1 00:00:05,166 --> 00:00:08,432 Good afternoon, ladies and gentlemen, my name is Oliver Jäkel 2 00:00:08,433 --> 00:00:11,733 and I am head of the Medical Physics Department in Radiotherapy. 3 00:00:11,733 --> 00:00:14,833 And that is also the title of my presentation, 4 00:00:14,833 --> 00:00:17,966 in which I would like to explain the basics of radiotherapy, 5 00:00:17,966 --> 00:00:21,166 and, above all, the question of the role of physics 6 00:00:21,166 --> 00:00:24,366 actually plays in radiotherapy. 7 00:00:24,366 --> 00:00:27,532 First of all, a brief answer to the question of why this International Day 8 00:00:27,533 --> 00:00:30,733 of medical physics 9 00:00:30,733 --> 00:00:36,766 on November 7 of each year? This has to do with the fact that Marie Curie was born on this day. 10 00:00:36,766 --> 00:00:42,966 Marie Curie is considered one of the first medical physicists, not in the modern sense, of course, 11 00:00:42,966 --> 00:00:48,932 but she was a pioneer in many areas of radiotherapy, particularly through her research 12 00:00:49,200 --> 00:00:55,200 and her research in the field of radioactivity and the subsequent use of radioactive substances for 13 00:00:55,200 --> 00:01:01,266 for the treatment of tumor diseases. She was just born on November 7. You may know 14 00:01:01,266 --> 00:01:04,499 She was awarded the Nobel Prize. She was the first woman ever to win a 15 00:01:04,500 --> 00:01:07,733 Nobel Prize, for physics in 1903, 16 00:01:07,733 --> 00:01:14,299 and she is one of only two people to have won another Nobel Prize in a different subject. 17 00:01:14,300 --> 00:01:20,733 In this case, it was in chemistry. The Curie family was interesting in that respect, 18 00:01:20,733 --> 00:01:27,133 because her husband, Pierre Curie, who did research with her, later received the Nobel Prize, as did her daughter, 19 00:01:27,133 --> 00:01:33,166 Iréne Curie, later received a Nobel Prize. So a real Nobel Prize family. 20 00:01:33,166 --> 00:01:39,366 The use for medical applications is not only in the field of radioactivity, but Mrs. Curie 21 00:01:39,366 --> 00:01:46,266 was also involved in the First World War and helped to build so-called mobile X-ray vans. 22 00:01:46,266 --> 00:01:52,299 and deployed them in the field, so that it was possible to examine the wounded on site. 23 00:01:52,300 --> 00:01:59,200 to examine them. And that is also the reason for their role model function in the field of medical physics. 24 00:01:59,200 --> 00:02:02,400 But back to the tumor diseases and the questions, 25 00:02:02,400 --> 00:02:05,633 that we want to deal with here, and first a few figures, 26 00:02:05,633 --> 00:02:11,866 What role do tumor diseases play in Germany? We have about half a million new cases 27 00:02:11,866 --> 00:02:18,732 every year, which is a very significant number. And this number is growing every year, so we have an increase that is 28 00:02:18,733 --> 00:02:24,833 is about 3%, even a little more than 3%, so that may not sound like very much, 29 00:02:24,833 --> 00:02:31,066 but if you think about it, in 10 years that's already 30%, in 20 years 60%, so a considerable increase. 30 00:02:31,066 --> 00:02:37,099 And there is not really any reason to assume that this increase will be smaller, and why that is so, 31 00:02:37,100 --> 00:02:43,133 I'll get to that in a moment. This stronger increase worldwide is mainly due to the development in those countries, 32 00:02:43,133 --> 00:02:49,499 that have not yet developed so far, i.e. the so-called “Third World”, where people are clearly 33 00:02:49,500 --> 00:02:55,866 more tumors because medical care is getting better and people are getting older. 34 00:02:55,866 --> 00:03:02,066 In Germany, the increase is somewhat lower, at just under 2%, but still a very significant figure. 35 00:03:02,066 --> 00:03:08,299 You can roughly say that about half of people today will develop a tumor disease in the course of their lives. 36 00:03:08,300 --> 00:03:14,833 will have a tumor, slightly less in women, 43%, slightly more in men, and that sounds 37 00:03:14,833 --> 00:03:21,033 sounds like a lot at first, but the good thing is that the survival figures are also increasing. 38 00:03:21,033 --> 00:03:27,333 For example, the 5-year survival rate has risen continuously in recent years. Today we have more than 60% 39 00:03:27,333 --> 00:03:33,599 probability of survival for five years, and that is a standard value. After five years, you usually say, 40 00:03:33,600 --> 00:03:40,100 the tumor has been cured, because of course you can't follow patients for as long as you like. 41 00:03:40,100 --> 00:03:46,300 The survival rate is significantly higher for women, again 66%, than for men, 62%. But that is also, if you look at the 42 00:03:46,300 --> 00:03:52,500 10-year survival rates, it's also quite considerable, at over 50%. So that's 43 00:03:52,500 --> 00:03:58,700 are definitely positive figures, and they continue to show an upward trend. Tumor diseases are still 44 00:03:58,700 --> 00:04:05,366 cardiovascular diseases, which account for just over a third of illnesses, tumors are not the most common disease, but the 45 00:04:05,366 --> 00:04:11,666 causes of death, I should say, followed by tumor diseases at 22%. So the 46 00:04:11,666 --> 00:04:17,999 Tumor diseases are a very important factor in the mortality of our population. 47 00:04:18,000 --> 00:04:24,133 These are figures from the Robert Koch Institute, they keep producing reports like this, this is the latest report from 2023. 48 00:04:24,133 --> 00:04:30,533 Here you can see the reason for the development of these tumor disease figures, 49 00:04:30,533 --> 00:04:36,566 And this is simply because we are getting older and older. And that doesn't just apply to our western industrialized nations, 50 00:04:36,566 --> 00:04:42,932 but actually for all parts of the world's population. And you can see that this trend has been 51 00:04:42,933 --> 00:04:49,599 over 80 years and there is still no change in sight. There are always short interruptions 52 00:04:49,600 --> 00:04:56,300 due to certain events in crises, even the last few years there has been a small disruption 53 00:04:56,300 --> 00:05:02,533 due to the corona pandemic, but the numbers are already on the rise again, so life expectancy is still increasing 54 00:05:02,533 --> 00:05:08,733 especially in Central Europe. That simply means people are getting older and the older people get, the 55 00:05:08,733 --> 00:05:15,066 higher the probability that they will develop a tumor. And that is precisely the effect that we are now 56 00:05:15,066 --> 00:05:21,399 are also seeing in Africa, for example. The nutritional situation is improving and medical care is also improving, 57 00:05:21,400 --> 00:05:27,900 despite all the bad news, but people are getting older there too, and that really does mean a considerable 58 00:05:27,900 --> 00:05:34,100 growth rate in tumor diseases. Which is actually a considerable problem 59 00:05:34,100 --> 00:05:40,366 in a global sense, if you extrapolate this over the next few decades. Here you can see this again for women 60 00:05:40,366 --> 00:05:46,399 and men graphically plotted as a function of age, the risk of suffering a tumor disease. 61 00:05:46,400 --> 00:05:52,533 And then you can see that this typically increases significantly after the age of 50, 62 00:05:52,533 --> 00:05:58,599 and then reaches its maximum at around 80. And then, of course, it goes down again somewhere, when, so to speak 63 00:05:58,600 --> 00:06:05,000 life simply comes to an end anyway. So in total, of course, it can't be more than 100%. 64 00:06:05,000 --> 00:06:11,300 But you can also see the difference here: the rate for women is actually much lower than for men, 65 00:06:11,300 --> 00:06:17,366 this is also a general trend. Here are a few more figures on the cause of tumor diseases, 66 00:06:17,366 --> 00:06:23,666 which I would simply like to mention here and must also mention here at the DKFZ. It is indeed the case that the most common 67 00:06:23,666 --> 00:06:29,699 preventable cause of cancer is still smoking, and has been for many years. That is still the case. 68 00:06:29,700 --> 00:06:35,866 That's why smoking prevention is still a big issue. And unfortunately it has to be said that here in 69 00:06:35,866 --> 00:06:43,666 Germany is in a very bad position internationally, so there is a lot of catching up to do in terms of advertising for 70 00:06:43,666 --> 00:06:46,966 tobacco products, etc., as well as non-smoking protection in general. In 2007, which is already somewhat older 71 00:06:46,966 --> 00:06:50,299 figures, as only I have an order of magnitude, 72 00:06:50,300 --> 00:06:56,333 has, 5.4 million people died as a result of smoking, that's one in 10 deaths worldwide. So that 73 00:06:56,533 --> 00:07:03,033 are quite remarkable figures, which is also impressive if you look at the statistics, 74 00:07:03,033 --> 00:07:08,933 these are American figures, which are once called the blue curve, the consumption of cigarettes, 75 00:07:09,366 --> 00:07:15,366 Prokop. Laue fￃﾼr of the years here, with a maximum, around 1960, 70 and then slow decline. 76 00:07:15,366 --> 00:07:21,432 And then you can see how this is reflected here about 20, 25 years later in the incidence of 77 00:07:21,433 --> 00:07:27,733 Lung tumors abzeignet here in men. This means that this curve plays a role in the behavior of the consumer. 78 00:07:27,733 --> 00:07:33,933 so to speak, but with a time lag of around 25 years. This is also visible in the curves, 79 00:07:33,933 --> 00:07:40,199 when comparing metallitￃﾤt, i.e. mortality due to lung tumors, in men and women. 80 00:07:40,200 --> 00:07:46,333 It's also quite impressive that this metallite goes down again in men, and someone here can also see this 81 00:07:46,333 --> 00:07:52,599 curve, because people are smoking less, because they are more aware of this risk, at 82 00:07:52,600 --> 00:07:58,533 There is still an increase in women. This ends here around 2010, but it is still the case that the increase 83 00:07:58,533 --> 00:07:58,999 is on the rise. 84 00:07:59,000 --> 00:08:06,000 And that's simply because women historically started smoking later. That was, so to speak, an emancipatory 85 00:08:06,000 --> 00:08:12,233 step, if you like, i.e. the maximum number of women who smoke, 86 00:08:12,233 --> 00:08:18,399 has probably already passed its zenith here, but the incidence of lung tumors, that is not yet so far, that 87 00:08:18,400 --> 00:08:24,733 will take a few more years, that will keep us busy. In Germany, we've just got to the point where the two curves are about 88 00:08:24,733 --> 00:08:30,866 intersect, so that mortality among men and women here is the same, and in future it will be the case that men 89 00:08:30,866 --> 00:08:37,232 have a lower mortality rate and women a higher one, simply because of this time lag. So I think these are impressive 90 00:08:37,233 --> 00:08:43,333 figures that show very clearly the connection between smoking and tumor diseases. There is of course a 91 00:08:43,333 --> 00:08:49,733 whole series of other risk factors that I won't go into here, but this is the number 1 factor, 92 00:08:49,733 --> 00:08:55,866 that we should consider. When it comes to the treatment of tumors, you all know the three big 93 00:08:55,866 --> 00:09:01,966 pillars of cancer therapy, the first of which is surgical treatment. Whenever possible, we try to 94 00:09:01,966 --> 00:09:07,999 to remove a tumor surgically, especially if it is localized, this is always the first therapy 95 00:09:08,000 --> 00:09:14,133 of choice. In the vast majority of cases, however, radiotherapy will then be added because 96 00:09:14,133 --> 00:09:20,233 it is often not possible to remove the tumor completely during surgery, for example because it is growing around vessels 97 00:09:20,233 --> 00:09:26,533 or around cranial nerves etc. and you can't resect everything there. But even so, if you have a solid tumor, 98 00:09:26,533 --> 00:09:29,566 it is often the case that you cannot be sure that individual tumor cells 99 00:09:29,566 --> 00:09:32,632 are located in the immediate vicinity of the operated area 100 00:09:32,633 --> 00:09:38,666 and then, after the radiotherapy, radiation will be administered here, simply to ensure that all 101 00:09:38,666 --> 00:09:44,932 tumor cells are also destroyed here. There are few cases where you actually surgery exclusively, 102 00:09:44,933 --> 00:09:47,966 but in the majority of cases, the combination is definitely 103 00:09:47,966 --> 00:09:51,032 is what is used. And very often there is a third 104 00:09:51,033 --> 00:09:57,333 pillar, that is chemotherapy, which is always used when you don't have cells locally 105 00:09:57,333 --> 00:10:03,433 or have tumor cells not just locally in one part of the body, but when they have spread, when they are 106 00:10:03,433 --> 00:10:09,666 have metastasized in the body. And in particular, it is not possible to say at which sites in which lymph nodes 107 00:10:09,666 --> 00:10:16,166 for example, where tumor cells have already settled somewhere in the body. And you also have to reach them, you also have to 108 00:10:16,166 --> 00:10:23,099 otherwise new tumors or metastases will develop there. And that can only be done by 109 00:10:23,100 --> 00:10:29,133 systemic therapy, which acts throughout the body and that is typically chemotherapy, 110 00:10:29,133 --> 00:10:35,333 which is very well established here. Unfortunately, it has to be said that chemotherapy is a difficult form of therapy in this respect, 111 00:10:35,333 --> 00:10:41,833 because on the one hand, I think if you look at the survival figures and the cure rates, 112 00:10:41,833 --> 00:10:47,933 the cure rates based on chemotherapy alone are not as good as those of surgical treatments or 113 00:10:47,933 --> 00:10:54,299 of radiotherapy. In combination, of course, there are very good results. At the same time, chemotherapy 114 00:10:54,300 --> 00:11:00,400 is of course often associated with very severe side effects, due to the fact that you actually have to use these 115 00:11:00,400 --> 00:11:06,966 toxins throughout the body. Nevertheless, it is a very important therapy, and in many cases it can also be very successful. 116 00:11:06,966 --> 00:11:13,066 be used. But very often it is this combination of three that is used. There are then of course 117 00:11:13,066 --> 00:11:19,432 other forms of therapy that I won't go into here. There is other systemic therapy, there is immunotherapy, 118 00:11:19,433 --> 00:11:25,799 There are so-called “targeted therapies” that specifically target certain types of tumors 119 00:11:25,800 --> 00:11:32,466 and antibodies are used for these tumors. But these are all things that are still in a trial phase 120 00:11:32,466 --> 00:11:38,566 and some of them are already being tested in drug trials with very good results, 121 00:11:38,566 --> 00:11:41,766 but I would not yet count them among the three major pillars of tumor therapy. 122 00:11:41,766 --> 00:11:44,999 Today, it is precisely through these combination therapies that 123 00:11:45,000 --> 00:11:51,100 almost two thirds of all tumor patients in Germany receive radiotherapy, or even 124 00:11:51,100 --> 00:11:57,133 should receive. This is actually the case worldwide, except that the provision of radiotherapy worldwide is not so good that really 125 00:11:57,133 --> 00:12:03,433 all patients can actually be given this radiotherapy. As I said, we have about half a million patients 126 00:12:03,433 --> 00:12:09,266 annually in Germany, which is almost the number, but not quite the number we see in radiotherapy. In addition, there is the fact that 127 00:12:09,266 --> 00:12:09,566 we of course also 128 00:12:09,566 --> 00:12:15,732 not treat patients who are not tumor patients. So there are also benign diseases that are treated here, 129 00:12:15,733 --> 00:12:21,966 which also count here. But the important thing is that in radiotherapy 130 00:12:21,966 --> 00:12:28,666 the goal is to really cure the tumor, i.e. to really destroy the tumor completely, 131 00:12:28,666 --> 00:12:34,966 in 75% of cases, i.e. in most cases radiotherapy is truly curative, 132 00:12:34,966 --> 00:12:40,999 or at least the approach is curative, because it is assumed that a cure can really be achieved here. And only approximately 133 00:12:41,000 --> 00:12:47,300 of cases is palliative treatment, where it is assumed that this tumor is unlikely to be cured. 134 00:12:47,300 --> 00:12:53,566 be cured by radiotherapy. But that is a very large number 135 00:12:53,566 --> 00:12:59,699 and I believe a very positive characteristic of radiotherapy overall. Perhaps explained again from the ground up, 136 00:12:59,700 --> 00:13:06,133 What is radiation therapy actually? It's about using ionizing radiation, usually X-ray radiation, 137 00:13:06,133 --> 00:13:12,266 high-energy X-ray radiation to prevent the unregulated division of tumor cells. 138 00:13:12,266 --> 00:13:18,799 Tumor cells have precisely this property, that they divide in an uncontrolled manner, in contrast to healthy tissue, where the 139 00:13:18,800 --> 00:13:24,933 cell division is regulated by the cell and the cell network, so that no tissue proliferation of any kind occurs. 140 00:13:24,933 --> 00:13:31,099 develop. But that is exactly what tumor cells do, they continue to proliferate and get bigger and bigger. 141 00:13:31,100 --> 00:13:37,633 And the division doesn't stop on its own, and that's what we're trying to prevent with radiation. Ionizing 142 00:13:37,633 --> 00:13:43,899 radiation because this ionization generates radiation damage, damage caused by 143 00:13:43,900 --> 00:13:50,066 ionization also to the genetic molecules of the DNA in the nucleus of the tumor cells, and this damage then leads to 144 00:13:50,066 --> 00:13:56,499 cause the tumor cells to lose their ability to divide and thus stop tumor growth. 145 00:13:56,500 --> 00:14:02,633 And if cell division stops, then you still have tumor cells, so to speak, but at some point they will be 146 00:14:02,633 --> 00:14:05,899 simply die and perish or can be combated by the immune system. 147 00:14:05,900 --> 00:14:09,200 So it's not so much about killing all the tumor tumor cells immediately, 148 00:14:09,200 --> 00:14:15,800 but above all to prevent this cell division and to stop the further growth of the tumor. 149 00:14:15,800 --> 00:14:22,233 The goal that we formulate in radiotherapy is called local control, it is really the prevention of further tumor growth. 150 00:14:22,233 --> 00:14:28,366 growth of the tumor, and this is typically observed in follow-up images, 151 00:14:28,366 --> 00:14:34,532 images, MRI images that we take, where we can visualize the tumors and where we can see and assess whether the 152 00:14:34,533 --> 00:14:39,499 tumor has continued to grow or whether it remains stable or, ideally, whether it is perhaps even getting smaller. 153 00:14:39,500 --> 00:14:41,500 I'll show you a few examples of this later. 154 00:14:41,500 --> 00:14:48,300 The nice thing about radiotherapy - what fascinates me and what makes it so interesting for me - is that it's a 155 00:14:48,300 --> 00:14:54,400 interdisciplinary field that touches on at least these three disciplines, namely medicine, of course, 156 00:14:54,400 --> 00:15:00,500 but also physics. Because we need a lot of physics, as I'll show him in a moment, to implement radiotherapy. 157 00:15:00,500 --> 00:15:06,900 And we need a biological understanding of the biology of tumors and normal tissue, which is not yet fully understood. 158 00:15:06,900 --> 00:15:14,066 understood. So research is really needed here in all areas, and that's the beauty of this interdisciplinary 159 00:15:14,066 --> 00:15:20,799 research. What I would actually have to add in the last few years is data science, 160 00:15:20,800 --> 00:15:26,866 i.e. modern computer applications, keyword AI, which are playing an increasingly important role 161 00:15:26,866 --> 00:15:33,266 in the implementation of our tools in radiotherapy. 162 00:15:33,266 --> 00:15:39,399 So which therapy or which rays do we use in therapy? That's just historically speaking, 163 00:15:39,400 --> 00:15:46,100 X-rays were the first to be used. You know that at the end of the 19th century Wilhelm Konrad Röntgen developed the 164 00:15:46,100 --> 00:15:52,233 X-rays and just a few years later, in the course of 2 or 3 years really, these rays were then 165 00:15:52,233 --> 00:15:57,233 were already being used to treat tumors. So that was more of an experimental approach, 166 00:15:57,233 --> 00:16:02,199 but was definitely successful in some cases. However, there were of course also serious side effects, 167 00:16:02,200 --> 00:16:04,733 not only in tumor patients, but above all 168 00:16:04,733 --> 00:16:11,033 also with the doctors who handled the radiation. It was recognized very quickly that X-ray radiation is not 169 00:16:11,033 --> 00:16:17,166 penetrates deep into the body, but can be used sensibly on tumors close to the surface. tumors, which is also where it is used today 170 00:16:17,166 --> 00:16:23,899 because the radiation does not penetrate deep into the body. So if you have deeper tumors, then you need 171 00:16:23,900 --> 00:16:30,233 higher radiation energy so that the radiation penetrates the body better. And this was made possible, for example, by 172 00:16:30,233 --> 00:16:36,966 radioactive substances. First of all, of course, radioactive emitters such as radium, which have energies that are in the range of 173 00:16:36,966 --> 00:16:44,499 2 to 3 times as high as those of classical X-rays, in the range of about 200, 250 kilo-electron volts, 174 00:16:44,500 --> 00:16:50,033 which is not really very much either. A breakthrough was achieved with Co60, which 175 00:16:50,033 --> 00:16:56,733 is an artificial radioisotope that can be produced in nuclear reactors and is therefore only available 176 00:16:56,733 --> 00:17:04,433 since the early 1950s, when this technology was available. And Co60 imitates gamma radiation, 177 00:17:04,433 --> 00:17:08,133 so this is a nuclear decay that takes place here, hence the other name, 178 00:17:08,133 --> 00:17:14,599 with gamma energy, i.e. radiation energy in the range of about one mega-electron-volt, i.e. 1 million electron-volts. 179 00:17:14,600 --> 00:17:20,900 And this has a much better penetration behavior into the body. They can therefore transport more energy into the body. 180 00:17:20,900 --> 00:17:26,400 However, it is still not really sufficient and still causes a lot of stress on the skin and skin redness 181 00:17:26,400 --> 00:17:34,233 or skin burns. And only with the use of even higher energy in the range of between 4 and 10 mega-electron volts, 182 00:17:34,233 --> 00:17:39,466 was it possible to largely avoid this skin damage, especially skin burns, 183 00:17:39,466 --> 00:17:45,866 are actually a thing of the past. This was made possible with really high-energy X-ray beams, which can be 184 00:17:45,866 --> 00:17:51,532 generated in so-called linear accelerators. This is similar to an X-ray tube, except that somewhat more sophisticated techniques are used. 185 00:17:51,533 --> 00:17:59,133 are used to accelerate the electrons to much higher energies. And when slowing down 186 00:17:59,133 --> 00:18:05,299 this high-energy X-ray radiation is generated. Electromagnetic radiation, but these are now different spectra and 187 00:18:05,300 --> 00:18:12,966 energies that we use here or have used historically, which is basically the same as light, i.e. electromagnetic radiation, 188 00:18:12,966 --> 00:18:17,799 only with different energies. But there is also another type of radiation, 189 00:18:17,800 --> 00:18:24,800 so-called particle radiation, which can be used and which also has an ionized effect on the body and the cells. 190 00:18:24,800 --> 00:18:30,433 And these are mainly the nuclei of atoms that are used here, so in principle you can use 191 00:18:30,433 --> 00:18:36,166 also use electrons, but they are very light, they scatter very strongly and it is also difficult, 192 00:18:36,166 --> 00:18:41,432 to let them penetrate deeper into the body, you need very high energies. What you do, and what you can control very well 193 00:18:41,433 --> 00:18:48,099 are the nuclei of hydrogen from protons or heavy ions such as helium or carbon. 194 00:18:48,100 --> 00:18:55,000 So protons and carbon ions in particular are two things that were used very early on, for example in the 195 00:18:55,000 --> 00:19:01,266 50s and since about the 90s of the last century there have been clinical facilities there have been clinical facilities where the 196 00:19:01,266 --> 00:19:08,066 proton therapy can be clinically implemented. I'll come back to proton and ion therapy at the very end, these are 197 00:19:08,066 --> 00:19:14,999 much more complex accelerators that we need here, which also make the whole thing much more expensive, 198 00:19:15,000 --> 00:19:20,066 so you really have to think about which tumors these types of radiation are used for. 199 00:19:20,066 --> 00:19:25,799 So the question is, of course, why and how does the radiation therapy specifically affect the tumor cells. 200 00:19:25,800 --> 00:19:27,600 You have to know that, of course, 201 00:19:27,600 --> 00:19:32,900 when I irradiate, I always have normal tissue in the radiation path as well as the tumor cells. 202 00:19:32,900 --> 00:19:39,200 But the decisive factor is that the tumor cells themselves are more sensitive to radiation than the normal tissue, at least than the tumor cells. 203 00:19:39,200 --> 00:19:46,933 the vast majority of normal tissue. The reason is that healthy cells have better repair mechanisms, 204 00:19:46,933 --> 00:19:52,066 to compensate for radiation damage and to undo it, so to speak. 205 00:19:52,066 --> 00:19:58,766 These are very sophisticated mechanisms that have developed over the course of evolution, because we are practically permanently protected by natural 206 00:19:58,766 --> 00:20:05,232 sources, are exposed to radioactive radiation. In addition to this biological effect, there is also, 207 00:20:05,233 --> 00:20:10,299 that we are, of course, trying to use physical principles - and this is really the domain of physics - to 208 00:20:10,300 --> 00:20:15,700 to really limit the area where we apply a high dose to the tumor. 209 00:20:15,700 --> 00:20:18,966 We call this conforming or dose conforming. 210 00:20:18,966 --> 00:20:25,732 And this is actually the main course of development in radiotherapy over the last 30, 40 years 211 00:20:25,733 --> 00:20:31,433 I would say, the development of linear accelerators, the way we apply them, the way we optimize them, 212 00:20:31,433 --> 00:20:36,699 these are all physical-technical developments that have improved this conformation. 213 00:20:36,700 --> 00:20:42,700 And here, of course, it's about better protection of the healthy tissue, removing more of the healthy tissue from the 214 00:20:42,700 --> 00:20:44,666 high-dose range. 215 00:20:44,666 --> 00:20:50,299 And finally, there are a whole series of effects that are still not really well understood, where we are still just at the 216 00:20:50,300 --> 00:20:55,000 the beginning. For example, we know for sure that the immune system plays an important role. 217 00:20:55,000 --> 00:20:59,633 When tumors are irradiated, a certain inflammatory reaction occurs, 218 00:20:59,633 --> 00:21:03,699 also locally, which feels that the immune system is activated certain inflammatory reaction, also local, which leads to activation of the immune system 219 00:21:03,700 --> 00:21:08,933 and in the best case turns against the tumor. But we also know that tumors try to 220 00:21:08,933 --> 00:21:15,466 to mask themselves to the immune system, i.e. to evade the immune system, i.e. not to be detected 221 00:21:15,466 --> 00:21:21,966 by the immune system, i.e. the cells that would then attack the tumor cells. And this is what they found out, 222 00:21:21,966 --> 00:21:27,799 that, depending on the dose and the way in which we apply it, and on the type of radiation, 223 00:21:27,800 --> 00:21:34,766 that it can actually lead to the radiation making the tumor more visible and activating the immune system. 224 00:21:34,766 --> 00:21:41,366 This is actually still the subject of research, how we can optimize the immune system here, synergistically 225 00:21:41,366 --> 00:21:46,832 in radiotherapy. I would like to emphasize again at this point, these physical principles, 226 00:21:46,833 --> 00:21:54,233 which play a very important role here, make radiotherapy truly unique in the toolbox of methods 227 00:21:54,233 --> 00:22:00,966 of medicine, it really is one of the methods that is very much based on physics. And therefore offers a whole range of advantages, 228 00:22:00,966 --> 00:22:05,766 because, first of all, we can calculate very precisely what we 229 00:22:05,766 --> 00:22:13,966 of radiation we apply to each patient. So we can calculate the dose point by point on CT images, for example. 230 00:22:13,966 --> 00:22:18,366 And we can do this with a very high degree of accuracy. So typically we can 231 00:22:18,366 --> 00:22:24,432 in phantoms, where we can also measure it, where we can quantify it. And that's where we try to measure the accuracy, or 232 00:22:24,433 --> 00:22:31,099 we can achieve an accuracy of 3%. Of course, we can't prove this in the patient without any further ado, 233 00:22:31,100 --> 00:22:38,033 and verify what we achieve here in terms of accuracy, but that is at least the goal, to get in this direction. 234 00:22:38,033 --> 00:22:43,499 It is also spatially very precise. And we can measure that very well. We can position the patient well, 235 00:22:43,500 --> 00:22:49,200 also through imaging procedures in the treatment room. And we can control our radiation very precisely. 236 00:22:49,200 --> 00:22:55,400 And this means that we can achieve spatial precision in the 1 mm range. We can do the whole thing, 237 00:22:55,400 --> 00:23:03,033 in phantoms. So we can build artificial bodies with materials similar to those in the human body, 238 00:23:03,033 --> 00:23:09,433 but we can introduce measuring systems there and really check whether what we have come up with in the computer works, 239 00:23:09,433 --> 00:23:14,299 really corresponds to reality. And in addition to verifiability, it is also 240 00:23:14,300 --> 00:23:20,300 predictable in terms of the side effects, perhaps not in the range of a few percent, but we can still 241 00:23:20,300 --> 00:23:26,933 make fairly good predictions about the probability of certain side effects occurring, 242 00:23:26,933 --> 00:23:34,633 specifically for each patient. Based on the therapy planning, which is individualized, and based on the dose values 243 00:23:34,633 --> 00:23:40,133 for each organ that we calculate, we also know which volume is affected, which parts of the organ, 244 00:23:40,133 --> 00:23:45,799 and what that means for possible side effects. If you think about it, this is one of the very few 245 00:23:45,800 --> 00:23:47,333 therapy options 246 00:23:47,333 --> 00:23:53,799 in medicine, where you have these possibilities to calculate it so precisely, to be so precise, to verify it and 247 00:23:53,800 --> 00:24:00,633 to really predict it. I think that really makes beach therapy unique as a method in medicine. 248 00:24:00,633 --> 00:24:05,599 And finally, of course, that it is a very safe method. We have developed procedures, 249 00:24:05,600 --> 00:24:13,966 which, in principle, make naturally dangerous ionizing radiation so manageable that accidents or incorrect radiation 250 00:24:13,966 --> 00:24:19,732 can be practically ruled out. And these are typically risk considerations 251 00:24:19,733 --> 00:24:25,933 and safety analyses that are very similar to those used in the aviation industry, for example, 252 00:24:25,933 --> 00:24:32,133 in aviation or space travel. In other words, you analyze errors, including near-accidents, 253 00:24:32,133 --> 00:24:37,699 and these things very precisely and try to further improve these issues. So we also have a very safe application. 254 00:24:37,700 --> 00:24:43,300 At this point, I would like to briefly discuss the radiotherapy treatment chain again. The treatment chain 255 00:24:43,300 --> 00:24:44,600 of radiotherapy 256 00:24:44,600 --> 00:24:51,133 should first of all symbolize that we have a sequence of steps, starting with immobilization 257 00:24:51,133 --> 00:24:57,499 of the patient, i.e. partly also the fixation on a table, then the imaging that we need, 258 00:24:57,500 --> 00:25:03,166 in order to then make a plan, a tumor localization, i.e. on the images 259 00:25:03,166 --> 00:25:09,832 we have to define what we want to irradiate and then plan the therapy on the computer, where we calculate this 260 00:25:09,833 --> 00:25:15,699 dose distributions. This is followed by the positioning of the patient on the treatment device 261 00:25:15,700 --> 00:25:22,166 and the actual treatment. Of course, there are further steps in between, depending on the type of treatment, in particular 262 00:25:22,166 --> 00:25:29,632 as a rule, there will be a verification of the exact patient position. What comes on top of that is quality assurance, 263 00:25:29,633 --> 00:25:36,133 in other words, these are verification measurements that are made for each patient to check whether the dose is correct, 264 00:25:36,133 --> 00:25:42,466 as it should be, and the application is also verified again by software systems, 265 00:25:42,466 --> 00:25:48,099 where everything is saved again, so to speak, and you can recapitulate where I actually stand at the moment 266 00:25:48,100 --> 00:25:52,666 in the treatment of this one patient that I have on the table right now. 267 00:25:52,666 --> 00:25:57,299 And finally, and this is a point that I have added here, which is also very important, is aftercare. 268 00:25:57,300 --> 00:26:02,600 That's also part of the treatment, because only if we monitor what really happens at the end, 269 00:26:02,600 --> 00:26:07,833 how the patient is doing, whether he has side effects, whether the tumor growth has really been stopped, 270 00:26:07,833 --> 00:26:12,833 we can also verify this whole chain at the end. And what's important, of course, is that 271 00:26:12,833 --> 00:26:19,099 symbolizes that a chain is only as strong as its weakest link, so all these steps play a very important role. 272 00:26:19,100 --> 00:26:26,466 role in making radiotherapy successful in the end. Here are a few examples of what that means in concrete terms. 273 00:26:26,466 --> 00:26:32,532 These are typical images, CT images of a patient in the abdominal region, 274 00:26:32,533 --> 00:26:38,166 You can see, simply by way of example, the accuracy and the high level of detail of these images, 275 00:26:38,166 --> 00:26:43,432 which are usually recorded using contrast media, and you can see the richness and detail here, 276 00:26:43,433 --> 00:26:50,333 a really detailed, anatomical picture of what we can see here. And that is now the initial situation, 277 00:26:50,333 --> 00:26:57,099 for the planning. Here are examples, this is now in the head area, where we can see these colorful squiggles. 278 00:26:57,100 --> 00:27:02,766 These are different organs. The red one is usually the volume that we want to irradiate, the so-called target volume. 279 00:27:02,766 --> 00:27:08,632 And here you can see, for example, the optic nerve junction, the brain stem, the two temporal lobes, which are known as particularly 280 00:27:08,633 --> 00:27:16,233 critical structures here. And what you then see here in color, as a blurred color representation, 281 00:27:16,233 --> 00:27:23,699 This is the dose distribution that we can now play around with, that we can optimize in the directions of irradiation, 282 00:27:23,700 --> 00:27:28,733 changing, adding different numbers of irradiation directions. 283 00:27:28,733 --> 00:27:35,299 And what we can then calculate are these distributions, that is, in the volume, we can then see which dose is being received in which 284 00:27:35,300 --> 00:27:40,933 volume is applied. And this can be represented in so-called dose-volume histograms, for example, which subsume 285 00:27:40,933 --> 00:27:47,733 what percentage of the dose is deposited in what percentage of the organ, and that gives us an important 286 00:27:47,733 --> 00:27:53,699 criterion for predicting side effects and also tumor control rates. So that gives us a 287 00:27:53,700 --> 00:27:59,233 measure of the quality and also the risks associated with this therapy. 288 00:27:59,233 --> 00:28:06,266 In general, perhaps here again to the color scheme. Blue always means low doses, in the range of about 10 percent in this case. 289 00:28:06,266 --> 00:28:12,966 And red is the 100 percent, i.e. the target dose. And in between, it goes from yellow to green to the low dose range. 290 00:28:12,966 --> 00:28:18,266 And you see here, especially in normal brain tissue, you really have very low dose values, in the range of 10, 291 00:28:18,266 --> 00:28:24,932 a maximum of 20%. So really uncritical figures. By the way, this is a plan for particle therapy, 292 00:28:24,933 --> 00:28:31,499 which has this particular characteristic of being so highly compliant with radiotherapy. 293 00:28:31,500 --> 00:28:37,500 Here is another example, a so-called intensity modulated radiation therapy, an IMRT, 294 00:28:37,500 --> 00:28:44,033 where you have even more irradiation directions. But here, too, you can see these blue areas outside, here in the case of the prostate, 295 00:28:44,033 --> 00:28:51,366 Protection of the femoral heads, the rectum and the bladder, which are only affected on the walls, so to speak. 296 00:28:51,366 --> 00:28:59,166 And that's exactly what you want to optimize and can optimize with this type of treatment planning on the computer. 297 00:28:59,166 --> 00:29:05,032 And here is a third example. What you can also do is have a three-dimensional model of the patient. 298 00:29:05,033 --> 00:29:09,099 We can also look at the patient from the outside, so to speak. 299 00:29:09,100 --> 00:29:11,133 also look at the skin dose, for example. 300 00:29:11,133 --> 00:29:16,433 In this head and neck patient, for example, we can assess the risk of skin damage, 301 00:29:16,433 --> 00:29:22,966 for skin reddening by looking at the local dose distribution resulting from the current status of this planning 302 00:29:22,966 --> 00:29:26,932 can be displayed. And this optimization is a very important 303 00:29:26,933 --> 00:29:30,733 reason for the accuracy that we can achieve in radiotherapy. 304 00:29:30,733 --> 00:29:34,599 And that overall - and I would just like to emphasize this again - radiotherapy is 305 00:29:34,600 --> 00:29:40,433 a very precise procedure, it is predictable, it is accurate and it is safe. And it really is because of 306 00:29:40,433 --> 00:29:46,166 because of the physical principles on which it is based and because of all the experience and technology, 307 00:29:46,166 --> 00:29:51,899 that has gone into this, also from medicine, also from radiobiology, of course. And that makes radiotherapy really 308 00:29:51,900 --> 00:29:58,300 a unique procedure. You won't find any drug therapy where you can predict this so precisely, 309 00:29:58,300 --> 00:29:59,433 where you can predict the dosage alone 310 00:29:59,433 --> 00:30:05,099 cannot estimate so precisely. And even with surgical procedures, it is often the case that you have to wait, 311 00:30:05,100 --> 00:30:10,966 when you have just started the operation, when you are “in situs”, to see what the anatomical conditions are like, 312 00:30:10,966 --> 00:30:13,299 what is really possible and what is not possible. 313 00:30:13,300 --> 00:30:17,766 This is more something that arises from the situation. You can plan that, 314 00:30:17,766 --> 00:30:22,832 but you can't always implement it as well as you can here in radiotherapy. 315 00:30:22,833 --> 00:30:29,799 What does such a treatment or treatment device look like? A linear accelerator is shown here, as it is used today in the 316 00:30:29,800 --> 00:30:36,233 most clinics today. Here you can see the radiation head from which the radiation is emitted, the actual linear accelerator is in 317 00:30:36,233 --> 00:30:42,733 hidden in this arm here, and the whole thing can rotate, here along this axis, so that this head can rotate once 318 00:30:42,733 --> 00:30:47,733 around the patient table. So you can beam in here from any direction. 319 00:30:47,733 --> 00:30:49,166 And the other thing you see here: 320 00:30:49,166 --> 00:30:55,299 these elements, right and left, that is an X-ray tube with an image pickup and another image pickup which is the 321 00:30:55,300 --> 00:31:02,266 direct radiation visible for therapy. In other words, imaging systems that allow us to record images, 322 00:31:02,266 --> 00:31:08,799 of the patient in the treatment position in order to recognize the exact position, and ideally 323 00:31:08,800 --> 00:31:13,700 also to react to changes that have occurred on the day in question. 324 00:31:13,700 --> 00:31:19,366 Here is another abbreviated representation of this chain, as you have to imagine it in radiotherapy. 325 00:31:19,366 --> 00:31:21,499 This is now the conventional sequence 326 00:31:21,500 --> 00:31:27,133 We do CT and MR imaging. We then have treatment planning. We have to take images 327 00:31:27,133 --> 00:31:33,299 on top of each other, we call this registration. We have to segment them, i.e. define volumes, and then we have to 328 00:31:33,300 --> 00:31:40,066 calculate and optimize a dose distribution. We then have the quality assurance of this treatment plan before the therapy, 329 00:31:40,066 --> 00:31:47,432 which is carried out by the physicist or the assistants, and then the positioning and position verification, 330 00:31:47,433 --> 00:31:53,333 here with these false color images, where you can see whether the target position really corresponds to the actual position. 331 00:31:53,333 --> 00:31:59,666 And then finally the irradiation after a position correction if necessary. And this is then repeated. 332 00:31:59,666 --> 00:32:06,699 Typically for five to six weeks, always motor to Friday, radiotherapy is then carried out. And now, of course, you can rightly ask, fￃﾼnf to six weeks, always motor to Friday, is then followed by radiation. And now, of course, you can rightly ask if 333 00:32:06,700 --> 00:32:12,133 when we are here at the end of these six weeks, is the anatomy that we have planned here in the 334 00:32:12,133 --> 00:32:18,366 still correspond to the anatomy that we recorded here more than six weeks earlier? 335 00:32:18,366 --> 00:32:24,166 And this question is justified. And that is precisely the principle of a newer concept, 336 00:32:24,166 --> 00:32:30,599 that has been pursued in recent years, the so-called adaptive therapy. So in part we can react to changes 337 00:32:30,600 --> 00:32:35,733 that we see here. But these are mainly shifts in position. 338 00:32:35,733 --> 00:32:38,199 We can of course take control shots 339 00:32:38,200 --> 00:32:43,633 to see if anything has changed in the tumor changed in the tumor, for example, but we can 340 00:32:43,633 --> 00:32:50,299 can only react relatively slowly. The goal today is adaptive therapy, that is, 341 00:32:50,300 --> 00:32:57,300 to treat each patient optimally every day and not with a plan that is already several weeks old. 342 00:32:57,300 --> 00:33:02,933 And this is achieved by the fact that after initial therapy planning 343 00:33:02,933 --> 00:33:09,533 a higher quality image in the treatment position each time. 344 00:33:09,533 --> 00:33:14,299 And nowadays, for example, this has been made possible by hybrid devices in which 345 00:33:14,300 --> 00:33:21,000 an MRI is integrated. In other words, we have a linear accelerator and MRI in one device. 346 00:33:21,000 --> 00:33:27,266 And we can now take MRI images every time before the therapy and also during the therapy and 347 00:33:27,266 --> 00:33:33,699 have highly accurate images that allow us to really see what has changed from yesterday to today, 348 00:33:33,700 --> 00:33:34,466 but also 349 00:33:34,466 --> 00:33:39,566 what changes, what moves in the target volume during therapy. 350 00:33:39,566 --> 00:33:45,732 And that is of course a challenge insofar as we then want to and have to react quickly to these images, 351 00:33:45,733 --> 00:33:49,499 because the patient is then lying on the treatment table and we want to start treatment. 352 00:33:49,500 --> 00:33:53,900 In other words, we have to carry out these planning steps, i.e. these image processing steps, 353 00:33:53,900 --> 00:34:01,366 the dose calculation and also a form of quality assurance, as automatically as possible and as quickly as possible, 354 00:34:01,366 --> 00:34:06,266 so that the patient does not have to wait too long on the table before treatment begins. 355 00:34:06,266 --> 00:34:11,366 And this form of therapy is one of the major issues in the development of radiotherapy today, 356 00:34:11,366 --> 00:34:17,699 adaptive therapy, which we believe will lead to a further improvement in many cases improvement in many cases, because we really 357 00:34:17,700 --> 00:34:20,033 on the day-to-day anatomy, 358 00:34:20,033 --> 00:34:24,333 if you like, but it still requires a lot of development work, 359 00:34:24,333 --> 00:34:31,533 because the automation of all these steps here essentially means that we need a lot more computer-aided 360 00:34:31,533 --> 00:34:36,333 algorithms. And that's the big domain of artificial intelligence, 361 00:34:36,333 --> 00:34:44,199 especially of deep learning networks, which we use here to automate all these steps and make them faster. and make them faster. 362 00:34:44,200 --> 00:34:49,133 Ideally, we want to get to a point where it doesn't just take minutes, but where we can perhaps even 363 00:34:49,133 --> 00:34:50,866 real time to such changes 364 00:34:50,866 --> 00:34:56,532 here. However, that is still some way off, that they are not actually that far yet. 365 00:34:56,533 --> 00:35:03,599 But that also explains why these AI applications play such an important role in radiotherapy. 366 00:35:03,600 --> 00:35:09,600 I said earlier that local tumor control is our goal, and here I just wanted to show that again, 367 00:35:09,600 --> 00:35:15,700 what that means. Here is a patient who was treated in 1996 for this tumor here at 368 00:35:15,700 --> 00:35:22,000 the base of the skull. She then received radiotherapy with protons, at that time in the USA, also in 1996, 369 00:35:22,000 --> 00:35:27,733 and then two years later, a little more than two years later, she has this tumor, which has grown again, which is now a 370 00:35:27,733 --> 00:35:34,399 recurrent tumor, which has grown again. And then in Heidelberg radiotherapy in Heidelberg. 371 00:35:34,400 --> 00:35:40,400 This was a combination of conventional therapy and carbon therapy. I don't want to go into the reasons now, 372 00:35:40,400 --> 00:35:47,333 but this is a good example because it shows two things: firstly, you can see here very nicely what 373 00:35:47,333 --> 00:35:53,466 tumor control means, or actually even remission. It looks like this here, that six months after radiotherapy, the 374 00:35:53,466 --> 00:35:59,899 tumor volume has become considerably smaller, i.e. not just stagnation, but a reduction in volume, 375 00:35:59,900 --> 00:36:05,933 and this is not atypical for this therapy with carbon ions, where we see such effects more frequently. 376 00:36:05,933 --> 00:36:12,266 So that also shows a bit why carbon ions are interesting, because other biological mechanisms of action are involved here. 377 00:36:12,266 --> 00:36:18,666 than in conventional therapy and also than in proton therapy. But that also shows what that means, 378 00:36:18,666 --> 00:36:25,132 what local tumor control really means. Here's another example, which is also radiation therapy, 379 00:36:25,133 --> 00:36:30,733 mixed with conventional therapy and carbon therapy, for a salivary gland tumor, 380 00:36:30,733 --> 00:36:37,099 an adenoid cystic carcinoma here in the nasopharyngeal region, so a very extensive volume, and here it is still 381 00:36:37,100 --> 00:36:43,566 even more astonishing: Here, the tumor volume has already decreased considerably six weeks after treatment. 382 00:36:43,566 --> 00:36:50,699 Again, this is not atypical for this tumor and for carbon therapy, I won't go into it here, 383 00:36:50,700 --> 00:36:56,900 that this is a great thing, but the main question is, of course, is it stable, is it longer lasting, 384 00:36:56,900 --> 00:37:02,600 It's no use to us if it continues to grow again six weeks later. But that just shows what we mean here 385 00:37:02,600 --> 00:37:10,766 with tumour control and stabilization or reduction of the tumour volume and you can see it very well here in these MR images. 386 00:37:10,766 --> 00:37:17,099 Here is another example of how the use of modern computer technology can help us 387 00:37:17,100 --> 00:37:22,766 not only in the actual implementation of the therapy, but also in the development of new approaches that allow us to 388 00:37:22,766 --> 00:37:29,799 that allow us to make predictions. The fact is that we have a neuronal network here. 389 00:37:29,800 --> 00:37:35,800 which is a research project here at the DKFZ, to achieve the following: we have image data here 390 00:37:35,800 --> 00:37:42,066 of patients, some of whom we have daily, but at least weekly in the course of therapy additional 391 00:37:42,066 --> 00:37:48,132 images, sometimes MRI images, sometimes CT images. And we have a follow-up, 392 00:37:48,133 --> 00:37:54,666 that is, we have a follow-up, we know how the patients have developed over the course of the months, whether they have had any side effects or not. 393 00:37:54,666 --> 00:38:00,332 have developed, whether tumor control has occurred, whether the tumor volume has decreased. 394 00:38:00,333 --> 00:38:07,833 And with this data, we can now try to train a network in order to make predictions, so to speak. 395 00:38:07,833 --> 00:38:14,133 predict what is likely to happen based on the images that we take during therapy. 396 00:38:14,133 --> 00:38:19,166 will happen. We are not yet at the end here, there will not yet be a result that we can say, 397 00:38:19,166 --> 00:38:24,766 we have algorithms that allow this, but we have good indications that there are possibilities, 398 00:38:24,766 --> 00:38:32,299 we call them image-based biomarkers, i.e. changes in the images, 399 00:38:32,300 --> 00:38:35,266 that allow us to draw conclusions about the result of the radiotherapy, so to speak. 400 00:38:35,266 --> 00:38:39,766 And these are changes that we cannot recognize with the naked eye in the images. So only the computer can do that, and 401 00:38:39,766 --> 00:38:46,266 that's exactly the idea behind it, if we then have such predictors for the outcome, as we call it, 402 00:38:46,266 --> 00:38:52,766 then we have a way of saying that this patient is very likely to react well, to respond well. 403 00:38:52,766 --> 00:38:58,299 And then you can consider, then the doctor can consider whether to perhaps increase the dose further, 404 00:38:58,300 --> 00:39:04,500 if the patient benefits from it. And vice versa, if the risk is more likely to be high, 405 00:39:04,500 --> 00:39:09,133 because it becomes apparent that side effects will occur, then you can reduce the dose in good time. 406 00:39:09,133 --> 00:39:14,299 and avoid these side effects if the patient does not benefit from them anyway. 407 00:39:14,300 --> 00:39:18,233 So there is another possibility for us, in the course of the therapy 408 00:39:18,233 --> 00:39:24,299 to adapt the therapy to the patient. So that, that would be a very great possibility if we had that in the future. 409 00:39:24,300 --> 00:39:29,966 That's another application for these innovative computer approaches, 410 00:39:29,966 --> 00:39:33,032 which are being worked on very intensively, not just here, but worldwide. 411 00:39:33,033 --> 00:39:36,399 So perhaps we can briefly return to the implementation 412 00:39:36,400 --> 00:39:42,333 of radiation therapy. So here we see an accelerator, which is then moved in different directions in order to 413 00:39:42,333 --> 00:39:47,999 from different directions, and the question is why is this being done? Well, that's relatively clear, 414 00:39:48,000 --> 00:39:55,366 the dose distribution of X-rays is such that they have a maximum somewhere, at the beginning it is low in the skin, 415 00:39:55,366 --> 00:39:58,766 but then gets higher and higher and somehow it decreases due to attenuation 416 00:39:58,766 --> 00:40:02,299 very slowly. In other words, this is a very penetrating form of radiation. 417 00:40:02,300 --> 00:40:06,800 Now, in order to achieve that you can really reach a certain depth here, a higher dose 418 00:40:06,800 --> 00:40:10,966 than in the surrounding tissues, you simply need several irradiation directions. 419 00:40:10,966 --> 00:40:13,166 We also call this a crossfire irradiation. 420 00:40:13,166 --> 00:40:16,066 Here is a very simple example from three directions, 421 00:40:16,066 --> 00:40:19,999 and then, of course, you only have a third of the dose in each field, 422 00:40:20,000 --> 00:40:26,966 and have thus already reduced it to a third in the entry area, so to speak, which are these yellow-green areas. 423 00:40:26,966 --> 00:40:31,532 This is not yet optimal, we can continue to work on it, but it shows the direction we are heading in. 424 00:40:31,533 --> 00:40:38,566 And that's also a very simple technique, by the way, three fields that simply always have the same volume, so to speak. 425 00:40:38,566 --> 00:40:42,832 of the tumor, and this can be optimized by also irradiating the 426 00:40:42,833 --> 00:40:45,499 intensity accordingly and modulating the fields, 427 00:40:45,500 --> 00:40:51,866 and can thus further adjust the dose distribution, and also add even more fields, up to continuous 428 00:40:51,866 --> 00:40:57,066 rotational irradiation, which then allows even better dose conformation. 429 00:40:57,066 --> 00:41:03,432 And this is also the point why it is interesting to use these particle beams in addition to X-rays. 430 00:41:03,433 --> 00:41:07,799 This dose curve that we have here, this red curve, is not optimal, 431 00:41:07,800 --> 00:41:12,033 because we always have less dose at depth than here in the entrance area. 432 00:41:12,033 --> 00:41:16,566 And with protons, for example this blue curve here, it looks completely different, 433 00:41:16,566 --> 00:41:22,299 because we have a low dose in the entrance area, and then they stop somewhere and release more energy, 434 00:41:22,300 --> 00:41:29,533 This means that we have a maximum at depth, and then the particles stop, there is no dose behind the tumor. 435 00:41:29,533 --> 00:41:32,833 And we can also control this penetration depth via the energy, 436 00:41:32,833 --> 00:41:36,666 and that's what makes this use of particle beams so interesting, 437 00:41:36,666 --> 00:41:42,566 and here you can see this in the example, if we were to take only one radiation field: with X-rays 438 00:41:42,566 --> 00:41:48,532 then it would look like this: high dose here in the entrance area, and then also a medium dose in the tumor volume, 439 00:41:48,533 --> 00:41:53,666 and then it slowly decreases further. But you have a considerable dose in the entire radiation channel. 440 00:41:53,666 --> 00:41:58,166 And with protons, for example, we can do it in such a way that we only have this tumor volume 441 00:41:58,166 --> 00:42:01,499 irradiate, we have no dose behind the volume, and still 442 00:42:01,500 --> 00:42:09,166 a lower dose here in the entry area than in the tumor area. And what you see here is already an energy modulation, 443 00:42:09,166 --> 00:42:16,099 so you have superimposed many energies here and you don't have individual peaks, but you can really achieve a plateau, 444 00:42:16,100 --> 00:42:22,033 and then this whole dose, this difference between the X-ray curve and the proton curve in this case. 445 00:42:22,033 --> 00:42:28,499 And also here behind the tumor, this is of course useless dose that we save, that we don't apply in the patient. 446 00:42:28,500 --> 00:42:34,166 And that's the big difference, and that's why we make this effort with the accelerator systems 447 00:42:34,166 --> 00:42:37,099 for particle therapy. 448 00:42:37,100 --> 00:42:41,833 Here is a typical application example and also one of the most beautiful application examples. 449 00:42:41,833 --> 00:42:48,933 This is a patient with so-called medulloblastomas, tumors that spread through the cerebrospinal fluid in the nervous system, 450 00:42:48,933 --> 00:42:53,599 can also spread along the spinal canal. Therefore, this entire spinal canal 451 00:42:53,600 --> 00:42:59,333 and irradiate the whole brain. And in the case of the spinal canal, this possibility is now 452 00:42:59,333 --> 00:43:05,799 of stopping the particles can be utilized very well. So you only irradiate the bony area of the spinal column, 453 00:43:05,800 --> 00:43:08,900 for reasons that I will not go into here. 454 00:43:08,900 --> 00:43:13,566 But if you do this with X-rays, you always have the effect of exposing a considerable dose of 455 00:43:13,566 --> 00:43:18,899 in the entire area of the abdomen, the mediastinum, i.e. the intestines, 456 00:43:18,900 --> 00:43:25,966 the lungs, the heart are all affected, and that naturally leads to considerable acute and late side effects. 457 00:43:25,966 --> 00:43:32,866 And if you don't have a dose here like with proton irradiation, then no more side effects can occur. 458 00:43:32,866 --> 00:43:38,666 And that's obviously an enormous advantage, especially here, because it's mainly children and adolescents. 459 00:43:38,666 --> 00:43:43,099 and young adults, in whom these tumors frequently occur. 460 00:43:43,100 --> 00:43:47,033 And here, of course, this dose saving is of enormous advantage. 461 00:43:47,033 --> 00:43:51,199 I have another cross-section of this image in the area of the mediastinum, 462 00:43:51,200 --> 00:43:55,400 where you can see that the sparing of the heart is significantly better in proton therapy. 463 00:43:55,400 --> 00:44:03,066 This is one of the few indications for proton therapy where it is clear that protons are better 464 00:44:03,066 --> 00:44:07,932 and that as many patients as possible should be given this therapy. 465 00:44:07,933 --> 00:44:11,799 I say should, because unfortunately we don't have enough facilities because they are expensive, 466 00:44:11,800 --> 00:44:16,600 so that we can't treat all the patients patients we would like to treat there. 467 00:44:16,600 --> 00:44:23,833 And that brings me almost to the end, this is now a look at our particle therapy facility here in Heidelberg, 468 00:44:23,833 --> 00:44:27,366 the so-called Heidelberg Ion Beam Therapy Center HIT. 469 00:44:27,366 --> 00:44:33,066 And you can see that this is a very large facility, larger than a pure proton facility, 470 00:44:33,066 --> 00:44:39,499 because we don't just work with protons, but also with heavier ions, namely carbon and helium, 471 00:44:39,500 --> 00:44:44,700 We can generate oxygen, but we don't have a license to do that in patients, 472 00:44:44,700 --> 00:44:47,366 but we can treat patients here with protons 473 00:44:47,366 --> 00:44:52,599 and above all with carbon, and we already have a lot of experience in this area. The point I want to make is, 474 00:44:52,600 --> 00:44:57,833 when you go from protons to carbon, you need bigger accelerators, and that's what you see here, 475 00:44:57,833 --> 00:45:05,766 an accelerator facility, a so-called synchotron, similar to the LHC at CERN, comparatively small in comparison, 476 00:45:05,766 --> 00:45:10,966 but still with a diameter of over 20 meters. These are the machines that are needed to create such 477 00:45:10,966 --> 00:45:18,432 ions to the high energies that are needed to be able to irradiate deep-seated tumors well. 478 00:45:18,433 --> 00:45:23,599 And then it's distributed here, we need strong magnets to deflect these beams, 479 00:45:23,600 --> 00:45:29,000 these charged particles and then distribute them to the rooms. And here you can see on the far right: 480 00:45:29,000 --> 00:45:37,700 the major part of this system is this rotating irradiation device, this rotatable beam guidance, 481 00:45:37,700 --> 00:45:43,066 a so-called gantry, which is now of course considerably larger than in conventional therapy. 482 00:45:43,066 --> 00:45:46,399 And all of this naturally leads to greater technical effort, 483 00:45:46,400 --> 00:45:49,100 to a higher price compared to conventional therapy. 484 00:45:49,100 --> 00:45:54,600 Proton therapy can be realized somewhat more compactly, but is also significantly more expensive, 485 00:45:54,600 --> 00:46:00,800 than conventional therapy with X-ray radiation. The point I want to make, however, is much more that it is 486 00:46:00,800 --> 00:46:05,533 is not so much about the price, or should be. So of course that's an obstacle, 487 00:46:05,533 --> 00:46:07,533 but what matters is that we have the 488 00:46:07,533 --> 00:46:13,333 right patients here, because not all patients need such complex therapy. 489 00:46:13,333 --> 00:46:18,933 We just have to carry out studies to see which patients can be optimally treated here, 490 00:46:18,933 --> 00:46:22,599 and which patients should be treated at the conventional facilities. 491 00:46:22,600 --> 00:46:27,233 That is then an optimal use of resources resources, which of course we have to strive for, 492 00:46:27,233 --> 00:46:30,799 in order to obtain a cost-effective form of therapy. 493 00:46:30,800 --> 00:46:38,533 This facility in Heidelberg has been in operation since 2009, and we have proton and carbon, which we started with, 494 00:46:38,533 --> 00:46:45,266 also put helium into operation. We have been treating patients here since 2021. Helium has even more different properties. 495 00:46:45,266 --> 00:46:50,932 This is mainly about physical and radiobiological properties, in which these particles differ. 496 00:46:50,933 --> 00:46:56,633 Protons have a very similar effect to conventional irradiation with X-rays, 497 00:46:56,633 --> 00:47:03,066 Helium ions have the advantage that they can be focused better, they can generate sharp beams, 498 00:47:03,066 --> 00:47:10,432 and carbon, on the other hand, has a much stronger, biological radiation effect on the tumors, so we can mainly use 499 00:47:10,433 --> 00:47:17,233 radiation-resistant tumors better than with conventional technology or with protons. 500 00:47:17,233 --> 00:47:22,766 That brings me to the end of my presentation. I have a brief outline here once again, simply to illustrate the point, 501 00:47:22,766 --> 00:47:28,999 how radiotherapy has achieved this dose conformation by improving 502 00:47:29,000 --> 00:47:33,200 of the physical principles. That was - if you treated a tumor like that - 503 00:47:33,200 --> 00:47:36,900 In the 1980s, a tumor at the base of the skull tumor, you had 504 00:47:36,900 --> 00:47:43,700 more dose outside the target volume than inside. And through more complex techniques, more fields, 505 00:47:43,700 --> 00:47:49,700 higher energies and more complex optimization methods, in this case 3D conformational therapy, 506 00:47:49,700 --> 00:47:55,866 for example in the mid-1990s. This is the first time we have a volume that is irradiated, 507 00:47:55,866 --> 00:48:01,432 that is adapted to the tumor volume, i.e. no longer such a square box. And this could be further improved by the 508 00:48:01,433 --> 00:48:02,599 IMRT 509 00:48:02,600 --> 00:48:08,666 and then you can also see how these areas here outside the tumor, so to speak, increasingly change from red to yellow, 510 00:48:08,666 --> 00:48:11,666 into green, disappear completely at some point. 511 00:48:11,666 --> 00:48:14,666 And this is achieved, for example, with proton therapy 512 00:48:14,666 --> 00:48:21,166 where you can now see that you only have very low doses and really the optimal adaptation to the volume of such tumors. 513 00:48:21,166 --> 00:48:23,799 And that's what we do with adaptive therapy, 514 00:48:23,800 --> 00:48:28,466 what we are working on is now, in addition to this spatial adaptation, also a temporal adaptation. adaptation. 515 00:48:28,466 --> 00:48:34,366 That would be the next step, so to speak. But you can already see where physics and technology play an important role here. 516 00:48:34,366 --> 00:48:37,866 That brings me to the end and thank you for your attention.