WEBVTT 00:00:08.360 --> 00:00:10.839 Welcome to Nuclear Matters from the Australian 00:00:10.839 --> 00:00:13.400 National University College of Systems and Society. 00:00:13.960 --> 00:00:16.719 I'm your host, Liz Williams, a nuclear physicist 00:00:16.719 --> 00:00:19.179 and nuclear systems discipline lead for the ANU 00:00:19.179 --> 00:00:23.320 School of Engineering. In today's episode, we 00:00:23.320 --> 00:00:25.399 explore how nuclear technologies play a role 00:00:25.399 --> 00:00:28.140 in enabling life -saving cancer treatments. Our 00:00:28.140 --> 00:00:31.679 guest, Eva Bezak, is Professor of Medical Radiation 00:00:31.679 --> 00:00:34.219 at the University of South Australia and President 00:00:34.219 --> 00:00:37.000 of Asia Oceania Federation of Organizations for 00:00:37.000 --> 00:00:40.920 Medical Physics. I've asked Eva to join me today 00:00:40.920 --> 00:00:43.039 to find out more about how nuclear technologies 00:00:43.039 --> 00:00:45.600 for medical applications get developed and used 00:00:45.600 --> 00:00:48.859 to treat patients across Australia. To get us 00:00:48.859 --> 00:00:51.119 started, I asked Eva to give us a sense of how 00:00:51.119 --> 00:00:52.920 many people's lives are likely to be touched 00:00:52.920 --> 00:01:01.070 by cancer. Cancer would be, you know, one of 00:01:01.070 --> 00:01:04.569 the number one diseases in the country that will 00:01:04.569 --> 00:01:08.969 be affecting one in three to one in two Australians 00:01:08.969 --> 00:01:13.030 in their lifespan, especially since we are living 00:01:13.030 --> 00:01:16.629 longer. And we have a couple of main sources 00:01:16.629 --> 00:01:20.170 of therapies, which is, of course, surgery, chemotherapy, 00:01:20.709 --> 00:01:25.359 immunotherapy. but not least radiation therapy, 00:01:25.640 --> 00:01:30.180 where we're using primarily radiation X -rays 00:01:30.180 --> 00:01:33.780 produced by medical linear accelerators or photons 00:01:33.780 --> 00:01:41.459 to deliver energy to cancer and causing enough 00:01:41.459 --> 00:01:46.959 cell damage to eradicate the cancer cells. Radiotherapy 00:01:46.959 --> 00:01:50.819 is actually extremely effective in treatment 00:01:50.819 --> 00:01:55.319 of localized cancer in particular and should 00:01:55.319 --> 00:01:59.620 be used for the treatment of about 50 % of cancer 00:01:59.620 --> 00:02:04.019 patients and the local control of the disease 00:02:04.019 --> 00:02:07.739 where the primary tumor is, it is as effective 00:02:07.739 --> 00:02:13.539 as surgery. So it actually represents a very 00:02:13.539 --> 00:02:17.639 cost effective as well as treatment -effective 00:02:17.639 --> 00:02:22.699 therapy. Where the radiotherapy has maybe disadvantage 00:02:22.699 --> 00:02:28.259 is when the disease spreads, and then we need 00:02:28.259 --> 00:02:31.539 to look at something like chemotherapy. So in 00:02:31.539 --> 00:02:34.060 many cases, radiation therapy is a really useful 00:02:34.060 --> 00:02:36.919 treatment. And what you're doing is using a linear 00:02:36.919 --> 00:02:39.099 accelerator to generate x -rays that you can 00:02:39.099 --> 00:02:42.080 then use to kill cancer cells. I want to understand 00:02:42.080 --> 00:02:44.919 how this kind of treatment is delivered in hospitals. 00:02:45.139 --> 00:02:47.620 So can you tell me what it's like to be involved 00:02:47.620 --> 00:02:49.500 in this kind of treatment from a clinician's 00:02:49.500 --> 00:02:53.479 perspective? Absolutely. So the day of a medical 00:02:53.479 --> 00:02:58.139 physicist is varied. Sometimes it can start early 00:02:58.139 --> 00:03:01.639 in the morning because before a first patient 00:03:01.639 --> 00:03:06.460 comes to the department. All the equipment, including 00:03:06.460 --> 00:03:11.340 accelerators, CT scanners, data servers need 00:03:11.340 --> 00:03:15.199 to be turned on. And in the morning, some initial 00:03:15.199 --> 00:03:19.099 quality assurance is performed. So what I usually 00:03:19.099 --> 00:03:22.360 teach the students that radiotherapy is a double 00:03:22.360 --> 00:03:26.900 blind date. You don't see the tumor and you don't 00:03:26.900 --> 00:03:30.340 see the radiation, yet you want to deliver that 00:03:30.340 --> 00:03:33.719 radiation with. utmost precision and accuracy 00:03:33.719 --> 00:03:38.280 to the target volume because radiation is also 00:03:38.280 --> 00:03:41.740 detrimental to a degree to healthy tissues and 00:03:41.740 --> 00:03:45.120 if you miss the cancer then you might be giving 00:03:45.120 --> 00:03:47.919 unwanted amount of radiations to the healthy 00:03:47.919 --> 00:03:52.860 tissues causing negative side effects so when 00:03:52.860 --> 00:03:56.599 the therapist turn on the machine They want to 00:03:56.599 --> 00:03:59.919 ensure that the right amount of radiation is 00:03:59.919 --> 00:04:03.620 coming in the right direction. And they trust 00:04:03.620 --> 00:04:07.659 medical physicists that we have done all the 00:04:07.659 --> 00:04:10.580 necessary testing and quality assurance measurements 00:04:10.580 --> 00:04:15.539 to ensure that the therapist can absolutely rely 00:04:15.539 --> 00:04:18.939 on the linear accelerator to perform its task. 00:04:19.120 --> 00:04:24.680 So often we are the people behind. calibrating 00:04:24.680 --> 00:04:28.540 and testing the accelerator and its performance. 00:04:28.920 --> 00:04:32.699 Okay, so let's just talk through this in kind 00:04:32.699 --> 00:04:35.579 of a step -by -step fashion. Let's say you have 00:04:35.579 --> 00:04:38.540 a tumor, you kind of know at least based on imaging 00:04:38.540 --> 00:04:41.480 where it is, how large it is, where it sits in 00:04:41.480 --> 00:04:44.519 the patient's body, right? We're starting with 00:04:44.519 --> 00:04:47.040 a scenario like that. And so for radiation therapy, 00:04:47.240 --> 00:04:50.910 you would want the linear accelerator. to produce 00:04:50.910 --> 00:04:54.769 the radiation you need and the intensity that 00:04:54.769 --> 00:04:58.449 you need, the shape that you need, right? Absolutely. 00:04:58.769 --> 00:05:03.410 To irradiate the tumor, but as much as possible 00:05:03.410 --> 00:05:06.930 to avoid the healthy tissue surrounding. So the 00:05:06.930 --> 00:05:09.350 calibrations that you're talking about, the quality 00:05:09.350 --> 00:05:11.689 assurance, it's all about ensuring that you have 00:05:11.689 --> 00:05:17.129 very high level of understanding about what radiation 00:05:17.129 --> 00:05:19.519 the machine is producing, what shapes. You know, 00:05:19.560 --> 00:05:21.860 it's irradiating, that kind of thing. Is that 00:05:21.860 --> 00:05:25.420 about right? Yes. In order to irradiate the tumor, 00:05:25.740 --> 00:05:29.060 we need to understand the linear accelerator. 00:05:29.120 --> 00:05:32.240 When the X -rays are produced, the treatment 00:05:32.240 --> 00:05:36.519 head sits on the rotating gantry. That gantry 00:05:36.519 --> 00:05:41.610 weighs around six tonnes, three Commodores. or 00:05:41.610 --> 00:05:44.149 I should call it three Fords since we no longer 00:05:44.149 --> 00:05:47.509 produce Holdens in the country. And it rotates 00:05:47.509 --> 00:05:51.069 around the patient with the accuracy of about 00:05:51.069 --> 00:05:55.350 two millimeters. Part of those checks are also 00:05:55.350 --> 00:05:59.569 mechanical checks as well as radiation checks. 00:05:59.910 --> 00:06:04.870 But before the patient even gets onto the linear 00:06:04.870 --> 00:06:09.529 accelerator, we need to perform the dose calculations. 00:06:11.000 --> 00:06:14.699 on the CT image of a patient. So we call that 00:06:14.699 --> 00:06:19.879 treatment planning. So in addition to just, you 00:06:19.879 --> 00:06:22.540 know, the patient doesn't just come and is positioned 00:06:22.540 --> 00:06:25.240 on the patient couch to deliver the treatment. 00:06:25.740 --> 00:06:29.399 There is this big preparation period when we 00:06:29.399 --> 00:06:32.459 acquire a CT, three -dimensional CT image of 00:06:32.459 --> 00:06:35.959 the patient, where we outline the target volume 00:06:35.959 --> 00:06:39.600 and the shape of the target volume. And we also 00:06:39.600 --> 00:06:44.000 outline the surrounding healthy tissues, which 00:06:44.000 --> 00:06:47.860 are also called organs at risk or critical structures. 00:06:48.180 --> 00:06:52.600 And then we use very sophisticated treatment 00:06:52.600 --> 00:06:57.500 planning, dose calculation algorithms. that allow 00:06:57.500 --> 00:07:02.480 us to optimize the intensity and direction of 00:07:02.480 --> 00:07:06.000 the radiation from the linear accelerator gantry. 00:07:06.240 --> 00:07:09.079 For example, we will not irradiate through spinal 00:07:09.079 --> 00:07:13.339 cord. Yeah, okay. I'm assuming that causes lots 00:07:13.339 --> 00:07:17.240 of problems. Absolutely, yeah. So only when we 00:07:17.240 --> 00:07:20.800 have pre -calculated how the dose should be delivered. 00:07:21.629 --> 00:07:25.170 and the clinician improves that dose calculation 00:07:25.170 --> 00:07:29.389 and dose distribution, that will be then transferred 00:07:29.389 --> 00:07:34.490 online digitally to the linear accelerator, and 00:07:34.490 --> 00:07:38.649 then that treatment can be delivered. I was also 00:07:38.649 --> 00:07:41.750 talking about that, you know, we don't see the 00:07:41.750 --> 00:07:46.199 tumor. Our modern linear accelerator have additional 00:07:46.199 --> 00:07:50.279 robotic arms that have an additional X -ray tube 00:07:50.279 --> 00:07:54.879 and imaging detector attached so that just before 00:07:54.879 --> 00:07:58.240 the treatment, we can take a snapshot of the 00:07:58.240 --> 00:08:02.300 patient anatomy and have a sneak peek where that 00:08:02.300 --> 00:08:06.100 target volume is just before the treatment fraction, 00:08:06.420 --> 00:08:10.680 adjust the position. and then deliver the radiation 00:08:10.680 --> 00:08:14.660 according to the treatment plan. And again, physicists 00:08:14.660 --> 00:08:19.899 are involved in calibration and testing of the 00:08:19.899 --> 00:08:25.319 CT simulator. We design the radiation beam models 00:08:25.319 --> 00:08:29.620 inside that dose calculation software. And we 00:08:29.620 --> 00:08:33.200 also look after that imaging equipment on the 00:08:33.200 --> 00:08:37.559 linear accelerator. to ensure that we get you 00:08:37.559 --> 00:08:40.419 know true fidelity images and when we adjust 00:08:40.419 --> 00:08:43.600 the position we are moving the patient in the 00:08:43.600 --> 00:08:45.980 right direction yeah i don't know if you can 00:08:45.980 --> 00:08:47.779 answer this question but what is this like as 00:08:47.779 --> 00:08:49.980 a patient i mean i imagine you have to stay very 00:08:49.980 --> 00:08:53.860 very still yeah uh so as soon as the patient 00:08:53.860 --> 00:08:57.659 and the families hear the c word it's one of 00:08:57.659 --> 00:09:01.840 the most scary events in their lives. So before 00:09:01.840 --> 00:09:07.159 a patient actually starts therapy they will be 00:09:07.159 --> 00:09:10.220 explained what's going to happen during the process 00:09:10.220 --> 00:09:14.159 and they might even have a visit to the department 00:09:14.159 --> 00:09:18.080 prior they're commencing the treatment so they 00:09:18.080 --> 00:09:23.519 can visualize the accelerator, the couch. and 00:09:23.519 --> 00:09:27.879 the process. I do think that it can be quite 00:09:27.879 --> 00:09:31.840 overwhelming. Yes, they have to hold their position 00:09:31.840 --> 00:09:37.419 once they are in therapy for a few minutes, but 00:09:37.419 --> 00:09:42.110 the patient does not really feel and see. the 00:09:42.110 --> 00:09:45.889 radiation. They can definitely see the gantry 00:09:45.889 --> 00:09:50.309 moving around them. What we see throughout the 00:09:50.309 --> 00:09:54.190 process, because the radiotherapy is not delivered 00:09:54.190 --> 00:09:57.190 in one treatment fraction, it's delivered in 00:09:57.190 --> 00:10:00.190 multiple treatment fractions, that once they 00:10:00.190 --> 00:10:03.269 are used to the system, they start relaxing a 00:10:03.269 --> 00:10:06.769 bit and it changes their body posture sometimes. 00:10:07.129 --> 00:10:09.899 But that's why we have that imaging. so that 00:10:09.899 --> 00:10:16.139 we can always adjust them appropriately to identify 00:10:16.139 --> 00:10:20.700 the target. If I can go to physics a bit and 00:10:20.700 --> 00:10:24.059 I'll start with a controversial statement. X 00:10:24.059 --> 00:10:29.840 -rays are actually very silly ionizing radiation 00:10:29.840 --> 00:10:34.860 to be used for radiotherapy. The reason being 00:10:34.860 --> 00:10:38.919 that the x -rays attenuate exponentially through 00:10:38.919 --> 00:10:42.440 the medium, including through the patient's body. 00:10:42.679 --> 00:10:45.700 And if the listeners can imagine the exponential 00:10:45.700 --> 00:10:49.820 curve, you know, you will have a high dose of 00:10:49.820 --> 00:10:52.960 radiation somewhere at the surface, closer to 00:10:52.960 --> 00:10:56.509 the surface of the body. Then you will be delivering 00:10:56.509 --> 00:10:59.769 lower dose of radiation, perhaps to your cancer. 00:10:59.929 --> 00:11:02.250 Let's say it's prostate in the middle of the 00:11:02.250 --> 00:11:05.870 pelvis. But because the exponential curve never 00:11:05.870 --> 00:11:10.570 reaches the x -axis, you will always have radiation 00:11:10.570 --> 00:11:14.710 also exiting the patient. Right. So potentially 00:11:14.710 --> 00:11:18.309 we're giving a dose before the tumor and after 00:11:18.309 --> 00:11:22.649 tumor. Right. only way we can resolve this problem 00:11:22.649 --> 00:11:25.129 and this is where that rotating gantry comes 00:11:25.129 --> 00:11:29.529 into place that we can never ever use a single 00:11:29.529 --> 00:11:33.590 radiation beam on radiation direction and we 00:11:33.590 --> 00:11:37.370 cheat a bit we irradiate the patient from multiple 00:11:37.370 --> 00:11:42.950 beams sometimes even in a 180 degree arc or more 00:11:43.919 --> 00:11:47.500 So that we, all those beams meet in the target 00:11:47.500 --> 00:11:50.000 volume in the cancer where they build up the 00:11:50.000 --> 00:11:53.559 dose. Yeah. And we spread that. unwanted dose 00:11:53.559 --> 00:11:57.139 around the larger volume of healthy tissues. 00:11:57.539 --> 00:12:00.320 Let's try and unpack that a little bit for our 00:12:00.320 --> 00:12:02.960 listeners. So basically what you have is a very 00:12:02.960 --> 00:12:06.139 high dose at the start and that drops off very 00:12:06.139 --> 00:12:08.179 quickly, again, exponential. If you don't know 00:12:08.179 --> 00:12:10.039 what that's like, it's a big, it's almost like 00:12:10.039 --> 00:12:13.700 a skateboard ramp. You're rolling down to the 00:12:13.700 --> 00:12:16.460 bottom of this well and that skateboard ramp, 00:12:16.679 --> 00:12:19.200 it's only one -sided and it keeps going and going 00:12:19.200 --> 00:12:21.899 and going. So you can imagine the dose get Getting 00:12:21.899 --> 00:12:23.460 lower and lower and lower, but never reaching 00:12:23.460 --> 00:12:27.539 zero. Exactly. And so if you are rotating that 00:12:27.539 --> 00:12:30.519 skateboard ramp dose, I don't know if that is 00:12:30.519 --> 00:12:35.299 a helpful image, around, you are basically distributing 00:12:35.299 --> 00:12:39.220 the dose that you don't want throughout healthy 00:12:39.220 --> 00:12:41.740 tissue. So it has a higher... chance of being 00:12:41.740 --> 00:12:45.159 able to repair back to normal. So if you think 00:12:45.159 --> 00:12:48.059 about, again, prostate cancer, which is sort 00:12:48.059 --> 00:12:51.500 of one of the most common cancers around the 00:12:51.500 --> 00:12:55.100 world, if you treat, let's say, through bladder, 00:12:55.299 --> 00:12:58.779 then we would be giving much higher dose when 00:12:58.779 --> 00:13:01.879 using a single beam to the bladder rather than 00:13:01.879 --> 00:13:07.000 to the prostate. So if we are rotating the skateboard 00:13:07.000 --> 00:13:10.629 ramp, around the patient, then we will maybe 00:13:10.629 --> 00:13:16.830 redistribute that dose through other pelvic organs, 00:13:17.250 --> 00:13:20.929 maybe including rectum, including kidneys, including 00:13:20.929 --> 00:13:27.269 muscle, including pelvic bones. But smaller amount 00:13:27.269 --> 00:13:31.600 of radiation to healthy tissues. is better because 00:13:31.600 --> 00:13:35.279 healthy tissues can repair it than giving a large 00:13:35.279 --> 00:13:38.460 amount of radiation to healthy tissues in order 00:13:38.460 --> 00:13:42.720 to reach the target volume that the cancer is. 00:13:43.159 --> 00:13:46.919 It's maybe worth noting that we humans have evolved 00:13:46.919 --> 00:13:48.899 in an environment where there is natural background 00:13:48.899 --> 00:13:52.220 radiation. Our body has a way of dealing with 00:13:52.220 --> 00:13:55.360 some reasonable level of radiation. So patients 00:13:55.360 --> 00:13:58.600 often ask me, you know, if radiation is so detrimental. 00:13:59.480 --> 00:14:03.740 Why can we use it for treatment of cancer? And 00:14:03.740 --> 00:14:06.980 the reason is that the cancer cells behave slightly 00:14:06.980 --> 00:14:10.120 differently or much differently to the normal 00:14:10.120 --> 00:14:14.240 cells. And cancer cells have also perturbed repair 00:14:14.240 --> 00:14:18.379 mechanisms. So they are much more radiosensitive 00:14:18.379 --> 00:14:21.820 or susceptible to radiation damage than normal 00:14:21.820 --> 00:14:25.980 cells. So if we give a small amount of radiation 00:14:25.980 --> 00:14:30.440 dose, it can kill a cancer cell. The normal cells 00:14:30.440 --> 00:14:33.820 will have some radiation damage, but they can 00:14:33.820 --> 00:14:37.220 repair it. And this is really why by large we 00:14:37.220 --> 00:14:40.720 are not doing radiotherapy in a single day. We 00:14:40.720 --> 00:14:44.879 fractionate it. So we're giving the 24 hours 00:14:44.879 --> 00:14:48.679 for normal tissues to repair the damage before 00:14:48.679 --> 00:14:53.259 we irradiate the patient again and keep accumulating 00:14:53.259 --> 00:14:56.850 the radiation damage in the cancer. So the differential 00:14:56.850 --> 00:15:03.750 effect comes in different responses of cancer 00:15:03.750 --> 00:15:06.889 to the radiation damage versus normal tissues. 00:15:07.309 --> 00:15:10.929 But having said that, that treatment planning 00:15:10.929 --> 00:15:13.850 that I spoke about in the beginning is one of 00:15:13.850 --> 00:15:17.889 the most important aspects of radiotherapy, where 00:15:17.889 --> 00:15:21.629 we are really investigating that we are not... 00:15:22.320 --> 00:15:26.139 giving unnecessary dose to any of the surrounding 00:15:26.139 --> 00:15:30.539 healthy tissues. Yeah. Well, you started out 00:15:30.539 --> 00:15:33.000 this discussion about this type of radiotherapy 00:15:33.000 --> 00:15:34.940 with a controversial statement. I'm wondering 00:15:34.940 --> 00:15:37.960 what alternatives there are. So the problem is 00:15:37.960 --> 00:15:42.940 that no matter how much you improve the linear 00:15:42.940 --> 00:15:46.399 accelerator for photons technology, how much 00:15:46.399 --> 00:15:50.159 you improve treatment planning algorithms, You 00:15:50.159 --> 00:15:53.960 can't change the physics of photons and they 00:15:53.960 --> 00:15:57.820 will always attenuate exponentially. So there 00:15:57.820 --> 00:16:01.820 is a limit to your improvements and you always 00:16:01.820 --> 00:16:06.059 will have an exit dose beyond the target volume. 00:16:06.480 --> 00:16:10.259 So in order to really overcome this conundrum, 00:16:10.399 --> 00:16:14.620 we have to move away from photons, from X -ray 00:16:14.620 --> 00:16:19.309 radiation. This is where nature is saving us 00:16:19.309 --> 00:16:23.710 again because charged particles such as protons 00:16:23.710 --> 00:16:28.250 or alpha particles or carbon ions deposit radiation 00:16:28.250 --> 00:16:32.730 dose inside a medium, which would be including 00:16:32.730 --> 00:16:37.570 patient bodies, completely differently. And I 00:16:37.570 --> 00:16:40.669 don't know how well to describe it for the listeners. 00:16:41.690 --> 00:16:46.730 But the dose deposition starts with fairly low 00:16:46.730 --> 00:16:52.470 dose plateau region. And most of the energy is 00:16:52.470 --> 00:16:56.409 deposited towards the end of the particle's path. 00:16:57.029 --> 00:17:00.309 Particles actually have a finite trajectory, 00:17:00.690 --> 00:17:03.789 finite distance in the medium when they come 00:17:03.789 --> 00:17:07.349 to a complete stop. And most of their energy 00:17:07.349 --> 00:17:12.940 is deposited about 80%. right at the end of their 00:17:12.940 --> 00:17:17.299 trajectory, generating very sharp peak of energy 00:17:17.299 --> 00:17:21.240 deposition. Yeah. And this peak is known as Bragg 00:17:21.240 --> 00:17:24.200 peak in the honor of the scientists who discovered 00:17:24.200 --> 00:17:28.920 it. The funny things about this Bragg peak also 00:17:28.920 --> 00:17:32.799 is that the position or the distance that the 00:17:32.799 --> 00:17:37.079 particle travels into the medium depends on the 00:17:37.079 --> 00:17:40.880 energy of the particle. So if I have a lower 00:17:40.880 --> 00:17:44.079 energy particle, that break peak can happen at 00:17:44.079 --> 00:17:47.480 two centimeters into the body. If I select another 00:17:47.480 --> 00:17:50.700 energy, it will be five centimeters in the body. 00:17:50.960 --> 00:17:54.740 If I have a target volume like prostate in 20 00:17:54.740 --> 00:17:59.740 centimeters in the body, then I will select appropriate 00:17:59.740 --> 00:18:04.700 energy of a charged particle such as proton and 00:18:04.700 --> 00:18:08.920 the bulk of that energy. will be deposited exactly 00:18:08.920 --> 00:18:12.839 in the prostate target volume. Okay. Which means 00:18:12.839 --> 00:18:17.299 that now I have lower doses before the target 00:18:17.299 --> 00:18:22.619 volume and I have zero doses behind the target 00:18:22.619 --> 00:18:25.420 volume. Right. So I have minimized the entrance 00:18:25.420 --> 00:18:29.799 dose, maximized the bulk of the energy bulk of 00:18:29.799 --> 00:18:32.710 the radiation dose in the target volume. And 00:18:32.710 --> 00:18:35.849 I have removed the exit dose. Right. So basically. 00:18:36.170 --> 00:18:39.690 Ideal. Yeah. So you basically have a scenario 00:18:39.690 --> 00:18:43.529 where that tumor, you can target it very directly 00:18:43.529 --> 00:18:47.970 by adjusting the energy of the charged particles 00:18:47.970 --> 00:18:51.670 that you're using for treatment. So maybe one 00:18:51.670 --> 00:18:54.970 way we can help people think about this is when 00:18:54.970 --> 00:18:57.950 you are, let's say you're throwing a ball into 00:18:57.950 --> 00:19:02.059 water. And if you are throwing a ball that's 00:19:02.059 --> 00:19:05.279 heavy and really fast, it's going to take a little 00:19:05.279 --> 00:19:08.480 while to slow down. But if you are throwing a 00:19:08.480 --> 00:19:12.519 lighter ball that you're throwing it slower, 00:19:12.799 --> 00:19:15.880 it's going to slow down or stop in that water 00:19:15.880 --> 00:19:20.880 much faster. Yes. But, you know, it's from what 00:19:20.880 --> 00:19:24.940 the objective of radiotherapy is. Charge particles 00:19:24.940 --> 00:19:31.940 are ideal. because it does give you that differentiation 00:19:31.940 --> 00:19:36.319 between accumulating high levels of doses in 00:19:36.319 --> 00:19:40.759 cancer while minimizing the doses in healthy 00:19:40.759 --> 00:19:43.859 tissues. So that's really what we want to achieve. 00:19:44.140 --> 00:19:47.420 So you might then ask, you know, if charged particles 00:19:47.420 --> 00:19:51.640 are so good, Why aren't we using charged particle 00:19:51.640 --> 00:19:55.220 accelerators? I was just going to get to, I know 00:19:55.220 --> 00:19:56.839 you've been doing some work on this. So what 00:19:56.839 --> 00:20:02.220 do you think about this? Photons are also what 00:20:02.220 --> 00:20:07.079 we call sparsely ionizing radiation. So they 00:20:07.079 --> 00:20:11.500 are not depositing the energy very intensely. 00:20:13.099 --> 00:20:16.579 However, the charged particles is something that 00:20:16.579 --> 00:20:20.940 we call the dense ionizing radiation. That means 00:20:20.940 --> 00:20:24.619 that they are losing, depositing much more energy 00:20:24.619 --> 00:20:30.559 along their trajectory. So while I can have 18 00:20:30.559 --> 00:20:34.500 MeV beam photons to reach the prostate at 20 00:20:34.500 --> 00:20:40.299 centimeters, I would need 200 MeV proton beam. 00:20:41.160 --> 00:20:45.839 to get to the same depth inside a patient. So 00:20:45.839 --> 00:20:49.140 the energies we have actually increased by one 00:20:49.140 --> 00:20:53.119 order of magnitude. And if I move to carbon beams, 00:20:53.440 --> 00:20:58.299 I need about 3000 MeB carbon beam. Because again, 00:20:58.420 --> 00:21:01.559 that energy loss, energy deposition of a carbon 00:21:01.559 --> 00:21:07.390 beam. per unit per micrometer is much more intense, 00:21:07.630 --> 00:21:13.529 much more dense compared to photons. And because 00:21:13.529 --> 00:21:16.950 they are losing their energy so rapidly, we need 00:21:16.950 --> 00:21:19.730 to start with much higher energies to actually 00:21:19.730 --> 00:21:22.490 have any energy to deposit in the target volume. 00:21:23.130 --> 00:21:27.450 And so in order to start with protons of 200 00:21:27.450 --> 00:21:31.220 MeV going back to the protons, I need different 00:21:31.220 --> 00:21:34.849 accelerators. And much more powerful ones, I 00:21:34.849 --> 00:21:37.809 would imagine. More powerful accelerators, larger 00:21:37.809 --> 00:21:43.410 accelerators. So this is increasing then demands 00:21:43.410 --> 00:21:47.609 on the technology and it also increases demands 00:21:47.609 --> 00:21:52.250 on the footprint of the facility because you 00:21:52.250 --> 00:21:55.690 now need a much larger facility that needs to 00:21:55.690 --> 00:22:01.210 be shielded with the concrete bunker. Then once 00:22:01.210 --> 00:22:04.630 you get that beam line into the treatment room, 00:22:04.869 --> 00:22:08.750 once again, we want the gantry to be rotating 00:22:08.750 --> 00:22:13.950 around a patient so that we can direct that radiation 00:22:13.950 --> 00:22:18.089 through the right body path length to reach the, 00:22:18.230 --> 00:22:23.230 what I call target volume or cancer. The gantry 00:22:23.230 --> 00:22:26.630 now weighs, I was telling you the linear accelerator 00:22:26.630 --> 00:22:31.170 was six ton. Now we can talk 100 tons, 200 tons. 00:22:31.450 --> 00:22:35.549 Wow. Or even the facility in Heidelberg in Germany, 00:22:35.690 --> 00:22:39.869 the Gantt, it weighs 680 tons. That's a major 00:22:39.869 --> 00:22:43.890 engineering project. Absolutely. And a huge addition 00:22:43.890 --> 00:22:46.549 to the costs. Yeah. I'd like to get into the 00:22:46.549 --> 00:22:49.430 health economics of these options a bit. So what's 00:22:49.430 --> 00:22:51.650 the cost of a linear accelerator facility like 00:22:51.650 --> 00:22:53.670 the ones we're using in hospitals across Australia 00:22:53.670 --> 00:22:57.089 right now? versus the cost of the charged particle 00:22:57.089 --> 00:23:00.210 facilities we're talking about? When we're treating 00:23:00.210 --> 00:23:04.509 patients with photons, the energy range of photon 00:23:04.509 --> 00:23:11.650 beams is from 6 mV to maybe 18 mV beams. And 00:23:11.650 --> 00:23:15.009 the accelerating structure is about one meter 00:23:15.009 --> 00:23:19.569 long. So you can put the whole accelerator in 00:23:19.569 --> 00:23:24.730 a single treatment room and you know, the cost 00:23:24.730 --> 00:23:28.170 of the modern day accelerator with all bells 00:23:28.170 --> 00:23:33.130 and whistles is two to $3 million. While I can 00:23:33.130 --> 00:23:37.210 maybe set up a linear accelerator facility with 00:23:37.210 --> 00:23:40.549 the bunker and everything, maybe for $5 million, 00:23:40.990 --> 00:23:44.730 you would need $50 million to set up a proton 00:23:44.730 --> 00:23:49.490 facility and maybe $200 million to set up a carbon 00:23:49.490 --> 00:23:54.609 facility. right what we know from photons that 00:23:54.609 --> 00:23:57.829 as i was telling you before they are as effective 00:23:57.829 --> 00:24:05.029 for low -class cancer as surgery so we can still 00:24:05.029 --> 00:24:10.619 use photons for many cancers and therefore Not 00:24:10.619 --> 00:24:13.900 only every capital cities, but even in smaller 00:24:13.900 --> 00:24:17.859 cities, we now have cancer radiotherapy facilities 00:24:17.859 --> 00:24:21.900 in Dabo or Wagga Wagga or south of Wollongong. 00:24:22.059 --> 00:24:25.740 We can set them up regionally and enable the 00:24:25.740 --> 00:24:29.559 access of local people to standard radiotherapy. 00:24:29.819 --> 00:24:34.380 With these expensive facilities, We potentially 00:24:34.380 --> 00:24:37.880 don't have to treat patients that already have 00:24:37.880 --> 00:24:41.880 fantastic outcomes with photons, but we will 00:24:41.880 --> 00:24:46.519 use it for specialized patients with cancer where 00:24:46.519 --> 00:24:49.799 the protection of normal tissue is of utmost 00:24:49.799 --> 00:24:55.279 importance. So maybe we only need one to five 00:24:55.279 --> 00:25:00.460 such facilities in Australia and make it a... 00:25:01.259 --> 00:25:05.619 preferred treatment option, for example, for 00:25:05.619 --> 00:25:09.880 pediatric cancer patients. Right. Yes. So if 00:25:09.880 --> 00:25:12.940 I am irradiating, for example, a brain cancer 00:25:12.940 --> 00:25:18.200 in a six -year -old patient and I'm using photons, 00:25:18.640 --> 00:25:22.960 we are very good at eradicating that brain tumor. 00:25:23.200 --> 00:25:26.720 But more likely, again, due to that exponential 00:25:26.720 --> 00:25:30.990 attenuation, I will include. a bit of optical 00:25:30.990 --> 00:25:35.710 nerve, bit of ear canal, bit of brain stem, bit 00:25:35.710 --> 00:25:39.450 of pituitary gland. Yeah. And all of these then 00:25:39.450 --> 00:25:42.630 can impact on the well -being and development 00:25:42.630 --> 00:25:46.450 of the child, impaired vision, impaired hearing. 00:25:46.730 --> 00:25:50.150 Then they will have development and speech delays. 00:25:50.829 --> 00:25:54.009 There could be a bit of growth delay because 00:25:54.009 --> 00:25:58.109 we are also impacting some of the... hormonal 00:25:58.109 --> 00:26:01.730 centers with the glands in the brain. So this 00:26:01.730 --> 00:26:04.529 is where something like protons are absolutely 00:26:04.529 --> 00:26:08.369 amazing. Can I step back a bit? I'm curious, 00:26:08.490 --> 00:26:11.150 these kinds of facilities, as I understand it, 00:26:11.210 --> 00:26:13.890 this kind of treatment started out as being delivered 00:26:13.890 --> 00:26:15.990 or experimented with at research facilities. 00:26:16.069 --> 00:26:18.990 Is that right? Oh, absolutely. Look, the break 00:26:18.990 --> 00:26:23.660 pig was discovered. 120 years ago. So the physics 00:26:23.660 --> 00:26:27.220 is not new, and I will make a bit of claim. Bragg 00:26:27.220 --> 00:26:29.940 Peak was discovered at the University of Adelaide 00:26:29.940 --> 00:26:33.700 here in Adelaide, while Sir William Henry Bragg 00:26:33.700 --> 00:26:37.720 was conducting the experiments here. It wasn't 00:26:37.720 --> 00:26:42.619 until we had accelerators in 40s and 50s of the 00:26:42.619 --> 00:26:46.000 last century that we could actually build the 00:26:46.000 --> 00:26:50.140 first nuclear physics accelerators. The theory 00:26:50.140 --> 00:26:53.539 for using particle therapy in medicine came from 00:26:53.539 --> 00:26:57.359 Dr. Wilson again in the 40s of the last century. 00:26:57.880 --> 00:27:02.980 But we simply did not have the technology. to 00:27:02.980 --> 00:27:06.819 apply them in medicine. Looking at the physics 00:27:06.819 --> 00:27:10.039 of the dose distribution is absolutely no -brainer. 00:27:10.400 --> 00:27:15.380 So physics understanding was ahead of engineering 00:27:15.380 --> 00:27:20.579 solutions. So we really had to wait. So particle 00:27:20.579 --> 00:27:24.000 therapy has been used for cancers for maybe 50, 00:27:24.160 --> 00:27:28.559 60 years, but research facilities use what we 00:27:28.559 --> 00:27:31.619 call static beamlines. Yeah, so they're fixed 00:27:31.619 --> 00:27:36.500 in direction. Exactly. So our biggest disadvantage 00:27:36.500 --> 00:27:41.039 is that you don't get that rotating gantry where 00:27:41.039 --> 00:27:45.339 you can actually change the orientation of the 00:27:45.339 --> 00:27:49.059 beam in respect to the patient anatomy. So the 00:27:49.059 --> 00:27:51.960 patients are also, because these are horizontal 00:27:51.960 --> 00:27:55.920 beamline, the patient either needs to stand or 00:27:55.920 --> 00:27:59.339 needs to be sitting in a chair. So they cannot 00:27:59.339 --> 00:28:03.079 lie on a couch. And the energies of the proton 00:28:03.079 --> 00:28:06.420 beams to begin with were more at the lower end 00:28:06.420 --> 00:28:11.440 of the spectrum, maybe 50 to 70 MeV. So the first 00:28:11.440 --> 00:28:14.839 areas where you only need a single fixed beam 00:28:14.839 --> 00:28:18.859 would be maybe treatment of eye melanomas or 00:28:18.859 --> 00:28:22.809 ocular cancers. Okay. And for those... Yes, all 00:28:22.809 --> 00:28:26.809 you need is a fixed static beamline, a patient 00:28:26.809 --> 00:28:31.529 sitting in a couch. Going back to physics, motion 00:28:31.529 --> 00:28:35.630 is relative. If you have a fixed beamline, potentially 00:28:35.630 --> 00:28:38.529 you can rotate the patient, which is cheaper 00:28:38.529 --> 00:28:42.069 to have a rotating chair than a rotating gantry. 00:28:42.130 --> 00:28:44.390 As I was telling you, the gantry is actually 00:28:44.390 --> 00:28:46.930 the most expensive part of the proton therapy 00:28:46.930 --> 00:28:51.960 unit. But if the patient is only sitting or standing 00:28:51.960 --> 00:28:56.700 and they cannot lie down, especially if the patient 00:28:56.700 --> 00:29:01.299 is unwell, it's a solution, but it's not the 00:29:01.299 --> 00:29:05.920 best patient -orientated clinical solution. So 00:29:05.920 --> 00:29:10.940 it wasn't really until about 30 years ago when 00:29:10.940 --> 00:29:15.569 the manufacturers had really moved to... proton 00:29:15.569 --> 00:29:19.269 accelerators, which are now cyclotrons or synchrotrons, 00:29:19.509 --> 00:29:23.029 because we need a different style of accelerators 00:29:23.029 --> 00:29:25.910 that can accelerate protons to those high energies. 00:29:26.230 --> 00:29:30.390 Yeah. With rotating gantries where the patient 00:29:30.390 --> 00:29:34.430 is on a couch and you can again rotate the gantry 00:29:34.430 --> 00:29:38.970 around a patient and target the cancer for multiple 00:29:38.970 --> 00:29:43.380 angles. We are not interestingly enough. So we 00:29:43.380 --> 00:29:46.819 have like a halfway solution. We can have the 00:29:46.819 --> 00:29:52.019 360 degree gantries, but we have 180 degree rotating 00:29:52.019 --> 00:29:55.240 gantries, but we can rotate the couch. Right. 00:29:55.519 --> 00:30:00.220 And then have access to the left or right side 00:30:00.220 --> 00:30:03.279 part of the body. So we use the combination of 00:30:03.279 --> 00:30:06.309 both. Okay. Rotating the beam and rotating the 00:30:06.309 --> 00:30:10.190 patient to get the best of both worlds. So that's 00:30:10.190 --> 00:30:13.089 at modern facilities that are being built for 00:30:13.089 --> 00:30:15.410 this kind of treatment. Correct. South Australia 00:30:15.410 --> 00:30:17.589 is building one right now, isn't it? South Australia 00:30:17.589 --> 00:30:20.869 is building one, yes. So the bunker is built. 00:30:21.630 --> 00:30:27.690 Just to maybe where the costs come, because the 00:30:27.690 --> 00:30:31.690 gantry is so heavy, the patient comes into a 00:30:31.690 --> 00:30:35.710 treatment room. That, of course, is height -wise 00:30:35.710 --> 00:30:39.869 and size -wise, maybe like a smaller lecture 00:30:39.869 --> 00:30:46.049 hall. But when you open the door, what's behind, 00:30:46.069 --> 00:30:52.990 you have the gantry -supporting structures and 00:30:52.990 --> 00:30:56.309 something that we call counterweight. Imagine 00:30:56.309 --> 00:30:58.910 you have something that's 100 tons that's rotating. 00:30:59.740 --> 00:31:03.619 It needs to have a big concrete or metal block 00:31:03.619 --> 00:31:06.119 on the other side that's called counterweight 00:31:06.119 --> 00:31:09.740 to balance it up. Yeah. There is like a three 00:31:09.740 --> 00:31:16.140 -story building space behind the treatment wall 00:31:16.140 --> 00:31:20.759 that the patient does not see. Wow. It's enormous. 00:31:21.630 --> 00:31:25.829 So the shielding structure for the Australian 00:31:25.829 --> 00:31:28.609 Brake Centre for Proton Therapy is completed. 00:31:29.089 --> 00:31:32.289 And I can tell you the amount of concrete there 00:31:32.289 --> 00:31:36.730 would fill in, I believe, 25 full -size Olympic 00:31:36.730 --> 00:31:42.049 pools. Wow. The amount of steel would build a 00:31:42.049 --> 00:31:46.529 two -rail... train line from Adelaide to Darwin. 00:31:47.170 --> 00:31:50.490 So, you know, that's why these facilities in 00:31:50.490 --> 00:31:55.609 addition to the accelerator itself are so, so 00:31:55.609 --> 00:31:59.490 expensive. So not every city will have one and 00:31:59.490 --> 00:32:04.299 we don't need. In every city one? Yeah. The latest 00:32:04.299 --> 00:32:08.019 numbers show that you can make this type of facilities 00:32:08.019 --> 00:32:12.160 cost effective one per every six million population. 00:32:12.819 --> 00:32:15.400 Okay. And hence where I was saying Australia 00:32:15.400 --> 00:32:18.220 could have maybe up to four. Okay. This might 00:32:18.220 --> 00:32:20.079 be a good time to talk about the life cycle of 00:32:20.079 --> 00:32:23.240 a facility like this. So if I go to photons, 00:32:23.359 --> 00:32:28.440 we usually use a photon accelerator for eight 00:32:28.440 --> 00:32:33.180 to ten years. and then we replace it the photon 00:32:33.180 --> 00:32:37.279 accelerators by large are very compact and if 00:32:37.279 --> 00:32:40.980 you are using the same energy you don't really 00:32:40.980 --> 00:32:44.880 have to do any difference to the any modification 00:32:44.880 --> 00:32:48.599 to the bunker you just bring a new accelerator 00:32:48.599 --> 00:32:52.940 in and install it and you can use it for another 00:32:52.940 --> 00:32:59.210 10 years with the proton cyclotrons Because the 00:32:59.210 --> 00:33:04.549 initial investment is so huge, the life cycle 00:33:04.549 --> 00:33:09.549 is more something between 30 and 50 years, so 00:33:09.549 --> 00:33:13.250 that you still use the same shielding, but you 00:33:13.250 --> 00:33:17.730 will maybe just do proper maintenance on individual 00:33:17.730 --> 00:33:21.990 parts of the accelerators. And let's say there 00:33:21.990 --> 00:33:25.859 is a new, better performing ion source. So you 00:33:25.859 --> 00:33:29.140 will just replace an ion source. Right. Or maybe 00:33:29.140 --> 00:33:31.799 there are better magnets. So we will install 00:33:31.799 --> 00:33:34.740 new magnets or, you know, better collimators 00:33:34.740 --> 00:33:37.880 for the treatment head. Yeah. So for the proton 00:33:37.880 --> 00:33:41.779 facilities, really what might be driving replacement 00:33:41.779 --> 00:33:44.019 of parts is more about the development of new 00:33:44.019 --> 00:33:46.559 technologies or better approaches. For the linear 00:33:46.559 --> 00:33:48.539 accelerators, what's shaping the life cycle? 00:33:48.619 --> 00:33:51.180 Like what's shaping that 10 -year period? So 00:33:51.180 --> 00:33:55.329 really sort of by the... how the x -rays are 00:33:55.329 --> 00:33:58.950 produced you accelerate the electrons and then 00:33:58.950 --> 00:34:01.670 the electrons will hit the target and produce 00:34:01.670 --> 00:34:05.490 the x -ray cones so you start having quite a 00:34:05.490 --> 00:34:10.769 lot of wear and tear in the accelerator and because 00:34:10.769 --> 00:34:13.530 the cost of the accelerator is two to three million 00:34:13.530 --> 00:34:16.900 dollars you might start thinking, okay, will 00:34:16.900 --> 00:34:20.199 I replace a waveguide for half a million dollars? 00:34:20.280 --> 00:34:25.480 Will I replace a target for $100 ,000? Which 00:34:25.480 --> 00:34:29.079 might happen if you need to in the earliest stages. 00:34:29.480 --> 00:34:32.739 But also what we do with the accelerators, there 00:34:32.739 --> 00:34:35.199 is maybe this new image guidance technology. 00:34:35.820 --> 00:34:40.199 There is new field shaping or radiation shaping 00:34:40.199 --> 00:34:43.519 devices that we call the multi -leaf collimators. 00:34:44.670 --> 00:34:48.110 So you might decide it's not economical for me 00:34:48.110 --> 00:34:53.530 to keep replacing expensive parts. Yeah. I can 00:34:53.530 --> 00:34:59.610 just buy turnkey new accelerator and have all 00:34:59.610 --> 00:35:04.190 the latest bells and whistles. Okay. Yes. I don't 00:35:04.190 --> 00:35:07.949 want to get into much details how the technology 00:35:07.949 --> 00:35:12.480 is evolving. For example, the new accelerators 00:35:12.480 --> 00:35:16.280 can have even increased the dose rates or they 00:35:16.280 --> 00:35:20.360 have technologies that called breast gating so 00:35:20.360 --> 00:35:25.239 that we can actually then irradiate or deliver 00:35:25.239 --> 00:35:30.380 the radiation only during certain portion of 00:35:30.380 --> 00:35:34.719 the breathing cycle of a patient. Okay. So it's 00:35:34.719 --> 00:35:38.269 not necessarily the accelerator technology. But 00:35:38.269 --> 00:35:43.289 it's the additional, we call it bells and whistles 00:35:43.289 --> 00:35:47.190 or heads on that make the delivery a bit more 00:35:47.190 --> 00:35:51.389 sophisticated. So I'm curious with these changes 00:35:51.389 --> 00:35:55.429 in accelerator technology, etc. how you go about 00:35:55.429 --> 00:35:58.909 developing a new treatment protocol for a type 00:35:58.909 --> 00:36:01.309 of cancer using a facility like this? Like, what 00:36:01.309 --> 00:36:04.030 would it look like to go from an idea about how 00:36:04.030 --> 00:36:05.909 to treat a patient with a particular condition 00:36:05.909 --> 00:36:11.170 to actual clinical practice? This is one of the 00:36:11.170 --> 00:36:15.530 most important questions. And the simple answer 00:36:15.530 --> 00:36:19.969 is it takes a lot of time because, of course, 00:36:19.989 --> 00:36:24.019 we need to collect evidence. that certain protocol 00:36:24.019 --> 00:36:27.400 works. And that's where we use clinical trial. 00:36:27.579 --> 00:36:31.280 And trials are exactly what they sound like. 00:36:31.400 --> 00:36:36.539 It's trial and see. How we usually work with 00:36:36.539 --> 00:36:42.780 is that we have now 70 years experience with 00:36:42.780 --> 00:36:46.260 X -rays or photon radiotherapy. That's as our 00:36:46.260 --> 00:36:51.519 benchmark. So when we create a proton plan, By 00:36:51.519 --> 00:36:54.800 large, we try to accommodate, to begin with, 00:36:54.880 --> 00:37:00.340 the same dose prescriptions as with photon radiotherapy. 00:37:00.960 --> 00:37:05.780 And we are comparing whether we, at least in 00:37:05.780 --> 00:37:11.260 clinical trials, getting the same outcomes as 00:37:11.260 --> 00:37:14.639 with the photon radiotherapy and are not making 00:37:14.639 --> 00:37:18.719 anything worse. So we are always comparing two 00:37:18.719 --> 00:37:25.420 things. Am I killing the tumor equally efficiently? 00:37:25.639 --> 00:37:28.679 And we are looking at something what we call 00:37:28.679 --> 00:37:35.179 five -year survival. Do I still have 95 % of 00:37:35.179 --> 00:37:37.920 patients, for example, surviving five years post 00:37:37.920 --> 00:37:41.800 -treatment? And then we are also looking at the 00:37:41.800 --> 00:37:46.619 side effects. Okay, now that I have used protons, 00:37:47.500 --> 00:37:51.380 Have I reduced side effects related, let's go 00:37:51.380 --> 00:37:54.920 to the brain cancer, to optical nerve inflammation? 00:37:55.719 --> 00:38:01.619 Have I reduced side effects? So this data, we 00:38:01.619 --> 00:38:04.699 start sometimes with smaller case studies of 00:38:04.699 --> 00:38:10.199 patients. just to get some indication, but it's 00:38:10.199 --> 00:38:13.679 not the highest level of evidence. The highest 00:38:13.679 --> 00:38:16.619 level of evidence needs to start from what we 00:38:16.619 --> 00:38:20.019 call level two to level three clinical trials. 00:38:20.099 --> 00:38:23.960 Okay. And then we have to collect patient data 00:38:23.960 --> 00:38:30.219 for five to ten years. to have definitive evidence. 00:38:30.719 --> 00:38:32.900 Okay, so let me ask a couple of questions about 00:38:32.900 --> 00:38:34.440 that. The first is that you talked about side 00:38:34.440 --> 00:38:36.860 effects. Are you talking across that 10 -year 00:38:36.860 --> 00:38:40.260 period? Is it near term? So the side effects 00:38:40.260 --> 00:38:44.960 are always multi -level. There will be early 00:38:44.960 --> 00:38:49.000 side effects and late side effects. So early 00:38:49.000 --> 00:38:54.980 side effects, for example, even in photon radiotherapy, 00:38:55.239 --> 00:38:59.530 could for breast. Could be skin burns. Yeah. 00:38:59.769 --> 00:39:04.070 And you will find them very, very quickly. Yeah. 00:39:04.130 --> 00:39:06.849 Early side effects come with early responding 00:39:06.849 --> 00:39:11.269 tissues, which is also bone marrow. So we will 00:39:11.269 --> 00:39:15.309 be monitoring blood changes in a patient. Again, 00:39:15.429 --> 00:39:18.170 this is more or less important depending what 00:39:18.170 --> 00:39:23.070 organ we are irradiating. So that can be identified 00:39:23.070 --> 00:39:26.809 very quickly. Many of these have been eradicated 00:39:26.809 --> 00:39:30.909 with modern technology. The latest side effects, 00:39:31.230 --> 00:39:37.230 you know, if they're going to children and the... 00:39:37.900 --> 00:39:42.260 brain irradiation, the growth development delays 00:39:42.260 --> 00:39:48.199 you may not or later onset of adolescence you 00:39:48.199 --> 00:39:53.579 may not find until few years later on. So data 00:39:53.579 --> 00:39:58.369 collection is extremely important. So that we 00:39:58.369 --> 00:40:01.730 have, you know, information about the early, 00:40:01.849 --> 00:40:06.090 late and very late side effects as well. And 00:40:06.090 --> 00:40:09.250 that's where we need national and international 00:40:09.250 --> 00:40:14.170 collaborations as well. We can pull all the information 00:40:14.170 --> 00:40:18.610 together. Most of the clinical departments are 00:40:18.610 --> 00:40:21.409 publishing the results of their clinical data 00:40:21.409 --> 00:40:25.269 in publications and the protocols for any clinical 00:40:25.269 --> 00:40:29.849 trials have to be lodged with clinical trial 00:40:29.849 --> 00:40:34.590 registries. So what we can do when we are developing 00:40:34.590 --> 00:40:37.349 our protocols in Australia, we don't have to 00:40:37.349 --> 00:40:40.389 reinvent the wheel. We don't have to start from 00:40:40.389 --> 00:40:44.360 scratch. We will conduct something that's called 00:40:44.360 --> 00:40:47.780 systematic review of the published literature. 00:40:48.139 --> 00:40:52.539 Yeah. And we compare all the protocols or all 00:40:52.539 --> 00:40:55.500 the trials that other centers have conducted. 00:40:56.000 --> 00:41:00.099 Then we perform analysis of the results and we 00:41:00.099 --> 00:41:04.059 can then identify which of those protocols provides 00:41:04.059 --> 00:41:10.090 the strongest evidence for improving the patient 00:41:10.090 --> 00:41:14.369 outcomes both in terms of treating cancer and 00:41:14.369 --> 00:41:17.289 in terms of minimizing the side effects okay 00:41:17.289 --> 00:41:21.349 so let's take a step back a bit and I think there 00:41:21.349 --> 00:41:23.730 are a few really interesting things from what 00:41:23.730 --> 00:41:25.690 you've just said that might be worth stepping 00:41:25.690 --> 00:41:29.119 through the first is that obviously This is a 00:41:29.119 --> 00:41:32.440 safety critical thing. You want to get this right 00:41:32.440 --> 00:41:34.800 if you're going to roll it out across a broad 00:41:34.800 --> 00:41:38.219 population. And so you start with small numbers 00:41:38.219 --> 00:41:40.980 and you sort of work up in size as you get a 00:41:40.980 --> 00:41:44.260 sense of, you know, how safe things are, whether 00:41:44.260 --> 00:41:45.780 things are working, whether they're achieving 00:41:45.780 --> 00:41:48.440 the goals that you think that that protocol will 00:41:48.440 --> 00:41:51.800 achieve. Is that that's correct? Yeah. Yes. What 00:41:51.800 --> 00:41:54.800 we have the big advantage, if I can jump in. 00:41:55.239 --> 00:41:58.460 We follow lots of the guidelines that are used 00:41:58.460 --> 00:42:04.480 by pharmaceutical developments. But in pharmaceutical 00:42:04.480 --> 00:42:07.739 developments, I think there is always a bit of 00:42:07.739 --> 00:42:10.440 blindness because you swallow a little white 00:42:10.440 --> 00:42:13.940 pill, you don't know what it does. Some of this 00:42:13.940 --> 00:42:18.019 blindness is removed in radiotherapy because 00:42:18.019 --> 00:42:21.599 we actually really understand well how radiation 00:42:21.599 --> 00:42:24.539 deposits the energy, what the radiation interactions 00:42:24.539 --> 00:42:29.280 are. So if I generate that treatment plan that 00:42:29.280 --> 00:42:33.000 I was talking about before with photon versus 00:42:33.000 --> 00:42:37.260 protons, It's not like we're really experimenting, 00:42:37.340 --> 00:42:40.539 even if we are starting with small numbers. Right. 00:42:40.619 --> 00:42:42.380 That's something we understand very well. Yes. 00:42:42.440 --> 00:42:45.739 We immediately see that, okay, I'm not going 00:42:45.739 --> 00:42:48.000 through optical nerve. I'm not going through 00:42:48.000 --> 00:42:54.159 brainstem. I can immediately see, at least in 00:42:54.159 --> 00:42:58.690 the theoretical dose distribution. how much sparing 00:42:58.690 --> 00:43:02.570 of normal tissue I am going to perform. But of 00:43:02.570 --> 00:43:05.489 course, maybe I'll just one step back. Before 00:43:05.489 --> 00:43:09.070 we even go to the patient studies, I don't know 00:43:09.070 --> 00:43:12.110 whether the listeners like it or not, we also 00:43:12.110 --> 00:43:16.590 perform in vitro experiment with cell lines in 00:43:16.590 --> 00:43:21.809 petri dishes. And we also do small animal experiments, 00:43:22.110 --> 00:43:27.710 primarily using laboratory mice. We will never 00:43:27.710 --> 00:43:32.929 get an approval to go to inhuman clinical trials 00:43:32.929 --> 00:43:38.289 unless we show preclinical evidence. Because 00:43:38.289 --> 00:43:40.550 if the preclinical evidence shows it doesn't 00:43:40.550 --> 00:43:43.530 work, it will never get approved for inhuman 00:43:43.530 --> 00:43:46.289 trials. Right. So again, the risk management 00:43:46.289 --> 00:43:50.500 actually is about starting in cells or... And 00:43:50.500 --> 00:43:53.440 then if that all looks good, then you go, OK, 00:43:53.599 --> 00:43:56.159 we can start considering humans very carefully. 00:43:56.280 --> 00:43:59.119 Exactly. The other part of this that I thought 00:43:59.119 --> 00:44:01.840 may be worth at least mentioning is different 00:44:01.840 --> 00:44:04.360 countries have different standards with regards 00:44:04.360 --> 00:44:07.300 to medical treatment and how they're regulated. 00:44:07.539 --> 00:44:10.940 Right. And so your discussion of looking at what 00:44:10.940 --> 00:44:13.119 has been found in other countries at these facilities 00:44:13.119 --> 00:44:16.219 and looking at what they've discovered and then 00:44:16.219 --> 00:44:18.440 adapting that, thinking about how you're going 00:44:18.440 --> 00:44:21.510 to make use of that. in an Australian context. 00:44:21.670 --> 00:44:23.349 Sounds like it's part of your practice. Is that 00:44:23.349 --> 00:44:26.630 right? Yes. Yeah, absolutely. Look, in terms 00:44:26.630 --> 00:44:31.980 of clinical trials. They all publish dosimetry 00:44:31.980 --> 00:44:36.420 data. So the interaction of protons will be the 00:44:36.420 --> 00:44:39.440 same in Australia as in Europe. I would hope 00:44:39.440 --> 00:44:46.000 so. Yes, exactly. So primarily we are after the 00:44:46.000 --> 00:44:49.739 dose and fractionation. You know, what is it? 00:44:50.019 --> 00:44:52.780 How much radiation dose per fraction? How many 00:44:52.780 --> 00:44:57.780 fractions? What is the total dose? Yeah. So that's 00:44:57.780 --> 00:45:02.110 irrespective. Because these facilities are expensive, 00:45:02.590 --> 00:45:08.130 you usually do have them in countries, maybe 00:45:08.130 --> 00:45:11.329 more your high income countries, even though 00:45:11.329 --> 00:45:13.710 we now see the onset of development of these 00:45:13.710 --> 00:45:17.409 facilities in middle income countries. But most 00:45:17.409 --> 00:45:21.750 of these have excellent both health and radiation 00:45:21.750 --> 00:45:27.989 regulations in place. We also all subscribe to... 00:45:28.440 --> 00:45:34.320 international regulations as published by international 00:45:34.320 --> 00:45:38.039 commissions for radiation protections or ICRP 00:45:38.039 --> 00:45:41.739 or international commission for radiation units 00:45:41.739 --> 00:45:46.739 ICRU. ICRU actually publishes series that inform 00:45:46.739 --> 00:45:50.219 clinical protocols. Right. And also we follow 00:45:50.219 --> 00:45:53.840 any guidelines by IAEA, International Atomic 00:45:53.840 --> 00:45:59.440 Energy Agency. So there is some form of uniformity. 00:45:59.599 --> 00:46:02.719 Yeah. Yes. And dosimetry standards are uniform 00:46:02.719 --> 00:46:07.659 to an extent as well. So, for example, most of 00:46:07.659 --> 00:46:12.139 our accelerated calibration protocols are referenced 00:46:12.139 --> 00:46:17.840 to IAEA. But where sometimes the changes come, 00:46:18.360 --> 00:46:21.639 and that's where the departments might work slightly 00:46:21.639 --> 00:46:26.019 differently. It comes to the cost of the therapy. 00:46:26.260 --> 00:46:30.519 One of the cancers that is very difficult to 00:46:30.519 --> 00:46:34.099 treat and has unmet demand is pancreatic cancer. 00:46:34.460 --> 00:46:38.800 And our theoretical studies show that I get a 00:46:38.800 --> 00:46:43.539 good result when I use three proton beams. We 00:46:43.539 --> 00:46:48.000 are collaborating with a center in Asia. but 00:46:48.000 --> 00:46:51.739 they are only using two proton beams because 00:46:51.739 --> 00:46:55.500 the patient is charged per beam. Right, okay. 00:46:55.760 --> 00:46:59.420 So to minimize the cost to a patient, they will 00:46:59.420 --> 00:47:03.039 be only treating with two beams. So that's where 00:47:03.039 --> 00:47:06.039 some of those differences might come. Okay. But 00:47:06.039 --> 00:47:11.000 that's where we have the trial stage and where 00:47:11.000 --> 00:47:13.599 we can do lots of things in treatment planning 00:47:13.599 --> 00:47:19.800 itself. without a real patient to identify the 00:47:19.800 --> 00:47:22.739 dose distributions and the beam arrangements 00:47:22.739 --> 00:47:26.019 that could lead to the best outcomes. So you 00:47:26.019 --> 00:47:28.699 basically have a way of testing in advance what 00:47:28.699 --> 00:47:31.380 potential trade -offs, if somebody is paying 00:47:31.380 --> 00:47:34.260 per beam, you're deciding between, okay. Yes, 00:47:34.300 --> 00:47:37.739 absolutely. So once we have the dose distributions, 00:47:37.860 --> 00:47:41.980 we have biological models. One is called tumor 00:47:41.980 --> 00:47:45.039 control probability, which is basically telling 00:47:45.039 --> 00:47:47.440 me, am I killing enough cancer cells or not? 00:47:47.679 --> 00:47:49.960 Yeah. And the other one is something that's called 00:47:49.960 --> 00:47:53.340 normal tissue complication probability, where 00:47:53.340 --> 00:47:56.639 we start thinking, okay, will this person develop 00:47:56.639 --> 00:47:59.940 this particular side effect? Yeah, okay. So we 00:47:59.940 --> 00:48:03.420 can, because the radiation simulations are so 00:48:03.420 --> 00:48:06.619 advanced, and this is, again, thanks to the, 00:48:06.760 --> 00:48:09.119 you know, 100 years of radiation and nuclear 00:48:09.119 --> 00:48:13.349 physics, We can do lots of things in that simulation 00:48:13.349 --> 00:48:18.050 domain and prepare the protocols in simulation 00:48:18.050 --> 00:48:23.110 domain before we even go to real patient treatment. 00:48:23.469 --> 00:48:27.510 Does access to a trained workforce for these 00:48:27.510 --> 00:48:29.909 kinds of facilities impact things at all, just 00:48:29.909 --> 00:48:33.349 out of curiosity? In radiation therapy, we are 00:48:33.349 --> 00:48:38.420 not doing at the moment too badly. We have large 00:48:38.420 --> 00:48:42.280 shortage in nuclear medicine. This is actually 00:48:42.280 --> 00:48:47.300 another aspect of cancer and other therapies. 00:48:47.460 --> 00:48:51.119 I was only talking about 50 % of cancer patients 00:48:51.119 --> 00:48:53.860 receiving radiation for treatment of the disease. 00:48:54.179 --> 00:48:59.920 100 % of cancer patients will receive some sort 00:48:59.920 --> 00:49:05.699 of X -ray or radionuclide intervention. for imaging 00:49:05.699 --> 00:49:08.860 and diagnostic purposes. So they will definitely 00:49:08.860 --> 00:49:12.659 have one or more CT scans. Many of them will 00:49:12.659 --> 00:49:15.820 have a maybe magnetic resonance imaging, but 00:49:15.820 --> 00:49:19.860 many of them will have either gamma camera or 00:49:19.860 --> 00:49:23.159 positron emission tomography or PET scan imaging 00:49:23.159 --> 00:49:29.280 as well. 100%. So we see a huge development in 00:49:29.280 --> 00:49:32.920 nuclear medicine and we have huge shortages in 00:49:32.920 --> 00:49:36.500 that space at the moment. With photon therapy, 00:49:36.800 --> 00:49:40.460 we are not doing that badly, but we don't really 00:49:40.460 --> 00:49:44.099 have a program for proton therapy as much, which 00:49:44.099 --> 00:49:46.880 is maybe an opportunity space for university. 00:49:47.500 --> 00:49:50.739 At the moment, what we are doing, look, we don't 00:49:50.739 --> 00:49:53.960 really have a functional facility at the moment. 00:49:54.039 --> 00:49:57.170 So it's a bit of a chicken and egg. situation. 00:49:57.289 --> 00:50:01.150 So at the moment, what we do, we send people 00:50:01.150 --> 00:50:05.510 to train overseas in the facilities that have 00:50:05.510 --> 00:50:09.989 a well -established program. But eventually we 00:50:09.989 --> 00:50:14.170 implement something locally. I know that professional 00:50:14.170 --> 00:50:17.070 bodies such as Australasian College of Physical 00:50:17.070 --> 00:50:20.730 Sciences and Engineers in Medicine or Australian 00:50:20.730 --> 00:50:23.550 Society for Medical Imaging and Radiotherapy 00:50:23.550 --> 00:50:29.130 have already starting courses at that professional 00:50:29.130 --> 00:50:32.929 organisational level rather than at the university 00:50:32.929 --> 00:50:36.949 undergraduate or postgraduate level. I would 00:50:36.949 --> 00:50:39.949 be thinking that we might maybe need postgraduate 00:50:39.949 --> 00:50:44.389 diploma in particle therapy and make it as an 00:50:44.389 --> 00:50:48.369 advanced practice to the undergraduate degrees. 00:50:49.070 --> 00:50:51.190 Okay. So it's probably the people who have been 00:50:51.190 --> 00:50:53.829 trained overseas and come back that might be 00:50:53.829 --> 00:50:56.389 involved in running those programs. Yes. Yeah. 00:50:56.510 --> 00:50:59.570 Okay. And what kind of timescale does it look 00:50:59.570 --> 00:51:01.250 like we will need those on? I mean, the facility 00:51:01.250 --> 00:51:04.070 is being built now. So I think some of the people 00:51:04.070 --> 00:51:07.250 are being trained now because we already look 00:51:07.250 --> 00:51:10.650 while we are not treating patients now, we are 00:51:10.650 --> 00:51:13.449 sending limited amount of patients overseas, 00:51:13.750 --> 00:51:17.480 particularly to the United States. How do you 00:51:17.480 --> 00:51:21.360 decide who to send? So this is where something 00:51:21.360 --> 00:51:24.659 is performed is the comparative planning that 00:51:24.659 --> 00:51:29.659 I was talking about. This again primarily involves 00:51:29.659 --> 00:51:34.000 children and often with brain cancer that you 00:51:34.000 --> 00:51:37.300 create a treatment dosimetry distribution plan 00:51:37.300 --> 00:51:40.880 with x -rays and treatment dosimetry plan with 00:51:40.880 --> 00:51:44.800 protons and you can demonstrate to the select 00:51:44.800 --> 00:51:50.400 committee. that this child will significantly 00:51:50.400 --> 00:51:53.719 benefit with proton therapy. Yeah, that makes 00:51:53.719 --> 00:51:55.960 sense. So it's not like you just like turn the 00:51:55.960 --> 00:51:58.059 facility on one day and it's all good. No, no, 00:51:58.059 --> 00:52:01.320 no. There is a huge lead time. Yes. Let's say 00:52:01.320 --> 00:52:03.239 when Australia is thinking about these kinds 00:52:03.239 --> 00:52:06.260 of things, like what kind of lead time are they 00:52:06.260 --> 00:52:08.500 needing to think about even developing the expertise 00:52:08.500 --> 00:52:11.760 they need to do the planning to work towards 00:52:11.760 --> 00:52:15.809 these kinds of major changes to the health? look 00:52:15.809 --> 00:52:18.409 in australia we have been talking about this 00:52:18.409 --> 00:52:23.079 for 25 to 30 years And we still do not have a 00:52:23.079 --> 00:52:27.239 facility. But I would say, depending on what 00:52:27.239 --> 00:52:31.599 you want to buy these days, maybe five years, 00:52:31.940 --> 00:52:35.980 there are now, especially with companies like 00:52:35.980 --> 00:52:40.360 IBA or Median, that there are turnkey solutions 00:52:40.360 --> 00:52:44.480 and they can already come. Okay, this is the 00:52:44.480 --> 00:52:47.440 accelerator. This is what you are. They can come 00:52:47.440 --> 00:52:51.289 with a footprint for the facility. and shielding 00:52:51.289 --> 00:52:55.469 recommendations. If you are going for something 00:52:55.469 --> 00:53:01.349 that's maybe going towards carbon therapy and 00:53:01.349 --> 00:53:05.639 it requires a synchrotron. you might need lead 00:53:05.639 --> 00:53:09.619 time of 10 years. What we do not have compared 00:53:09.619 --> 00:53:13.980 to Europe or Japan, because we are not an accelerated 00:53:13.980 --> 00:53:19.099 country, we don't have inside Australia know 00:53:19.099 --> 00:53:22.400 -how. Right. Couple of carbon proton facilities 00:53:22.400 --> 00:53:27.860 in Italy and in Austria were based on the know 00:53:27.860 --> 00:53:31.659 -how coming from CERN. Right. Because they have 00:53:31.659 --> 00:53:35.099 this huge nuclear physics facility that uses 00:53:35.099 --> 00:53:37.980 the colliders and synchrotrons and everything, 00:53:38.360 --> 00:53:42.579 you have great accelerator know -how, great engineering 00:53:42.579 --> 00:53:46.500 know -how, understanding magnets and beam steering 00:53:46.500 --> 00:53:50.579 and everything. So you can design and fine -tune 00:53:50.579 --> 00:53:55.599 your own accelerator structure. Right. And we 00:53:55.599 --> 00:53:58.380 don't have that in Australia. So we are more... 00:53:58.809 --> 00:54:02.489 dependent on turnkey solutions, which now do 00:54:02.489 --> 00:54:06.949 exist, or on collaboration with a company that 00:54:06.949 --> 00:54:11.510 can design maybe something a bit more different, 00:54:11.869 --> 00:54:14.929 especially if you want to maybe increase the 00:54:14.929 --> 00:54:19.349 energy of the protons than the standard turnkey. 00:54:19.530 --> 00:54:24.090 Japan is in a similar space because they have 00:54:24.090 --> 00:54:29.190 Sumimoto, Hitachi. I think now fourth and then 00:54:29.190 --> 00:54:32.730 fifth carbon facility. Yeah. But they are learning 00:54:32.730 --> 00:54:36.429 from each of the facility and bringing that know 00:54:36.429 --> 00:54:39.210 -how to the new facility. Actually, some of the 00:54:39.210 --> 00:54:43.110 images I saw out of Japan is superconducting 00:54:43.110 --> 00:54:47.809 synchrotrons and so much reduce the footprint. 00:54:48.869 --> 00:54:52.769 It's just amazing. So, you know. I don't need 00:54:52.769 --> 00:54:56.429 diamonds. Give me a new superconducting synchrotron 00:54:56.429 --> 00:55:10.070 and I will be so excited. Nuclear Matters is 00:55:10.070 --> 00:55:11.869 a production of the Australian National University 00:55:11.869 --> 00:55:14.849 College of Systems and Society. We acknowledge 00:55:14.849 --> 00:55:16.730 the Traditional Owners of the lands on which 00:55:16.730 --> 00:55:18.730 this podcast is being recorded on or listened 00:55:18.730 --> 00:55:21.320 to and pay our respects to their elders. and 00:55:21.320 --> 00:55:24.320 all First Nations people. If you liked what you 00:55:24.320 --> 00:55:26.719 heard today, please share this episode with friends, 00:55:26.840 --> 00:55:29.599 family, and colleagues. 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