All about radiation therapy. Radiation therapy is actually one of the oldest therapies there is for multimyaloma. In fact, it predates chemotherapy by decades. And after radiation was developed therapeutically, there are reports that appear as late as I believe around the 1920s about using radiation to treat myeloma. And the way radiation is thought to work is that it causes damage either directly to DNA. That's that chromosome, the material inside chromosomes that encodes basically the structure of cells, what proteins are in there, what enzymes are in there. And so if you destroy DNA, that cell can't replicate. Radiation can also create what are called free radicals. And these are particles that are charged that can then sort of bombard DNA as well and create damage that way. So there's a number of different ways that radiation can work. How is radiation used to treat myeloma? Now, we use radiation in a number of different forms still to this day to treat myeloma. And if a person has a situation where they have a plasma cytoma, so what that is, is an area of a plasma cell tumor that is confined. So typically it'll show up in a bone, but you can also have plasma cytomas that show up in tissues like sinuses or sometimes in a lung. And if the person who has this plasma cytoma is thought to have only that and no other site of myeloma after they go through a very thorough workup, then radiation therapy is often used to treat that area with the hope that you will cure somebody of their plasma cytoma and hopefully they will never go on to get myeloma. And people with bone based plasma cytomas, unfortunately, do have a relatively high risk of recurrence despite the radiation. The other thing that we use radiation for is if a person is having really severe pain and more and more it's turning out that you can use even single treatments of radiation that can be quite helpful in reducing a person's pain. We do like to be careful with radiation therapy, particularly when somebody is just newly diagnosed. For example, sometimes maybe some years ago, a person would come in with many, many portions of the spine involved with myeloma. And sometimes people would be offered radiation therapy for a whole large segment. But we do try to avoid that in a newly diagnosed person if we can, because that can affect the ability later on to collect stem cells, particularly if a transplant is thought about. So we try to use radiation therapy strategically if possible. One therapy going back to the 1950s in myeloma was what was called hemi-body radiation. And again, this is where we didn't have any drugs really to treat myeloma, but they would literally just radiate the top half or the bottom half as a way to control myeloma and actually cause a lot of side effects. So that's not done. But for a while, irradiating the entire body, because we knew myeloma was sensitive to radiation, was used typically during the stem cell transplant, what we call the conditioning regimen. And that's the name for the chemo and radiation in this case that's given before the stem cells or bone marrow is given back. And there was a study that was conducted about 20 years ago based in France where they compared the drug melphalan with melphalan plus total body radiation and found out that the radiation really didn't add much except for side effects. And so that's been largely abandoned. There are some experimental ways to give radiation that people are investigating or something called tomo therapy, where they hope to target that radiation a little bit more specifically just to say bones and no other area. So one of the problems with total body radiation was that you weren't just hitting myeloma, but you were hitting other very important organs like your lungs and your heart and your brain. And you could end up with some long term side effects from that. But one of the ideas with this technique called tomo therapy is that you will be targeting the myeloma more specifically inside of bones and not other places. Is there a limit to the amount of radiation you can receive? There's an organ limit and it varies by tissue type. So some tissues are way more sensitive to radiation than others. And for example, some of the areas that are quite sensitive would be your spinal cord. So if a person had radiation therapy given for a myeloma spot, there might be great reluctance to go back and treat that again. If that was if that same area was involved again with myeloma, the heart and lungs, as I mentioned, in the brain really do have limits as to how much radiation you can give them. What will happen is you can cause scar tissue. And so this was this was kind of learned, if you will, the hard way with with people who for other diseases getting radiation, for example, young people receiving radiation therapy for a type of lymphoma called Hodgkin lymphoma. And these are people in their late teens and 20s getting this kind of radiation therapy later on. A decades later, they would end up developing things like breast cancer because of breast tissue being irradiated or premature coronary artery disease. In other words, hardening of the arteries caused by radiation. And there was also a increase again in secondary cancers related to radiation of tissues at a young age. So we do not think it is a great idea to give radiation. Now, it's a balance. So there are some situations where that radiation is really life, life saving for people. And one of the things that's happened over time is the ability to target radiation more specifically has gotten a lot better. So, you know, it used to be that that people had big wedges of tissue irradiated that could potentially cause some scar tissue developing. Nowadays, if you have, say, an isolated tumor or a plasma acetone, they really, really try to make sure that those beams of radiation are are targeted right to that area and not to any other normal tissues. What are the side effects of radiation therapy? Well, it again, it depends on what's being irradiated. But I would say most of my patients who go through radiation of any type find that the side effects are actually delayed. So at chemotherapy, side effects often appear right as soon as you get the drug. So maybe a day or two later or after a transplant with Melphalan, for example, a week later with radiation therapy, often you don't start to see some side effects until the therapy is over. And I would say one of the very common side effects is just fatigue that can last for several weeks. And that seems to occur regardless of the area that's radiated. If a person is getting, say, radiation for myeloma to the thoracic spine, so right behind the heart, the esophagus is in front of that area. And so a person could get irritation of the esophagus related to that radiation and have some difficulty swallowing. Or if they're having, say, a cervical spine irradiated, your throat is right in front of that. So, again, people can have difficulty swallowing or a dry mouth or even mouth sores that show up. As I mentioned, you do not want to have a area that is close to the spinal cord or actually near the spinal cord or radiated too much because you can get some damage to the spinal cord where people can get some resulting paralysis. Now, that's a very unusual side effect and something called transverse myelitis that we rarely, rarely, rarely see. So typically, the radiation therapist isn't going to let that happen. That is an older problem. Like I said, they really try to with what's what called a linear accelerator, which is maybe some of the more common equipment that's used for radiation therapy. They tend to kind of do an intersection of the beams. And so the older side effects of skin irritation tend to happen much less frequently than they used to. It's it varies a little bit if a person is receiving radiation along with chemotherapy drugs. That's not a typical scenario and people getting treated for myeloma, though. So so most of the time, at least in the patients that I've had for radiation therapy, the skin side effects are really not there. External radiation is what most people with myeloma are going to get. And by external, it means where the source of the radiation is coming from. So in other words, this is and there's different there's photons, there's protons, there's electrons, there's different particles or energy rays that could be used. But basically, the source is coming from outside. There are some types of radiation therapy where a person has a radiation source implanted temporarily or in some case permanently. So this is mostly occurring in people who have things like a cancer of the gynecological system. So like uterine cancer or cervical cancer, they sometimes place a radiation source in the vagina. And for example, men with prostate cancer, they sometimes use what are called radiation seeds that they will place in the prostate. And these are these are kept in temporarily and then removed. So that would be internal radiation. We're part of an investigation using radiation actually as an injectable drug. And in this case, we're using a phosphoethyl ester called CLR 131. So so these small packets are carrying a little bit of radiation coming from radioactive I1 31. And these are injected with the idea that myeloma cells are much more permissive to these particles to get inside. And they are affected by this kind of if you want to think about it this way, an intravenous radiation source. So we're currently testing that in a larger phase two study. This has to do with the property of cancer cells in generally and particularly in myeloma called altered lipid raft. So the wall of a cell is made out of essentially fats or cholesterol. And so the feeling is, is that those fats in the walls of cancer cells are different than normal cells. And they with this particular compound are much more permissive to allowing these compounds to get inside and then release the I1 31. So it's basically like giving a tiny little bit of radiation locally. So it's not targeting BCMA. Well, I think radiation really has its role in myeloma treatment. And certainly, if somebody is coming in with a very degraded area of bone, you know, so what we don't want somebody to do is break something, particularly a very important bone like a femur, a thigh bone or a hip bone. And sometimes radiation, if a person has a very involved area of bone with myeloma, that can be the best possible thing that they get. And sometimes they actually need a combination of surgery after radiation to try to protect that bone and prevent a fracture. You know, at the end of the day, the best possible way, though, to protect your bones, if you have myeloma, is to keep your myeloma in check. I think everybody would agree with that. Too much radiation could, but fortunately, bones are pretty resilient. And like I said, one of the areas of investigation, radiation, particularly if you're offering a pain relief, is to use what are called single doses or the term is used fraction, which is just one treatment of radiation. So that is done, I think, more and more. And actually, that can be quite helpful for people to have that kind of very limited radiation exposure.