Prof. dr. med. Attila Kovács has over 26 years of experience in treating oncology with interventional procedures. Even more, since 2012, he has been the Head Physician of a Department of Interventional Radiology. The department uses advanced techniques – like TACE – in the complex treatment of different malignancies with focus on liver tumors and liver metastases.
In the interview, Prof. Kovács discusses the role of TACE in cancer treatment: when therapy is most effective, how it's combined with other treatments, its importance in palliative care. He also shares insights on the latest developments in minimally invasive oncology – what patients can expect from this rapidly evolving field.
Hello, Prof. Kovács! Thank you for agreeing to this interview. Could you please introduce yourself?
My name is Attila Kovács. For over 13 years, I have been the Head Physician of the specialized Department of Interventional Radiology, which focuses on interventional oncology and the full range of minimally invasive procedures in interventional radiology and neuroradiology. I have over 26 years of experience performing minimally invasive procedures. During this time, I have gained extensive experience with a wide variety of procedures, ranging from neuroradiological to interventional procedures for oncological and vascular diseases.
At the very beginning of my career, I specialized in cardiac surgery. However, after 4 years in this field, I decided for myself that minimally invasive therapy had much greater potential. And now, 30 years later, my assumptions have been fully justified.
As for my private life, I'm happily married and have two wonderful children. Of course, I'd like to spend much more time with my family. However, that's quite difficult in our profession because we have to respond to numerous patient requests and, of course, devote a lot of time to providing medical care.
We also conduct numerous research projects. This is also part of our work because, ultimately, it is impossible to claim a leading position in this modern and rapidly developing field of medicine without a solid research base.
Science and medicine go hand in hand. Moreover, everyone knows that research is time-consuming, requiring not only a significant investment of time but also a great deal of passion. But the truth is, it's all wonderful, because, fortunately, we all absolutely love it. We don't do it out of compulsion. On the contrary, we truly enjoy our work. We stay up-to-date on the latest developments, which allows us not only to apply advances in our clinical practice but also to partially catalyze them and be personally involved in the development of innovations.
It's truly wonderful to have the opportunity to play a very significant role in shaping such an innovative field of medicine as minimally invasive therapy. That's why, of course, I attend many conferences. Here at the clinic, we also independently conduct at least 20 workshops, and to be more precise, about 25-26 workshops. Furthermore, I am also a certified instructor. This gives us the opportunity to teach a lot to colleagues who want to improve their skills in minimally invasive therapy, which is very valuable to us.
What types of TACE are currently used in your clinic?
TACE (transarterial chemoembolization) is an umbrella term for minimally invasive procedures that involve highly precise local delivery of drugs directly to the tumor site. Since it is an umbrella term, various combinations of drugs and carriers exist. First and foremost, TACE is one of the most successful advances in minimally invasive therapy in recent decades that has become an indispensable tool in modern multimodal, multidisciplinary oncology.
In the case of TACE, we are talking not only about the treatment of hepatocellular carcinoma, but also about a wide range of therapeutic options for various types of tumors in different locations. These options involve a combination of various drugs and various carrier substances, offering a high degree of individualization and adaptation to specific clinical situations.
If we are talking about traditional TACE, liquid carriers are used as carrier substances. If we are talking about DEB-TACE, which is transarterial chemoembolization using electrostatically charged drug-loaded microparticles, embolic microspheres act as the carrier substances. Their advantage lies in their ability to provide a prolonged delivery of the drug to the tumor over a certain period of time – up to two weeks, resulting in an enhanced therapeutic effect.
Our clinic also offers TARE (transarterial radioembolization) or SIRT (selective internal radiation therapy). This treatment involves delivering targeted radiation to the tumor by combining radioactive substances with microspheres, rather than using drugs.
For what types of tumors do you think TACE is currently considered the "gold standard"?
TACE is particularly effective in treating highly vascularized tumors. In professional language, we call these tumors hypervascular.
Initially, this method was intended for treating liver cancer, hepatocellular carcinoma. Today, however, the indications for transarterial chemoembolization have expanded significantly. First and foremost, the procedure is now used to treat other highly vascularized tumors, but it can also be an option of choice for medium and moderately vascularized tumors. This is significant because a paradigm shift has already occurred. This means that TACE is no longer exclusively reserved for the treatment of highly vascularized tumors. With a proper approach to adapting this therapy, it can effectively treat medium, moderately, and even low vascularized tumors.
As for the limitations of TACE, I believe the first one is a significant increase in tumor burden, for example, in the liver. I mean, if the tumor burden is so high that 40-50% of the liver is affected, then hepatic artery infusion (HAI) or chemoperfusion would be better options than TACE. Therefore, targeted drug delivery is necessary to saturate the cancer cells, but without embolization. Alternatively, the aforementioned TARE (radioembolization) procedure can be considered. This treatment approach offers the best results.
How do you determine which TACE option is best for each patient?
Ultimately, there are 4 parameters or 4 criteria that help make this decision.
The first criterion is, of course, the type of tumor diagnosed in the patient. More specifically, the type of tumor that requires treatment.
The second important factor is the degree of tumor vascularization, which we just discussed. This criterion determines the intensity of blood flow to the tumor.
Another important factor is previous treatments, such as systemic therapy or partial surgical resection, for example, of the liver, as well as the number of previous TACE procedures. Ultimately, all of these treatments lead to a decrease in the liver functional reserve, so it is necessary to adapt the TACE technique wisely, taking into account the variety of available options. It is important to note that TACE should not be considered a standard treatment for all cases. Rather, it should be viewed as a valuable tool that can always be adapted to individual circumstances and specific clinical cases thanks to its variety of options.
The fourth criterion limiting the use of TACE or requiring appropriate adaptation is the presence of intratumoral vascular shunts in patients with advanced cancer. These intratumoral vascular shunts are short-circuited connections between arteries and veins. This means there is no capillary bed. Because of this, embolic microspheres or even liquid embolic agents can ultimately migrate uncontrollably through these shunts into the venous system and end up in areas of the body that are normally free of both drugs and embolic agents. In cases with these shunts, the TACE procedure must be adapted accordingly, or alternative methods must be considered.
What is the role of imaging studies (for example, CT, MRI, DSA) in TACE planning and monitoring?
Imaging methods, especially advanced technologies, are of enormous importance, and their role cannot be overstated. This question is beyond the scope of this interview, but I'll try to highlight a few key points.
Unlike conventional surgery, interventional therapy lacks tactile control. Therefore, treatment planning before interventional procedures must be performed with such precision that one can virtually understand how to access the tumor or lesion and how to best deliver the necessary treatment through imaging. In particular, when preparing for TACE, it is important to determine which blood vessels can be used to access the tumor.
With adequate pre-interventional imaging, doctors can determine which blood vessels to access to reach the pathological focus. They can also determine if one or several blood vessels are needed to approach the tumor and whether the organ has a standard anatomical structure or any peculiarities.
The next crucial step is to define the tumor boundaries precisely. Some imaging techniques reveal only the central necrotic core of the tumor. This is the area where cancer cells cannibalize themselves. Does this area require therapeutic procedures? No.
The infiltration barrier around the tumor is much more important. This is the so-called "battlefront," where cancer cells attempt to invade adjacent healthy tissue and where the body's immune system attempts to stop this invasion, known as infiltration. It is in this zone that we consciously want and must conduct therapy. To do so, we need adequate imaging methods to determine the boundaries of this zone. Is it wide or narrow? This is closely related to the subsequent therapeutic effect and treatment outcomes.
We have been teaching this discipline for over ten years now, and I am very happy that there is now an understanding and awareness that such an infiltration zone should be considered not only as a treatment target but also as an "ally" of minimally invasive therapy in general.
Finally, imaging techniques play a crucial role in analyzing and monitoring treatment efficacy to determine if the lesion has been adequately and completely treated as planned. Imaging also helps monitor treatment results over time to ensure local control and to rule out tumor recurrence or new metastases elsewhere.
In what cases do you combine TACE with other local ablative procedures (for example, RFA or MWA) or systemic therapy?
Various minimally invasive treatments are often combined. For example, endovascular procedures such as TACE are increasingly combined with percutaneous methods and local ablation procedures. The ultimate goal should be achieving local tumor control, rather than simply relying on a single treatment option and hoping for the best outcome. We need to think more broadly. Our goal is to achieve optimal local tumor control. This can be done by combining two or even three different procedures.
The classic indication for combining TACE with thermal ablation, radiofrequency ablation, or microwave ablation is, of course, large hepatocellular carcinomas, which, due to their large size, are no longer treatable with thermal ablation alone. This means that devascularization and tumor shrinkage ultimately allow for additional thermal ablation, ensuring reliable tumor control that would otherwise be impossible without prior tumor reduction therapy.
At the same time, we know that combining such endovascular percutaneous procedures can achieve effective results in treating other tumors. For example, this approach is effective in treating liver metastases from colorectal cancer.
Another point is that systemic and endovascular chemotherapies complement each other perfectly. For example, if a patient has multiple liver metastases and most of these metastases respond to systemic therapy, while a small portion do not, it can be assumed that a specific mutation has occurred that ultimately causes resistance to systemic therapy.
In this case, it makes sense to perform TACE without making radical changes to systemic therapy. If only a small proportion of metastases are known to be resistant to systemic therapy, they can be effectively targeted with TACE.
Therefore, we definitely cannot abandon multimodal imaging. It's a key component of the process. For this reason, we also advocate that imaging tests, treatment, and subsequent follow-up care should ideally always be performed by the same specialist. There's no point in performing standard diagnostic examinations that ultimately offer little insight into planning further treatment. And it's even less practical to perform only a few necessary follow-up examinations that ultimately fail to fully assess the success of the treatment.
Ideally, one specialist should oversee all stages, which provides a structure for managing the entire treatment process. Patients always welcome this approach because they themselves, their families, loved ones, and everyone involved in the therapeutic process know there's a specialist who is aware of what's been done and what remains to be done.
Based on your experience, what other types of tumors respond well to TACE besides hepatocellular carcinoma (HCC)?
TACE is particularly effective not only for hepatocellular carcinoma. We now know that this procedure is also very successful in treating other tumors, including bile duct cancer, neuroendocrine tumor metastases, as well as breast cancer and melanoma metastases, and, last but not least, – I mention this because the incidence of this type of cancer is steadily increasing, – liver metastases of colorectal cancer.
I strongly recommend paying special attention to this very point, because due to cultural dietary habits, we are increasingly seeing young patients, I would even say very young patients with colon cancer who already have metastases in the early stages, even though they are very young. This raises the question of what factors could trigger such an aggressive malignancy.
We're not dealing with a typical disease of old age. This type of cancer is increasingly being seen in young and, unfortunately, very young patients. This week, we had a German patient born in 1987 who was an athlete and a vegetarian. The logical question is, "Why is this happening?"
Are there any specific criteria that you use to rule out the possibility of performing TACE for a particular patient?
There are some exclusion criteria. First and foremost, we take into account the tumor burden on the liver. If 40-50% of the liver is affected by the tumor, the TACE procedure cannot be performed effectively in the usual manner without increasing the risk of liver decompensation or liver failure.
Another reason is the creation of biliary anastomoses, for example, after certain surgical procedures or the placement of bile duct stents. In this case, when performing the TACE procedure – leading to the devascularization of liver tumors, which is essentially the desired treatment outcome – the risk of secondary infection through the bile ducts via these biliary anastomoses and stents significantly increases.
If a bile duct infection (cholangitis) ultimately leads to inflammation, it requires urgent treatment because the patient suffers from pain. This almost always delays ongoing cancer treatment. This means a significant gap or pause in cancer therapy, which is certainly something we want to avoid.
The same applies to patients with cholestasis. If the bile ducts are dilated, the classic TACE procedure should be performed with special caution because, unlike the liver, which has a dual blood supply, the bile ducts have only an arterial supply. Thus, performing TACE in this situation may ultimately worsen cholestasis and contribute to its progression.
How are patients with reduced liver function or portal hypertension who are candidates for TACE treated?
For patients with reduced liver reserve or function, as well as portal hypertension, the TACE procedure must be tailored to their individual needs. This is absolutely essential. The good news is that it's possible to perform TACE in these cases.
The first option is to perform TACE with maximum selectivity or even superselectivity, targeting only tumor-affected regions while minimizing damage to healthy liver tissue. Another option is to reduce the dosage of current medications or switch to alternative drugs.
Moreover, it's crucial to choose the right embolic agent from the wide variety available today. In recent years, temporary embolic agents have become increasingly popular, and for good reason. These embolic agents are mixed with a drug or loaded with medication in the form of microspheres. These microspheres temporarily occlude the vascular bed, meaning they only exist for a limited period of time.
The exact duration of action ultimately depends on the specific drug. For example, vascular bed occlusion may last only a few minutes, resulting in blocked blood flow through the targeted vessels for several hours or days. This allows for an effective treatment that spares healthy liver tissue while accurately assessing the patient's liver reserve.
What is the role of TACE in multimodal treatment regimens? For example, can it be used as a bridge therapy before a liver transplant?
TACE is an established bridge therapy for patients awaiting liver transplants. The main problem with liver transplants is that existing liver damage can lead to a decline in liver function at varying rates. This often results in patients not surviving long enough to receive a donor organ.
One of the factors that predetermines or determines this is the number of metastases, or, in other words, the degree of tumor burden. This means that if it is possible to reduce the tumor burden or shrink the size of hepatocellular carcinoma using the targeted TACE procedure, more time can be gained until a liver transplant is performed, with the hope that the patient will ultimately survive in good health until receiving the donor organ.
Furthermore, the lower the tumor burden on the liver to be replaced, the better the results will be after the liver transplant.
Do you use TACE in palliative care, and if so, for what purpose?
TACE plays an incredibly important role in palliative care for cancer patients. When patients receive palliative care, which means a cure for cancer is impossible due to the current clinical situation, two things ultimately matter most to them: prolonging life expectancy and maintaining quality of life.
Clearly, increased life expectancy is achieved through local tumor control. When cancer affects multiple organs, metastasis or the spread of secondary tumor foci to vital organs always occurs, and this often occurs to the liver. Targeted treatment is available for these metastases, which can compress the bile ducts, inferior vena cava, and so on. Of course, we can't influence other secondary tumor foci in the body, but we already have a solution to this serious problem: we can eliminate metastases from this vital organ.
Quality of life is primarily determined by symptom management. If certain metastases cause pain, such as those affecting the pleura, liver capsule, or bone, then this pain becomes the determining factor for the patient, which clearly has a major impact on their quality of life.
When the pain disappears, cancer patients live with the knowledge that they have been diagnosed with a malignancy, yet their quality of life remains unaffected because they are no longer in pain. This is a crucial aspect of palliative care that, through the expert and professional use of minimally invasive procedures – not only TACE, but also cryoablation, electrochemotherapy, and perineural infiltration – it is ultimately possible not only to prolong the patient's life but also to improve its quality.
In short, yes. Minimally invasive treatments – and I'm referring to the full range of such procedures – definitely play an extremely important role in palliative care. Unfortunately, this very fact is very rarely considered in everyday clinical practice, as experience shows, especially when it comes to colon cancer. In our practice, we have seen many patients who survived for an additional 10 years thanks to interventional treatment, whereas systemic therapy would have only extended their life expectancy by 17 months. Extending a patient's life by more than a year versus more than 10 years makes a huge difference. Furthermore, this treatment ensures a good quality of life. This is a crucial factor that we should always discuss openly with patients, which is exactly what we do at our clinic.
I also have a patient who was initially given a "poor prognosis" but still completed her first round-the-world trip. She has now completed 4 such trips, and we continue to receive postcards and photographs from her travels. That's the essence of it all!
We don't know what the near future holds for multimodal cancer treatment, and no one does, including the experts. In this context, it's crucial to get through this transitional period, during which we must bring patients to a point where new medical advances are available for them. If we succeed, the benefits will be enormous. Given our current understanding of and resources for cancer treatment, it's simply impossible to imagine them remaining the same in the next 5 years.
Are there any new TACE developments or studies that you find promising?
There are now a huge number of publications on this topic, so I suggest we focus on a specific and extremely relevant issue – the treatment of colon cancer metastases.
Not long ago this year, the European professional association CIRSE published data from a targeted registry study in which we demonstrated that the TACE procedure provides highly effective results for metastatic colorectal cancer. Furthermore, it is effective not only in advanced stages but also when used in combination with systemic therapy, as previously mentioned, as well as in combination with local ablative therapies.
I'd also like to remind you that more than 10 years ago, 11 years ago to be exact, the results of a prospective randomized trial conducted by a research group led by Giammaria Fiorentini and his colleagues from Italy were published. The trial compared local TACE therapy and systemic therapy for early-stage metastatic colorectal cancer. They demonstrated that overall survival, progression-free survival, and treatment tolerability were significantly better with TACE.
This is often overlooked, but I always emphasize it in my training workshops and conference presentations. It would be a shame if the results of this prospective randomized trial were simply forgotten due to negligence, because they confirm the effectiveness of TACE. Personally, I'm always willing to dig deeper.
I would also like to highlight the results of our own study: we studied the effectiveness of TACE for colorectal cancer liver metastases in patients with primary tumors located in the right and left colon. In most patients – 80-85% of cases, to be precise – the primary tumor was located in the left colon. It was in this group of patients that we managed to at least double the survival rate. An important finding is that, especially in cases of primary tumors located in the left colon, that is, in the descending colon and sigmoid colon, TACE should be performed as early as possible. This is because timely repeating TACE significantly benefits patients, as our personal clinical experience confirms. Some of our patients have survived metastatic disease for over 10 years.
What advances do you see in the coming years in the development of embolic microspheres, carriers, or combination therapies?
As in the recent past, we anticipate numerous innovations in the near and medium term. And that's exciting! Significant changes are currently taking place in the field of minimally invasive cancer treatment.
First of all, I'd like to note the significant advances in microcatheter production technology. We're already seeing that these improved technologies allow us to access tumors more quickly and with greater precision. These improvements will continue in the near future. Catheters are becoming increasingly more controllable and even thinner, ultimately allowing us to more effectively provide a superselective approach to specific vascular structures.
Occlusion catheters also play an important role in this regard because they can prevent embolic materials from entering healthy blood vessels and body areas. In other words, they prevent non-target embolization.
As previously mentioned, technologies for producing microspheres for embolization are also significantly improving, with temporary embolic microspheres appearing on the market. Consequently, compared to previously used embolic materials, microspheres are now not only manufactured to extremely precise parameters, i.e., they have the same diameter and volume, but also have different disintegration times.
Well, we now have a very diverse arsenal of tools that greatly help us treat patients, although these capabilities were unavailable to us not long ago. Therefore, now more than ever, it makes sense, and I sincerely encourage colleagues working in this field of medicine to attend conferences and advanced training courses. So much is happening right now that the knowledge we had 10 years ago is simply insufficient. It's impossible to make much progress with that knowledge. Moreover, it's impossible to provide patients with the individualized treatment and good therapeutic results they rightfully demand.
Finally, the last point I'd like to touch on is combination therapy. As mentioned previously today, the goal of treatment is to achieve optimal local control of a tumor in a specific location using one or more modalities, in other words, combination therapy. This treatment combines endovascular and percutaneous procedures and isn't limited to TACE combined with RFA and microwave ablation, which is already a common approach for treating certain tumors, as we discussed previously today.
In 2017, we developed electrochemotherapy together with other specialists, which quickly became one of the most effective and well-tolerated methods for treating large tumors and metastases. According to our publications this year, combining endovascular procedures with electrochemotherapy provides even more effective results. Our study found that this combination therapy achieves tumor control and complete or partial remission in 94% of cases.
Does artificial intelligence or automated image analysis currently play any role in the planning or follow-up of TACE procedures?
In the near future and in the future in general, artificial intelligence will play an invaluable role in minimally invasive therapy and interventional oncology.
Clearly, interventional oncology will be impossible without artificial intelligence. We expect and hope to achieve more accurate tumor boundary determination in the near future using artificial intelligence, as we've discussed previously. This is a crucial factor, ultimately determining recurrence rates and local tumor control.
It may sound bold, but someone who can clearly see the tumor boundaries is already on the path to achieving local control over the neoplasm.
This is extremely important. We need to acknowledge that, unfortunately, in this regard, our optical perception is effectively limited to shades of gray, but we simply cannot demand more from our eyes and visual system. Therefore, AI can help us with this. AI is a huge asset, especially in fields such as interventional oncology. This field is certain to undergo many more changes.
What happens during follow-up after TACE, and how is treatment effectiveness assessed?
Structured processes play a vital role in everyday clinical practice. That's why meticulous work was undertaken to develop protocols for planning interventional procedures, their performance, and patient follow-up after this treatment. These protocols have been developed and constantly refined over the years. Of course, they will continue to improve as innovations are introduced.
You just need to think of it as a workflow. Several points are particularly important here. First, peri-interventional drug therapy is administered immediately after therapy, primarily aimed at minimizing or eliminating the symptoms of post-embolization syndrome after TACE. Second, the early postinterventional phase involves the monitoring of the effectiveness of therapy, during which we aim to see complete tumor necrosis in the target area. A follow-up MRI is performed 48 hours after the procedure. This period of time is required for complete tumor disintegration and necrosis.
Subsequently, other follow-up examinations are performed, also using MRI. In this regard, we have a very clear protocol for follow-up MRI examinations because we know that CT is unable to fully assess tumor burden, and we need accurate results. Multimodal magnetic resonance imaging, or multiparametric magnetic resonance imaging, is a significantly better diagnostic method in this regard. As for follow-up examinations at regular intervals, they naturally serve not only to monitor local tumor control but also to exclude recurrences or the development of new metastases in the affected organs.
What role do you think interventional oncology methods will play in cancer treatment in the long term? Will they complement or replace conventional treatments for certain indications?
Over the past decades, interventional oncology has established itself as the fourth pillar of multimodal, interdisciplinary cancer care. Alongside oncohematology, surgery, and radiation therapy, interventional oncology has now become the fourth pillar. This is obvious and undeniable. This is due to the extremely rapid development of this field of medicine and emerging innovations, both in endovascular and percutaneous interventional procedures. New procedures are becoming increasingly precise and sparing.
Ultimately, we are moving toward minimally invasive oncology and, in part, toward the use of non-contact (non-invasive) procedures, such as histotripsy. We know that minimally invasive procedures are already replacing conventional treatment methods. This is especially in the early stages of cancer, when tumors are detected quite early, in their nascent stage, so to speak.
Also, for example, the effectiveness of ablation procedures for liver cancer (hepatocellular carcinoma) or kidney cancer (renal cell carcinoma) is comparable to the results of surgical tumor removal, but in this case, patients experience significantly fewer side effects.
This means that in such cases, minimally invasive therapies can already replace conventional treatments for early-stage cancer. For advanced stages of cancer, such as oligometastatic cancer, when the patient has a limited number of metastases, minimally invasive treatments offer significant benefits.
Numerous studies, such as that by Prof. Klok from the Netherlands, show that combining ablation and systemic therapy increases the survival rate of colon cancer patients by four times after 8 years of having the disease, which means that not after 4 weeks or after 4 months, but after 8 years of having the disease, four times more patients survive with the combination therapy than with systemic therapy alone. First, you need to understand and interpret this information for yourself.
This is why I keep saying that minimally invasive methods are indispensable to modern multidisciplinary treatment, at least for ethical reasons, and their use should never be ruled out. Therefore, all interdisciplinary tumor boards should also include interventional oncology specialists who can provide their recommendations about the advisability of multimodal therapy.
I would like to appeal to specialists, to all oncology experts – hemato-oncologists, surgeons, and radiation therapists – to promptly and early use of minimally invasive treatments in a multidisciplinary setting. Clinical experience shows that patients seek our help eagerly, but often too late. This is a decisive factor in these situations because, unfortunately, even minimally invasive treatment options are limited in the advanced stages of cancer.
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