Welcome to Nuclear Matters from the Australian
National University College of Systems and Society.
I'm your host, Liz Williams, a nuclear physicist
and nuclear systems discipline lead for the ANU
School of Engineering. In today's episode, we
explore how nuclear technologies play a role
in enabling life -saving cancer treatments. Our
guest, Eva Bezak, is Professor of Medical Radiation
at the University of South Australia and President
of Asia Oceania Federation of Organizations for
Medical Physics. I've asked Eva to join me today
to find out more about how nuclear technologies
for medical applications get developed and used
to treat patients across Australia. To get us
started, I asked Eva to give us a sense of how
many people's lives are likely to be touched
by cancer. Cancer would be, you know, one of
the number one diseases in the country that will
be affecting one in three to one in two Australians
in their lifespan, especially since we are living
longer. And we have a couple of main sources
of therapies, which is, of course, surgery, chemotherapy,
immunotherapy. but not least radiation therapy,
where we're using primarily radiation X -rays
produced by medical linear accelerators or photons
to deliver energy to cancer and causing enough
cell damage to eradicate the cancer cells. Radiotherapy
is actually extremely effective in treatment
of localized cancer in particular and should
be used for the treatment of about 50 % of cancer
patients and the local control of the disease
where the primary tumor is, it is as effective
as surgery. So it actually represents a very
cost effective as well as treatment -effective
therapy. Where the radiotherapy has maybe disadvantage
is when the disease spreads, and then we need
to look at something like chemotherapy. So in
many cases, radiation therapy is a really useful
treatment. And what you're doing is using a linear
accelerator to generate x -rays that you can
then use to kill cancer cells. I want to understand
how this kind of treatment is delivered in hospitals.
So can you tell me what it's like to be involved
in this kind of treatment from a clinician's
perspective? Absolutely. So the day of a medical
physicist is varied. Sometimes it can start early
in the morning because before a first patient
comes to the department. All the equipment, including
accelerators, CT scanners, data servers need
to be turned on. And in the morning, some initial
quality assurance is performed. So what I usually
teach the students that radiotherapy is a double
blind date. You don't see the tumor and you don't
see the radiation, yet you want to deliver that
radiation with. utmost precision and accuracy
to the target volume because radiation is also
detrimental to a degree to healthy tissues and
if you miss the cancer then you might be giving
unwanted amount of radiations to the healthy
tissues causing negative side effects so when
the therapist turn on the machine They want to
ensure that the right amount of radiation is
coming in the right direction. And they trust
medical physicists that we have done all the
necessary testing and quality assurance measurements
to ensure that the therapist can absolutely rely
on the linear accelerator to perform its task.
So often we are the people behind. calibrating
and testing the accelerator and its performance.
Okay, so let's just talk through this in kind
of a step -by -step fashion. Let's say you have
a tumor, you kind of know at least based on imaging
where it is, how large it is, where it sits in
the patient's body, right? We're starting with
a scenario like that. And so for radiation therapy,
you would want the linear accelerator. to produce
the radiation you need and the intensity that
you need, the shape that you need, right? Absolutely.
To irradiate the tumor, but as much as possible
to avoid the healthy tissue surrounding. So the
calibrations that you're talking about, the quality
assurance, it's all about ensuring that you have
very high level of understanding about what radiation
the machine is producing, what shapes. You know,
it's irradiating, that kind of thing. Is that
about right? Yes. In order to irradiate the tumor,
we need to understand the linear accelerator.
When the X -rays are produced, the treatment
head sits on the rotating gantry. That gantry
weighs around six tonnes, three Commodores. or
I should call it three Fords since we no longer
produce Holdens in the country. And it rotates
around the patient with the accuracy of about
two millimeters. Part of those checks are also
mechanical checks as well as radiation checks.
But before the patient even gets onto the linear
accelerator, we need to perform the dose calculations.
on the CT image of a patient. So we call that
treatment planning. So in addition to just, you
know, the patient doesn't just come and is positioned
on the patient couch to deliver the treatment.
There is this big preparation period when we
acquire a CT, three -dimensional CT image of
the patient, where we outline the target volume
and the shape of the target volume. And we also
outline the surrounding healthy tissues, which
are also called organs at risk or critical structures.
And then we use very sophisticated treatment
planning, dose calculation algorithms. that allow
us to optimize the intensity and direction of
the radiation from the linear accelerator gantry.
For example, we will not irradiate through spinal
cord. Yeah, okay. I'm assuming that causes lots
of problems. Absolutely, yeah. So only when we
have pre -calculated how the dose should be delivered.
and the clinician improves that dose calculation
and dose distribution, that will be then transferred
online digitally to the linear accelerator, and
then that treatment can be delivered. I was also
talking about that, you know, we don't see the
tumor. Our modern linear accelerator have additional
robotic arms that have an additional X -ray tube
and imaging detector attached so that just before
the treatment, we can take a snapshot of the
patient anatomy and have a sneak peek where that
target volume is just before the treatment fraction,
adjust the position. and then deliver the radiation
according to the treatment plan. And again, physicists
are involved in calibration and testing of the
CT simulator. We design the radiation beam models
inside that dose calculation software. And we
also look after that imaging equipment on the
linear accelerator. to ensure that we get you
know true fidelity images and when we adjust
the position we are moving the patient in the
right direction yeah i don't know if you can
answer this question but what is this like as
a patient i mean i imagine you have to stay very
very still yeah uh so as soon as the patient
and the families hear the c word it's one of
the most scary events in their lives. So before
a patient actually starts therapy they will be
explained what's going to happen during the process
and they might even have a visit to the department
prior they're commencing the treatment so they
can visualize the accelerator, the couch. and
the process. I do think that it can be quite
overwhelming. Yes, they have to hold their position
once they are in therapy for a few minutes, but
the patient does not really feel and see. the
radiation. They can definitely see the gantry
moving around them. What we see throughout the
process, because the radiotherapy is not delivered
in one treatment fraction, it's delivered in
multiple treatment fractions, that once they
are used to the system, they start relaxing a
bit and it changes their body posture sometimes.
But that's why we have that imaging. so that
we can always adjust them appropriately to identify
the target. If I can go to physics a bit and
I'll start with a controversial statement. X
-rays are actually very silly ionizing radiation
to be used for radiotherapy. The reason being
that the x -rays attenuate exponentially through
the medium, including through the patient's body.
And if the listeners can imagine the exponential
curve, you know, you will have a high dose of
radiation somewhere at the surface, closer to
the surface of the body. Then you will be delivering
lower dose of radiation, perhaps to your cancer.
Let's say it's prostate in the middle of the
pelvis. But because the exponential curve never
reaches the x -axis, you will always have radiation
also exiting the patient. Right. So potentially
we're giving a dose before the tumor and after
tumor. Right. only way we can resolve this problem
and this is where that rotating gantry comes
into place that we can never ever use a single
radiation beam on radiation direction and we
cheat a bit we irradiate the patient from multiple
beams sometimes even in a 180 degree arc or more
So that we, all those beams meet in the target
volume in the cancer where they build up the
dose. Yeah. And we spread that. unwanted dose
around the larger volume of healthy tissues.
Let's try and unpack that a little bit for our
listeners. So basically what you have is a very
high dose at the start and that drops off very
quickly, again, exponential. If you don't know
what that's like, it's a big, it's almost like
a skateboard ramp. You're rolling down to the
bottom of this well and that skateboard ramp,
it's only one -sided and it keeps going and going
and going. So you can imagine the dose get Getting
lower and lower and lower, but never reaching
zero. Exactly. And so if you are rotating that
skateboard ramp dose, I don't know if that is
a helpful image, around, you are basically distributing
the dose that you don't want throughout healthy
tissue. So it has a higher... chance of being
able to repair back to normal. So if you think
about, again, prostate cancer, which is sort
of one of the most common cancers around the
world, if you treat, let's say, through bladder,
then we would be giving much higher dose when
using a single beam to the bladder rather than
to the prostate. So if we are rotating the skateboard
ramp, around the patient, then we will maybe
redistribute that dose through other pelvic organs,
maybe including rectum, including kidneys, including
muscle, including pelvic bones. But smaller amount
of radiation to healthy tissues. is better because
healthy tissues can repair it than giving a large
amount of radiation to healthy tissues in order
to reach the target volume that the cancer is.
It's maybe worth noting that we humans have evolved
in an environment where there is natural background
radiation. Our body has a way of dealing with
some reasonable level of radiation. So patients
often ask me, you know, if radiation is so detrimental.
Why can we use it for treatment of cancer? And
the reason is that the cancer cells behave slightly
differently or much differently to the normal
cells. And cancer cells have also perturbed repair
mechanisms. So they are much more radiosensitive
or susceptible to radiation damage than normal
cells. So if we give a small amount of radiation
dose, it can kill a cancer cell. The normal cells
will have some radiation damage, but they can
repair it. And this is really why by large we
are not doing radiotherapy in a single day. We
fractionate it. So we're giving the 24 hours
for normal tissues to repair the damage before
we irradiate the patient again and keep accumulating
the radiation damage in the cancer. So the differential
effect comes in different responses of cancer
to the radiation damage versus normal tissues.
But having said that, that treatment planning
that I spoke about in the beginning is one of
the most important aspects of radiotherapy, where
we are really investigating that we are not...
giving unnecessary dose to any of the surrounding
healthy tissues. Yeah. Well, you started out
this discussion about this type of radiotherapy
with a controversial statement. I'm wondering
what alternatives there are. So the problem is
that no matter how much you improve the linear
accelerator for photons technology, how much
you improve treatment planning algorithms, You
can't change the physics of photons and they
will always attenuate exponentially. So there
is a limit to your improvements and you always
will have an exit dose beyond the target volume.
So in order to really overcome this conundrum,
we have to move away from photons, from X -ray
radiation. This is where nature is saving us
again because charged particles such as protons
or alpha particles or carbon ions deposit radiation
dose inside a medium, which would be including
patient bodies, completely differently. And I
don't know how well to describe it for the listeners.
But the dose deposition starts with fairly low
dose plateau region. And most of the energy is
deposited towards the end of the particle's path.
Particles actually have a finite trajectory,
finite distance in the medium when they come
to a complete stop. And most of their energy
is deposited about 80%. right at the end of their
trajectory, generating very sharp peak of energy
deposition. Yeah. And this peak is known as Bragg
peak in the honor of the scientists who discovered
it. The funny things about this Bragg peak also
is that the position or the distance that the
particle travels into the medium depends on the
energy of the particle. So if I have a lower
energy particle, that break peak can happen at
two centimeters into the body. If I select another
energy, it will be five centimeters in the body.
If I have a target volume like prostate in 20
centimeters in the body, then I will select appropriate
energy of a charged particle such as proton and
the bulk of that energy. will be deposited exactly
in the prostate target volume. Okay. Which means
that now I have lower doses before the target
volume and I have zero doses behind the target
volume. Right. So I have minimized the entrance
dose, maximized the bulk of the energy bulk of
the radiation dose in the target volume. And
I have removed the exit dose. Right. So basically.
Ideal. Yeah. So you basically have a scenario
where that tumor, you can target it very directly
by adjusting the energy of the charged particles
that you're using for treatment. So maybe one
way we can help people think about this is when
you are, let's say you're throwing a ball into
water. And if you are throwing a ball that's
heavy and really fast, it's going to take a little
while to slow down. But if you are throwing a
lighter ball that you're throwing it slower,
it's going to slow down or stop in that water
much faster. Yes. But, you know, it's from what
the objective of radiotherapy is. Charge particles
are ideal. because it does give you that differentiation
between accumulating high levels of doses in
cancer while minimizing the doses in healthy
tissues. So that's really what we want to achieve.
So you might then ask, you know, if charged particles
are so good, Why aren't we using charged particle
accelerators? I was just going to get to, I know
you've been doing some work on this. So what
do you think about this? Photons are also what
we call sparsely ionizing radiation. So they
are not depositing the energy very intensely.
However, the charged particles is something that
we call the dense ionizing radiation. That means
that they are losing, depositing much more energy
along their trajectory. So while I can have 18
MeV beam photons to reach the prostate at 20
centimeters, I would need 200 MeV proton beam.
to get to the same depth inside a patient. So
the energies we have actually increased by one
order of magnitude. And if I move to carbon beams,
I need about 3000 MeB carbon beam. Because again,
that energy loss, energy deposition of a carbon
beam. per unit per micrometer is much more intense,
much more dense compared to photons. And because
they are losing their energy so rapidly, we need
to start with much higher energies to actually
have any energy to deposit in the target volume.
And so in order to start with protons of 200
MeV going back to the protons, I need different
accelerators. And much more powerful ones, I
would imagine. More powerful accelerators, larger
accelerators. So this is increasing then demands
on the technology and it also increases demands
on the footprint of the facility because you
now need a much larger facility that needs to
be shielded with the concrete bunker. Then once
you get that beam line into the treatment room,
once again, we want the gantry to be rotating
around a patient so that we can direct that radiation
through the right body path length to reach the,
what I call target volume or cancer. The gantry
now weighs, I was telling you the linear accelerator
was six ton. Now we can talk 100 tons, 200 tons.
Wow. Or even the facility in Heidelberg in Germany,
the Gantt, it weighs 680 tons. That's a major
engineering project. Absolutely. And a huge addition
to the costs. Yeah. I'd like to get into the
health economics of these options a bit. So what's
the cost of a linear accelerator facility like
the ones we're using in hospitals across Australia
right now? versus the cost of the charged particle
facilities we're talking about? When we're treating
patients with photons, the energy range of photon
beams is from 6 mV to maybe 18 mV beams. And
the accelerating structure is about one meter
long. So you can put the whole accelerator in
a single treatment room and you know, the cost
of the modern day accelerator with all bells
and whistles is two to $3 million. While I can
maybe set up a linear accelerator facility with
the bunker and everything, maybe for $5 million,
you would need $50 million to set up a proton
facility and maybe $200 million to set up a carbon
facility. right what we know from photons that
as i was telling you before they are as effective
for low -class cancer as surgery so we can still
use photons for many cancers and therefore Not
only every capital cities, but even in smaller
cities, we now have cancer radiotherapy facilities
in Dabo or Wagga Wagga or south of Wollongong.
We can set them up regionally and enable the
access of local people to standard radiotherapy.
With these expensive facilities, We potentially
don't have to treat patients that already have
fantastic outcomes with photons, but we will
use it for specialized patients with cancer where
the protection of normal tissue is of utmost
importance. So maybe we only need one to five
such facilities in Australia and make it a...
preferred treatment option, for example, for
pediatric cancer patients. Right. Yes. So if
I am irradiating, for example, a brain cancer
in a six -year -old patient and I'm using photons,
we are very good at eradicating that brain tumor.
But more likely, again, due to that exponential
attenuation, I will include. a bit of optical
nerve, bit of ear canal, bit of brain stem, bit
of pituitary gland. Yeah. And all of these then
can impact on the well -being and development
of the child, impaired vision, impaired hearing.
Then they will have development and speech delays.
There could be a bit of growth delay because
we are also impacting some of the... hormonal
centers with the glands in the brain. So this
is where something like protons are absolutely
amazing. Can I step back a bit? I'm curious,
these kinds of facilities, as I understand it,
this kind of treatment started out as being delivered
or experimented with at research facilities.
Is that right? Oh, absolutely. Look, the break
pig was discovered. 120 years ago. So the physics
is not new, and I will make a bit of claim. Bragg
Peak was discovered at the University of Adelaide
here in Adelaide, while Sir William Henry Bragg
was conducting the experiments here. It wasn't
until we had accelerators in 40s and 50s of the
last century that we could actually build the
first nuclear physics accelerators. The theory
for using particle therapy in medicine came from
Dr. Wilson again in the 40s of the last century.
But we simply did not have the technology. to
apply them in medicine. Looking at the physics
of the dose distribution is absolutely no -brainer.
So physics understanding was ahead of engineering
solutions. So we really had to wait. So particle
therapy has been used for cancers for maybe 50,
60 years, but research facilities use what we
call static beamlines. Yeah, so they're fixed
in direction. Exactly. So our biggest disadvantage
is that you don't get that rotating gantry where
you can actually change the orientation of the
beam in respect to the patient anatomy. So the
patients are also, because these are horizontal
beamline, the patient either needs to stand or
needs to be sitting in a chair. So they cannot
lie on a couch. And the energies of the proton
beams to begin with were more at the lower end
of the spectrum, maybe 50 to 70 MeV. So the first
areas where you only need a single fixed beam
would be maybe treatment of eye melanomas or
ocular cancers. Okay. And for those... Yes, all
you need is a fixed static beamline, a patient
sitting in a couch. Going back to physics, motion
is relative. If you have a fixed beamline, potentially
you can rotate the patient, which is cheaper
to have a rotating chair than a rotating gantry.
As I was telling you, the gantry is actually
the most expensive part of the proton therapy
unit. But if the patient is only sitting or standing
and they cannot lie down, especially if the patient
is unwell, it's a solution, but it's not the
best patient -orientated clinical solution. So
it wasn't really until about 30 years ago when
the manufacturers had really moved to... proton
accelerators, which are now cyclotrons or synchrotrons,
because we need a different style of accelerators
that can accelerate protons to those high energies.
Yeah. With rotating gantries where the patient
is on a couch and you can again rotate the gantry
around a patient and target the cancer for multiple
angles. We are not interestingly enough. So we
have like a halfway solution. We can have the
360 degree gantries, but we have 180 degree rotating
gantries, but we can rotate the couch. Right.
And then have access to the left or right side
part of the body. So we use the combination of
both. Okay. Rotating the beam and rotating the
patient to get the best of both worlds. So that's
at modern facilities that are being built for
this kind of treatment. Correct. South Australia
is building one right now, isn't it? South Australia
is building one, yes. So the bunker is built.
Just to maybe where the costs come, because the
gantry is so heavy, the patient comes into a
treatment room. That, of course, is height -wise
and size -wise, maybe like a smaller lecture
hall. But when you open the door, what's behind,
you have the gantry -supporting structures and
something that we call counterweight. Imagine
you have something that's 100 tons that's rotating.
It needs to have a big concrete or metal block
on the other side that's called counterweight
to balance it up. Yeah. There is like a three
-story building space behind the treatment wall
that the patient does not see. Wow. It's enormous.
So the shielding structure for the Australian
Brake Centre for Proton Therapy is completed.
And I can tell you the amount of concrete there
would fill in, I believe, 25 full -size Olympic
pools. Wow. The amount of steel would build a
two -rail... train line from Adelaide to Darwin.
So, you know, that's why these facilities in
addition to the accelerator itself are so, so
expensive. So not every city will have one and
we don't need. In every city one? Yeah. The latest
numbers show that you can make this type of facilities
cost effective one per every six million population.
Okay. And hence where I was saying Australia
could have maybe up to four. Okay. This might
be a good time to talk about the life cycle of
a facility like this. So if I go to photons,
we usually use a photon accelerator for eight
to ten years. and then we replace it the photon
accelerators by large are very compact and if
you are using the same energy you don't really
have to do any difference to the any modification
to the bunker you just bring a new accelerator
in and install it and you can use it for another
10 years with the proton cyclotrons Because the
initial investment is so huge, the life cycle
is more something between 30 and 50 years, so
that you still use the same shielding, but you
will maybe just do proper maintenance on individual
parts of the accelerators. And let's say there
is a new, better performing ion source. So you
will just replace an ion source. Right. Or maybe
there are better magnets. So we will install
new magnets or, you know, better collimators
for the treatment head. Yeah. So for the proton
facilities, really what might be driving replacement
of parts is more about the development of new
technologies or better approaches. For the linear
accelerators, what's shaping the life cycle?
Like what's shaping that 10 -year period? So
really sort of by the... how the x -rays are
produced you accelerate the electrons and then
the electrons will hit the target and produce
the x -ray cones so you start having quite a
lot of wear and tear in the accelerator and because
the cost of the accelerator is two to three million
dollars you might start thinking, okay, will
I replace a waveguide for half a million dollars?
Will I replace a target for $100 ,000? Which
might happen if you need to in the earliest stages.
But also what we do with the accelerators, there
is maybe this new image guidance technology.
There is new field shaping or radiation shaping
devices that we call the multi -leaf collimators.
So you might decide it's not economical for me
to keep replacing expensive parts. Yeah. I can
just buy turnkey new accelerator and have all
the latest bells and whistles. Okay. Yes. I don't
want to get into much details how the technology
is evolving. For example, the new accelerators
can have even increased the dose rates or they
have technologies that called breast gating so
that we can actually then irradiate or deliver
the radiation only during certain portion of
the breathing cycle of a patient. Okay. So it's
not necessarily the accelerator technology. But
it's the additional, we call it bells and whistles
or heads on that make the delivery a bit more
sophisticated. So I'm curious with these changes
in accelerator technology, etc. how you go about
developing a new treatment protocol for a type
of cancer using a facility like this? Like, what
would it look like to go from an idea about how
to treat a patient with a particular condition
to actual clinical practice? This is one of the
most important questions. And the simple answer
is it takes a lot of time because, of course,
we need to collect evidence. that certain protocol
works. And that's where we use clinical trial.
And trials are exactly what they sound like.
It's trial and see. How we usually work with
is that we have now 70 years experience with
X -rays or photon radiotherapy. That's as our
benchmark. So when we create a proton plan, By
large, we try to accommodate, to begin with,
the same dose prescriptions as with photon radiotherapy.
And we are comparing whether we, at least in
clinical trials, getting the same outcomes as
with the photon radiotherapy and are not making
anything worse. So we are always comparing two
things. Am I killing the tumor equally efficiently?
And we are looking at something what we call
five -year survival. Do I still have 95 % of
patients, for example, surviving five years post
-treatment? And then we are also looking at the
side effects. Okay, now that I have used protons,
Have I reduced side effects related, let's go
to the brain cancer, to optical nerve inflammation?
Have I reduced side effects? So this data, we
start sometimes with smaller case studies of
patients. just to get some indication, but it's
not the highest level of evidence. The highest
level of evidence needs to start from what we
call level two to level three clinical trials.
Okay. And then we have to collect patient data
for five to ten years. to have definitive evidence.
Okay, so let me ask a couple of questions about
that. The first is that you talked about side
effects. Are you talking across that 10 -year
period? Is it near term? So the side effects
are always multi -level. There will be early
side effects and late side effects. So early
side effects, for example, even in photon radiotherapy,
could for breast. Could be skin burns. Yeah.
And you will find them very, very quickly. Yeah.
Early side effects come with early responding
tissues, which is also bone marrow. So we will
be monitoring blood changes in a patient. Again,
this is more or less important depending what
organ we are irradiating. So that can be identified
very quickly. Many of these have been eradicated
with modern technology. The latest side effects,
you know, if they're going to children and the...
brain irradiation, the growth development delays
you may not or later onset of adolescence you
may not find until few years later on. So data
collection is extremely important. So that we
have, you know, information about the early,
late and very late side effects as well. And
that's where we need national and international
collaborations as well. We can pull all the information
together. Most of the clinical departments are
publishing the results of their clinical data
in publications and the protocols for any clinical
trials have to be lodged with clinical trial
registries. So what we can do when we are developing
our protocols in Australia, we don't have to
reinvent the wheel. We don't have to start from
scratch. We will conduct something that's called
systematic review of the published literature.
Yeah. And we compare all the protocols or all
the trials that other centers have conducted.
Then we perform analysis of the results and we
can then identify which of those protocols provides
the strongest evidence for improving the patient
outcomes both in terms of treating cancer and
in terms of minimizing the side effects okay
so let's take a step back a bit and I think there
are a few really interesting things from what
you've just said that might be worth stepping
through the first is that obviously This is a
safety critical thing. You want to get this right
if you're going to roll it out across a broad
population. And so you start with small numbers
and you sort of work up in size as you get a
sense of, you know, how safe things are, whether
things are working, whether they're achieving
the goals that you think that that protocol will
achieve. Is that that's correct? Yeah. Yes. What
we have the big advantage, if I can jump in.
We follow lots of the guidelines that are used
by pharmaceutical developments. But in pharmaceutical
developments, I think there is always a bit of
blindness because you swallow a little white
pill, you don't know what it does. Some of this
blindness is removed in radiotherapy because
we actually really understand well how radiation
deposits the energy, what the radiation interactions
are. So if I generate that treatment plan that
I was talking about before with photon versus
protons, It's not like we're really experimenting,
even if we are starting with small numbers. Right.
That's something we understand very well. Yes.
We immediately see that, okay, I'm not going
through optical nerve. I'm not going through
brainstem. I can immediately see, at least in
the theoretical dose distribution. how much sparing
of normal tissue I am going to perform. But of
course, maybe I'll just one step back. Before
we even go to the patient studies, I don't know
whether the listeners like it or not, we also
perform in vitro experiment with cell lines in
petri dishes. And we also do small animal experiments,
primarily using laboratory mice. We will never
get an approval to go to inhuman clinical trials
unless we show preclinical evidence. Because
if the preclinical evidence shows it doesn't
work, it will never get approved for inhuman
trials. Right. So again, the risk management
actually is about starting in cells or... And
then if that all looks good, then you go, OK,
we can start considering humans very carefully.
Exactly. The other part of this that I thought
may be worth at least mentioning is different
countries have different standards with regards
to medical treatment and how they're regulated.
Right. And so your discussion of looking at what
has been found in other countries at these facilities
and looking at what they've discovered and then
adapting that, thinking about how you're going
to make use of that. in an Australian context.
Sounds like it's part of your practice. Is that
right? Yes. Yeah, absolutely. Look, in terms
of clinical trials. They all publish dosimetry
data. So the interaction of protons will be the
same in Australia as in Europe. I would hope
so. Yes, exactly. So primarily we are after the
dose and fractionation. You know, what is it?
How much radiation dose per fraction? How many
fractions? What is the total dose? Yeah. So that's
irrespective. Because these facilities are expensive,
you usually do have them in countries, maybe
more your high income countries, even though
we now see the onset of development of these
facilities in middle income countries. But most
of these have excellent both health and radiation
regulations in place. We also all subscribe to...
international regulations as published by international
commissions for radiation protections or ICRP
or international commission for radiation units
ICRU. ICRU actually publishes series that inform
clinical protocols. Right. And also we follow
any guidelines by IAEA, International Atomic
Energy Agency. So there is some form of uniformity.
Yeah. Yes. And dosimetry standards are uniform
to an extent as well. So, for example, most of
our accelerated calibration protocols are referenced
to IAEA. But where sometimes the changes come,
and that's where the departments might work slightly
differently. It comes to the cost of the therapy.
One of the cancers that is very difficult to
treat and has unmet demand is pancreatic cancer.
And our theoretical studies show that I get a
good result when I use three proton beams. We
are collaborating with a center in Asia. but
they are only using two proton beams because
the patient is charged per beam. Right, okay.
So to minimize the cost to a patient, they will
be only treating with two beams. So that's where
some of those differences might come. Okay. But
that's where we have the trial stage and where
we can do lots of things in treatment planning
itself. without a real patient to identify the
dose distributions and the beam arrangements
that could lead to the best outcomes. So you
basically have a way of testing in advance what
potential trade -offs, if somebody is paying
per beam, you're deciding between, okay. Yes,
absolutely. So once we have the dose distributions,
we have biological models. One is called tumor
control probability, which is basically telling
me, am I killing enough cancer cells or not?
Yeah. And the other one is something that's called
normal tissue complication probability, where
we start thinking, okay, will this person develop
this particular side effect? Yeah, okay. So we
can, because the radiation simulations are so
advanced, and this is, again, thanks to the,
you know, 100 years of radiation and nuclear
physics, We can do lots of things in that simulation
domain and prepare the protocols in simulation
domain before we even go to real patient treatment.
Does access to a trained workforce for these
kinds of facilities impact things at all, just
out of curiosity? In radiation therapy, we are
not doing at the moment too badly. We have large
shortage in nuclear medicine. This is actually
another aspect of cancer and other therapies.
I was only talking about 50 % of cancer patients
receiving radiation for treatment of the disease.
100 % of cancer patients will receive some sort
of X -ray or radionuclide intervention. for imaging
and diagnostic purposes. So they will definitely
have one or more CT scans. Many of them will
have a maybe magnetic resonance imaging, but
many of them will have either gamma camera or
positron emission tomography or PET scan imaging
as well. 100%. So we see a huge development in
nuclear medicine and we have huge shortages in
that space at the moment. With photon therapy,
we are not doing that badly, but we don't really
have a program for proton therapy as much, which
is maybe an opportunity space for university.
At the moment, what we are doing, look, we don't
really have a functional facility at the moment.
So it's a bit of a chicken and egg. situation.
So at the moment, what we do, we send people
to train overseas in the facilities that have
a well -established program. But eventually we
implement something locally. I know that professional
bodies such as Australasian College of Physical
Sciences and Engineers in Medicine or Australian
Society for Medical Imaging and Radiotherapy
have already starting courses at that professional
organisational level rather than at the university
undergraduate or postgraduate level. I would
be thinking that we might maybe need postgraduate
diploma in particle therapy and make it as an
advanced practice to the undergraduate degrees.
Okay. So it's probably the people who have been
trained overseas and come back that might be
involved in running those programs. Yes. Yeah.
Okay. And what kind of timescale does it look
like we will need those on? I mean, the facility
is being built now. So I think some of the people
are being trained now because we already look
while we are not treating patients now, we are
sending limited amount of patients overseas,
particularly to the United States. How do you
decide who to send? So this is where something
is performed is the comparative planning that
I was talking about. This again primarily involves
children and often with brain cancer that you
create a treatment dosimetry distribution plan
with x -rays and treatment dosimetry plan with
protons and you can demonstrate to the select
committee. that this child will significantly
benefit with proton therapy. Yeah, that makes
sense. So it's not like you just like turn the
facility on one day and it's all good. No, no,
no. There is a huge lead time. Yes. Let's say
when Australia is thinking about these kinds
of things, like what kind of lead time are they
needing to think about even developing the expertise
they need to do the planning to work towards
these kinds of major changes to the health? look
in australia we have been talking about this
for 25 to 30 years And we still do not have a
facility. But I would say, depending on what
you want to buy these days, maybe five years,
there are now, especially with companies like
IBA or Median, that there are turnkey solutions
and they can already come. Okay, this is the
accelerator. This is what you are. They can come
with a footprint for the facility. and shielding
recommendations. If you are going for something
that's maybe going towards carbon therapy and
it requires a synchrotron. you might need lead
time of 10 years. What we do not have compared
to Europe or Japan, because we are not an accelerated
country, we don't have inside Australia know
-how. Right. Couple of carbon proton facilities
in Italy and in Austria were based on the know
-how coming from CERN. Right. Because they have
this huge nuclear physics facility that uses
the colliders and synchrotrons and everything,
you have great accelerator know -how, great engineering
know -how, understanding magnets and beam steering
and everything. So you can design and fine -tune
your own accelerator structure. Right. And we
don't have that in Australia. So we are more...
dependent on turnkey solutions, which now do
exist, or on collaboration with a company that
can design maybe something a bit more different,
especially if you want to maybe increase the
energy of the protons than the standard turnkey.
Japan is in a similar space because they have
Sumimoto, Hitachi. I think now fourth and then
fifth carbon facility. Yeah. But they are learning
from each of the facility and bringing that know
-how to the new facility. Actually, some of the
images I saw out of Japan is superconducting
synchrotrons and so much reduce the footprint.
It's just amazing. So, you know. I don't need
diamonds. Give me a new superconducting synchrotron
and I will be so excited. Nuclear Matters is
a production of the Australian National University
College of Systems and Society. We acknowledge
the Traditional Owners of the lands on which
this podcast is being recorded on or listened
to and pay our respects to their elders. and
all First Nations people. If you liked what you
heard today, please share this episode with friends,
family, and colleagues. If you want to send us
some feedback on an episode, please email us
at nuclearmatterspodcast at anu .edu .au Keep
in mind that this podcast is intended for information
and education only. or the university as a whole.