Ion beams for cancer therapy: new technologies for treating inoperable tumours - July Lectures 2020

before we begin i'd like to acknowledge the waranjari people who are the traditional custodians of the land on which the university is built i'd also like to pay respect to their elders both past present and emerging of the kulin nation and extend that respect to other indigenous australians present [Music] well hello and uh welcome to the third of our july lectures in physics for 2020 my name is david jamieson i'm the organizer of the july lecture program and i'd like very much to introduce the new organizer of the july lecture program for 2021 and beyond uh dr susie she susie is an accelerator physicist uh who divides her time between melbourne and the university of uh uh and so this uh july lecture has the record of the uh most distant uh speaker from our traditional uh in lecture program uh brought to you by the miracle of the internet uh today susie heads up a major research program directed at using accelerators particle accelerators for cancer therapy and other applications she is adapting new technology that's been driven by the particle physics community for health applications she started her physics studies here in melbourne but then completed a d fill at the university of oxford on the design of new types of particle accelerator like our previous uh speaker last week she has held prestigious research fellowships including the same royal commission for the exhibition of 1851 fellowship and a royal society university research fellowship her research interests are truly global not just melbourne and oxford but she collaborates with researchers in switzerland the united states japan nigeria botswana and indonesia she is a talented science communicator and has shared her work uh on particle accelerators with uh tens of thousands of people at major festivals uh through the royal institution uh the discovery channel and indeed uh has been a speaker at the uh ted talk program that's now gathered more than 1.8 million uh views that's uh remarkable uh and if that's not enough she's also about to publish a popular science book which is due out next year so it's my great pleasure uh to introduce uh susie to you tonight that's a lovely introduction and um hello everyone uh we are here in my living room in oxford um but you can see i brought a little piece of australia along with me and tonight's light show is going to be about precision uh particle therapy applications of particle accelerators and i'd like to start today with a demonstration now i want you to watch this quite closely it's a little bit subtle this is a cloud chamber and it was invented in 1911 by charles wilson who was working in the cavendish lab in cambridge at the time and for about 11 years he would sit in his glassblowing laboratory blowing intricate pieces of glassware to try and come up with an apparatus which could recreate clouds in the laboratory now he was interested in atmospheric effects of light actually but what he found in around 1911 was something completely different what he found was when radiation x-rays or charged particles traveled through his chamber it would create little streaks with some threads of cloud as he called it now the version that you're watching at the moment and hopefully you can see some little streaks coming across every now and then um is a modern version of the device he invented and the way it works is there's a vapor of alcohol at the top which then falls down toward the bottom where there's a metal plate and underneath the plate is dry ice and that's the reason why i'm showing you a video i'm not doing it live because unfortunately i don't have dry ice at home um but what happens then is the alcohol enters a state called supersaturation where it really really wants to form droplets but it can't do without something called a condensation nucleus something on which the droplets can form and in the formation of clouds in the atmosphere usually dust plays this role but what wilson figured out was that the ionization that is radiation coming through the chamber and knocking off electrons from gas or air or water would cause enough energy to form one of these nucleation sites and to form a droplet and so what you can see in this chamber now is little streaks and threads of cloud that come through from charged particles traversing the chamber and this is a picture of wilson on the side from from around that time in 1911 in the cage right so one of the first things that wilson noticed when he was looking at these tracks in the chamber was that different types of radiation looked different uh now remember no one has ever seen radiation before at this point right no one has seen it in this way all they'd ever seen was alpha particles or x-rays impinging on a scintillating screen so they can see some one dimensional as it were image of it and now they could actually see the tracks of these particles going through the cloud chamber so i've shown some examples here of the different kinds of tracks that wilson and his colleagues and later people would have seen and so you can tell that there's clear differences between x-rays and electrons muons the heavy version of the electron which were discovered quite a few years later and alpha particles or helium nuclei and the big question really that underpins today in today's lecture is why do these look different and the reason is because x-rays and electrons sort of hang around and have many many interactions as they traverse through the chamber and that means that they they sort of scatter out the way that they do because they're quite lightweight and they interact fire by the electromagnetic force now neurons i'll leave until later but they're a little bit heavier and a little higher in energy but the the track i want you to focus most on is the alpha particle track this sort of short fat track it's leaving much more ionization in its wake than the electrons or the x-rays and the reason for that actually uh comes back to someone who was working in australia before wilson actually he moved to australia in 1904 and that's william henry bragg the father of the two braggs um who i think were mentioned in harry's lecture last week and he was working at the university of adelaide and looking at how alpha particles traverse through air and through different materials because they knew that alpha particles didn't travel very far um but they didn't know sort of what the effect was going to look like and their prediction was that the ionization rate that is how much the alpha particle interacted would decrease with depth so that as it came out of radium which was the source of alpha particles in those days as it came out of radium it would interact mostly when it had the highest energy and then it would sort of slow down and stop at the end but what bragg found was the exact opposite of that that the ionization caused by heavy charged particles like alpha particles and later we'll see protons and other ones as well actually increases sharply at the end of its range and he drew this uh picture which you can see in the middle these straight tracks and then at the end um you see they become sort of more wiggly they move around a little bit more and this was his prediction of what an alpha particle track would look like if it was traversing through if he could see it at the time right and this is this is sort of seven years before wilson was able to actually to to show it um and so actually wilson and bragg knew each other and so at one point in about 1912 wilson showed bragg what um the tracks of his alpha particles looked like in reality and wilson comments in his nobel prize lecture which he won for the cloud chamber later on that the similarity between the photograph and the ideal picture that brac had come up with was astonishing so now for the first time they could predict and understand the ionization of heavy charged particles as it went through mata and bragg actually drew uh later on he actually drew this kind of curve and this we'll come back to this later in the lecture which shows the depth in a material and in this case it was just air but the depth in the material versus the ionization rate which if we were talking in medical terms we would call that the dose so you see that there's a little interaction on the way in and there's more interaction right at the end of its range and the reason for that as opposed to x-rays and electrons is because the alpha particles are heavier and they're more similar weight to the the atoms that they're traveling past once they slow down a little bit and then they get sort of pulled in the cross section as we call it in physics the interaction rate gets higher and higher and higher and they lose a lot more energy in each of those collisions so suddenly this rate of collision and rate of ionization ramps up now even back in those days from the very early days of discovering radiation there were medical applications this isn't really a new thing you know radiation and x-rays were discovered in 1895 1896 and almost immediately they were being they were being used and here i've put two examples so on the left is radium therapy and radium as i said is an alpha particle emitter and there's a man here on the right hand side of the picture who is having his skin exposed to the alpha particles from radium who knows what was being treated but that was that was it and on the right hand side is an artistic view of a woman being treated using x-rays using a small x-ray tube and you can see she's holding up in front of her face a piece of metal with a small hole in it um so that the x-rays go only to the area of skin that she that they were trying to treat and actually radiation protection and the dangers of radiation are clearly known at this time as well right look at these images she's protecting the rest of her face from x-rays so they're not exposed and on on the other image the doctor is clearly standing meters away from the radium source so that he's not as exposed to it as the patient so just to be clear that first of all this process is is an old process but also that radiation protection has been important since the very start now why were they treating in that way well because at that time x-rays with small x-ray tubes and alpha particles which were emitted naturally couldn't reach very far under the skin in fact really they could only ever get a surface effect a skin effect and that's why they were using it in that way it wasn't possible for them to reach deep inside the body to reach things like cancerous tumors but that all changed in the 1930s and 1940s and the reason it changed started with ernest rutherford new zealander who was working in cambridge at the time and he was then the president of the royal society the preeminent physical society in the world and in his inaugural address to the society he was supposed to lay out the groundwork of what you know what these people what scientists should be doing in the future now at this point rutherford had discovered that the atom had a nucleus but it had been about 12 years since he'd actually made a major discovery and he was actually getting a bit frustrated because what he realized that he needed was as he describes it a copious supply of atoms and electrons which have individual energies far transcending that of the alpha and beta particles so he wanted to go beyond the energies that could be created from naturally occurring radiation sources and boost them up to higher energies so that he could overcome the electrical repulsion of the nucleus get particles into the nucleus and really start jostling them around to see what was happening inside the nucleus of the atom so this was driven by a desire to understand what we would now call nuclear physics and what happened as a result of that was that around the world physicists electrical engineers and researchers tried to create the first particle accelerators so and the way that they knew to do that at the time was that they knew that if they moved a charged particle through a voltage so if you move it through one volt it gains an energy and in physics terms we call that one electron volt of energy but to get particles into the nucleus they calculated that they might need up to something like a million volts in order to gain sufficient energy for for protons in particular to get into the nucleus and they tried all kinds of different ways to do this so they tried tesla coils um mel tube in the usa in that image actually worked with giant tesla coils like robert van der graaff who you might have heard of he invented a large dome structure with a charging belt which you might have remembered from school when you put your hand on top of one of those domes and your hair stands on end it builds up a very high voltage and in uh in cambridge in the uk coccraft and walton um built a sort of condenser rectifier system in order to slowly step up and double and double and double a voltage such that they could use it to accelerate protons now these weren't the only attempts these were actually just the most successful ones there were all kinds of other attempts and in germany there were actually researchers who went out into the mountains with lightning conductors and tried to conduct lightning to capture the high voltage there to use it to accelerate particles that's how desperate they were to actually get this high voltage and get these particles to explore the atom now the one of those german researchers actually died in doing that so obviously that is not a safe way to use high voltage but it's a good warning because at that time in the 1920s it was only in the late 1920s most homes even had electricity most people weren't really very familiar with electricity and here these guys were trying to use hundreds of thousands or millions of volts it was actually quite a frightening activity but they were successful and they built the first particle accelerators and they successfully got inside the nucleus and as we call it smashed atoms for the first time and the history of nuclear and particle physics is the result now i actually have a question for you and i'm not going to answer the question now i'll come back to it later on but it's it's one which i ask almost all my audiences and um unfortunately we don't have a mechanism to poll today so i'm going to ask you to hold the question in your mind or hold your answer in your mind until later in the lecture so i've just introduced the very first particle accelerators and you know you're going to hear about some more of them so i want you to take a guess of how many particle accelerators there are in the world and if you look closely i said not including cathode ray tube televisions so i want machines over about half a million half a million volts there's your categories one to a thousand thousand five thousand five to twenty thousand twenty to fifty thousand or more than fifty thousand so if you just remember a b c or d a b c d or e we will come back to it later in the lecture so thirties and forties we had the first particle accelerators world war ii then happens right and during world war ii was the development of radar and this made a big difference because to make radar work they needed high power radio frequency sources of electromagnetic waves and there were two different devices invented just before and during the war one was called a magnetron and one was called a quiestrum now we don't have time to go into the details of how they work but the most important thing is that after the war these high power voltage generating devices made the ability for particle accelerators to to shrink in size and in particular for electron accelerators it meant that they could build much more compact linear accelerators so in one of these images i'm showing you on the right is four guys standing in a row with what is a particle accelerator on their shoulders and now actually mimicking a photo from another group who built a proton accelerator on which there was 20 people sat on top of the accelerator because it was so large um and now these guys with their very high frequency high power devices were able to make them much much smaller so inside that device is is a series of what we call cavities so it's a metallic structure with a series of of cavities kind of like your microwave into which we pump electromagnetic radiation and that meant that instead of having one very high voltage like in cockroft and walton's case or van der graaf's case um they could use a lower voltage which oscillated up and down in time very quickly and then the particles would pass through the structure and gain energy as they went through and again as soon as this was invented it was almost immediately put to use in clinics in hospitals and by the 1950s radiotherapy in hospitals had started to take off and one of one of the pictures i've shown here is one of the very first linear accelerators in a hospital in the usa treating a cancer patient so how do these things actually affect cells well there's two different mechanisms there's either direct damage or indirect damage and the name of the game of course in something like cancer treatment is to treat the tumor cells and not the healthy cells but if you can deliver radiation to the tumor cells and we'll get to that in a bit you can either directly affect them by the radiation breaking strands of the dna directly and that will lead to apoptosis or cell death or indirectly where the radiation interacts with the material around say the water or something else um creates electrons through that process which are called in biological terms they're called free radicals and then it's those free radicals which do the dna damage and again it leads to cell death so it's direct and indirect methods the direct method with radiation is more effective if you can make it work better so i now have a problem for you so we have now these high energy accelerators and they create electron beams and they hit targets and they generate x-rays and those x-rays now are high enough energy that they can penetrate into the body now imagine that it's the 1950s and you're a doctor and you're treating a patient who has a tumor and that tumor rather than being on the surface is deep inside the body and you have this beam of x-rays now that can destroy the cancer cells but they're also going to destroy healthy tissue so the question is how do you treat the patient while you're thinking about that i have a little story for you so this is a fortress and inside the fortress lives a dictator and there's a general with a large army who wants to overthrow the dictator but all the roads around the fortress are armed with landmines that will go off of too many people um walk over the path at the same time so to solve the problem the general has a great idea and he says okay i'm going to divide up the army into small groups and each group is going to take take a different road into the fortress so all the all the army meet at the same time at the fortress and they take the fortress back from the dictator hopefully that gives you an idea now in physics we call this kind of thinking this way of bringing um an idea from one area like a story um into another area it's called analogical reasoning and we actually as physicists we're trained quite specifically to think in this way to think of concepts and ideas from our everyday life and then apply them in other situations and so the solution hopefully most of you have come up with it independently apparently after after giving the hint of the fortress 60 of people actually get the solution but i suspect in this audience this will it was more like 99 to 100 of you so the solution is that you send in the beans of x-rays with less intensity or lower lower number of electrons lower damage from many different angles so that the same amount of radiation is absorbed by the tumor cells that you want to treat but there's less damage to the healthy cells around it and that is the solution that they came up with so this image is a picture of a radiotherapy accelerator with the edges of the nice plastic enclosure kind of grayed out so we can see what's inside and inside is this long metallic structure which accelerates electrons between roughly six and 25 million electron volts the electron beam is then bent around 270 degrees and sent downwards onto a metal target which generates x-rays to a process called brimstradling then these x-rays are shaped using a complex collimation system called a multi-leaf collimator which is individually controllable and even dynamically movable during a patient treatment this whole device then is mounted on a structure called a gantry which can rotate 360 degrees around a patient in order to deliver beams from many different angles and the job one of the jobs of medical physicists is to calculate a treatment plan that best optimizes the maximum dose to the tumor where it's required and the minimum dose to the healthy tissue because that is the whole game of radiotherapy is increase the dose where you want it decrease the dose where you don't want it and radiotherapy has been phenomenally successful since its invention in roughly the 1950s and today it's used in about half of all cancer cases where it's available now it is a sad fact that roughly one in three people in the uk or australia or the usa will be diagnosed with cancer at some point in their lifetime but techniques like radiotherapy along with chemotherapy and other methods have meant that cancer is no longer a death sentence in fact cancer survival rates have more than doubled since the 1970s and it's partly because of the invention of all this amazing technology that that that is true so your chances of living after being diagnosed with cancer have never been higher so that was radiotherapy but at the same time that all of that story was happening physicists of course were still in the lab and they were still trying to come up with particle accelerators for their purposes which was to try and smash atoms to try and delve into the nucleus and later to try and even find new particles that have led to our current understanding of particle physics and back in 1932 while cockroft and walton were doing their thing another guy ernest lawrence in the usa came up with a different way of accelerating particles and instead of accelerating them in a straight line he wanted to accelerate them in a circular structure so that he could use a lower voltage on each turn but send the beam around in a circle using a magnetic field and by doing so it would go back through the voltage again and again and again and gain a little bit of energy on each turn and the concept he came up with was called the cyclotron now the first cyclotron is in the top left of the screen here and it's literally small enough to fit in your hand and that was enough to give protons 80 000 electron volts of energy much smaller than the other devices now of course this is just the beam chamber in which the protons spiral the magnet itself was a little bit larger but it was still roughly table top size but over the next decade or so ernest lawrence and his student milton stanley livingston who's the one who actually built and designed and operated most of the machines came up with larger and larger machines to reach higher and higher energies to delve further and further inside the atom and the culmination of that program actually moved up the road up the street um to a place which is now called lawrence berkeley national lab in the usa and they built this enormous cyclotron with 184 inch pole face and now it's so large that the entire team which you can see has grown actually fit inside the pole of the cyclotron and this really is the first era of um of big science lawrence was really great at bringing together multi-disciplinary teams to create solutions to problems that that couldn't have been found using just physicists or engineers or small teams so they had this enormous cyclotron and by the way along the way here ernest's brother john who was a medical doctor came and joined the laboratory and so medicine and accelerators kind of grew up together in their space and what emerged was first of all radioisotope production which is used for a lot of diagnostics in the body but also the first um the first use of different types of particles in the medical field and this by the way is just a schematic of what the particles do inside one of these cyclotrons um and it's from ernest lawrence's original patent so one of lawrence's students then after the war robert wilson decided like many other physicists that they now wanted to use what they knew about physics you know they were no longer at the behest of the government to try and make nuclear weapons or radar or anything else they could do what they liked with the knowledge that they had gained and robert wilson became quite interested in using um what they what they learned in medicine and he published a paper in 1946 which has become the the pinnacle you know the the absolutely first important paper in the field of what's now called proton therapy so what he realized was that now that they have these large accelerators with hundreds of hundreds of millions of electron volts of energy that these beams of charged particles were now fast enough that they could penetrate into the body and i've underlined in red here but i'll read it out what he notes is that the dose is many times less where the proton enters the tissue at high energy than it is for the last centimeter of the path where the ion is brought to rest and hopefully this reminds you of what bragg was doing in 1994 and the cloud chamber that we saw at the start but now now the energy is high enough that the particles can reach deep inside the body and what wilson had actually come up with was another analogical reasoning solution to the fortress problem and to the radiation problem that i showed you before only the analogy that we're using this time is a different myth or a different um story it's what the one of the trojan horse so that is another valid solution to the problem that we saw before right you can either deliver from all different directions or you can send something in which doesn't set off the minds and once it's inside it unpacks and delivers more of a punch and that's effectively um the difference between radiotherapy and proton therapy so as physicists i like to draw a plot about this so when you look at the depth versus dose or ionization of the different types of radiation it's really really starkly clear as as you get deeper into the body the um the ionization and the dose from protons increases towards the end of its range and the opposite is true for photons or x-rays the highest dose is actually under the skin and then it drops off as you as you go in and this is now a modern measurement of what that looks like this isn't just just a concept this is this is real if you get high enough beam um of protons or heavy ions like carbon ions you actually get this sharp peak towards the end of the range and this is this is the idea on in on which proton and heavy ion therapy are actually based and you'll see in the plot that i've just brought up there on the right hand side that there's actually two peaks there's a red and a green one the green one is for protons and the red one is for heavier ions like carbon and i'll come back to that idea in a little while so that was 1946 when robert wilson first came up with this idea and when accelerators looked like they could do it but as a therapy it didn't take off until roughly the 1970s now there were all kinds of clinical trials that happened especially at berkeley lab at lawrence's laboratory using that big cyclotron i showed you before but to make it really work what we needed was the emergence of computing technology on the left there is one of the first computers in the world the eniac and on the bottom right is what a personal computer would have looked like at the end of the 1970s and using that computing technology combined with things like x-rays and other physical effects also caused a revolution in imaging um and that was required so that people could actually see where tumors were and where lesions were inside the body without having to cut open the patient so the top right there is the first ct scanner computed tomography scanner which is now in the science museum in london and that was used to make the first scan of the brain at first and then they built a full body one in 1971 on the bottom right is a picture of the development of magnetic resonance imaging or mri scanners which has a whole other story linked to particle physics but that's a different lecture but now what we had is the ability to image inside the human body so we had computing revolution the imaging revolution and we also continued to have evolutions in the design and development of particle accelerators so now for particle physics these machines got larger and larger and larger um the photo the large photo there is of the bevertron also at lawrence's laboratory at berkeley and the top right is called the cosmetron which was at brookhaven national lab now on the bottom right there you can see that the beam chamber the chamber through which the proton being traveled was actually so large you could drive a car through it and developments over time have allowed us to shrink down the size of that vacuum chamber by having stronger focusing and stronger magnets so now all those different parts came together and from the late 70s onwards people were able to think about how to use charged particles to treat cancer and the cases in which that might be more effective than using x-rays so here's an example which is a slightly unfair example because it just uses a single field of x-rays and a single field of protons but it illustrates the point nicely so this is a ct scan of a child so the side view and then the views that have cut through as a cross section and this is a case where the child had surgery at first to remove a tumor from the base of the skull called a medulloblastoma and then what they need to do is treat down the spine with radiation in order to prevent um what was left over from the tumor metastasizing and spreading down the spine now if you were to use x-rays and you probably wouldn't in this case because you can see that there's a whole lot of extra radiation dose in the child's body that you don't want to be there you don't want to add that additional dose because especially with a young patient that could cause um secondary cancers later in life if you if you deliver too much radiation to healthy tissue now if you use protons instead because they come to a stop at the end of their range you can actually get a much better shaping of that radiation field and deliver no dose at all in the rest of the body as i said this is a slightly unfair comparison but it does tell you the point and nowadays most oncologists estimate that proton and ion therapy could be better and useful in around 10 to 20 of cancer cases i've said 10 because estimates vary and there are oncologists out there who believe it would be unethical to use anything other than protons and carbon ions on pediatric patients in particular because of the because it delivers dose more precisely to the area um that they're trying to reach so in 1992 now there were all these clinical trials over time right but in 1992 that this was the first time when people built a full-on particle accelerator for proton therapy in the basement of an actual hospital at loma linda in california so that was 1992 and you can see over time i know you're used to seeing lots of exponential curves at the moment but here's another one you can see over time you know the sort of exponential growth uh in facilities as as this as this protocol really took off now i entered the field in about 2007 when i started my phd and there were about 23 different centers around the world for proton and ion therapy at that time and when my phd student the other day went to give a presentation in his slides he said there's over a hundred and i said go and check the number that can't be right that's too many are you sure and it was it was right it it surprised even me how many facilities have been built even in the time that i've been working on them and nowadays for proton therapy most of the facilities use a cyclotron and those cyclotrons have come down in size using superconducting technology and there's a picture of one on the left here that's um that's at psi in switzerland that's actually not a superconducting one but the supernatural ones are even smaller now this isn't about just big technology right the main point in doing all of this is about the patient and so here's an example myla adams of a child who had a tumor behind her right eye now using x-ray therapy using surgery using chemotherapy which she went through as well which is why she's losing some of her hair there was no way to both fully treat that tumor and preserve the child's brain function and and the eyesight of the child but because of the precision of proton therapy they were able to fully remove the tumor using protons and maintain preserve the eyesight of that child and the difference in quality of life um for a patient i mean you know imagine the difference in quality of life of a child who loses eyesight and loses brain function because of having a tumor when she's young versus you know the current situation for myla who will now go on and lead a normal life as normal as every other child who never had a tumor and in my career i've had the absolute privilege of meeting a number of patients who've had a similar experience who've had eyesight preserved who've had brain function preserved who've had organ function preserved within the body because of the precision of this treatment so that's what it's all about the patient is really at the center so over time now roughly 250 000 patients have now been treated with proton therapy this is not an experimental treatment at all it is completely mainstream but you'll see a lower number at the bottom there the orange curve shows the numbers that have been treated with carbon ions with heavier ions now this is a slightly different story protons are the easiest particle that we can use this for because it's one of the lightest heavy charged particles that we have so it has the brag peak it has this precision but actually what they found in the early clinical trials at berkeley and what they're slowly gathering evidence of since then is that heavier ions like helium carbon oxygen and nitrogen are actually most effective in treating treating cancer and there's two ways that i've chosen to show this so the plot on the left is actually taken from a recent a recent paper and this shows the dose on the x-axis versus the surviving fraction of cells that have been irradiated on the y-axis and it's a little not obvious to read it at the start but the red lines there are protons and the black lines are x-rays so what that tells you because they overlap is that to kill um the same number of cells you require the same amount of dose to the tumor of protons or x-rays and it's roughly a factor of 1.1 actually protons are slightly more effective but the blue lines show you what happens with carbon ions and it turns out carbon ions are actually more radiobiologically effective for the same amount of dose they kill more cells than protons or x-rays and that's what makes them more effective so on the bottom right there is a little sort of cartoon diagram of why this why this is so x-rays and and protons in the middle there they cause damage to the dna as i described the protons are a little bit more likely to make direct damage which is more effective giving that 1.1 factor but carbon ions and heavier ions are much more likely to break not one but two strands of the dna which makes it even more effective now i'm sure by this stage you've heard enough from my voice so i just want to show you a video of one of those facilities which has come now not just using protons but also using carbon ions and i want you to notice the scale of this facility which we'll come back to in a minute the first hospital-based synchrotron at a clinic in europe exclusively devoted to medical treatment with protons and ions is located in germany in the heart of heidelberg's hospital complex it is called hit which stands for heidelberg iron beam therapy center and it was inaugurated in 2009. and under the hill we find the synchrotron a circular particle accelerator 65 meters circumference it's essentially made of a vacuum tube that we find here inside particles ions of carbons or protons and it is surrounded by a series of magnets the red ones dipoles they bend the beam the yellow ones quadrupoles they focus the beam inside the vacuum tube the hadronic particles protons or carbon ions they come from behind that wall where a linux a linear accelerator pre-accelerates them and injects them into the synchrotron where they do quite a few tours before reaching three quarters of the speed of light let's follow them in their circular [Music] orbits once the particle beam has reached three quarters of the speed of light and the necessary energy to kill tumor cell it is extracted right in this point canalized and it reaches three different treatment rooms plus one destined to medical research before reaching the patient the carbon iron beam that comes from behind that wall has to go through this gigantic apparatus 60 600 tons it's a gantry and it's necessary to orient and steer the beam in the most accurate way and with the right angle right on the tumor [Music] hit is the world's first therapy facility with a gantry with this movable radiation source radio oncologists can guide the iron beam into the patient at the optimal angle as the beam head can be rotated by 360 degrees and numerous angles of irradiation can be selected so that is currently what a hadron therapy including protons and carbon what one of those facilities actually looks like and i hope you'll agree it is a very impressive piece of technology designed simply to be able to treat inoperable and sometimes incurable cancers now let's talk a little bit about the situation in australia because at the moment we don't have one of these facilities operating and just a few patients each year are actually selected to be sent abroad to usually the usa for treatment but not for much longer because there is a proposed network of facilities in australia for protons and later for heavier ions as well now in australia there's 145 000 new cases of cancer diagnosed each year and as i said up to 10 of those cases could benefit from proton or ion therapy and the very first center likely to get online which has broken ground and is currently being built is called the bragg center for proton treatment and research and that's based in adelaide but there are also plans for a national coordinated network of four different centres in sydney melbourne brisbane and adelaide and that is where we come in um so one of the reasons that i have come back to australia after 13 years in the uk is to get involved in this movement in australia to bring proton and ion therapy to australia now australia shouldn't just be the kind of country that buys the technology developed from somewhere else but we should be a country that are at the cutting edge development of this kind of technology so my new group is called medical in is in the field of medical accelerated physics what we plan to do and these are some of my students in the photograph with me here is to study and design new types of accelerators that can try that can try and solve some of the issues with the existing ones and to optimize this kind of treatment and we're standing here at one of these large facilities called medostron in austria and this is again a synchrotron that provides carbon ions and proton or therapy so what are we working on well of course we'd like this technology to be smaller cheaper we'd like it to consume less energy that's important and of course to deliver the most optimal treatment possible and we don't have that many years experience especially with carbon ions so a lot of these things are still being done as radio biological research as clinical trials and so forth but at the same time there are so many new technologies that have come from the development of mostly particle physics experiments that we can think about bringing these different strands together to try and create the next generation facility so there's take away words that are being talked about in the center of my side here in new studies that are happening especially in europe led by cern to as to what these facilities would look like in the future so they need to be smaller and cheaper they need to deliver being fast so there's a high patient throughput they need to have real-time imaging uh lower energy consumption high intensity beams so there's no limitation in the intensity or the dose that's delivered possibly with on-board mri scanning so that you can image and treat on the same system and once again everything comes back to the patient start at the patient the patient's quality of life and their outcomes and so there are two two or three technical options on the board at the moment one is a super conducting synchrotron so that's trying to shrink down the size of the machine itself by using high field magnets that are super conducting but somewhat like the large hydrogen collider magnets and then the other option is a linear accelerator which for many years hasn't been thought of for proton and carbon therapy but now the rate of acceleration we can get in these machines is starting to look like perhaps they might be applicable to this technology and my group at the moment are involved in this international design study and actually the underlying design of the synchrotron is actually coming from one of my phd students who will be highly embarrassed um to be mentioned in my talk i'm sure but he's doing a wonderful job the other aspect that we're looking at is actually the treatment gantry now if you remember back to that video this enormous blue rotating structure that was 600 tons it's the size of a cathedral and it rotates around the patient now as the patient i should be clear you don't see it right inside the treatment room where the movable couches are they have wonderful um movable walls around you so that you don't see this enormous enormous equipment sitting behind it but one of the aims of my group is to also look at new options for these treatment gantries to make those smaller more compact more efficient and better suited to the type of treatment that we're trying to do so i want to come back because there's an open question that i left earlier and one of those was how many particle accelerators are there in the world now i've only really covered hydrogen therapy accelerators which are a tiny proportion the actual number for those of you who like a pat on the back is between 20 and 50 000 and that number is creeping up all the time last time i checked it was 46 000 so i'm gonna have to change the quiz soon to have different categories um so where are all these accelerators well this is a rundown of what where they were at in about 2011 and since this time actually the graph has changed ever so slightly slightly but roughly almost half of them are radiotherapy they're used for for cancer treatment those small machines that rotate around the patient delivering x-rays that are the mainstay of cancer treatment there's about 12 and a half thousand of those in the world um most of the rest of the other half are industrial applications iron implantation things like that now this graph has actually changed ever so slightly since 2011 because the industrial applications have actually grown so let me show you some of the applications very quickly outside medicine of these of these kinds of themes and of the development of this technology now in the usa alone there are about 500 billion dollars worth of products annually that are treated with things of radiation using accelerators they scan cargo they sterilize medical equipment so all this all the um yeah all the masks all the syringes everything that's currently being used in hospitals has to be sterilized and that's often done using themes of electrons or even high energy gamma rays which means that you can sterilize something without having to chemically treat it which might destroy it they treat waste water from chemical plants they can change the color of gemstones by changing the crystal lattice structure and they even make the chips inside your mobile phones by implanting individual ions into silicon substrates so they are everywhere so they're the small scale ones that are more similar to the ones that were invented right back in the 1930s and as time has gone on and as accelerators have gotten bigger and bigger more and more applications have emerged and one of them you already have in australia which is a synchrotron light source which is outside melbourne and that's used for all kinds of fascinating research and harry actually pointed to some of the methods used on that crystallography um in last week's lecture so that's done things like uncovered the structure of the nucleosome it's uncovered the structure of foot and mouth virus and around the world every synchrotron light source right now is being used um to uncover the structure of the corona virus in order to to make new vaccines based on on the structure of it which is exactly how a virus works um so if there are brand new vaccines that come out you can be guaranteed that they originally came from uh from a synchrotron synchrotron light source but it's used in all sorts of things in um in heritage studies looking at ancient manuscripts and then on the flip side the proton accelerators the large proton accelerators which is more of what i've worked on in my career can also be used to generate things like neutrons and muons and they're complementary to synchrotron light sources so then these particles travel all the way through and interact most strongly with things like water and so these can make safer planes trains and cars they can go all the way through metallic objects to look at for example the stresses and strains in an aircraft wing like the airbus a380 which i'll be flying on over to australia in about a month and a half's time now if i if i am if i'm going to leave you with one thing to remember about this lecture is that all of this all these cancer treatment applications all the imaging technology and a lot of other things have all come from curiosity driven research and i've plotted here or found a plot which which covers the energy of particle accelerators on the y-axis over time and you can see that as people have explored deeper into the atom deep into the world of particle physics more and more and more uses for what we've found have sprung up which have changed society so i want to kind of leave you with the idea that if you were to ask yourself where do the ideas behind our modern technology come from the answer is almost always curiosity driven research it may take 50 or 100 years to come to fruition but that is where it comes from and much of the technology we have today from smartphones to the internet to cancer treatment comes from research in physics and we can't predict today where the kinds of research that we're doing will take us and i've shown you here the large hadron collider the saber dark matter experiment in a minor victoria and a neutrino detector but i can guarantee you one thing and that is it's going to be an incredible adventure and one that i'm really proud to be part of and i'm just going to finish with a quote from john wallacely who's former ceo of the research council in the uk who said particle physics is unreasonable it makes unreasonable demands on technology and when those technologies those inventions those innovations happen they spread out into the economy and they generate a huge impact they'll leave you with that thought thank you very much for watching well susie thank you very much for for that very wide-ranging uh uh lecture as you know in our school we we have uh uh one of the earliest except we had one of the earliest accelerators in the world just a few years after they were first invented in cambridge and of which the palatron in my lab is the descendant of that early machine tell me why do you think australia has been so slow to adopt this uh this technology and why do we why are we still sending uh patients over to the united states for the therapy so i think i think there's a couple of reasons so um this has been looked at in australia for about 20 years there's been people trying to lobby for this kind of treatment and the truth is that actually our radiotherapy our x-ray radiotherapy wasn't yet up to international standard and wasn't what it wasn't yet accessible to all to all citizens of australia because we have an unusual geography globally um and so when you concentrate cancer centers around the major cities um there was a study that was done that showed that for every hundred every sorry for every 100 kilometers that's right that someone lived from one of those cancer centers their chance of actually taking up that treatment decreased by 10 so if you lived over a thousand kilometers from a cancer treatment center you know your equity of access to cancer treatment wasn't there so that um that issue has now you know people have been trying to address that issue first before jumping in with um larger more expensive infrastructure more precise technologies so so that's i think you know we looked in our own backyard first as it were um i think there's two other aspects one is yes it is a large investment in infrastructure um these facilities don't come cheap they're quite large that's why we're starting with proton facilities they are a lower um financial investment but obviously you know not uh not uh not much lower in terms of treatment outcomes right it's that's what you want that's what you should do um finally i think the other thing is we didn't really develop accelerators in this country we haven't um for many many years since roughly the 60s when there was a novel cyclotron actually developed at the university of melbourne um and that's part of the reason the physics community and ansto and the government have sort of come together and gone oh we need you know actually we need to support this area of research and um you know to my to my benefit and my pleasure to come back and be a part of that building up that research to make sure that we don't just as i said have the capacity to buy these facilities um but we also have the capacity to influence the future direction of the field i should remind uh the audience that if they go to the bottom of the screen they should see the q a button where they can type in uh some questions okay so we let me go over to the audience questions uh kenton thompson asks will ultra high dose rate flash be a game changer great question thank you um so so flash for those of you who haven't heard of it is there's studies that have come out and now clinical trials as well that show that using a very high dose rate of radiation and most of the studies have been done with x-rays rather than charged particles um show that there is a saving effect on normal cells and obviously an increased killing effect from the higher dose on on cancer cells so that's a very exciting prospect so the way in which that could change the game is actually reducing the number of fractions that patients have to go in for so at the moment if you go for radiotherapy or proton carbon therapy treatment it's not just one treatment right you have to go back 25 times usually um so monday to friday five days a week for five weeks um that can be very disrupting to people's lives but the reason is because that gives a chance for healthy tissue and healthy cells to recover and they recover preferentially compared to tumor cells within that time so we're really playing that game with trying to save healthy tissue while damaging the tumor cells so if this mechanism is very high dose delivery mechanism turns out to be successful then yes we could reduce the number of times the patients have to come to clinic while delivering them an optimal treatment and that would massively change the gain in terms of the cost of all kinds of different treatments and people there are consortiums around the world looking at how we can do that for protons and heavier ions and that is one of the considerations trying to increase that dose rate that we're looking at in the future design of the facility yeah i might just take one further question which i'll paraphrase i think you showed the uh figures for the number of facilities uh in operation around the world which implies there are a lot of people being treated uh with this new technique or not so new technique would you say it's uh still uh in the optimization phase or would you say proton and the emerging carbon beam therapy is now a mainstream uh therapy i would i would call them both mainstream therapies and that's what they're not being done in you know in physics clinics or anything like that under clinical trials these are these are therapies that doctors know about and refer patients to um they're just slightly more expensive and rarer to get hold of than say radiotherapy so they're absolutely mainstream but i will point out that you know medicine and medical treatments even radiotherapy treatments is a constant evolution right it's a constant optimization as technology improves and so occasionally you know usually you'll get incremental improvements but occasionally in these fields you can also get sort of quite game game-changing improvements as well whether that's a new accelerated technology um a new treatment protocol like flash as we were talking about um or even a new particle species or something so there's so while it's a mainstream treatment um there's always room for improvement okay well look i will leave it there so uh let me thank uh thank the audience stay safe out there everyone

Channel: The University of Melbourne

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Length: 59min 13sec (3553 seconds)

Published: Sun Sep 20 2020