Surgery, radiotherapy and drug therapies are the three important components of oncological treatment. Depending on each case, the disease stage and the location of malignant tumors, physicians recommend the association of several types of therapies, including surgery, chemotherapy, targeted treatments and immunotherapy, and last but not least, radiotherapy belts. Radiotherapy has evolved greatly over the last 20 years due to advances in technology. Physicians today work with advanced devices that allow the application of radiation doses with the utmost accuracy, with fewer side effects, protecting the healthy tissues around the tumors and with the possibility to monitor in real time the application of the radiation beam according to the body’s physical processes breathing or blood circulation. One of the world’s top specialists working with the latest radiotherapy technologies is Prof. Dr. Ufuk Abacioglu, who works with ACIBADEM hospitals. The doctor has over 25 years experience in radiotherapy, and today he works with the best technologies in the treatment of cancer patients. New devices and protocols manage to prolong life expectancy even in advanced stages of disease, with metastases, in cases that could not be treated 10 years ago. Here’s how Prof. Dr. Ufuk Abacioglu continues to describe advances in advanced radiotherapy, available at ACIBADEM clinics for patients around the world.
Prof. Dr. Ufuk Abacioglu: In the last 10 years, much progress has been made in cancer radiotherapy. We talk primarily about how this is being managed, but also about how it is going. Thus, during treatment, a lot of things happen: patients go through daily treatment sessions, but every day there may be major changes in the body. Tumors can be reduced, the patient’s body can go through transformations, vital organs near the tumor can change their position. We, as doctors, must consider all these possible changes. Thus, if the tumor decreases, we need to adjust radiation therapy and doses. These are what we call “adaptive treatments”. Thus, the treatment plan adapts and changes according to the changes occurring daily, the radiation doses being adjusted according to the volume changes of the treated tissues. If these adjustments are not made, treatment can no longer be applied correctly. Therefore, adaptive treatments are one of the major changes in radiotherapy. Another major change is what we call fractional therapy. Normally, in the human body, permanent changes occur due to breathing, pulse, digestion. Obviously, they also occur during therapy. Thanks to modern technology, we can apply high doses of radiation to each fraction, considering intra-fracture changes. In the past, I used different markers, which I drew on the surface of the body, for example, and I then followed them in infrared. Or we insert some markers into the tumor tissues and guide us through X-ray therapy, for example. But now we have the possibility to monitor all the changes, all the movements that occur in the area to be treated by using magnetic resonance. Thus, one of the most important improvements is the combination of radiotherapy with imaging guidance provided by magnetic resonance. This is one of the recent developments, and at ACIBADEM we started using MR Linac technology as early as September 2018. So far, we have treated more than 60 patients and most of the tumors have been located in the abdominal area, pelvis or chest. In addition, the technology that uses magnetic resonance allows us to see the tumors much better. Most cancers are actually soft tissues that can be visualized and monitored very well by magnetic resonance. For example, in patients with liver cancer or liver metastases, in the past, we were making a computer tomography exam to determine treatment targets, but it was difficult to visualize metastases. Now, we get better images with magnetic resonance and we can see the targets, the liver tumors much more accurately and we apply the radiotherapy according to the new imaging. Ultramodern imaging for accurately setting the targets for radiotherapy is now based on magnetic resonance.
Prof. Dr. Ufuk Abacioglu: Yes. For example, in the case of a primary pancreas tumor, if it is not resected through surgery or if there is an associated problem that prevents resection, we can apply radiotherapy to increase the chances of tumor resection. These are patients who can benefit from local high-dose radiation treatments. Recently, we have begun to apply these therapies in 5 fractions to these types of patients. That means the treatment ends in two weeks. At this time, we select patients who can get the most out of this type of therapy. We usually start with chemotherapy, and after 3 or 4 cycles of chemotherapy, we evaluate the patient. If the disease is limited in the pancreas, then we apply the treatment. If the disease is disseminated or does not respond to chemotherapy, then we do not apply radiotherapy.
Prof. Dr. Ufuk Abacioglu: Today, all modern radiotherapy technologies and methods are available in many hospitals around the world, including ACIBADEM hospitals. The choice of each type of technology and radiotherapy is made personalized, depending on the benefits it has for each patient. For example, we opt for tomotherapy in patients who have large tumor volumes, such as, for example, the cranial or spinal cord or those diagnosed in children. There are brain tumors for which the entire skull and even the first part of the marrow must be irradiated: in these situations, we opt for tomotherapy. Tomotherapy makes a spiral treatment that can cover the skull and its base, where the marrow begins. We apply it to cancers that affect children such as medulloblastoma. In TrueBeam, we have several possibilities: we can apply fractional stereotactic radiotherapy or fractional radiosurgery. We use the 6-dimensional correction system that helps us irradiate a cancer with a 0.5 mm accuracy. Usually, we prefer to apply small volumes of irradiation with TrueBeam. As for CyberKnife, we can apply fractional stereotactic radiotherapy for both cranial locations and other locations. With Gamma Knife, the newest version of ICON, we have the flexibility to apply performance treatments using only thermoplastic masks, which helps us apply more than one irradiation fraction at a time. In the past, we could only apply a fraction, and the volume we could handle was limited to 3-4 cm in diameter. Now we can handle larger volumes by applying 3 or 4 fractions. Gamma Knife is a robust solution for many brain tumors and for small volumes located close to critical structures.
Prof. Dr. Ufuk Abacioglu: This is a very good question. In the past, radiotherapy was only applied to patients with metastases who had severe symptoms and needed to be treated palliatively. For example, if they had bone pain, we would use palliative radiotherapy doses. If they had bleeding, they were having radiotherapy applied to stop the bleeding. But in recent years, we have noticed that some of the patients to whom we apply aggressive local therapies have a longer survival rate, sometimes the same as patients who do not have metastases. The first evidence came from the area of colorectal cancers treatment: for example, we have a patient who has been treated with a primary colorectal tumor, but then over time developed liver metastases. If these are removed, patients may have a long-term survival rate, the same as patients without hepatic metastases. Or if they have primary tumors and metastases at the same time, they can be removed, and patients may have the same time prognosis as patients without metastasis. These patients now fall into the category called “oligometastatic”, meaning there are some metastases, up to five, up to 2-3 organs, so dissemination is not major. In these patients, the therapeutic attitude is more radical. Of course, it is not always possible to cure all these tumors, so we are using stereotactic radiotherapy programs if they have a limited number of tumors and metastases. For example, there are patients with prostate cancers and bone metastases that are treated both systemically and locally by radiotherapy, and life expectancy may increase. Lately, some studies have been published showing a better survival rate in these patients than those who are only palliatively treated: groups of palliatively treated patients were compared with groups treated with more radical therapies, and preliminary results have shown that patients treated more radically can live longer.
Prof. Dr. Ufuk Abacioglu: Exactly. With the help of new technologies, we can apply large doses, much more precisely, with a good coverage of the target treatment area, with fewer side effects on the internal organs near the tumors.
Prof. Dr. Ufuk Abacioglu: For example, let’s say we have a patient with an abdominal metastasis in a lymph node or near the intestines, which are very sensitive organs from the radiotherapy point of view. High doses of radiotherapy involve a major risk of perforation, which may be a lethal complication. In these patients, MR Linac technology enables us to monitor intestinal movements from day to day and during treatment. Thus, with the help of advanced imaging, we carefully monitor the position of the intestines, and if they move in the area we treat, the application of radiation stops automatically. We adjust the parameters again accordingly to the new data, and the therapy can be resumed. With the help of new technologies, we can apply radiotherapy to breathing and abdominal movements: the patient has a strong inspiration, breathing for a few seconds, and during this time we apply radiotherapy. In the past, we could only look at the external markers. Now, with the help of MR Linac, we can accurately assess the position of the tumor and, depending on breathing and physiological movements, apply radiotherapy with great precision. So, it increases the accuracy of radiotherapy, even in patients who have tumor sites in delicate areas.
Prof. Dr. Ufuk Abacioglu: I have been working on oncology radiotherapy for more than 25 years. I remember that in the past, we were just guided through the markings we made on the patients’ skin and we could not make simulations of treatments. Now, we can consider many details. Basically, the doses we apply now were impossible to conceive then. Gradually, progress has been made in both radiology and computerized technology. Thus, radiotherapy has improved, and the success rate of treatments has increased over the years. Now, we have a probability of controlling tumors of over 90 percent in patients receiving high doses of radiation. Even large tumors respond very well to radiotherapy. In the past, we could not do this: for example, in lung cancer, we started treatment, lasting for 8 weeks, but during this time, the patient could develop metastases. I mean, it was almost in vain. Also, improvements in systemic treatments, chemotherapy, targeted therapies and immunotherapy have also increased implicitly the success rate of radiotherapy if co-administered with drug treatments. The effect is much better if we combine them. On the other hand, in some cases, the application of radiotherapy before immunotherapy, increases the chances for the patient to respond well to it. In recent years, studies have been conducted on the effects of combining oncological therapies. For example, in cervical, lung, head and neck cancer, in the case of brain tumors, combinations of drugs and radiotherapy are used. And the efficacy is higher than if we applied them separately.
Prof. Dr. Ufuk Abacioglu: The therapy period may be shorter for many patients. Let’s take the example of prostate cancer. In the case of localized cancer, radiotherapy lasts for 8 weeks. So, the patient came for two months for 40 treatment fractions. Today, in some patients, we can apply the treatment in 5 fractions, which implies a radically beneficial change for the patient. The patient only comes for two weeks, the toxicity is very low, and the results are similar. There are studies done over the past 5 years that compared the results of two-month treatments with the shortest, five-stage treatments. And this research continues to see what the long-term results are. In some patients, the number of fractions and the treatment period may be reduced. I think that in the future there will be more and more patients treated with a small number of fractions.
Prof. Dr. Ufuk Abacioglu: Maybe not through radiotherapy, but maybe through other means, through vaccines. In terms of radiotherapy, imaging techniques – such as body surface tracking with cameras or tracking of the target area of treatment – are likely to be further improved. Combined, we could make a 3D model of the patient that could guide us in the application of radiotherapy. Highly guided application of radiotherapy is extremely important: at present, magnetic resonance imaging in radiotherapy helps us a lot. Magnetic resonance integrates with radiotherapy, and although the magnetic field and radiation can interfere, the development of technology allows the existence of the two technologies in the same therapy room.