 can hear me? Great. My name is Lydia and I am a Ph.D. candidate at Louisiana State University in medical physics. So not at all about this kind of stuff. And I'd like to tell you a little bit about radiation therapy. So let me start after asking you guys the questions. How many people here know someone who's been diagnosed with cancer? Now look around yourselves. It's a lot of people, right? And unfortunately, the story gets worse. So we look at the cancer incidence rates. So it's the number of new cancer diagnoses each year over about the past 40 years. What we see in pretty much every country that we look at is that these rates have been rising. So cancer is not an issue that we expect to go away anytime soon. So that's the bad news. And if you stick with me for about the next 14 minutes, we'll get to the good news. Deal? Deal. Alright. So cancer is apparently all around us. So what is cancer? Well cancer is a collection of related diseases that are caused by an accumulation of DNA mutation. And these mutations need to give the cancer cells or the cells two defining characteristics. So the first characteristic is that these cells will start to divide without stopping. So here we start out with a nice orderly row of cells. And at some point some of these cells acquire some mutations that allow them to go out of control with dividing. And before you know it, we have a mass of cells. And this is what we call a tumor. But this alone is not enough to be considered cancer. In order to call it cancer, they need to acquire another defining characteristic, which is that it has to be able to spread and invade surrounding tissues. And once we have cells that can do both of these things, we have cancer. So let's say we found a patient who has cells that exhibit both of these characteristics. What happens next? Well this patient will have three main treatment options available to them. First we have surgery. And with surgery we basically just remove the area of their tissue that contains the cancer. And unfortunately the problem with this is that if we leave one cancer cell behind, that cancer will come back. And when we're doing surgery we don't have the ability to look and see, oh look this cell is cancer but it gets that one. And oh look that one's cancer so you better get that one. So there's always some chance that we'll leave one cell behind and the cancer will come back. So surgery often is not enough on its own. So in addition to that we have chemotherapy. And this is where we give the patients cancer killing drugs. And this is a global type of treatment. So those drugs go to the patient's entire body. And that means that they'll affect the patient's entire body. So this is why when someone's getting chemotherapy even just for cancer in their stomach they'll lose the hair in their head. And that's really perfect for some types of cancer. Things like leukemia and lymphoma, chemotherapy is exactly what we need. However there are other types of cancer where we'd really like to be able to only affect a small portion of the body. And for those things we have radiotherapy. And actually it's a little more complicated than that. So all of these types of treatment are not mutually exclusive. Most patients are going to get a combination of two or even all three of these types of treatment. And the combination, how much of each one, when we give them, that depends on the specific patient and their specific cancer. But what we'd like to focus on today is this part right here, radiotherapy. And so that obviously has two parts to it, the radio and the therapy. So let's take the first part, radio, which refers to radiation. And radiation is the emission and propagation of energy in the form of waves or particles. Radiation is completely naturally occurring. It's all around us all the time. It's the light that's allowing you to see me right now. And in fact did anyone eat a banana today? Anyone? Okay there we go, you guys have good nutrition. So it turns out that all bananas have a lot of potassium in them, as you probably knew. Also a small portion of the potassium is also completely naturally radioactive. So all bananas are just a little bit radioactive. So congratulations you got your daily dose of banana dose. But obviously we're not treating cancer with bananas. Maybe you guys have heard of some other radioactive elements like uranium or radium, plutonium, things like that. And with radioactive elements there are three types of radiation. So first we have alpha particles, and alpha particles do not travel very far. Just our skin is enough to stop them. So they're not really that useful to us in terms of treating cancer, which is often below the skin. So other than that we have beta particles which are able to travel a little bit further. They can get through the skin, but then they don't go a whole lot deeper than that. And finally we have gamma rays. And these are waves instead of particles. And these are extremely penetrating. So gammas are able to get through our skin, travel deep into our body, and even travel all the way through our body. So betas and gammas are what we typically use in radiotherapy to treat cancer. So now we come to the other part of radiotherapy, the therapy. Which is where we need to expose the portion of tissue that contains the cancer to radiation. And of course that portion of tissue is not just a portion of tissue, it's part of a patient. And that patient is living. So what happens when we expose living things to radiation? Does anyone have any guesses what's going to happen to this turtle and expose it to radiation? Anyone? So that's not exactly what happens. We don't create anti-fighting cells. How many of you thought that this turtle would then become radioactive itself? Also a common misconception, but exposing things to radiation does not make them radioactive. But in order to answer this question we can actually think about radiation as like little tiny footballs. So we said radiation was traveling energy. If I pick a football, I've given it energy that football becomes traveling energy. So now what happens if I pick this football at that base? Any guesses? It'll break. And that is very similar to what happens when we expose living things to radiation. We take a whole bunch of tiny little footballs at the thing, and we don't break the turtle. But what is this turtle made up of? Cell. Good job. Inside of these cells is DNA. And that's actually what the radiation is going to hit and break apart when we expose the living thing to radiation. So the radiation comes in, it causes damage on the DNA, and we end up with DNA that's all broken up. And this actually isn't necessarily a problem for the cell right away. So remember our goal is to kill the cancer cells. But just breaking up the DNA isn't necessarily going to kill the cell right then. But it will be a problem for the cell when it goes to divide. So during normal cell division the first thing that happens is this DNA will arrange itself into chromatids. Those chromatids then get copied, and then these two identical copies get pulled to opposite sides of the cell until it divides into two new cells that are identical to each other and also identical to that original parent cell. However, if we've exposed this cell to radiation and this DNA is now all broken up, those chromatids can't be formed properly. And now when we make copies of the chromatids, instead of getting this kind of structure that we can easily pull apart, we see things like this. So when the cell goes to divide, it can't complete the process properly, and this leads to cell death. Now it turns out that our healthy cells are actually really good at identifying this kind of damage and hitting the brakes and saying, wait, stop, we need to fix this. Fixing the damage, and then being able to continue on and complete cell division and not be affected by that radiation damage. However, do you guys remember the two main characteristics of cancer that we talked about in the beginning? What was the first one? They divide out of control. So do you think the cancer cell is going to stop and say, wait, we need to fix this? Absolutely not. So cancer cells are just going to blow right through the cell cycle and continue trying to divide and end up dying from the radiation. And this is the basic principle on which radiation therapy works. It turns out that our healthy cells are actually less sensitive to radiation damage than the cancer cells. So if we look at a graph, we're on the x-axis, we have the radiation dose and how much radiation we've exposed to this tissue. On the y-axis we have how much damage we see in that tissue. We have this blue line which is showing us the damage in cancer, and this red line is showing us the damage in a healthy tissue. And you can see that for the same dose level, we can achieve a lot of damage in the cancer for only very little damage in the healthy tissue. And this is actually how we can also target cancer almost on a cell or their level using radiation. So we can have two cells sitting next to each other, one healthy and one cancer. And the healthy cell will be able to survive this damage and continue living while the cancer cell will be killed by it. And this is exactly how we get what I think are some of the coolest radiotherapy outcomes. So here we have a picture of a little girl who has this massive tumor on her head. And if we were to treat this cancer or this tumor with surgery, we would have to remove a significant portion of her head and she would be disfigured for the rest of her life. However, by treating with radiation therapy, the radiation can kill the cancer cells and leave behind the healthy cells. And you can see that three and ten years later you can barely even tell that there's even anything wrong with her. The same thing here with this skin cancer on someone's nose. You can see clearly where the cancer is here. And they think that there's probably cancer that's invaded all the way out to this region, but again, there's no way of being sure where the furthest cancer cell is. So if we were to treat this with surgery, we'd have to take a large portion of this person's nose, leaving them disfigured. But delivering radiation, you can see just three months later you can't even tell there's even anything on their nose to begin with. So you'll remember that I mentioned are healthy cells are we going to achieve more damage in the cancer than in the healthy tissues. But that doesn't mean that there's absolutely no damage in the healthy tissues. And this damage that we do cause in the healthy tissues can lead to side effects. And so some of the side effects that we see from radiation therapy include things like cataracts and skin burns. The skin burns are basically like really bad sunburns. They do go away after treatment typically within a couple of weeks. But also cancer, so we're breaking up the DNA this can cause other cancers in the healthy tissues and cause infertility. And so some of these are very long lasting, severe effects to our patients. And basically all of the radiation therapy research that has been done over the past almost 100 years has been related to answering this question of how can we continue killing the cancer in treating our patients but avoid or minimize these side effects in the patients. And so with research like that, we've had some pretty cool new findings. One example is that we've developed a lot of new technologies and techniques to deliver the radiation. This is a picture of a more modern radiotherapy treatment machine that you would find in any typical cancer clinic and it's called a linear accelerator. So remember in the beginning we talked about radioactive elements and now we have machines that can create the radiation without any radioactive element present. So there's actually a particle accelerator located right here and this means that when the machine is turned on, radiation is present. When it's turned off, there's absolutely no radiation present. So we accelerate our particles here. There's a magnet located right here that bends the beam to come and exit the machine right here. And this whole machine can rotate all the way around the patient and so that means that we can focus that radiation beam to direct it exactly at that patient's cancer. And also if we were to look up in this whole right here where the radiation is coming out, you would see something like this. So we have a bunch of plates of lead or tungsten, something really thick and heavy, and using those we can shape the radiation beam to create any arbitrary shape. And so this means that now we can create completely personalized radiotherapy treatments where the radiation beam is the exact size and shape of that patient's cancer. So another recent advancement is that we've found we can use other types of radiation to better target the cancer. So here we have a patient who has cancer in their brain. So this is three different views of their head from different directions. And you can see the cancer is located right here, here and here. And the color wash on this, the different colors, is showing you the amount of the severity of the radiation damage, with red being a lot of damage and blue being a little bit of damage. And this is kind of a typical treatment plan using gamma radiation which is everything that we've been talking about up until now. And remember I said that gammas are very penetrating. So while we can cause a lot of damage in the cancer, the gammas don't stop at that point. They keep going all the way through the head. And so there is some damage that is caused outside of that in the healthy brain tissue. However, kind of a newer, fancier treatment that's coming into use now is using protons. And protons are a lot more like betas. So remember we said that betas can travel deeper, but then at some point they are going to stop. And so we can tune these protons to only travel exactly as deep as the cancer is. And in that way we can cause a lot of damage right in the cancer with almost no damage outside of that, because the protons simply don't travel that far. So it looks like you guys are due for your good news. Congratulations. So remember we said in the beginning that cancer is one of the most significant healthcare problems in the world today, and only appears to be getting worse. However, luckily thanks to these improvements, or improvements like these in cancer treatment if you look at the cancer mortality rate, so it's the number of people dying from cancer each year, in almost every country we see this downward trend. So even though more and more people are being diagnosed with cancer every year, we're seeing fewer and fewer people die from it. So, one more question. How many people here know someone who's a cancer survivor? Yeah, still a good number of people. So hopefully with continued research like this, we will never again have someone who raises their hand in the beginning and not in the end. Yeah, that's a really great question. So those are kind of, I wouldn't want to call them competing areas of research, but they're more... The question was about heavy ions. So this proton therapy that I showed you a picture of, protons are heavier in a way than gammas, and so that's one of the reasons that they stop in addition to that they're particles. But if you use something even heavier like carbon ions, then there's research that shows that they will similarly stop at the edge, but they will cause more damage as they're going. So we can deliver less radiation and get more bang for your buck with the carbon ion. So that's the basic idea behind doing it. I'm unfortunately in this kind of area of things. I'm not really an expert on proton and carbon ion differences, but they're both very promising. And there are people... Most people I know kind of do research in both, so I think that they both have their advantages. A big difference between them would be cost. It's a lot more expensive to deliver carbon ions than protons. So I think it's more of a... when you think about implementing something clinically, then you have to think about all aspects of it, not just the science behind it. So that's where it really comes to be differentiated. In engineering from 3D printing, they use crossing rays to generate hotspots in any position. Would that be an application for, for example, better rays? That is a great question. So that is exactly what we do. And that's why this treatment here, if we were to just use a single photon beam, then it really wouldn't be very effective at all. There's very little differentiation in dose from the entrance to the exit, but this is for a number of different beams that all cross at where the tumor is, and therefore you get a lot of dose right in the tumor and very relatively less dose out around it. And we do the same thing with protons. I think this looks like it's not a ton of beams, but for something that's more centrally located deep in the patient like a prostate, for example, we would typically treat that with two proton beams that come from either side and meet up in the middle to cause the most damage. Good question. We have time for one more question. Before you show that with a certain dose, like 95% of cancer cells die, do you have to kill all of them or is that a kind of a threshold to cure a cancer? That's a great question. So we do need to kill all the cancer cells, but this 95% isn't necessarily, we've killed 95% of the cancer cell. This is more looking at a population and we say that 95, we have a 95% chance of having killed all of the cancer cells, which I guess if you're looking at one cell, yeah, it's all probabilities. So we do need to kill all of the cancer cells. We typically try to treat at the 95% level saying that we've cured, you know, there's a 95% chance of us having killed all of them. Great. So there, talk some more. Thank you.