miracles, which were unthinkable in radiotherapy only years ago.
And this, that we continue our teamwork between these major specialties allows for a radical break and refraction of the disease. Pathologists have a special place in this whole team, which give us more and more, clear and accurate information, which we want; colleagues, who deal with molecular-biological-genetic analysis, which give us the exact targets, targetite, which we can strike with modern therapies.
These therapies have begun to become routine and fortunately available in our country. They allow for a treatment, which I can safely say in our clinic is applied at European and world level, even in patients, in which the disease, Unfortunately, is extremely advanced. Of course, there our possibilities are more limited. Often we cannot eradicate the disease, but only to prolong the lives of patients, but even this in these extremely advanced patients with previously incurable forms of cancer already provides some opportunities, which were not expected before.
Even for example, if we look at lung cancer. Honestly until less than 10 for years it was a localization with such modest possibilities for influence, that in practice there was a great deal of reticence about the activity of treatment, which took place, insofar as, with its modest capabilities, it not only worsens the quality of life in these patients and a number of other aspects.
Of course, this is a past, because we have achieved unique results in the treatment of lung cancer with targeted therapies, and of course, immunological treatment. Prostate cancer was a disease, which to the development of castration resistance, it was considered, that these patients have a verdict over themselves. This is no longer the case. We have second-line endocrine therapy, which in specific ways overcomes resistance and gives many years of life in excellent quality. As well as a number, a number of other methods of influencing.
All this is so close to my heart, that I could talk for hours, but I just want to say, that there are unique opportunities to influence cancer and I strongly advise everyone, who has such a problem, who has such a suspicion of a problem, to look for the nearest oncology treatment facility directly, because there are now additional difficulties in the patient's path – no one will be returned, a diagnosis will be sought. The medical oncologist should be the conductor of the treatment, to tell when to perform an operation, when to perform chemotherapy, when to conduct radiotherapy and what exact tests to do, so that the subsequent treatment can be in the maximum interest of the patient and with the maximum result.
The European Commission continues to prioritize the development and implementation of anti-cancer plans in all Member States.. Is there any change in connection with the COVID pandemic such as new requirements and a change of plan?
The EC has long been trying to give a boost to member states to build anti-cancer plans, which cover a longer period, to have a horizon of action, which allows us to first know what part of the population is covered. Second – what are the gaps, who, of course, are individual for each country, what is the specific characteristic of the patients, and I would say in general about the demographic indicators of each country, which is important for building such a plan. You need to know what the financial capabilities of health systems are, what part of the finances of a health care system should be directed to such patients through such an anti-cancer plan?
Last but not least, they are aimed at the whole society, because screening programs are included in anti-cancer plans, ie. for active search for some forms of cancer, in which this is possible, in order to improve survival in already ill patients. These are really very important things, which I think, that for obvious reasons in the past 2020 g., these 20-20 they will really be remembered for a long time, went a little into the background.
Of course, there was also a fear of what would happen to cancer patients, they are undergoing severe treatment, whether the conduct of COVID-19 will be fatal for them or for some of them and a number of other questions. Fortunately, it turned out, that is not true. As sensitive as they are, it is indisputably so, a sensitive and sensitive part of the sick, more likely to be more severe, there was no mass morbidity in this group with pronounced adverse events.
Of course, the mixing of oncological medical establishments and COVID units in them, I personally think, that it is not the most reasonable thing. However, no matter how difficult the resources of a health care system, various maneuvers could be sought, which allow a minimal connection of these groups of patients, especially there, where the building stock or other factors do not work in favor of mixing such units, but of course, it is a matter of individual organization and a matter of policy.
Speaking of anti-cancer plans, there are a number of conclusions, which we are still making from the treatment of cancer patients, those of them, who spent COVID-19, this, which we observed in them. And they need to go into cancer plans, but at the moment, I say it honestly, the emphasis of the legislature and the state in each country is on another place and that thing, which will probably return as an element in a later period, which must be clearly and accurately signed, to know what will happen to patients.
I would say not only because of COVID-19, and because of that, that at any given time there may be some similar pandemic or other medical, I would say without a strong word, disaster, for which we must be ready. Just from our generation, the former seemed to be so favored, see medical disasters, they see wars, but here you see, that we make plans, but another decides exactly what to do. In this regard, it is now more important to draw the right conclusions, to be involved in the development of anti-cancer plans in each country.
And I think there needs to be some centralization at European Commission level, European Council, because giving some guidance is wonderful, of course, that each country adapts an anti-cancer plan to its individual characteristics, but there must be more control. I'd say – and imperative by the EU leadership, because this is understandable, now all of Europe, the whole world is entering an economic recession and the means, which in principle have always been insufficient will be even more insufficient.
And it must be clear why such a plan must exist and why funds must be given, so as not to get into even greater difficulties, because besides money there is a greater value, which can be lost, this is health and, unfortunately, sometimes people's lives.
