My name is Jim Hayman. I'm a radiation oncologist at the University of Michigan and a large part of my clinical practice involves treating patients with thoracic malignancies, including lung and esophageal cancer. And today, I'm going to start with an introduction to radiation therapy. The objective of this session is to provide some basic information on external beam radiation therapy, which is the most common modality of radiation that we use to treat patients with lung cancer. Question 1, prior to the lecture is the unit of radiation dose is a blank and the machine typically used to deliver radiation is called a blank? A, rad and linear accelerator. B, gray and CyberKnife. C, gray and linear accelerator. And D, Joule and Gamma Knife. So in terms of the types of ionizing radiation, they're broken into two main categories. The first category, the most common, is Electromagnetic/Photon radiation, and this type of radiation can be created one of two ways and is named differently accordingly. So X-rays are electromagnetic radiation that's created electronically. Well, gamma rays are electromagnetic radiation that's released from a nucleus as part of a nuclear interaction. Another type of ionizing radiation is particle radiation, and these can be either electrons, which are most commonly used of the three protons, a type of radiation that this gaining increase in use, and neutrons. So in terms of just some general principles about radiation energy and dose. The energy of an external beam radiation is generally defined in terms of mega voltage. And these beams that are in regular clinical use, can range from 4 to 20 megavolts for MV. As far as dose of radiation, how do we describe dose? The common term that's used these days is gray or sometimes centigray. And this is energy per unit mass and is defined as a joule absorbed per kilogram of tissue, so 1 gray is equal to 100 centigray, sort of like a meter and a centimeter. And then an older term is rads, you'll sometimes see that used but that's pretty much fallen out of common use but 100 rads is equal to 100 centigray. So how does radiation work in general? Well, radiation tends to interact with either DNA or the cell membrane, those are the primary targets. And it's possible that there could be a direct effect on either of those things, but probably more commonly, what we see clinically is indirect effects. That are mostly through the production of free radicals related to the radiation interacting with water molecules. How does radiation kill cells? Well, it can cause apoptosis, which is a fancy term for programmed cell death, and that generally occurs in the course of hours. Or radiation can kill cells through reproductive cell death, in that the radiation interferes with the ability of the cells to reproduce, and generally that the image is expressed after several cell divisions more on order of days. An important concept in a clinical radio therapy is something that we referred to as the therapeutic ratio. And what this means is that tumor and normal tissues basically sustain the same amount of damage after radiation therapy. But the normal tissues are better able than the cancer cells to repair what's generally considered sublethal damage. So it's damage that doesn't cause apoptosis for example. And one way we exploit this clinically Is by dividing the radiation that we give, into smaller doses on a daily basis, allowing some time for that repair to occur. And in the practice of radiotherapy, the terminology that is used is, we refer to that as fractionation. And so, what we're trying to do, is we want to deliver a high enough dose of radiation to achieve our desired effect, which is to eradicate the tumor, but with the least toxicity. So getting back to this concept of fractionation in radiation therapy, there's a number of different ways that we can define the dose that we give. So one factor is obviously the total dose but then the dose per fraction, or the dose per treatment is also an important component of the fractionation. And in general, that dose, that daily dose, is the primary determinant I want to constellate toxicity. The overall treatment time, the amount of days for instance, we deliver the dose in, tends to be the primary determinant of acute toxicity. So if we give that dose, a given dose over a shorter period of time, we're going to expect there's going to be more acute toxicity. And there is actually a mathematical formulation that we use where we can convert different fractionation schemes into what is referred to generally as a biologically equivalent dose or BED. So that we can compare one fractionation regiment to another. So what are some of the common fractionation schedules that are used in the treatment of lung cancer? Well, for curative regimens, we had some very short schedules that we use. For something that we call SBRT or stereotactic body radiotherapy, and I'm going to get to that when we talk about the management of early-stage lung cancer. But in that regimen, we might use 18 gray of 3 fractions each for a total of 54 gray, so that treatment might be given, say, over the course of a week. When we're treating more locally advanced disease which I'm again going to talk about in a subsequent lecture. We might give a dose of two gray over 30 fractions for a total of 60 gray, so you can see that those regimens are quite different. And then in the palliative, non-curative setting, we're trying to relieve symptoms. And again, I'm going to talk about this in a subsequent lecture, we might use a single 8 gray fraction, say to treat a bone metastasis. But for a treatment of brain metastasis, we would commonly use 3 gray for treatment, for 10 treatments, or a total of 30 gray. So again, you can see there is quite a bit of range of doses that we use, depending upon the situation. So what about external beam radiation therapy in general? Well, we tend to use high energy, ionizing x-ray beams. Again, in the megavoltage range. Those beams are generated by a machine that's referred to as a linear accelerator, which accelerates electrons through a very high speed. And then as those electrons hit a metal target, radiation is produced. And as the beam passes through tissue, dose, or energy is gradually deposited. And how that energy is deposited depends on the type of beam and the energy of the beam. So here is a picture of a linear accelerator down in the lower left hand corner is the table that the patient lies on. The beam of radiation comes out at the top of the machine and then, you can also see on the, we refer to it as the gantry which can rotate around the patient 360 degrees. This particular machine also has additional capabilities to do imaging, so there's an X-ray tube and an X-ray detector. That can help us to make sure the patient is in the right position for treatment. So this is a graph just demonstrating how energy is deposited based on the type of radiation beam that we're using and also the energy of the beam that we're using. So let's focus initially on photon radiation. You can see the blue curve is for six megavoltage photon beam and the red curve is for a 15 megavoltage photon beam, so a higher energy beam. And what you see is that at a depth of zero centimeters which is depicted on the X axis there is what we call a skin-sparing effect. Meaning that right at the surface of the skin the dose of radiation that's being deposited is only about 50% of the maximum. But as you travel into patient along the X-axis to deeper depths we reach a maximum point where we have 100% of the dose deposited. And then, the dose of radiation that's deposited in the tissues falls off gradually with greater penetration for the higher energy photon beam then for the lower energy photon beam. A type of radiation that we use less frequently for the management of lung cancer but that's worth commenting on Is something that I mentioned earlier called an electron beam. And electrons are good for treating superficial lesions. So you can see the green curve is for a lower energy electron beam and the pink curve is for a higher energy 12 MeV electron beam. And as you can see with electrons there's less skin sparing so we're getting close to 90% of the dose at the skin surface. But then the dose of radiation falls off much more quickly as it moves through tissues again as I mentioned earlier, which is helpful when we're treating very superficial targets. So what is involved in treating a patient with external beam? Well, generally, we'll see the patient in consultation. The next step, once we decide to treat the patient with radiation, is to do what we call a simulation, or a planning appointment. And generally, that takes about one to two hours, typically for lung cancer we're doing a CT scan. And then in fact, it's a special type of CT scan where we're able to capture emotion of the tumor that might occur as the patient breathes or that generally referred to as a 4D CT scan. After we capture the information that we need In that planning appointment, there's work that goes on behind the scenes by some professionals that work with us dosimetrist. Will generate a treatment plan for us after we identify what areas we want to target to what doses and that might take a day or three. And then once we're ready to get started on treatment as I mentioned before for lung cancer, commonly it might be as few as 1 treatment, as many as 30 treatments. Where we're treating patients once a day, Monday through Friday. Door-to-door, most patients are in the radiotherapy department about 30 minutes, but the time that the beam is on is actually, typically less than a minute. So they're changing, checking in, waiting their turn, and being set up for treatment on the linear accelerator. And then, it's our routine practice that we see all of our patients once a week for a treatment visit to make sure that they're not having any side effects that might need to be managed. So in conclusion, some of the take home points for this talk are that the most common form of treatment of lung cancer, is high energy photon external beam radiation. Radiation is measured in Gray. It's generated by a linear accelerator, and it's typically fractionated, or given over multiple treatments. So Question 1, after the lecture. A unit of radiation dose is a blank, and the machine typically used to deliver radiation is called a blank? And answer A.is Rad/Linear Accelerator. B is Gray/CyberKnife. C.Gray and Linear Accelerator. And D.Joule and Gamma Knife. And the answer is C. Gray and Linear Accelerator. Thanks a lot for listening and in the next lecture we're going to be talking about the use of radiotherapy for the management of early stage lung cancer.