Adrianna Sobol: Health begins in your head. Adrianna Sobol.

Welcome warmly in the next episode of my podcast. Today’s topic, I want to say that it is a difficult topic, but actually that is the wrong word. This is a very real-life topic. Today we will talk about how to diagnose cancer digitally.

I hope this introduction has already caught your attention. And I will talk to an exceptional expert, because my guest today is Witold Rezner, MD, PhD, Consultant Pathologist, co-founder of the Digital Pathology Team, a company working on the TwiceView project, where patients can get a second pathomorphological opinion. And we’re going to talk about it more today. This second opinion is prepared using artificial intelligence. And in addition, Witold Rezner is an employee
of the Holy Cross Cancer Center.

Hello.

Witold Rezner: Good morning.

Adrianna Sobol: I had to introduce in such great detail to let everyone know why, what for, and what it is all about. in particular, because the role of the pathomorphologist,from the point of view of patients, is completely invisible. They don’t see the person, they don’t see the specialist, but unfortunately they see the result. I say unfortunately, because receiving a cancer diagnosis is the kind of situation in life, that turns everything upside down.

At the same time, let’s clarify, because I feel that sometimes patients don’t understand some situations, they don’t understand why a procedure takes so long, what is actually done with their sample with the particular neoplastic change. Why is this happening? I would like the patient to understand this, following the principle: the more the patient knows and understands, the better he/she heals.

So let’s start with this role of the pathomorphologist. What is it all about?

Witold Rezner: First of all, I want to say that modern way of dealing with an oncology patients, diagnostics, treatment, are based on the action of multidisciplinary teams. And the pathologist is one of the elements of this team. You cannot say that any of the elements is more or less important.

Adrianna Sobol: It all comes together.

Witold Rezner: That’s exactly right. The better the team works together and the individual components work, the better the patient is diagnosed and treated. The role of the pathomorphologist: the pathomorphologist is the diagnostician.Patomorphologists, my colleagues, you might say, provide the final diagnosis. That means, the diagnosis on the basis of which quite important decisions are made.

Adrianna Sobol: Crucial, I would even say, for the life of the patient and further treatment.

Witold Rezner: Yes, for further treatment. For a treatment plan that is established. Besides the communication within this team is very important and the ability of the pathomorphologist to explain, to show the other members of the team, whether it be a surgeon or a clinical oncologist, whether it be a radiation therapist, to show them well what the diagnosis is. Sometimes what the diagnostic problem is, which we face quite often.

Adrianna Sobol: Exactly, this is sometimes not obvious at all. I often observe this myself, working in the ward with patients who say: the result is unfortunately unclear. Something needs to be repeated. The questions appear and a lot of emotions – we’ll talk about all that in a moment. I said that the role is invisible, because pathomorphologists consult and talk to other specialists. The patient already gets this result.

But let’s explain, perhaps in more detail, as much as we are able, how does modern diagnostics look like? For example, of such most common cancers as breast cancer or prostate cancer. How does it look like? And what the patient should know, what he/she should pay attention to, when they receive the results?

Witold Rezner: Modern diagnostics is about trying to detect cancer as early as possible. And in the case of both breast cancer and prostate cancer, first there is the physical examination, which is kind of a classics. There are imaging tests and based on suspicion of cancer, suspicion of malignant tumor, a biopsy is performed. And this biopsy is what the pathomorphologist evaluates.

As for the way a biopsy has been evaluated so far, it was evaluation under a microscope. For decades pathomorphologists have been working with microscopes, evaluating the image they see under the microscope.

However, a new era of diagnostics is beginning to enter the pathomorphology,
of diagnostics based on digital images. Imaging diagnostics can be an analogy, where X-ray examinations were evaluated on film until a several years ago. But nowadays practically all of it is evaluated on digital images.

Pathomorphology faces a similar evolution, perhaps even a revolution. Slowly the microscope image is being replaced by digital images.It is still as valuable image as this one under the microscope. In my opinion in some cases even more valuable, clearer. But this is my subjective opinion.

Adrianna Sobol: I want to add, that from a point of view of the average Mr/Mrs Smith, who received a diagnosis, when considering this direction of changes, that can mean, at least it seems to me, fewer errors. Certainly some difficulties and mistakes can happen in every area and in every field. So, more accuracy? Speed? Faster results?

Because I sometimes hear from patients, as a psycho-oncologist, that they most often complain about the moment of waiting for the results. It is the most difficult moment for them in the whole treatment process. And to be honest, while supporting patients on this path, it is such a moment that you can’t find words of consolation. It is because at that moment the patient imagines different things, and it can not be based on facts yet. So that’s how different scenes are build up. Patients relate to the various stories they hear and there’s a lot of anxiety.

Can I interpret this to mean that this development, this direction of digital diagnostics, is something that meets the needs of patients?

Witold Rezner: I think so. Diagnostics based on digital images, especially with the support of AI algorithms, artificial intelligence, gives the hope of speeding up the process.

What I can tell patients and what patomorphologists usually say, because we understand that patients are very anxious, they are experiencing this time very much, when they are waiting for the diagnosis. Anyone can put themselves in this situation, get into it, put their person in such a role, a role of a person waiting for the result.

Basically, from our point of view, the diagnosis simply has to be precise enough, it has to be good enough, and simply worth wait for a good quality result, for an accurate result. It is worth waiting for a well-consulted result. This is essentially what I could tell patients.

Adrianna Sobol: How about we try to refer to a specific example. I think our patients who are listening us will be able to imagine it somehow.

For example: we have a breast cancer patient who has a biopsy taken. As we know, breast cancer has many different subtypes. There is a need to check whether HER2 is positive or not. Sometimes I hear from my patients who say: unfortunately I have to wait, something else needs to be ordered, there is something extra. Enormous tension .

Please explain it to us. Why is it taking so long? What happens in this process? And how digital diagnostics could help, for example a breast cancer patient? Because she knows so far, that she has breast cancer, but she doesn’t know anything else. And how will this translate later into her treatment?

Witold Rezner: Perhaps without going too much into detail….

Adrianna Sobol: Sure, so that we can understand it.

Witold Rezner: The process of processing pathomorphological material, the evaluation process, is quite complicated. Some steps can not be accelerated. But for example the use of an artificial intelligence algorithm allows the automatic ordering of additional tests. And then such a sample does not have to go first to a pathomorphologist who initially evaluates this sample and orders additional tests, which means more days of waiting for the patient. But at the stage of let’s call it laboratory processing the sample is already evaluated by AI, artificial intelligence, and additional tests are automatically ordered. This is only one of very many examples.

Adrianna Sobol: This accelerates the situation. Normally a patient would wait. How long is the average wait? Three weeks for the result? More or less?

Witold Rezner: I think in Poland, these are the kind of waiting times. The situation has been improved a bit by the introduction of Rapid Oncology Diagnostics. But I will say that it is not only the waiting time in Poland, it is also the waiting time in other countries around the world, in the European Union.

Adrianna Sobol: So let’s clarify it right away, because it raises a lot of emotions. This waiting time is due to the fact that certain processes (medical, chemical) simply have to take so much time?

Witold Rezner: Also, but it must be said that, I can speak about actually both Poland and the whole world,there is a great shortage of pathomorphologists. There are not enough specialists, they are very heavily burdened with work.

In the past a diagnosis of breast cancer was a single sentence. Just 30-40 years ago it was a single sentence. Now the report contains 2 pages of mandatory information that should be included in such a report. Our digital image-based reports are actually even more elaborate, even longer, and have much better documentation of what we do. They contain photos just to facilitate communication. And this does not necessarily mean that it will take longer to prepare such a report, because we are talking about some kind of automation here.

Adrianna Sobol: These reports are more detailed and this translates into a sense of security. I’m talking about a sense of security because I’m kind of the voice of the patient. Patients often say with various things in the background that it’s a mistake of the world, it can’t be true, let’s repeat tests. Sometimes it also happens that some tests are already done, but the pathologist says: no, it needs to be repeated again, or specific parameters needs to be measured what again extends this path. And the patient thinks: well, how am I supposed to deal with this?

And still using this example of a woman with breast cancer, how does this precision, using artificial intelligence, translates into the treatment and life of the patient?

Witold Rezner: In the pathomorphology report already very much developed nowadays,we have a number of elements, not only the diagnosis of the tumor itself, the type of cancer, but that’s where it is determined whether the cancer is HER-positive, the status of the receptors. And based on all this information further treatment is planned. This precision of the report and all this information, they are crucial to specific decisions.

Adrianna Sobol: Choosing the right treatment…

Witold Rezner: Yes, choosing the right treatment or deepening the diagnostics. With digital pathology and work on digital images these reports can be much more accurate.

Adrianna Sobol: So maybe we can eliminate something? There is always a margin for error. Can we think of it that way?

Witold Rezner: Definitely. This is what second opinion supported by artificial intelligence is based on, that the artificial intelligence re-checks, or perhaps even pre-scans a given image of a given sample and marks suspicious areas. It marks the areas where the pathomorphologist should pay attention to certain things, so that he/she doesn’t miss anything.

It’s not that artificial intelligence replaces the pathologist at this point, instead it supports her/him.

Adrianna Sobol: This is impossible, I think.

Witold Rezner: I can compare evaluating slides, and this may be even a brutal comparison, but this is my opinion, evaluating slides on a digital image backed by artificial intelligence versus a microscope, is like typing versus typing on a computer in a word processor.

Adrianna Sobol: It sounds like a total revolution.

Witold Rezner: This is my opinion, because digital images can be processed. We cannot process typed text in any way, but if we have a digital image, we can use various additional software. Again the comparison: having something written in a word processor, we can click and the artificial intelligence will translate it for us.

Adrianna Sobol: That sounds great. And it sounds also awkward, because we are talking about cancer. Often when I go into the room, still using the example of a woman with breast cancer, three ladies lying down with breast cancer ask: why don’t we get the same as this lady? I always tell them because this is the progress of medicine when we can, thanks to the work of pathomorphologists and the development of oncological treatment, tailor this treatment appropriately to the particular patient.

Adrianna Sobol: So, as if we were to summarize, you say that the digital reports are much broader and more detailed. What does it mean? So that the patient can understand. What does this give the oncologist who will choose the treatment?

Witold Rezner: For example, if we determine quite an important prognostic factor giving the patient a prognosis, but also predictive showing how the patient may respond to a given treatment. Here I mean the proliferation index, showing how intensively tumor divides, how intensively cells divide, how intensively the given tumor grows. This is a very important factor. To determine this the cells are stained with special antibodies, which are seen later in the image, they stain brown. And these brown dots are counted in a specific defined area. And now it is very important whether, for example, 10% of the cells in that tumor are stained, or 15% of the tumor cells are stained, or 20% is stained. Very important therapeutic decisions depend on it, sometimes whether or not the patient receives a very strong treatment.

Adrianna Sobol: Intensity, frequency of administration of this treatment, all that matter. Also for the patient’s quality of life.

Witold Rezner: Yes. Using digital images, the pathologist supported by an algorithm, can count every one of these stained cells, literally every one. And every non-stained one. So this is a very accurate calculation. And if it is traditional evaluation, under the microscope, then the pathologists estimate what that percentage might be, more or less. As one presents a given sample to several patomorphologists, even very experienced ones, even excellent experts, their evaluations will diverge.

Adrianna Sobol: Because these are estimates. Someone just estimates more or less.

Witold Rezner: On the other hand, the computer will always evaluate and count the same way. Of course the pathologist still has to check, at this stage of technology development, whether what should be counted is being counted, whether there are any technical disturbances in the process. But the process of evaluating this indicator itself is much more accurate. It’s like measuring distance. It used to be measured by steps, but now it is measured by a laser pointer.

Adrianna Sobol: All this is fascinating, because I also know in practice how this translates into managing the disease.

But let’s put digital diagnostics aside for a moment. What should the patient know when receiving the result of histopathological examination? What should she/he pay attention to? What should be included in this report? I understand that there are certain standards, but does it happen that, something was not done for some reason? Or someone did not check something? I don’t want to sound conspiratorial here, absolutely not. It’s more about reassuring the patient that report should include this and that. And if it’s not there, talk to your doctor. I say this because patients like to be in control. They always want to know what else they can do. And I wonder if there is something that is not done as standard.

Witold Rezner: There are relevant recommendations, such as the Polish Society of Pathologists and the patient can check for himself what should be included in the report according to these recommendations.

Well, but of course, we are all human, doctors are also human, pathomorphologists are also human. We work in the required regime,we have the appropriate procedures to help avoid such a situation that the quality of this result is not correct. On the other hand I can also say that there is a subjectivity in the essence of pathomorphological diagnostics. As I mentioned about those experts evaluating staining, it’s simply subjective.

And moving on to a second opinion, it is simply worth, sometimes, or even every time,to get a second opinion and check if these opinions are not different. If these opinions differ, then this can be discussed with the pathologist who gave the original opinion. This is the so-called consensus procedure, very well known in pathomorphology. If there are any discrepancies in opinions, discussion begins, agreements begin, and maybe, some more tests are done.

Everything for the good of the patient. Everything in order to set up the best possible treatment, so that this patient is managed in the best possible way.

Adrianna Sobol: You mentioned a second opinion. This is, by the way, a very important term. And it has been strongly promoted for some time by patient organizations which say: dear patient, when dealing with a doctor, you need to feel comfortable, you need to feel listened to, you need to know what the next steps are. And when you feel uncertain, or simply at the very beginning, before starting treatment, get a second opinion. Not to keep looking for a better specialist, because sometimes this leads to the not starting treatment at all. And we care most about starting treatment as soon as possible.

But the second opinion in the field of pathomorphological diagnostics, when we are talking about the evaluating samples and about a possibility to start whole process in general, I feel that this is an abstract term for most patients. And it turns out that you can get a second opinion also at this stage of diagnostics, of these histopathological tests.

When, for whom this second opinion? How can it be made? If you could tell us few words about it.

Witold Rezner: Until now, pathomorphology second opinions have been performed in the case of diagnostically very difficult tumors. And that was sort of the traditional role of a second opinion, when that diagnosis led to very serious, radical treatment.

But the beginning of digital pathomorphology, in my opinion, expands this range of possibilities of the second opinion a bit, because diagnostics on digital images, diagnostics supported by AI, is still not widely available to patients. And I’m not just talking about Poland, I’m also talking about the European Union, the United States. This is still a technology that is slowly entering, in small steps. And I believe that in some time it will be completely common, but at the moment it is not yet widely available to patients.

Adrianna Sobol: So, we must emphasize that at this point we are only moving toward such a second opinion, although it is already possible. Here, as you can see, there are slides scrolling all the time, for those people who are watching us, not just listening, showing where you can receive such a second opinion.

When is the best time to ask for such a second opinion? I mean not to interfere with the whole treatment process.

Witold Rezner: The point is obviously not to delay treatment and not to disrupt the whole process. And I would also say that there are some diagnostic windows when this second opinion can be implemented. And it doesn’t take so much time. I would absolutely advise patients against dragging out the start of treatment, just to get a second opinion.

Adrianna Sobol: It could be dangerous for them.

Witold Rezner: Therefore, we try to organize our process to be as fast as possible and not to delay the treatment.

On the other hand, there is a certain period of time, even few weeks, from the time the diagnosis is received, until the start of treatment, when such a second opinion can be made. Of course, in consultation with the leading physician, or the entire team, that decides on the conduct of treatment, the treatment of the patient. I believe that there is the time to conduct such a second opinion. And in fact, the first window opens before treatment begins.

Unfortunately, not all patients complete their treatment on the first try.

Adrianna Sobol: First-line.

Witold Rezner: First-line. Unfortunately, some patients will have a recurrence, will have metastasized. And here again…

Adrianna Sobol: A space for deeper diagnostics appears.

Witold Rezner: Yes, diagnostic space. Because in order to plan treatment of advanced cancer, in order to plan second-line treatment, often a very extensive re-diagnosis is performed. In order to diagnose the current state, the current status of the cancer.

Adrianna Sobol: Because the disease can also change morphologically, pathomorphologically.

Witold Rezner: It can and does change. Pathomorphology is one of the levels where it is seen. Here talking about tumors, malignant tumors. We see this pathomorphological image, but this is of course reflected in the biology of this tumor, in the genetics, the interaction of this tumor with the patient’s body. And a lot of this information can be extracted from the image. This is a certain level of information, a certain picture. And it is also worthwhile, such are the tendencies in the world, to evaluate this tumor very carefully, the biological state of this tumor before any further therapeutic step.

Adrianna Sobol: We are at such a stage of development of medicine. Medicine is developing constantly, especially if we look at oncology. Even in this podcast I have already hosted specialists who spoke about personalized medicine. All the time something new is popping up.

I feel that now when we are talking about digital diagnostics this is another novelty that both specialists and patients faces, who, I will use that phrase, sometimes can take charge of it, can do more for themselves.

At the moment, such a second opinion with use of digital diagnostics is not available to all patients. But at the same time your company meets these needs. And if someone would be interested he or she can come to you for a consultation to see if he or she is the right candidate, if this is the right time for that person to do such a second opinion.

Where such patients who are interested can specifically apply? What is your website address? How to contact you?

Witold Rezner: The name of our venture is in English, because we target this service to patients from all over the world. Because, as I said, there are still many patients around the world who don’t have access to digital diagnostics.

The project is called TwiceView – TwiceView.com. It’s like a double look, not only by a second team of pathomorphologists, because at least two pathomorphologists work on a case and sign the opinion, but also a double look of artificial intelligence algorithms, which suggest, point, count. Hence the name TwiceView.

Adrianna Sobol: Great! TwiceView – double look, double vigilance. And again, so that no one here misunderstands it, it doesn’t mean that a machine describes it, it’s a combination of artificial intelligence and of course specialists. And indeed, there are few pathomorphologists and these are high-class specialists, so this is even more a good cooperation.

I invite you all to contact TwiceView.com and take a look at this new technology. For me, this is also a new look at medicine. I have been showing for a long time and many times that this knowledge, this access to modern forms of diagnostics and therapeutics translates very effectively not only into the length of the patient’s life, but also into its quality.

Thank you very much. It was a very important conversation for me,because it really does add hope, what also needs to be emphasized.

Thanks again and please visit TwiceView.com

Witold Rezner: Thank you very much.

Adrianna Sobol: Thank you.