OncoDaily Dialogues #2 – Piotr Wysocki / Hosted by Roupen Odabashian

We continue our series of “OncoDaily Dialogues”. This initiative by OncoDaily is designed to spotlight leaders in the field of oncology, sharing their stories of success, challenges, and life lessons.

Today, we are honored to host a renowned oncologist from Poland, professor Piotr J. Wysocki, who is the Head of the Clinical Oncology Department at University Hospital and Head of the Faculty of Oncology at Jagiellonian University-Medical College (Krakow), the Past-President of the Polish Society of Clinical Oncology, and the chair of the ASCO European Regional Council. He graduated from the University of Medical Sciences in Poznan, Poland in 2000, obtained Ph.D. in molecular biology (2000), and got board-certified in medical oncology in 2007. In 2012 he received the title of titular professor of medicine, which is a life-time title granted by President of the Republic of Poland. In addition he was trained at the Department of Molecular Biology at Roswell Park Cancer Institute Buffalo, NY (1997) and Department of Oncology at the Princess Margaret Hospital in Toronto, Canada (2008). During his medical carrier prof. Wysocki was a promoter of four PhDs and trained dozens of medical oncology residents. He is a lead author of national guidelines for the treatment of genitourinary tumors and coauthor of guidelines in breast cancer. Prof. Wysocki serves as an advisor for the Polish Ministry of Health in the process of the development of a national cancer strategy. Over the last decade prof. Wysocki established two early-phase clinical study units in Cracow and Szczecin. His areas of clinical expertise include systemic treatment of breast, gynecologic, and GU cancers and the development of original metronomic chemotherapy-based therapies (chemo-endocrine, chemo-targeted, and metronomic polychemotherapy) for the treatment of advanced, pretreated cancer patients. Scientific interests include the development and application of immunopheresis for the treatment of solid tumors and the mitigation of immune-related adverse events. Prof. Wysocki has performed first-in-human studies with therapeutic immunopheresis and developed clinical study protocols for studies on apheresis-based systemic treatment in various solid tumors. Over the last 15 years prof. Wysocki acted as principal investigator in >70, phase I-III international clinical studies in oncology conducted in Poland. Prof. Wysocki has published >100 peer-reviewed articles on translational, clinical, and preclinical cancer research. His educational activities involve lectures and online courses for oncologists, residents and medical students (Jagiellonian University, Poznan University of Medicine). His portfolio comprises >1000 lectures and presentations given during national and international meetings, webinars, and symposia over the last 20 years. Since 2023, he has become a member of the American Society of Clinical Oncology International Affairs Committee.

Our host is Dr. Roupen Odabashian, hematology/oncology fellow at Karmanos Cancer Institute in Detroit, USA. Beyond his clinical practice, Dr. Odabashian possesses an unwavering passion for delving into the intricacies of healthcare policy, regulations and Oncology. He understands the multifaceted nature of cancer as a medical condition and acknowledges the various stakeholders and regulatory bodies that influence the delivery and administration of cancer treatments. In alignment with this commitment, he has joined OncoDaily, where he plays a pivotal role in conducting interviews with Leaders of the Cancer world.

You may view the previous series through the link below:

OncoDaily Dialogues #1 – Harout Semerjian / Hosted by Roupen Odabashian

About OncoDaily 

OncoDaily was founded in 2023. It is a US-based oncology media platform, which features the latest news, insights, and patient stories from the world of oncology. Within a short period of time it became one of the leading oncology media platforms globally.

OncoDaily gathers content from various sources, including social media posts from renowned oncologists from all over the world, news from oncology societies and cancer centers, patient and survivor stories, and career-related information for professionals.

The mission of OncoDaily is to empower patients, survivors, and professionals with the knowledge and inspiration they need to fight cancer. The motto of OncoDaily is “Cancer doesn’t take a day off – neither do we”.

Follow the transcript below

RO: Welcome to OncoDaily. Today we have the privilege of hosting Professor Piotr Wysocki, a distinguished figure in the world of clinical oncology. Currently, he leads the clinical oncology department at University Hospital and heads the faculty of oncology at Jagiellonian University Medical College in Krakow, Poland. A graduate from the University of Medical Sciences in Poznan, he earned his PhD in molecular biology the same year he graduated and furthered his skills at esteemed institutions like Roswell Park Cancer Institute in Buffalo, New York, and the Princess Margaret Hospital in Toronto, Canada. Professor Wysocki’s contributions to the field are manifold; he’s been the president of the Polish Society of Clinical Oncology twice and has played a pivotal role in shaping Poland’s National Cancer Strategy as an advisor to the Polish Ministry of Health. His clinical expertise spans systematic treatment of various cancers, and he’s been at the forefront of developing innovative chemotherapy-based therapies. With over 100 peer-reviewed articles to his name and a role as the principal investigator in more than 70 international clinical studies, Professor Wysocki’s impact on oncology is undeniable. His dedication to education is evident in his extensive portfolio of lectures, online courses, and presentations, benefiting oncologists, residents, and medical students alike. As of 2023, he’s also a proud member of the American Society of Clinical Oncology International Affairs Committee and the chair of ASCO’s European Regional Advisory Council. Welcome to OncoDaily, Professor Wysocki.

PW: Welcome to the podcast. Thank you so much for being here. I really appreciate that. Um, could you share with us what inspired you to pursue a PhD in molecular biology, especially early in your career? What inspired you to become, or to investigate this field more?

PW: Well, actually, it was during my university years. I had the option and opportunity to start working in a lab because, in Poland, students in the early stages of their training, and actually their university career, have the option to be linked with some basic scientific, well, laboratories. And I actually chose a molecular biology lab, and then an immunology lab, because this was the first actually opportunity I had, and I was so overwhelmed by all aspects and all those scientific backgrounds that were explored at that time. It was so interesting that I decided to explore it while being trained as a medical doctor but then having the opportunity to do some basic research during medical school. It was extremely important for my future career because it opened my eyes to what molecular biology was, and what cancer immunology, and everything was concentrated on oncology because the lab I was involved in some basic research was based in a comprehensive cancer center in the city where I did my medical school. So, this is how it started. But you know, being well, actually as a chance, an opportunity that I could have found something else, but I found a lot that was involved in cancer research, and it actually sped up the whole idea of further medical development and choosing the speciality which was clinical oncology.

RO: Yeah, I completely agree with you. I really find molecular biology and basic science very important. If you want to become a good clinician, if you don’t understand how things work on a molecular level, you can’t really understand what are the tools that you are using. Eventually, when you prescribe a treatment for someone, it’s like you are using a tool that has its own benefits and its own risks. So, if you don’t understand the molecular level, how this chemotherapy or drug works, you can’t really translate that to the clinical science. I do share lots of your love for molecular science, but unfortunately, I didn’t have the chance to work in a lab yet. So hopefully, I’m working on that. And we talked earlier about your career, and as I mentioned, you are the current head of the Clinical Oncology Department at University Hospital and the Faculty of Oncology at Jagiellonian University Medical College. So, what are some of the pivotal leadership responsibilities that you undertake in this role?

PW: Well, actually, Jagiellonian University is the most important university in Poland, and oncology was something that was underdeveloped at the time when I came to Krakow, and I got the position there as a head of the department. I was asked to actually improve the university oncology, to improve the importance of the University Cancer Center, because there were some other Comprehensive Cancer Centers in the city where I’m now residing, but the university oncology, in terms mainly of medical oncology, was underdeveloped. What I did, and what I have achieved over the last eight years, was actually from a relatively small cancer treatment side, I have created one of the biggest medical oncology units in Poland, with more than 2500 patients in continuous treatment at our site. So, we have like 2500 individual patients being consulted and treated every single month. And the responsibility, well, actually, you have to know that the numbers in Poland, in relationship to the general population with this 38 million, it’s like 200,000 new cancer cases a year. So, it’s a huge number, and there is like 1,200 medical oncologists in Poland. So just imagine the extent of work and the workload that medical oncologists are facing every day, having so many patients requiring systemic treatment. And the workload is really high. We have achieved the generation of a really huge cancer treatment site, and this is something that is beyond comparison to other Medical Systems in Europe because the number of cancer patients, the reimbursement of many new drugs, and the improvement in cancer patient survival, is not actually followed by the number of medical oncologists in Poland. So many, well, many of my colleagues from different countries in Europe, they cannot believe how big the workload is for medical oncologists in Poland. But it is really the problem, and the challenge that all of the heads of cancer sites in Poland are facing is how to deal with huge numbers of patients, having really small numbers of nurses and oncologists. And this is the huge challenge which requires a lot of organizational skills. How to, you know, make all this work in the case of a really difficult situation.

RO: And like you mentioned, the numbers are really high. Like, is it comparable to Europe? Is it comparable to the general incidence of cancer cases per world? And why do you think the incidence of cancer is higher in your area, or do you have fewer oncologists per capita? Where do you think the problem lies?

PW: Well, this is a multi-directional problem. The main reason is that actually, the medical, well, the health system in Poland is insufficient in comparison to other Western European countries. The number of medical doctors per 100,000 people is the lowest or almost the lowest in the European Union. And again, we have seen tremendous progress in the efficacy of systemic treatment of cancer patients in Poland because actually, the number of doctors is not increasing, but the availability of novel drugs is increasing. So, we see improvement in the outcomes, and the numbers of patients requiring continuous systemic treatment are rapidly increasing. Yeah, but the number of medical oncologists is not increasing at the same pace, and additionally, since we have low numbers of general practitioners, of radiologists, or of surgeons, many patients are being diagnosed at more advanced stages than it should be if we had a better general health system. So therefore, you have more patients who require neoadjuvant treatment, who require more aggressive treatment, and this is also something that should not be that often if we had the sufficient number of well, general practitioners, and surgeons, because then those patients can be diagnosed earlier, can be treated with surgery alone, and there will be not that high load for medical oncologists. 

Additionally, the well, many former East European countries, the Soviet bloc countries, the understanding of healthy lifestyles or of some preventive measures how to decrease the risk of cancer have not been well known at the time. The health lifestyle, this is something that is now being understood but for many older Poles, the problem is that they have been exposed to various carcinogenic agents, to air pollution, to non-healthy lifestyles, and we are now facing the problems that have been accumulating over the last three or four decades. So, this is a very multi-directional problem; there’s not an easy solution for this. But I am, well, I think that many former countries that were in Eastern Europe under the influence of the Soviet Union, they face similar problems but actually in Poland, due to the low numbers of doctors, it’s more evident.**

RO: Gotta. Since we’re talking about Poland and the healthcare system there, can you give me some insight into how oncology is practiced? How does the healthcare infrastructure operate? Is it a private healthcare system? Is it a public healthcare system? Who pays for the treatment?

PW: Well, in Poland, starting with the communism and just after the Second World War, it was said that everything is for free, and actually, even after we got free from the Soviet Union, everything is still for free. We have only one centralized healthcare system. Everyone is well actually made to pay for this, but the treatment is the same for all Poles. So actually, everyone has its well national health policy. Everyone is in the system, so there is no private insurances. Everything is paid by the government, which is not the best option because, well, there is a trend to, and there is increasing willingness to introduce the private health system because it will improve the efficacy, it will improve the quality, and also the access to novel drugs. But it’s very difficult politically to now introduce the private health system just to define that there are some Poles that will have some better options like, you know, better access to, or faster access to some very unique medical technologies, faster access to drug reimbursement. Because for the last, well, it’s now almost 70 years, everyone had the same access to the health system, so no one wants to change it because it may be very difficult in political terms.

RO: Yeah, I hear you. Like, I did my training in Canada and currently in the US, and it’s, it’s so, that sounds like the Canadian Healthcare System where like everyone pays taxes and those taxes go toward the healthcare, um, like the fund that goes to pay for healthcare. It has its own like pros and cons. When I moved to the US, I think also here, like it’s, people paid for insurance, so it’s private. There are some government-paid programs like Medicare or Medicaid. But that being said, like, um, being in both countries, Canada and the US, both of them have their own pros and cons. Like, for example, for example, in the US, I had last couple of weeks, I had two patients, one of them I couldn’t treat, uh, because like they didn’t have insurance, uh, so, uh, patient who presented with like pancytopenia, and then we thought it’s APML or AML, and then we found that he’s like severely deficient with vitamin B12. So, it was like simple treatment, um, but we couldn’t establish a follow-up. So, we just, uh, recommended for him to get an insurance or family help to start them on treatments. And then, like another patient who had an insurance but they couldn’t come and see me where I work because like their insurance is not accepted, uh, in the hospital where I work. So, they had to go to another healthcare provider or an oncologist, uh, which I find interesting. So, each country has its own pros and cons, um. So, we talk about, uh, on the healthcare, um, practice. Tell me about like, uh, the oncology research. How would you describe the state of research and the availability of different treatments in Poland when compared to the global, when compared it globally?

PW: Well, uh, regarding the access to novel drugs, Poland is the so-called HTA country, so where all the reimbursement decisions are made based on health technology assessment, and the, well, uh, evaluation of the prices, right in terms of the benefit the patients get from particular treatment. So, it takes time, uh, till the analysis, uh, and, uh, then risk-sharing discussions are made, uh, just, you know, to, uh, well, make the decisions whether a drug will be rebuffed or not. So, what we see is that we don’t have access to the drugs as soon as, for example, in Germany, when they get reimbursement once the drugs are approved in the European Union. But on the other hand, the HTA policy which is typical for Poland, for example, also like in the UK, it takes time till the drugs are reimbursed, but the cost of the drugs is much lower than in other countries because the government is discussing with the pharma companies, and are discussing the real, uh, benefit, the, uh, the, uh, for economic analysis, and, uh, you know, Poland is not a small country, so the pharma companies, actually, they, uh, strive to, uh, sell the drugs in Poland, but, uh, on the other hand, they know that they have to decrease the price or they have to make some risk-sharing agreements while they, for example, offer some other of their drugs, uh, much cheaper just to have the novel drug, uh, rebuffed. So, this is why, even though we don’t have any private health system, many of the relatively novel innovative drugs are being rebuffed. So, this is from the medical point of view, this is well, it could be faster, but it’s okay that we have the access to the drugs in the general population. But, uh, while talking about research, it’s not only basic research, it’s also some translational research and clinical research. It’s not that easy, uh, first, this is Poland, uh, even though it’s a European country, uh, European Union country, uh, the, uh, money that is spent for, uh, science and for research for GDP is one of the lowest in the European Union. And if we are talking about clinical research, uh, it’s also very difficult because, uh, in order to pursue any medical studies, you have to have the team, and the team of people who are dedicated and have some free time to spend for the clinical research. And since there is not too many medical doctors, and actually, the number of medical doctors is insufficient for the healthcare needs, it’s even harder to find doctors or dedicated people who will take part in the clinical studies. So, we wish it would be better, but we are, you know, looking for options to attract more and more residents, uh, for, uh, to attract them for medical oncology, showing also the opportunity of taking part in clinical trials, and, and you know, it’s not only, you know, uh, doing the clinical research, but it’s also a way to get some additional salary, because in po, the system, the sub-investigators, and then study nurses, and then data managers to be renumerated for their activities and clinical trials. So, this is also, uh, an incentive to do the, uh, clinical studies.

RO: Got you, um, yeah, I think the research, that’s, that’s where the problem lies, right? Like, it’s, you mentioned like, you, you can hardly find people who can able to fulfill the clinical requirements, and then it’s much more harder to find people to do the research. It’s, um, it’s sometimes bit tricky because, like, all researchers, all over the world, I think, research, it comes really from people who are passionate about it. It’s hard, and you need passion, and not everyone is willing to sacrifice the time, it, it needs tons and tons and tons of hours, um. Talking about that, I was going through your background, you had extensive publication record, and you have more than like 70 international, even more, clinical studies. So, what advice would you have, or would you extend to early stage oncologists, let’s say like me, who are aiming to thrive in academia and the clinical research?

PW: Well, uh, first of all, it’s, say, well, medical oncology, oncology, hematology, is extremely unique field because, actually, everything that happens and everything that you may be involved in can have immediate impact on, uh, cancer cure. I mean, this is something so, well, unique and overwhelming for people involved in the clinical studies that actually what you are doing, you can feel it like in two, three years after you are conducting the clinical study, that your work, your engagement, can change the fate of patients. This is something that cannot be compared to any other specialty, and this is very important. And other aspect is, actually, that medical oncology, and I think also hematology, is such a wide field for research. You can find your own place in that, and you can pursue your goals, and you, you can do some unique studies, even though they are, they can be small, but all those well-constructed and well-designed studies can finally have some impact on the activity of cancer treatment, on the safety of cancer treatment, on the quality of life of patients. So, there’s so many aspects you can improve by being engaged in clinical research, in basic research, in translational research, which is beyond comparison to any other specialty. How would you, what is like, if you’re going to give like a secret recipe that help you to be proliferative researchers, and research and publish a lot, what would you say help you the most?

PW: Well, there’s difficult, well, there’s different options, but I think the most important is to have, uh, proper mentor because especially when you are young, uh, and you are in the training to become oncologist, uh, you have to, you know, concentrate on, on your main goal, which is, being, becoming the consultant, be being, uh, well approved by the board word, and if you don’t have a mentor who can actually take you by hand, and and show you what is important, where to concentrate, and can help you develop your skills, it is very difficult to do it alone. So, I think that for young oncologists, finding a proper mentor, it’s the, the most important point because once you have someone who takes care of you, and who will actually help you to develop your unique scientific abilities, it will actually speed up all other, uh, processes, and will actually pave you the way to do your own research. And I think this is the, the most important point because the mentor knows what’s this, what is interesting, knows how to pursue your goals, how to do the research, step by step, and he is responsible to teach you how to do this. But once you get the knowledge, you will know by yourself how to do it further.

RO: You touch base on very important which is, is close to my heart too. I think having the right mentor, in residency, I, I struggled in this until I found the right, found the right person who was a great mentor for me, um, Dr. Mark Kerr. He’s like, he was amazing, he, he used to meet with me, um, every week or two, and like, uh, take time off just to meet me, me half an hour, and that helps a lot just to keep me on track, um. I found that very helpful. From your own perspective, what are the things that young, uh, oncologist who are studying in this field, they should look for when they are looking for a mentor? Let’s say if you’re going to go back in your early career, and you’re going to start looking for a mentor, what are the, the things that you look for in the mentor, and how would you find them?

PW: Well, uh, this is a difficult question, but actually, you have for, well, you have to do some research regarding mentors, uh, because there’s opinions on, on some mentors by their mentees who are, and the mentees can say if it was what they expected or not. So first is just doing research and, and looking for some well recognized, uh, persons not only recognized from the scientific point of view but also from purely human point of view because to be a mentor, it’s not enough to have the knowledge because especially in oncology, uh, it’s also very important how, uh, the person, uh, who is about to be the mentor behaves, how he, because it’s not only that someone has to learn, teach you how to, you know, do some research, and some, some experiments, but for medical oncologists who are looking for mentors who would help them not only, uh, develop the, the scientific part of their activities, but also the clinical part of their activities because, well, it’s very difficult to do, to have a mentor who are helping you to develop your clinical, uh, uh, potential, and another mentor who will help you to develop your scientific skills because then it may be difficult, you know, to, uh, put it all together. So, it’s the best option is to have a mentor which can help you to develop your clinical skills and will, will help you to develop your scientific skills. So especially in the field of oncology, it’s very, very important to, uh, know the personality of, of the mentor, how he, uh, talks to the patients, what’s the his level of empathy because how he, uh, acts in the front of patients, it is actually the same how he will act in the front of you as a mentee. So, this is very important because you have to learn actually at the same time how to be a good oncologist and how to be a good scientist, and it’s, you know, having the proper mentor can solve all the problems because he will teach you the empathy, the way of talking to patients, the way of treating the patients, the way of understanding the disease, and at the same time, how your understanding of the disease can pave the ways to, uh, doing research because otherwise, it may be very difficult, you know, doing some very basic research in the lab, totally unrelated to your medical oncology or hematology training. So the best option is to have a mentor that can help you develop your skills, uh, simultaneously.

RO: Yeah, I can’t agree more. When especially when it comes to basic research, like I find, like basic research, like, it’s a, it’s a hidden, uh, scary part that not lots of clinician go there, but like if you don’t have a mentor, it could be even much scarier, like, it’s, it’s, it’s very challenging especially in the lab spending tons of hours, uh, by yourself doing experiments, writing down the results, um, yeah, but you know what I find, it, it’s, it’s hard, it’s bit hard, I don’t know if it’s different in Poland, is, um, especially like at the size of organization so sometimes when you are in a medium to small size organization, you know people closely, right, and you can develop like one-to-one, one relationship with them, and then when you go to a bigger organization, it becomes very hard to develop that one-to-one close relationship with one mentor that can help you in both, uh, clinical and research because like there’s also like lots of turnover so for example one week you work with this person another week you work with that person so it becomes bit harder to develop, uh, that relationship but I agree with you about the point that you mentioned that asking other mentees how the relationship was, was with the mentor that’s a huge indicator on how or like it gives you idea how or what would you expect from your relationship with them.

PW: Yeah, definitely, I mean, uh, and well, uh, doing, uh, oncology residency and some basic scientific research is extremely difficult because sometimes when you talk to guys who are involved in basic research, uh, you may notice that they are pursuing some goals which are clinically irr, irrelevant. I mean, they are looking for some answers which are actually not needed in the clinics. And what is very important is you know having the option to connect both worlds because and this is what translational research is because as a, as an oncologist, you understand the clinical problem, you have some ideas of the biology of the disease, and you know what the questions can be important that require answers in order to improve some, some clinical aspects. And, uh, this is, uh, something that people involve totally in basic research cannot understand, they actually do not know what is relevant from clinical point of view and this is what the research for oncologists is, the translational studies. So having the question, clinical question, and trying to answer it, you can, of course, talk to guys who are involved in basic science, you have the problem, you ask them to help you to find the way how to answer the question so what, what basic studies, some cell cultures can well give you some hints to, to answer the question but the most important part is you have the clinical background and you want to make it into research and the translational research, the question, why, why something that I see in the clinic is looking this way, uh, to find the answer, uh, and if you have the mentor, he will help you to, know, find a way, contact the proper people who can, uh, help you to answer this question. You don’t have to do this by yourself, you have to know, with, with whom to talk about it.

RO: Yeah, I can’t agree more. I can’t, you’re bringing lots of flashbacks from residency and remembering the people who helped me, um, and so on, um. Okay, so, sh, sh, shifting gears a bit, uh, you’ve been in the field, and you have lots of experience, um, how do you feel like, uh, the field of clinical oncology, uh, especially in areas of immunoparesis and metronomic chemotherapy based therapies change, uh, since you started your career?

PW: Well, uh, imuno raises, this is a concept of, uh, you know, getting rid of some soluble factors from bloodstream, this is a, an idea which is very interesting but unfortunately, at this time point, some pharma companies that have developed this idea, they do not have enough, FS to, you know, pursue clinical studies but this, the concept is very interesting, if you have the proper platform that can, you know, based on some, as you do, AES in hematology, you just, you know, uh, you don’t have to collect blood cells, but you just, uh, pour the plasma through the filter and you get rid of some soluble factors which may improve the outcomes of patients, improve the quality of life, decrease the, uh, toxicity but at this time point, it’s too early to, to talk about the clinical relevance of, of this strategy but talking about metronomic chemotherapy, this is something, uh, so extremely important for clinical practice especially in medical oncology that I couldn’t, uh, stress more how important the area of metronomic chemotherapy can be for medical oncology worldwide. This is something that you can, you know, teach old drugs to do new tricks because metronomic chemotherapy, this is a way of, uh, a way of giving chemotherapy agents, cytotoxic agents at low dose, uh, but in short intervals, um, unlike in hematology where the majority of, uh, uh, diseases, neoplastic diseases are actually single-cell based diseases with high proliferation rate and medical oncology especially in the solid tumors the proliferation rate of, uh, tumor cells is relatively low so when we talk about for example breast cancer proliferation rate expressed by ki67 above 20% is pretty high and many patients have much lower proliferation rate like 15, 10% and when you think about how chemotherapy works, it actually blocks proliferation of cells and while it stops proliferation, the cells undergo apoptosis but the common way of giving chemotherapy which has been developed over the last 70 years was giving chemotherapy at, at maximum tolerated doses so the doses that have been defined in clinical trial miles how much you can give at one time point and then you have like three weeks of, uh, uh, recovery period, uh, until you can give the maximum tolerated dose again but if you have tumors with low proliferation rate like 20%, you can even though you give the maximum tolerated dose you actually can kill approximately 20% of cells if the proliferation rate is like 20% of t67 and then you have like three weeks of the recovery period for your, uh, bone marrow to recover but also for the tumor cells, for the tumors to recover and the 80% of nonproliferating cells at the time of chemotherapy can then repopulate and the cells which are more resistant to chemotherapy can repopulate, uh, faster and the whole concept of metronomic chemotherapy is just giving the chemotherapy in shorter intervals and lower doses just to, you know, have the impact on those, uh, slower proliferating tumors and the most unique concept of metronomic chemotherapy is giving the chemotherapy on a daily basis which can be done with orally available drugs and metronomic chemotherapy, uh, was actually ignited by the availability of oral chemotherapy agents like capecitabine, cyclophosphamide, methotrexate, vinorelbine, topotecan, and, uh, the well, the concept is not very young because orally available drugs have been used in clinical practice, uh, for the last I think 30 years but what we have, uh, developed in the area of metronomic chemotherapy, uh, it was based on some preliminary discussions and studies that, uh, especially for the low and middle income countries, metronomic chemotherapy which possesses not only antiproliferative activity but also because it’s given on a continuous basis it can act as an anti-angiogenic therapy because in order to stop proliferation of endothelial cells, uh, you have to have a continuous concentration of the cytotoxic agent so then it turns out that you can act as an anti-angiogenic therapy using metronomic chemotherapy and additionally it turned out that metronomic chemotherapy can also decrease the tumor induced immunosuppression because unlike high dose chemotherapy which is totally immunosuppressive metronomic chemotherapy can, uh, decrease the activity of some immunosuppressive cells like t-regulatory cells or myeloid-derived suppressor cells and, uh, there were some discussions that maybe metronomic chemotherapy can be the option to overcome the inability of, uh, unique molecular targeted agents in low and middle income countries but, uh, also in Poland we had problems with the access to novel drugs as I said we had to wait for reimbursement till our government, uh, came to an agreement with some pharma companies and we have faced lack of access to CDK4/6 inhibitors in breast cancer patients because, uh, the drugs were very popular in Western Europe many of our patients asked to be treated with the CDK for6 inhibitors but we have not, uh, we didn’t have access to the drugs and it took like four years to for the drugs to be REM so it was a very, very long time because you know there was no overall survival data and if you don’t have overall survival data it’s really difficult to evaluate the quality adjusted live years and therefore it was so difficult you know to, to get the reimbursement and we decided at that time so looking at the mechanism of action of CDK4/6 inhibitors which are actually cycle-specific anti-proliferative agents we decided to give our patients metronomic chemotherapy combined with endocrine treatment and it turned out that it’s very, very efficient I mean it we’ve seen so many patients with dramatic responses to this kind of combination of combination of endocrine treatment and metronomic chemotherapy that we have started to use the combinations in various clinical settings in various tumors combining it with the standard, uh, uh, targeted agents, uh, when it was possible because it’s very well controlled in Poland if patients are treated, uh, with the reimbursed drugs according to the defined standards so it is difficult to give the patients some, uh, let’s say off the books, uh, agents but we, we, we were able to do this and we were able to show for example that patients treated with anti-ER 2 agents receiving metronomic chemotherapy even though they are progressing on anti-ER 2 agents alone, uh, for example HER2 positive breast cancer patients who have been treated with docetaxel and pertuzumab and trastuzumab after stopping those attacks so they were receiving pertuzumab and trastuzumab and they showed some signs of progression introducing metronomic chemotherapy could just revert the progression process and the patient, uh, started to respond again, uh, we have seen the same and heavily pretreated patients with, uh, gastrointestinal stromal tumors who, they have been treated with targeted agents and they, they actually were resistant and we decided to, to use the, the matin combined with metronomic chemotherapy the patient started to respond again even though they could not respond to Tin anymore and to standard metronomic chemotherapy they also are not responding but combining the drugs actually improve the, the outcomes we see the same situations combining with PARP inhibitors and the history goes, uh, really, uh, uh, in a really fascinating way it’s of course difficult to conduct large-scale clinical studies because no pharma company is interested in supporting this kind of trials but we are looking for ways how to, uh, pursue the, the clinical studies with metronomic chemotherapies and it’s really fascinating because unlike with other, uh, chemotherapy regimens using metronomic chemotherapy having the option to give the drugs on a daily basis having like three or four metronomic cytotoxic agents given, uh, simultaneously you can adjust the treatment based on the toxicity and efficacy so we see like giving three drug regimens for example the, the standard regimen and, and breast cancer which is Vex so it’s venorelbine, cyclophosphamide, and capecitabine sometimes combined also with methotrexate you see if the patient develop any signs of toxicity for example hand and foot syndrome in the case of capecitabine you can just decrease capecitabine but increase for example venorelbine so you keep the patients controlled that you keep the disease controlled but you can like adjust like in the old hi-fi music systems The Equalizer you just you know increase one dose of one drug you decrease another and in the case of chronic cancer treatment because metronomic chemotherapy this is not a way of curative treatment it’s a just a purely palliative systemic treatment you can do such a wonderful, uh, personalized, uh, treatment approaches that is well mind-blowing and, and we have, we have so many examples of patients like we had a patient with, uh, squamous cell cancer of his perianal region we didn’t have access to immunotherapy at the time but using some well, uh, constructed chemo metronomic chemotherapy regimens we achieved complete response and the patient is disease-free, uh, now more than three years after we started the treatment so this is something especially for low and middle income countries where having very cheap drugs but using those drugs wisely you can really make a difference.

RO: Wow, that’s very interesting like and I think the need is the mother of invention having that need to figure out something what we can what you can do with the tools available, uh, led to the more innovation in this field, um, it’s, we are almost at time I don’t want to take your time more but I just have one last question, um, are there any, uh, new technologies or techniques in your view that will significantly influence the treatment paradigm, uh, or advance cancer care in the soon future, uh?

PW: Well, I think better understanding of the disease not only you know using the novel drugs the novel drugs are very, very important especially if you have a novel targets and then novel technologies but what is for me a very sad situation is actually that with the novel drugs you forget your old lessons and this is for example what what we see with chemotherapy I mean many novel drugs are very active but also very toxic and sometimes you have to look at the old lessons on the old options how to you know using wisely older drugs, uh, how you can mitigate some toxicities of novel agents which is, uh, actually not well known but what I think and what I hope it will change in oncology it will be that not only the novel unique agents are critical for the progress and oncology it is a wise using of all available options and this is also understanding and it’s happening slowly but it’s happening that every patient is really unique not only in the terms of comorbidities and tumor type but also of his expectations his goals and many times less is more so you don’t have to treat all the patients with all the newest drugs at the very early stage of the disease I mean the first line of palliative treatment understanding what’s this really important for the patient understanding how to talk to the patient providing him or her options of less intensive treatment to improve quality of life and to prolong the disease control is extremely important and what makes me upset is that with a very intense pressure made by pharma companies we tend again to move the novel but also aggressive treatments to the early stages yes I agree with that and you know some improvement in terms of overall response rate for example but it’s not only that you have to concentrate on the first line of treatment you have to keep in mind that our patients will live longer and longer and it’s not only activity but it’s also toxicity and sometime being too aggressive at the first or at the earlier stages of the systemic treatment it also means you are you you are more aggressive and the aggressiveness sometimes is, uh, more evident than the benefit so I think and I hope that the field of oncology will move finally to the situation that we will look at the disease and decide if the disease is aggressive we act in an in an aggressive manner if the disease is not in hurry we are not in hurry so it’s not only that the tumor types matter that the, uh, patient comorbidities matter but also the vision of the patient and of the doctor and the patient has to be the most important actor in the whole process and we have to adapt our decisions to what the patient needs wants and craves for.

RO: No thank you so much I really appreciate that I you you said many things that really resonates with me it’s not about the number is not about only over the overall survival it’s also like the quality of life that the person will have during that time and I hope with the new technologies that we have um we can have a better way to Unique to to treat every cancer in a unique way I think cancer uh one of my great mentors said like uh to me cancer is an orphan disease each cancer is unique there is no cancer that looks like to each other so knowing the the activity of or the progression of a specific cancer in a specific patient will help you to treat that patient in unique way and you cannot generalize the treatment on everyone and and what what is also very important it’s not only that the disease is unique in particular patient especially in solid tumors every single metastasis can be unique and you have to understand the disease because sometimes for example in breast cancer it’s yeah really evident that for example you treat the patient with bone mets with endocrine treatment and you see that the patient progresses she develops liver mets so you switch your treatment for example to chemotherapy to treat the liver mets you control the liver mets but the bone mets are progressive why that’s right because because if you understand and this is what I always want my residents to understand you talking in in the case of disseminated metastatic disease you are talking about the standard Darwinian law the fittest will survive and therefore you have you know various diseases in various regions and you have to think how to combine your treatment because you cannot concentrate only on one enemy because you have different enemies or well uh who are developing in a different way or achieving different features and the longer r treat the patients the more difficult is it is to treat the patient and you have to understand you have to have a holistic view of the disease to be really effective in what you’re doing wow that’s really interesting way because like you know like we think about it sorry I don’t want to take your time but I think this is very interesting way of thinking about metastasis which I never thought about because like okay so the disease metastasize and then we spe treatment that means treatment failure but that’s another way of looking at it I think tailoring the treat treatment based on the micro environment of the disease and where disease survive because like as you said I don’t think the micro environment of the bone is similar to micro of the liver uh maybe the vasculature in the liver and maybe like antivascular vascul growth factor work better for liver mets versus bone mets you need for example denosumab or andronic acid yeah but again you have also a genomically unstable disease so every single cell exactly and get random mutations and the mutations can drive the disease in a different way just exactly as Darwin said I mean mutations make the clones and the fittest will survive so you make the pressure like like you know there was a pressure on on on the uh some some organisms on the islands that Darwin explored and you are putting the same pressure on tumor cells and they have you know to find a random feature which will help to survive but for example a cell and the lung uh will find a different way how to become resistant than the cell in the liver and then you have to well look at this and sometimes you know come to the idea how to treat the uh disease and here comes the metronomic chemotherapy very handy because we are using like for example four drug regimens which in which in uh medical oncology is totally unaccepted if you are talking about like intravenous three drug regimens you cannot do this it’s so toxic but using like metronomic chemotherapy combined with like oral daily chemotherapy combined with some weekly chemotherapy agents you can really combine like four or even five drugs together and you have a mixture that is totally unique to the patient and if you follow the history of the patient and you know which  metastatic lesions responded to which kind of treatment you can then you know combine it based on your previous experience so this is this is the personalization of cancer treatment and it really works in in I don’t know like in in hematology but in medical oncologist it’s really kind of personalization.

RO: I can’t agree more um this has been fascinating hour for me I learned a lot and there are many things now for me lots of food for my thought thoughts, so I have to grasp thank you so much I don’t want to take your time I know it’s now almost like 9 or 10 o’ your time.

PW: It’s 7 

RO: Okay almost dinner time I appreciate your time and thank you so much for joining me today!

PW:  Was a pleasure!