Billy Loo: “FLASH” radiation therapy brings hope to cancer patients

(bright music) – [Narrator] From the campus of Stanford University– – [Russ] People are worried about data, they’re worried about.


(bright music) – [Narrator] From the campus
of Stanford University– – [Russ] People are worried about data, they’re worried about their
privacy and their security. They should be. We need secure systems. – [Narrator] This is The
Future of Everything. – [Russ] But we can’t have a system that closes that data off,
it’s too rich of a source of inspiration, innovation and discovery for new things and medicine. – [Narrator] With your host, Russ Altman. – Today, on The Future of Everything, the future of radiation therapy. So, cancer, we all don’t like cancer. And it continues to be a major problem. We’ve heard about great
advances, but globally, there are still millions of
cancer deaths every year. So despite these advances, we still need more and better treatments. When you think about cancer therapy, a lot of things come to
mind to me immediately. One thing is chemotherapy, the
dreaded word, chemotherapy. These are, very toxic drugs,
that try to kill the cancer, and usually have very big, toxic side-effects on the patients. You also think of surgery. Let’s go in and remove that cancer. But we know the surgery
doesn’t always work, because there might be little bits of cancer that the surgeon doesn’t see, or that are distant
from the primary cancer. And so surgery, also,
is not always working. Then the third thing that
some people think about, and that we’re going to
be talking about today, is radiation therapy. The idea, is that radiation,
I’m talking about X-rays, like radiation from the atomic bomb, or from linear accelerators
that can create these X-rays are harmful to cells. And the cause damage to the DNA and other cellular processes. The cells cannot recover, and especially, if you’re a rapidly dividing cell, that needs to make copies of
your DNA in order to divide, this damage can be lethal.
And this, cancer cells, die. That’s the theory. And we often use radiation
therapy in combination with chemotherapy and surgery, and
anybody who knows a relative or a friend that has had cancer knows that they might go through
a series of treatments, involving all three of these. In particular, cancer of the lung, is a very important target
for radiation therapy. Because of the difficulty of doing some of those surgeries,
the difficulty of getting high levels of chemicals into the lung. Radiation therapy has a really clear and important role
there, among others. It has it’s benefits, there’s no surgery. No extra surgery, there’s no pills. You can focus the
radiation, at least that’s what people are trying to do. And you can kill the cancer
in a very, very, specific way. Doctor Bill Loo, is a
professor radiation oncology, radiation therapy at Stanford University. And his research is devoted
to improving the utility and uses of radiation in cancer therapy, and even in other diseases. Bill, can radiation therapy cure cancer? Or is it always gonna
be limiting the disease without completely removing it? – Thanks Russ, I’m really
excited to be here, I appreciate the invitation. Yeah, so, I think your
introduction is right on target. I think what many people don’t
realize is that radiation is, in fact, one of the pillars
of cancer treatment, along with other treatments
like surgery and drug therapy. And that includes chemotherapy, and some of the newer approaches we have, with molecular targeted
drugs and immunotherapy. – I didn’t mention all of the new systems that are using the immune
system to combat the cancer. – And radiation plays into
that as well as it turns out. But absolutely. Radiation is used today, in the United States at some
point in the course of therapy, for about 2/3 of patients with cancer. – So it’s not rare at all.
– So it’s not rare at all. And in fact, in the
majority of those cases, it is with the intent to cure. In other words, the goal of the treatment is to try to eliminate the cancer. And so yes, absolutely.
Radiation is an important part of curative treatment of cancer. – So what are the frontiers, I mean, I’ve read stories about in the old days, they would literally
take a radioactive block of radium, and just stick
it near the patient’s chest wall, hoping that those
rays would kill the cancer. And of course they did huge damage to the skin and to the underlying tissue. Where are we now in terms of being very precise in the
delivery of that radiation? – Yeah, so, with the
techniques that we have now, we are much better
targeted with radiation. In other words, we’re able to create a pretty exquisite 3D
sculpting of radiation doses. And so, in that way,
we’re able to accomplish one of the key things that is
needed for all cancer therapy. It’s a big word, but the big
word is therapeutic index. And what that means is being
able to eliminate the cancer, without causing too
much collateral damage. And that’s a key principle,
regardless of the treatment. You know, it turns out that
what makes cancer incurable, in those cases that it
is, is when what it takes to eliminate the cancer, is more than what the patient can tolerate.
– Yes. – And so it doesn’t matter if it’s a drug, or if it’s surgery, or radiation. Basically, I can give enough
radiation to eliminate a cancer, that’s actually
not a fundamental problem. The fundamental problem is
when the patient is not able to tolerate that, then
we’re really limited. – So tell me a little bit about
how we get this precision. You said that you can even
do like a 3D sculpture. And I know in some of your papers, you even referred a four dimensional. So, tell me about 3D and
then maybe we can move to 4D, in terms of, what are
our capabilities now, and how does it actually work. – Yeah, absolutely. So, there’s different ways
of delivering radiation, but there’s some common
principles to all of them. And the most common
type of radiation we use is high-energy X-rays.
– Okay. – And the way that we create
a 3D sculpting of radiation doses to create focusing of the radiation, is by coming in from multiple
different directions, and where radiation beams
cross, the dose adds up. – So you have a bunch
of maybe, not so strong, X-rays, but there’s a lot of
them coming into this point. – That’s right. – And so they add up so that
the surrounding tissue gets a little bit, but that one point where it’s all focused, gets a lot. – Exactly. And we are able
now to guide that precisely, with the better imaging that we have. So, CT-scanning, PET-scanning, MRI, all of those we’re able to incorporate, to get the best picture
of where’s the cancer, where are the normal
tissues that we wanna spare, how do we kind of create
that dose sculpting. – Yes, so now let me
ask, when you use these images, CTs, MRIs, are you
doing it before the treatment, or are you doing it during the treatment, in order to watch the effects
as it’s happening, perhaps. I’m just making that up. – Yeah, absolutely. So it’s both. We use
it before the treatment in order to plan it, so we
identify what’s the area that needs to be treated, where’s
the tumor in relationship to the normal organs, and create that plan of various sculpted treatment. And then during the treatment, we also use imaging and up till now, the imaging that we can
use during treatment is a little bit more
limited than what we have, you know, for diagnoses,
but it allows us to see, for example, whether we’re on target. And is the radiation going
where we want it to go. – So this is great. This is great. And so the 4D, so obviously
3D is the shape of the tumor, and you wanna match that
as closely as possible. And then is the 4D
overtime, I would presume? – That’s right, yeah. – And is it the time over
many weeks and months while the patient is
getting the treatments, or do you mean the time during the delivery of the X-rays, or both? – Again, it’s both. And so, I think what people, you know, may realize, if you think
about it a little bit, right. During the treatment, every
part of the body moves, all the time. Some parts
move more than others. So for example, when I’m
treating a lung tumor patient– – We do have to breath, yes. – And so the people are breathing, organs move, lungs and other
parts of the body move. So we’re always treating moving targets. And that’s where the 4D comes in, is, understanding what motion is going on, and how do you compensate for it. – And then you can adjust
so that even if you had an initial plan, stuff
happens, and you might need to, in mid-stream, adjust how
you’re delivering the X-Rays. – That’s right. – This is The Future of Everything. I’m Russ Altman, I’m speaking
with Doctor Bill Loo, about frontiers of radiation therapy, and the opportunities going forward. So, so many things to ask
but let’s talk about timing. We’ve talked about time,
the fourth dimension, the traditional story
about radiation therapy, is often a patient going
in on a regular basis over weeks or months,
staying for quite a long time in a very rigid position, while you guys deliver the radiation. But I understand that there’s been some breakthroughs recently,
where the treatment times have been getting much shorter. And I want to ask about
what’s the source of those innovations and is it
having a positive impact on the patient experience, ’cause, having cancer is terrible as it is, but having to go everyday to a clinic and spend two or three hours in a rigid position can’t be fun. – Yeah, absolutely. So there’s, basically,
developments over time, that have given us insights
into the new breakthrough that, I hope we’ll be touching on,
which is the PHASER technology that we’re working on.
– Oh my goodness. This sounds like Star Trek.
– Absolutely, yeah. – PHASER, so that’s a real
thing. So tell me about PHASERs. – Sure, well, so, PHASER
is, I mean it stands for, a mouthful, it’s what the acronym is for. Pluridirectional High-energy Agile Scanning Electronic Radiotherapy. – There you go, PHASER. – But, to be honest, you
know, the motivation for that comes from the fact that, you know, probably like you and
others of our listeners, I’m a sci-fi nerd, right, and
I was influenced by Star Trek. – Of course, is that what
PHASER stands for on Star Trek? – Good question, that’s
something we need find out, yeah. But, yeah, you know, growing
up watching Star Trek, you know, that was the
future of medicine, right. In fact, the future of everything. – Exactly. Star Trek was
filled with medical things. You remember the doctor
had that little thing that they put, the scanner,
that figured everything out. I would love to have one of those. – The tricorder.
– The tricorder, thank you. So what is the PHASER techonology? – Right, so, we were talking about time, and treating moving targets right, and so a lot of the work
that I’ve done together with my colleagues over the years,
is implement technologies in the clinic to compensate for motion. We call it motion management. All kinds of tricks like, you know, turning on the radiation beam, synchronize with the breathing cycle, or following tumors around
with the radiation beam. Very complicated things that we now able to do on a routine basis,
but it’s hard to do, hard to do right, easy to do wrong. Very hard to translate out
into the rest of the world. – Yeah I imagine this involves maybe, robotics and artificial
intelligence type technologies. And you don’t have to just get it to work in your clinic and in your lab,
but you have to figure out, how do I export this so that
everybody can benefit from it. – Exactly. – So the PHASER, is the
PHASER technology this, very intelligent tracking of the tumor, and deciding when to send the beam? Is it also more intense beams? Is that how we get a time
shortening for the treatments? – Right, so, all of the
strategies that we’ve developed in the past have been based
on the fundamental assumption that it takes longer to give
the radiation treatment, than it does for the body to move. But over time, as we’ve
implemented these various technologies, we’ve sort of realized that the treatment times, you
know, we’ve successfully decreased gradually, so when
we first started doing this in the early 2000s to give a
big focused dose of radiation, using the new technologies in the time, that maybe three hours,
two to three hours, the patient would be on
the table getting treated. Now, we do those similar
treatments in about three minutes. – So that’s a huge difference.
– It’s a huge speed up. But still a long time compared
to the motion in the body. But the insight that came from that is, what if we flip the problem around? What if the treatment was done so fast like in a flash, like flash photography, that all the motion is frozen. And that’s a fundamental solution, to this motion problem that
gives us the ultimate precision. – Yes. That makes sense. – And that leads to therapeutic index. Because if we’re able
to treat more precisely, with less slop, less
spillage of radiation dose into normal tissues, that
gives us that benefit of being able to kill the cancer, and cause less collateral damage. – This is The Future of Everything. I’m Russ Altman speaking
with Doctor Bill Loo, about the advances in radiation therapy. And we’re now talking about
PHASERS and flash treatments. So, when I think, so flash
sounds like a great analogy to just imagine what it’s like. And we all know that, the
thing about flash photography, is it’s extremely bright. So yes, it captures our motion, but or that, you know,
several milliseconds, we’re almost rendered incapable
of doing anything else because of the overwhelming light. So, is there an analogy in the treatment. So, first of all, it
must be very stressful for you to turn on such a bright beam, even if it’s for a short period of time. The first time you do that,
it must be very stressful, I would imagine, because
if you’ve over-exposed, so to speak, the patient, or
if you’ve missed the target, you might be doing a lot of damage to the wrong part of the body. So, how do you even begin to
do, to test these technologies, to the point where you’re comfortable using them in patients. Right, well so one key part
is integrating something that we’ve been doing for
a good period of time now, which is that image guidance
aspect of it, right. So it’s very important
to have a clear picture of what’s going on in the patient’s body so that the beam is turned on at exactly the right place and the right time. – It’s like you’re a marksman.
– Yeah, exactly. – When we have it in the
cross hairs, press the button. – That’s right, yeah. And so, you know, so some of
those imaging technologies, we already used to some extent. In fact, you know, the way
it works right now is that even though our radiation
treatments aren’t so fast, right. We line everything up perfectly, you know, we hit go on the radiation. The imaging that we have on the table, is a little bit limited, and so, even now, we’re not seeing everything, all the time, you know, as we’re treating. But, if you have fast enough radiation, where you can get a clear picture right at the beginning, right
when you’re about to fire, and then everything’s lined up and you go, that’s actually got the
potential to be more accurate than what we do now, and
all the motion’s frozen. But the really exciting
thing that we’re discovering, and this is now in laboratory research, we’re developing the
technology to do this very fast flash treatment in humans,
but using some existing technologies, we’re able to test this in very small patients like mice. And what we found is– – Who can be given a range of cancers that can be then used as test grounds. – And what we found preliminarily– – And even a big tumor, forgive me. – Sure yeah. – But even a big tumor in
a mouse is gonna be little tumor in a human, so if
you can get good with that, you can imagine it being very reassuring. They are also not very good at holding their breathe on purpose for you. – Right, and so there,
the question is not even the precision part, right, but just, what’s the fundamental
biology that happens, when very fast treatment is given. And what we, and a few
other labs around the world, have started to see, is that
when the radiation is given in a flash, we see equal
or better tumor killing, but much better normal tissue protection, than with the convention
speed of radiation. – So this is very interesting. So you’re saying that
the biological response to the radiation actually
might be different based on if it gets a lot in a short time, versus a little bit over a long time. And then you’re telling me also, that this is actually
kind of good news that, for whatever reason, normal
tissues seem to be able to withstand this high
flash a little bit better than the cancer tissues. Do we
understand why that happens? – That’s a very active
area of research right now. So we’re just at the beginning
of trying to understand that, but what we have seen is this
consistent phenomemon now, across multiple labs, and
even in a few different species of animals that
this effect is occurring. And if that translates to humans, that’s a huge breakthrough. – So speaking of the biology, let me ask you about resistance. Everybody knows that in chemotherapy, the big thing that you worry about is that you’re gonna become
resistant to the chemotherapy. It’s not gonna work anymore. The cells stop dying because they figure out a way around it. Is resistance a thing
in radiation therapy? – To a much less extent. Because radiation cuts
across many more molecular pathways than, you know,
drugs that may work on a few molecular pathways. So, the cancer cells can
have different sensitivities to radiation, but resistance
is still much less of an issue with radiation
than with the drug therapies. – So that’s quite good news. This is The Future of Everything. I’m Russ Altman, more
with Doctor Bill Loo, about radiation therapy and it’s future, next on Sirius XM Insight 121. (bright music) – [Narrator] From the campus
of Stanford University. – [Russ] People are worried about data, they’re worried about their
privacy and their security. They should be. We need secure systems. – [Narrator] This is The
Future of Everything. – [Russ] But we can’t have a system, that closes that data off. It is too rich of a source of inspiration, innovation, and discovery
for new things in medicine. – [Narrator] With you’re
host, Russ Altman. – Welcome back to The
Future of Everything. I’m Russ Altman, I’m
speaking with Doctor Bill Loo about radiation therapy, it’s
applications, and it’s future. So Bill, one of the
really fascinating things in preparing for our conversation, was the idea that radiation
therapy might actually be useful for things other than cancer. And I think you’ve kind
of led in some areas. So what would be the theory of using radiation for other diseases? – Right, well so radiation
in cancer is used, we think, primarily to kill cancer cells. It actually has a lot of
other biological effects that can kinda contribute to that, that, you know, it’s much
more complicated than that. But some of the effects that
are not directly related to cell killing, you know,
it may modify the function or response of cells,
scar tissue formation, or changes in electrical
conductivity of conducting cells. And so some of the applications, you know, where we’ve looked at
diseases that are potentially treated by surgery, but in
patients who maybe cannot tolerate surgery because
it’s too dangerous for them. – Right, sometimes you’re
just not a surgical candidate and the surgeon says I can’t operate on this person. – Right, and so a couple of
the applications that have emerged, that in clinical
studies, is for example, patients who have bad
emphysema of the lungs. A portion of their lung
is not working because it’s basically a big air bubble. – That’s right. So all the
fine structure of the lung, has been damaged and
removed, so they don’t have a surface area for exchanging oxygen with their blood stream. – Exactly. And one of
the treatments for severe emphysema is, in fact,
remove those non-functioning parts of the lung, so the
other parts can work better. And we found preliminary evidence, and we’re doing a clinical trial now where we use very focused radiation to– – Which we know you know how to do from our previous part of our discussion. – Right. To create an area
of basically like scarring, to shrink down the portion
of the emphysema lungs. – Yeah, it kinda pulls together
all of that useless tissue, and lets the other tissue
expand and do its thing. – Correct, yeah. – So where is this in development? Is this a brand new idea,
or are you actually doing some trials, where are we
in the research pipeline? – So, it’s, well it has
roots that are quite old. But we actually have a
current clinical trial that’s ongoing that’s run in collaboration with Joe Shrager, who leads our
thoracic surgery group here. – So is it possible that
this would wind up being even better than surgery,
and that for even people who could tolerate the surgery, they might elect to do this instead? Because, I mean, just thinking about it, if you told me that I could
either go on a surgical table, or go to the radiation therapy suite, and some, you know, zap in my lungs, so, I guess it’s too
early or do we have any– – Yeah it’s still very early days, but I think the way that we’ve seen these sorts of things evolve, is that it’s not an either or, it’s not one replacing the other, but what it is, is it
allows us to individualize for a given patient, you know, expanding the options, and
what might be better, you know, depending on what their risk factors are. So it allows us to kind of
tailor the treatments better if we have more options. – So I’m struck, and that’s very exciting. And people and emphysema is
very different from cancer. And so it’s fun to think about novel uses of these technologies. And I did want to just briefly ask you about the technologies, like, what is your laboratory look like? What are the kinds of work that you’re scientists in your lab, the technicians, the students,
the post-doctoral fellows, what does it look like? – Well for one thing it’s
very multidisciplinary. Because it pulls in
collaborators from a lot of different areas, so physics,
engineering, biology. And so, for example, the core
linear accelerator research that we’re doing for
PHASER, is being done, led by my colleague Sami Tantawi at SLAC National Accelerator Lab. – So SLAC, for those who are not familiar, it used to stand for
Stanford Linear Accelerator. But I think now it just stands for SLAC, and it’s a big physical
facility in the Bay Area, with a one or two mile long tunnel, that accelerates these
particles to very high energies. – Exactly. – And so they’re using
this for medical research, ’cause everybody thinks of it as kind of energetics and nuclear research, but this is for medicine as well. – Well it turns out that pushing the limits of that technology, to study very high-energy physics, has other applications, and
translates into, you know, the medical technology as well, and that’s what we’re capitalizing
on in this collaboration. – And I would guess that you have people who are essentially,
robotics experts as well, in terms of this tracking
and moving the beams. Is that true? – Well, in this particular incarnation, because of the speed, we
actually wanna eliminate all mechanical moving parts, so
it’s all done electronically. – No robots.
– Yeah. – This is The Future of Everything. I’m Russ Altman, and I’m
speaking with Bill Loo about radiation therapy. I wanted to kind of, also ask you about, okay, now you do this discovery you get these amazing new technologies, there’s a responsibility to
get it out into the world, and how do you do that? And I can imagine it as one issue, getting it out in the
U.S., where you’re based, but I imagine that there’s another issue and set of opportunities with
getting it even more broadly around the world. How do
you even think about that? – Yeah, absolutely.
Well, the major problem that we face in cancer is
that about half the patients, in the world today, despite
the fact that radiation is such an important treatment, about half of patients
have no access at all for technological and logistical reasons. – Whereas they could definitely benefit. – Correct. Yeah so, that means
that millions of patients, who could potentially be
receiving curative cancer therapy, or getting treated purely palliatively. So that’s a huge tragedy that, you know, kind of, it’s an emergency
of our day here now. And so, if you know, whatever revolutions that we come up with in technology, if it’s gonna impact that, it needs to be something
that can be practical, in the sense of, it has to be compact, it has to be economical,
it has to be reliable, it has to be clinically efficient. And so those are sort of
core design principles that we’ve kept in mind
from the very beginning, when thinking about the PHASER technology. Because we don’t wanna create
a solution that, you know, everyone in the world
has to come here to get. That would be great, but it’s gonna have a limited impact, right. And so that’s been a core
principle from the beginning. – So that is a really fascinating problem. ‘Cause of course, one of the
things that comes to mind is, it has to be robust, you know, you’re working in a very
high-end, medical facility, but the people who have to account these 50% of people with
cancer around the world, many of them are living
in very harsh conditions, in villages and what not, and we have to figure out
how to get these machines, and have them be robust
and well powered, and safe. So, is this something
you do as a side project, or are there people who
are devoted to this kind of robustification, a word
that I just made up, of these technologies,
like whose problem is that? – So, it’s a problem that, you know, we’re tackling from the very beginning. Not only do we wanna increase
the performance of the technology, but it has
to be robust as well. And that’s one of the breakthroughs that, you know, on the accelerator side, from my colleague Sami
Tantawi, making discoveries about that.
– ‘Cause you can’t take a two mile accelerator around the world. So you obviously need to turn that accelerator into something. Is that gonna be technically possible to get those kinds of
energies, in smaller devices? – We believe that the entire
system that we’re developing will end up being able to fit into a standard cargo-shipping container, and be powered by solar
power and batteries. So really a portable solution. – Now how do the companies
that build these– so you make the inventions,
you make the protocols, there has to be some industrial
interest that kind of scales it and makes as many as are needed. How do they think about
these markets where perhaps the levels of
income are not as high, the ability to pay, it
seems like there’s some real challenges in getting
high-tech innovation out into the developing world. – Yeah, that is definitely a challenge. You know, but, I think
there are resources, at least to some degree,
to pay for cancer, gather initiatives to do that, if that needs to be worked on, you know, from a health policy angle as well. – I would imagine it might be some foundations who would take a
particular interest in this. And also there has been, I’ve noticed, a tendency sometimes, for
things that you design for robust deployment in the field, actually become useful even at home. – Exactly. And I think
that’s the key thing. It’s like, you know, your cell phone. It’s burying the complexity. You know, you have a super
computer in your pocket, that even kids can use, right. And yet that power is
something that’s very relevant to all of us everyday. So, in fact, the ultimate
machine for Africa, or other underserved areas in the world, is exactly what I would
wanna use in my clinic. – Thank you for listening
to The Future of Everything, I’m Russ Altman. If you
missed any of this episode, listen anytime, on demand,
with the Sirius XM app.

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