to talk about cervical cancer, and key thing is about toxicity. So that's really, and like I said, it's short and sweet, but I am going to talk about toxicity of radiation therapy. But let's just talk first about treatment. So for locally advanced cervical cancer, and I know a lot of you guys have already seen these slides, but there are some new slides, I promise. Radiation therapy is really the mainstay treatment for locally advanced cervical cancer. Key for radiation therapy is you've got to treat it correctly, right? So what does that include? What does that involve? Treating the volume encompassing the known disease in its microscopic extension. To make sure you give the right dose, 85 to 90 gray or even to 95 gray to point A, which is what we traditionally talked about. To use brachytherapy, whether it's low dose rate or high dose rate, whatever possible. And the key, and I'm going to show some data on this, that the treatment time should be between 56 to 60 days. So these are just traditional 3D fields that were used for locally advanced cervical cancer if there's only pelvic nodal involvement or no nodes, right? So we normally treat with four fields. So this is your lateral field, this is your AP field, and this is what it looks like on a CT scan. So you treat all the sacral nodes, and this is important because you need to know what we treat so you know what our toxicities are, right? So this is your typical 3D field. So most of the rectum is in the field, so is the bladder. And the other thing that I want to show is the bone because we're going to talk about the toxicity of radiation therapy and bone is one of the biggest toxicities, okay? But radiation therapy works and we know it works. So here's a huge tumor on the MRI, three months later, all gone. So radiation therapy really does work for these treatments, these locally advanced tumors, and it is very important. Radiation therapy by itself cures over 50% of stage 3B tumors, 2B it's 80%, but we can improve. And how can we improve? By using concurrent chemotherapy, right? And as we all know, in 1999, all these trials showed that concurrent chemotherapy plus radiation was better than radiation therapy alone. So let's just, and I just want to go there, go through this trial briefly because it's important to know that even if you can't give chemotherapy, radiation therapy is still important, right? And it's still relevant. So don't think that if you can't give concurrent chemotherapy that you should treat this patient palliatively. These patients still should be treated curatively. So this is just a study that shows some data that I want to just point out. So 1901, old study, and what it did was it looked at extended field radiation therapy versus pelvic radiation therapy plus chemo. So we all know this, right? And the chemo was a little bit different, this is platinum M5FU. But what was important was that the radiation therapy was given correctly, 85 to point A, given within 58 days, and majority of the patients finished it. But this is what I want you guys to see, okay? So this is the update that was published a long time ago, but still an update. So chemotherapy was better than radiation therapy alone. For stage one and two, it was significantly better, 79 versus 55 percent. This is important. For stage three and four, it was trending to be better, 59 versus 45, but it wasn't significantly better. Just to go over overall treatment time, this is really important. And I know you guys don't have chemo radiation therapy where you are, but this is important. Every day past 60 days, you lose one percent local control. So as a treatment is being extended, every day past 60 days, one percent every day. So it's really important to really coordinate the care and make sure that you try to do external beam plus brachytherapy within 60 days. So they did a meta-analysis and they looked at, okay, is the type of chemotherapy that you give with radiation important? And so it's not. Key is, you should give chemotherapy with radiation whenever possible, but it doesn't have to be platinum. But this is what I want you guys to see. Key is, yes, chemotherapy and radiation therapy should be the standard of care for patients with cervical cancer. And it really is significantly better for stage one through two B. But for stage three B, the improvement was only three percent. So for the three B's where you can't put nephrostomy tubes in, you can still treat with radiation therapy alone and really get at least 50 to 60 percent cure rates. So even those patients should really be treated definitively if they have disease confined to the pelvis or even the periodics, but the periodics will, they do have less survival. But if they have disease confined to the pelvis, three B patients, even if you can't give chemotherapy, should be treated definitively. This meta-analysis also looked at if you should just do concurrent chemo-RT versus chemo-RT followed by more chemo, found that adjuvant chemotherapy may have an advantage. We have lots of trials presently looking at this, so we should have data on that later. But the conclusion is chemo-RT should be the standard. But remember, the radiation works well by itself, so if you can't give chemo, you should still try to treat the patient definitively. And we only had three percent improvement in stage three, so there's a lot of ways we can improve and there's many studies looking at how we can improve this. But that's not the point of this talk because we're really going to talk about toxicity, which is really what you probably still see. But let's briefly just go over brachytherapy. So brachytherapy is really important. So external beam is important because it takes care of your microscopic disease and it decreases your cervix so that you can do the brachytherapy. Brachytherapy is important because it can give you that dose to the cervix while reducing dose to the normal tissue like your rectum and your bladder. You can do either high dose rate or you can do low dose rate, and these are the different regimens. We are moving from, again, 2D to 3D to 4D, so we are using more image-guided brachytherapy. So we're using more CT scans or MRIs to try to see if we can conform the dose to the uterus and cervix while reducing the dose to the normal tissue so we can reduce toxicity. So key, for locally advanced cervix cancers, you should treat with external beam and brachytherapy and use concurrent chemotherapy whenever possible. We have high cure rates. 3Bs with concurrent chemoRT, we can cure over 70 to 80 percent. Nodal disease does decrease survival rate, but again, they're still curative as long as the periortics and the pelvis. So chemoRT works and we have very, very high cure rates, but there's still side effects, right? Both acute and late side effects of radiation therapy. So let's first talk about how do we follow these patients after radiation therapy. So these are standards in the United States, and I don't know how you guys do it in Africa, but I do know in Zambia this is pretty much what they try to do, right? So the first two years, you should follow the patients every three to four months and have a pelvic exam, have a physical exam that includes the pelvis. We are now doing pap smears only once a year. So it used to be we would do it every time we saw the patient, but now the recommendations for cervix cancer is pap smears once a year, chest x-rays once a year. Now we do a PET scan at three months to six months after the radiation therapy, and then we don't do imaging unless they're symptomatic. So for the first two years, you see them every three to four months with blood work and physical exam. Two to five years is every six months, physical exam, including pelvis, again, chest x-rays, and like we talked about, pap smears are only once a year. After five years, we actually will refer them back to their gynecologist for just regular annual exams. So acute side effects. So what is acute side effects? Acute side effects are the side effects that occur during radiation therapy and chemotherapy. So the most common side effects that I'm going to talk about, okay, so the most common side effects that patients have during radiation, diarrhea, it usually starts about the third or fourth week into treatment, and it can be controlled with Imodium or Lamodil and diet, low fiber diet. So we tell patients not to eat raw vegetables or raw fruits. They could have symptoms of cystitis that feels like a, and sometimes it can be a urinary tract infection, but the other thing you can do is antispasmodics that can help control it. They will get tired. Fatigue takes the longest time to come back. What I tell my patients is it's naps are going to bed early, but they should be able to do everything else. Skin reactions are very rare unless you're treating the vagina or the vulva where you are treating the skin. Chemotherapy related, hematological toxicities, nausea, vomiting, or heartburn. Combined is decreased appetite and weight loss, and other infections include yeast. So like I said, treatments for acute diarrheas, low fiber diet, Imodium or Lamodil. For cystitis, I use AZO a lot or cranberry pills. We do definitely have to rule out an infection. A lot of times they do get infection, so you have to treat that. For nausea, vomiting, anti-emetics, and skincare, we do use Aquaphor. We will use Silverdene if they have moist discrimination or really second to third degree burns. But all these side effects and what I tell my patients should go away two to three weeks after we get done. By the time I see them back for the one month follow-up, they're actually feeling better and almost 80% back to their normal self, and that's important. That's a key thing I tell my patients. Acute side effects occur during treatment and should improve within a month after the treatment. So chronic side effects. So what is chronic side effects? Chronic side effects by definition is three months after treatment, okay? Three months after treatment and then for the rest of their lives. What are some of the chronic side effects? And we're going to talk about how to treat these, right? So the most common side effects are second malignancies, menopause, fractures, bowel toxicities, bladder toxicities, necrosis, and vaginal toxicities. I am not going to talk about vaginal toxicities in this talk because it's a much bigger discussion and we can do that later because the sexual toxicity talks are even longer. So chronic side effects are correlated with dose, field size, and field arrangement. Diet. Smoking. Patients who have past medical history including high blood pressure or diabetes. The size of the patient. The bigger patient, the more obese patient has more bladder toxicity. The skinnier patients, especially patients who weigh less than 90 pounds, have higher GI toxicity. Connective tissue disorders. We do not treat any patients with scleroderma. Patients with scleroderma have huge toxicity with radiation therapy. Lupus does not as much, but scleroderma is really, we do not treat. Menopausal status and previous pelvic or abdominal surgery. So how are we improving our toxicity with radiation therapy? Well, the way we're improving our toxicity is using IMRT. And we've actually looked at IMRT versus Forefield and found that IMRT actually does reduce both acute and chronic bowel and bladder toxicity. And again, this is another talk we can talk about later because I really want to talk about how you guys can take care of some of the side effects. But as radiation oncologists, we are trying to reduce side effects by changing our technology. The other way we're changing our technology is doing this image guided brachytherapy. By using CT and MRI during brachytherapy, we have shown that we can reduce toxicity as well. But how can you guys treat it? Because we still cause toxicity, right? So let's talk about how, maybe, how you guys can manage it. So what is, so let's talk about the incidence. So overall the incidence, and this is a study we did at MD Anderson, and this is actually pre-chemo. So the incidence is a little bit higher than this, but it just gives you an example. At 10 years, about 11% to 15% chronic toxicities, okay? Rectal toxicity is about 3% to 5%. Small bowel toxicity, again, about 3% to 5%. And bladder toxicity is about 3%. It's really important to know bowel toxicity, whether it's rectal or small bowel or sigmoid, usually occurs within the first two years. It can occur slowly past that, but the highest incidence of the complication is within the first two years. Bladder toxicity, however, really starts at five years and then continues to go up. So this toxicity continues to go... Can you guys still hear me? Yes, yes, we can hear you. I'm sorry, just I've been losing internet back and forth, so I wasn't sure if you can still hear me. So it's really important to know that you can... So the first two years are really important for bowel toxicity, but bladder toxicity, you still need to watch for a long, long time. So let's talk about the toxicities. Secondary malignancies, what do I tell my patients? So young patients are at higher risk of secondary malignancies than older patients are. So what I usually tell my patients is about 1% to 2%, but younger patients probably have a higher incidence of it. But then I also talk about the pros and cons, and the benefit of radiation therapy overcomes the con of getting the secondary malignancies. But key factors to what causes secondary malignancies is smoking. So I do tell my patients to stop smoking, right? Diet, environmental pollution, and genetic factors, as well as chemotherapy and hormonal agents. But you do need to know that there is still an incidence of secondary malignancies, and key is sarcoma. And you will see that in the uterus, maybe 10 to 15 years later. So that is something that these patients need to be followed for, because sarcoma is huge, especially soft tissue sarcoma, as well as uterine sarcoma. So really important to follow these patients for secondary malignancies. The pelvic fractures, again, very important. This is a study that we did at MD Anderson, 300 patients with cervix cancer. There was about a 10% incidence of pelvic fractures, and 45% of these patients were symptomatic. Majority of these pelvic fractures occur within the first two years. Again, that's why those first two years, why we see them every three to four months, is because we see most of our toxicities at that time, as well as relapse, right? So the first two years, you're following these patients for toxicity, as well as relapse. So this is just an example of a pelvic fracture in one of my patients. So here's your symphysis, right? And you can see, look, right there. So it's a symptomatic pelvic fracture. And this really is the most common place for you to see pelvic fractures. You're not seeing them as much with IMRT, because we're trying to block this area. But when we treat with forefields, this is the most common place that we see pelvic fractures. So how do you prevent? So we can prevent pelvic fractures, and this is really important. Prevention is key. Doing bone densities. I know it's tough in Kenya. I know, and Al's shaking his head. But you do need to look for osteopenia and osteoporosis, because you should treat it if they have either or. Big thing, at least in the United States, vitamin D deficiency. And it's not calcium, it's vitamin D. Majority of our patients are actually vitamin D deficient. We do check vitamin D levels, and we are replacing them. But the biggest way to prevent pelvic fractures is doing weight-bearing exercises. And that does not mean that you have to do weights. I tell my patients they can walk in a swimming pool, and that would be a weight-bearing exercise. Pilates, yoga. I highly encourage all my patients to do weight-bearing exercises, period, because I'm making a menopause, right? By making a menopausal, they have a higher risk of osteopenia and osteoporosis. So we have to prevent pelvic fractures. I do put patients on hormones up to the age of 50, because that will help with the bone. So these are important things. You've got to treat the menopausal symptoms, the hormonal replacement, up to 50. And the reason why they've changed it from 40 to 50 in the United States is because of bone density and osteopenia and osteoporosis. So what do you look for when you're trying to diagnose pelvic fractures? Pain, that's out of the ordinary. I had a patient where I was trying to do a pelvic exam. I couldn't even put a finger in her vagina, because it hurt so much. And it wasn't because of the radiation. It wasn't because she had scarring or anything. It was because she actually had a fracture in her symphysis pubis. And once we got that fixed, I could do a pelvic exam. So what are the treatments? The easiest treatment is to limit activity for two to six months, and the symptoms resolve, and the fracture does heal. We do cement in the United States. And the question about bifostamates is really very, very questionable. But the key is limit activity. Cement really does work if you can get it. Radiation necrosis. So radiation necrosis is very common. You see it one to 16 months post-treatment. Symptoms are bleeding and pain. It usually occurs where we give the highest dose of radiation, which is right at the apex of the vagina or near the cervix. It really is dose-related. And this is actually a radiation necrosis where you can see, this is a patient with cervix cancer that was treated. And we did a PET three months afterwards. And this looks like recurrent disease, right? Because it's still light. We actually biopsied it, and there was no recurrent disease. So the way to treat radiation necrosis is estrogen cream. And I actually will give my patients estrogen cream right after radiation. And we use it up to three months to six months later. But the patient that I just showed you, we treated her with estrogen cream, and we gave her a douching, and a six-month PET scan. All that area had completely resolved. You can treat with antibiotics. Flagyl is the most common, but you can use Flagyl and Levaquin. And vitamin E and Pitoxifilin actually can help. If it doesn't improve with all these measures, then you use hyperbaric oxygen or do surgical debridement. But that's really your last resort. Estrogen cream works. Be patient, use estrogen cream. It really will heal that vaginal necrosis. It's the key treatment for vaginal necrosis, or radiation necrosis in general. Practitis. The incidence is about two to 39%. Patients present with rectal bleeding. Again, it's associated with the dose that we give to the rectum. And this is just some of the dose data. This is actually one of my patients. And you can see where she really, she came in with bleeding. They did a scope, and you can see this is what it looks like in the rectum. And this is proctitis. This is her proctitis. So what they did was they actually did aragon plasma coagulation, and she actually had no longer any bleeding. But what do you start with? You start with first steroid enemas or steroid therapy. So suppositories or enemas that have steroids. You can use, I can't even say the word, suffocate enemas, and then hyperbaric oxygen. But nowadays we really do, again, this is high resource setting. We use argon plasma coagulation, and it works great. And that's really our treatment of choice if we can't control it using steroid therapy. So our first choice is using steroid therapy. If it doesn't improve, we will send it to use argon plasma coagulation. Surgery is last resort. Key is if this enemas don't work and you can't do argon plasma coagulation, you could try hyperbaric oxygen. Cystitis, 5% to 10% for grade three or higher, up to 50% for grade one. Again, very, very dose related. Key is you got to rule out infection. You got to rule out symptoms are urinary urgency or incontinence, pain, or bleeding. So I'm going to, this is the disclaimer. This is actually a patient who was treated for prostate cancer. So this is a male patient, but this is what your bladder would look like if you had cystitis. So you can see this is a standard treatment of the, a look of the bladder where you can see the cystitis. So treatment, prevention, cranberry pills. I use cranberry pills all the time. Management is initially Ditropan or Vesicare, so an anticholgenic. Chronic is bladder lavage, laser coagulation, and then again, last resort hyperbaric oxygen. So I usually start off with the AZO, but again, I'm going to have to tell you, we use a lot of laser coagulations here if we see it because of the bleeding. But this could be miserable. I had a patient who had severe bleeding and it took, you know, several laser coagulations to get better and she was miserable. So you've got to be very careful about this. And I think that's it. Questions or things I can answer.

radiation therapy

locally advanced cervical cancer

toxicity

concurrent chemotherapy

brachytherapy

side effects