Radioterapia de Baixa Dose em Doença Benigna Muscucolesquelética 📱

Added: 2026-05-15

[00:00:57]SP Dispatched.

[00:00:58]It's dispatched.

[00:01:00]She says she's quick to respond. She's proactive, isn't she?

[00:01:02]Unraveled. AND.

[00:01:13]I'll go to you now.

[00:01:40]No, no, but it 's not about you understanding.

[00:01:51]Yes, I'll specify there.

[00:04:36]Because he had told me that the two of them hadn't succeeded. Then I spoke with Karine. Then Carinho spoke with the doctor who works at the clinic that Luan worked with at his private clinic.

[00:04:58]Yeah, I already passed by, I said you had given a dead signal. No, no, I, I, I left the class.

[00:05:22]No.

[00:06:24]It's because even his part takes 10 minutes.

[00:06:39]Nursing week starts later, or else it's just the legacy that I'm going to talk about, you understand? Just grab the spot here. Her name is Isa.

[00:07:12]Good morning.

[00:07:15]Good morning.

[00:07:18]Before we begin, I just want to give a heads-up to the doctors present, uh, the entire multidisciplinary team. This Tuesday night we're going to have another Legacy Insights event at the Ônix restaurant, which is a nighttime event we hold to discuss a specific topic. This time, on Tuesday of this coming week, the topic is from staging to decision-making: the smart shortcut to the right therapeutic route. So, I'm counting on everyone's presence. So, I wanted to announce that we're going to post on the Teaching and Research Instagram account about the first psychiatry legacy event, which will take place on June 16th. And then the legacy of psychiatry will be opened to all categories, medical, multidisciplinary, it doesn't happen here, just to remind you, it happens externally.

[00:08:16]Normally we choose a restaurant and we have everyone there. Since this will be open to the entire hospital, we'll need to register beforehand, right? So we have these two events, and then next Friday I'll bring information about the cardiology one as well. It's the day of the return, right? The date will be June 16th. Legacy Insiders usually, well, not usually, always happen on Tuesday nights so as not to clash with football or the weekend. So, on Tuesday night.

[00:08:51]Thanks.

[00:08:58]Okay, folks.

[00:09:03]Well, folks, good morning. Yes, it does, right? I don't have it, but we were just waiting for the rheumatologist, Marcelo, but he's coming up now, we're starting things here. Yes, today we're going to have a completely innovative clinical session here in the radiotherapy department, in terms of the lecture, which is exactly about the use of radiotherapy in benign lesions, in situations that are not cancer.

[00:09:36]We've had this for many years, but in more adverse situations, but that already happens, right? You'll see Thiago's class there, and it's something very common, especially in Europe. And I think this needs to be implemented in Brazil, especially in a country where there is a great lack of access to specialists, such as rheumatologists and traumatologists, and we need to be part of that group in the day-to-day work, in the routine of these patients. What I'm seeing is a very significant improvement, especially in terms of quality of life, okay?

[00:10:12]Thiago will be the one to tell us.

[00:10:14]Thiago, for those who don't know him, was our resident here. Thank God he's back home. He's someone I respect and have always respected since he was a resident, a dedicated and committed resident, you know? And I always had this intention of bringing him to be part of our team, right? And that's what we achieved. He's here today and he's going to die here, right, Thaago? And so, in the sense of always staying in the department, right, Dr. Sérgio, as long as it's not too early, right, Dr. Sérgio, okay? Be careful with the cars, with thieves, right? Okay, let's go, Thaago.

[00:10:51]You have your class time there. I'm already being impressed here that we have to hand over the auditorium 10 minutes early and we... Welcome, Marcelo.

[00:10:59]You can sit down and let's begin. The topic is low-dose radiotherapy in benign musculoskeletal diseases.

[00:11:10]Well, folks, good morning, right?

[00:11:13]Once again, it's an invaluable honor to be here today. Well, it's actually something that transcends honor, isn't it? It even becomes a personal satisfaction.

[00:11:23]But today's topic brings something different, as Dr. Fernando himself said at first glance, when you read the topic of this class, low- dose radiotherapy in benign musculoskeletal disease, you think that it's something innovative, right? But actually, radiotherapy used for benign musculoskeletal diseases, especially arthritis, is as old as radiotherapy itself. The discovery of X-rays was made in 1895, and the first publication of a treatment using radiotherapy Partite was 3 years later, in 1898, right? So, during that time, radiotherapy played an increasing role in the treatment of joint injuries, reaching its peak in the 1930s and 1960s, even being considered the gold standard in joint treatment, bringing incredible results and low morbidity.

[00:12:27]However, despite many patients being treated, there were only prospective and retrospective studies, but no study with a significant impact from a methodological point of view. There was no randomized, double-blind study.

[00:12:42]A study emerged in 1970, but the study that had the greatest negative impact was a 1975 Finnish study by this author, Valtoney, right? Later, if anyone is curious, I can share the article; you can take a look. This study simply destroyed the indication for radiotherapy in joint treatment. In his conclusion, he even went so far as to, I think he wasn't even ethical from the point of view of dismissing the treatment, that he said in his summary, you know, quote, he said that radiotherapy was nothing more than a potent placebo and should be immediately contraindicated.

[00:13:22]By a twist of fate, you know, let's say, a year after this study, the pharmaceutical industry came in strong, with the advent of anti-inflammatory drugs, in the proxene, uh, diclofenac and ibuprofen, all in the following year. So, the pharmaceutical industry used VTONE's work as a shield to implement the mass use of anti-inflammatory drugs. So much so that the treatment in the United States, which at that time generated a growing power, right, in radiotherapy as well, practically abolished radiotherapy, right?

[00:14:00]These are just some important points to report about this work. Although it was a double-blind study, it was extremely flawed because the sample size was very small; they only used 30 patients in each arm. These patients had various types of arthritis, arthrosis, and even spinal cord injuries, which led to questions about whether it was a herniated disc. The dose was outside the optimal dose for the anti-inflammatory effect that we will see in this lesson. He used 1.5 EG, we 'll see that this dose is 1.5 to 2.5 EG, we'll see that this dose causes practically no beneficial effect from the joint treatment.

[00:14:41]So this study had these serious flaws, right?

[00:14:45]Well, it was still used to resolve the issue of radiotherapy at that time. Germany, and indeed the countries of Eastern Europe, have always been very strong in the area of radiotherapy for benign diseases, especially Germany. Even after all this historical movement here, Germany continued to perform radiotherapy and even launched a task force, right, through the German Society for Radiotherapy, which has this acronym for Gro. And they published a great article, right, a great guideline in the year 2000, so much so that it was so well received that they ended up implementing low- dose radiotherapy in their Unified Health System, in quotes, right, like their SUS ( Unified Health System), right? So perfect, that's right. Germany's numbers are incredible, aren't they? They treat around 30,000 patients a year with radiotherapy alone.

[00:15:44]Well, to give you an idea, 1/3 of all radiotherapy in Germany is for benign diseases, just 1/3. And of that, 40% is just arthritis. It's as if something around 20% of all radiotherapy volume in Germany is just for arthritis, right?

[00:15:59]Converting this to our reality at ICC, we currently have five machines. It's like our machines are only for arthritis, right? These are the numbers for Germany.

[00:16:09]And they get incredible results, right?

[00:16:11]Something around 70 to 90% in their papers, right? We'll look at them in a little more depth. Although the lesson is about musculoskeletal diseases, right? We do n't have much time to focus on all of them, so I decided to focus more on the one with the greatest epidemiology and the biggest impact, which would be osteoarthritis, right?

[00:16:32]Osteoarthritis is a global disease, right?

[00:16:33]It affects roughly around 500 million patients, right? It is a very high prevalence. It's as if it were double the total number of patients living with cancer, right? So that's a lot of people. And osteoarthritis ends up having an impact not only physically on the patient, but also in a very severe social way, right?

[00:16:51]1/3 of patients with arthritis develop depression, and the fact that a person has advanced arthritis already carries a risk of death, right, from cardiac arrest, of around 50%, right? So that's an incredible impact on public health. And not just the health aspect, but also the financial impact, right? The United States estimates that there is a loss of 80 billion dollars per year because it draws professionals away from their fields.

[00:17:19]And we have to remember that osteoarthritis is not a single disease; in fact, it's a multifactorial disease, right? We have repetitive strain injuries that can cause... We have advanced age as a risk factor.

[00:17:33]We also have the female sex itself, obesity with overload on the knee and hip, the patient's own metabolism, diabetes, lipidemia, all of this can contribute, right? And the genetic predisposition, right? [snoring] Before moving on to the lesson, it's very important that we understand this joint staging, right, which is done by this scholar who bears the name of this staging, right, Laurence Kelgren, right? It's simply a way for us to stage the patient based on the articular space profile, or rather, the articular space. So, we're going to have a zero degree, a four degree. Grade zero means the complete absence of radiographic changes, right? And grade four would be the most advanced grade at this point, which presents large osteophytes, right, with very pronounced articular growth.

[00:18:21]So, uh, we're going to see that the studies that were used, right, they're largely based on this, on this staging, right, and they, just to give you a little preview, kind of concluded that in more advanced stages, like stage four, it responds less, right?

[00:18:37]And current treatments for osteoarthritis follow certain principles, which are to restore the patient's mobility, reduce pain, and improve quality of life. Well, it's a multidisciplinary treatment, right?

[00:18:49]Almost everyone is involved. Well, the treatment follows a pyramid-shaped structure, where the base of the treatment represents the largest number of patients, and all patients should begin treatment for osteoarthritis from this base. So, educational measures, weight loss, physiotherapy, muscle strengthening, all of that is related to starting arthritis treatment. So, the guidelines recommend that all arthritis treatment should begin, in a way, with this foundation, and the treatment progresses according to the failure to respond, right? Socio-educational measures were not sufficient. You start with an anti- inflammatory treatment, a treatment with topical anti-inflammatory agents, right, but it 's not enough. You move on to oral tablets, even antidepressants are associated with improved response, and you keep escalating, escalating until you reach intra-articular corticosteroid injections. And if that doesn't resolve the issue, you have the apex of this pyramid, which would be surgery, right?

[00:19:53]That has the risks of immortality, an arthroplasty, right? So, where does radiotherapy come into play? In this pyramid, is there room to include radiotherapy as a complementary treatment, a treatment that can replace another? Could that happen? Before we answer that question, let's [clear our throats] understand a little bit about the paradigm shift in radiotherapy, shall we? Radiotherapy, in general, has a destructive, ablative effect, right? Every time we treat a cancer patient, we want to destroy that cell, we want to destroy that tissue.

[00:20:27]We know that the effect of radiotherapy happens in two ways, right? One-third of its effect is the direct destruction of cellular DNA. He literally kills the cell by destroying its most valuable part, which is the DNA. And 2/3 of the effect of radiotherapy is through free radicals, right? They cause an intense inflammatory process that ends up destroying the cell over the days, right? Often, that cell doesn't have its immediate toxicity, but it ends up suffering the effects of radiotherapy later, right? So this is the principle that we practically use every day here doing radiotherapy.

[00:21:06]Doses above one gray already begin to have this intense anti-inflammatory effect. And doses below one gray, that's already on the other end of the radiotherapy spectrum, right? It acts as an inflammatory modulator.

[00:21:20]Studies will show that this dose of 0.1 mg of grey has this effect, but we want to try to utilize the best of this effect.

[00:21:31]Before we move on in this lesson, let's get a sense of the magnitude, shall we? Here I compared a [clearing throat] full dose, right, a complete dose, to the dose used to date, right, to the best, most efficient dose to treat a joint, which would be a dose of three grams of treatment with 0.5 grams. Here I've put a comparison with the dose we use to treat head and neck cancer, right, with conventional treatment, with two grays a day, right, this gray nomenclature is an international unit that we use to refer to the absorbed dose, right? Well, we can estimate how much radiation we want in that specific treated volume, right? So we have a difference here; if we were to use a mathematical number, we would have a difference of 22 times more doses in cancer treatment than in joint treatment. But if we get more specific and calculate a biologically effective dose, we'll see that this number is even more different, right? We have a difference of 33 times there, right? an increase in an oncology dose to an increase in an arthritis dose. That would be around 3% as a percentage, right? So I use a 3% dose for arthritis, which is the same dose I would use to treat cancer, right? It's a really low dose. This is actually quite interesting in clinical practice.

[00:22:53]Sometimes we're treating an oncology patient, right, who has multiple pains, and sometimes, I even remember Dr. Carlos Eli's residency, those were the cases I didn't like to treat, polymetastatic patients who have a lot of disease. That's a consultation that 's more difficult for me because I'm like, "Oh my God, where am I going to get treatment?"

[00:23:11]Comrade, there are 10 diseases there, 10 outbreak locations. Then the doctor at the residency program even said, "Dude, focus on the main ones."

[00:23:19]Where he said he has the most pain, go to those areas, that will help you. So we do this treatment and then at the follow-up appointment, doctor, I've improved in every way. So, reviewing it, you know, moving forward and studying a bit more, I saw that maybe when he said he got better in every way, it was this little bit of the dose here, that affected the other joints, something that he had pain in, for example, right? So, perhaps that 's the reason for the quotation marks, right?

[00:23:44]I've improved in every way, haven't I? Even though we haven't dealt with everything yet, right?

[00:23:49]So, the most incredible thing about low-dose radiotherapy is the immunological aspect, the immunological mechanism behind it. We already know that doses below one gram have this potent anti-inflammatory effect, right?

[00:24:04]Well, we're already somewhat familiar with this radiobiological mechanism for low doses of a gremo. It's a complex mechanism where the radiation field, at this dose, creates these effects synergistically, right? It is not an effect that depends on another effect to occur; it is a multifactorial effect occurring simultaneously. That's why the answer is so satisfactory, right?

[00:24:30]Such a powerful response, because you act at the endothelial level in the capillaries, right, reducing the expression of endothelial cell adhesion molecules.

[00:24:40]You act at the other moment, all at the same time, okay? In the increased expression of anti-inflammatory cytokines, right? You're already starting to see the inflammation go down. Then you increase the reduction of reactive oxygen species, right? The famous hydrogen peroxides, those free radicals that we know end up destroying cells. So you reduce that too, you do some kind of magic with the macrophages, right? There are M1 phenotype macrophages, which are more inflammatory, and M2 phenotype macrophages, which are anti-inflammatory. So this low dose causes a polarization, a change from the M1 macrophage to the M2 macrophage, which is anti-inflammatory. [clearing throat] So it also alters the design, the phenotype, right, the cellular function, right, it also induces apoptosis of cells that are more aggressive from an inflammatory point of view and more sensitive, in this case CD8 T lymphocytes, right?

[00:25:41]And it ends up also decreasing, it also ends up causing a decrease in pro-inflammatory cytokines, right?

[00:25:51]So it increases the expression of anti-inflammatory TGF beta, right, or interlokine 10. And it decreases the pro-inflammatory ones, so it causes a double effect, right? It reduces inflammation and increases the anti-inflammatory process at the same time, right?

[00:26:10]So this potency comes from that anti-inflammatory process. [snoring] Uh, but after studying a little more, I found this article. This article is amazing. Perhaps I'll allocate about 20% of class time solely to it. This article is a pre-clinical study, a relatively recent South Korean study, from 2022.

[00:26:34]This study was so incredible.

[00:26:37]He did something that I imagine was a two-for- one. He conducted an in vitro study and an in vivo study.

[00:26:44]The in vivo study will confirm what he found in the in vitro study. How did this in vitro study go? He took cells from patients with osteoarthritis, advanced arthritis. From these patients who went to the operating table for an arthroplasty, he isolated the synovium and chondrocytes of these patients and cultured these cells and separated these cultured cells into several plates.

[00:27:17]So they had the idea of ​​irradiating these cells with a zero-gram spectrum, that is, not irradiating them up to two grams. It radiated zero greay, 0.5 greay, 1 greay, 1.5 greay. And he observed what was happening at the molecular level, right? And what happened was something incredible, the mitochondria from our high school days, right, the mitochondria, those organelles, right, of eukaryotic cells that we remember from the oxygen process, right, cellular respiration. So, the mitochondria, the famous mitochondria, they are what make the great magic of radiotherapy happen. When a low dose of radiation reaches the mitochondria of these cells, it activates an alert state in the mitochondria, as if the radiation were saying to the mitochondria, "You are now going to be in a state where you need to completely reduce inflammation."

[00:28:18]This is achieved through a protein called GDF15. When mitochondria receive radiation, they end up synthesizing and producing this protein, this cytokine GDF15.

[00:28:31]This protein will cause intense suppression of inflammatory factors, including TNF alpha, and also the annulment, the non-production of the mmp13 protein.

[00:28:46]This protein is what causes the degradation of the collagen matrix. So why is radiotherapy so effective in treating arthritis, for example, in musculoskeletal diseases? Because of this, we said this study showed, right? because of this protein that causes the suppression of these factors. So, when this protein reaches the site where degradation is supposed to occur, the degradation stops, allowing the cell to return to normal. What does a chondrostellum cell tend to do when it functions normally? It's producing its cartilage matrix, right? So this study showed that there is a non-linear response, that is, from the irradiation beams that he applied to those plates with synovial cells and contritiocytic cells, which are cells of cartilage tissue. He saw that the ideal answer lies within that range, right? So, [clearing throat] so what did the radiotherapy cause? It caused mitochondrial stress.

[00:29:47]So, low-dose radiotherapy does n't act like the classic anti-inflammatory drug we imagine, like taking a pill. In fact, it acts on the underlying mitochondrial dysfunction of osteoarthritis, inducing a mild adaptive stress that forces the cell to restore its own structure.

[00:30:11]So, this study didn't just end with this incredible discovery, in my interpretation. He wanted to confirm this in the same study. So how did he confirm it? He then separated two groups, right, of plates with the same synovial membranes and chondral membranes on one plate, and on the other plate he took the synovial membranes and chondral membranes but without the gene expression to produce this GDF15 protein. So now we have two groups of cells. One group consists of normal cells that can produce GDF15 when exposed to low-dose radiation, and another group of cells that cannot. Upon re- irradiating these two groups, he observed that the cells that can no longer produce GDF15 showed no anti-inflammatory effect whatsoever. Zero. And in the other group that was able to synthesize this protein, it also had... So he confirmed that GDF15 was responsible for this anti-inflammatory process through this test, right? So that was incredible because GDF15 is what cancels out the production of mmp13, which is an enzyme that degrades the collagen matrix, right? In that same study, just to conclude, he saw that the synovial membranes are the real factories for the production of GDF15.

[00:31:40]They produce so much, so much, so much, that the cell ends up overflowing in part, and this overflow ends up, so to speak, contaminating the chondrocytes, right?

[00:31:52]And he also demonstrated cell viability, meaning that even when using a higher dose spectrum, which isn't used for low-dose radiotherapy—in this case, two GRESs, right?—a higher dose, it didn't have any beneficial effect. But he also wanted to show that this treatment isn't cytotoxic; it didn't cause any cell destruction.

[00:32:13]He showed here that doses below 1.5, right? Well, at doses below one gray, he was able to reduce, you know, that little evil cell, right? Let's say, for this little evil enzyme, you know, related [snoring] to joint degradation, right? And remember that when the chondrocyte cell re-establishes its homeostasis, its balance, it begins to function in the way it was predestined by God, right? Producing its own natural collagen, right? So, there was an increase in collagen type two, right? This was the in vitro study. Now, this same study aims to put into practice what it theoretically found in the in vitro study, but this time in a vivo study. The in vivo study used mice, right? And arthritis was surgically induced in these mice, in the knees of the mice. The surgeon, the orthopedist, the veterinarian, I do n't know, I don't remember that part of the study, but what was done was a joint injury and healing after that surgery, the mice developed this arthritis and they irradiated those mice, those two groups of mice.

[00:33:25]One group of mice served as the control group, receiving no radiation, while the other group of mice was subjected to radiation at 0.5 degrees Celsius to one gray. After about 2 or 3 months, they analyzed the articulated tissue of these mice, and the study confirmed the efficiency, which came right here. Look at the histological tissue, right, of the joint, this red dye, it stained the joint, look, the cartilage, sorry, look. So, in the mice that underwent radiotherapy, there was a recovery of cartilage, right? And in the control group, oh, it remained destroyed, oh, it tried to re-establish itself here. So, this study showed that low-dose radiotherapy increases the GDF15 protein. And this protein will do two things: one, increase the production of type II collagen and aggrecan. And the other path he will take is a dramatic drop in MMP13 and TNF Alpha. And as a bonus, they also saw that this study reduces the activity of osteoclasts that cause bone degradation and stimulates osteoblasts to synthesize bone matrix, right? So, the outcome of this study was [clearing throat] mitigation of osteoarthritis progression, preservation of the matrix, and structural integrity.

[00:34:59]This other study is also a recent German study, from 2021, 2022.

[00:35:05]This study was interesting because it associated the effect of low-dose radiotherapy on the peripheral blood of patients. So, he collected blood before a patient underwent knee radiotherapy and collected this blood serially.

[00:35:22][snoring] He saw that in addition to relieving pain and improving morning stiffness, low-dose radiotherapy decreased the activation of immune cells, especially monostites, a possible biomarker of response. So, the patients underwent radiotherapy at that time, and this study followed the peripheral mononuclear cells, right? So, the patient's response was correlated, right, concomitant with the level of peripheral blood monosomes, right? So, this study showed a pain level of 7.3, ending up around 3.8, [while snoring] this peripheral blood sample was taken, right? There was a safety factor, because many might think, if it's reducing monocytes, it's causing an immune system boost in patients, right? But no, the level of leucostasis remained the same, right? Only a specific type of monosyphilis, type one and type three, was reduced, and that decreased along with the patient's pain clinical presentation, right? So this study here, in fact, it brought something that should be further researched, right? The next step, according to the study, is that in the future, peripheral blood tests may be able to predict exactly which refractory patients will respond best to radiation months before the first dose is administered. So, in summary, this study showed that some patients may benefit more than others depending on their blood type, their blood profile, right?

[00:36:59]So, patients with very high monosomy levels before radiotherapy, that patient will benefit more than that other patient, right? So, open that window of investigation, right? And now that we understand the process behind the effects of radiotherapy, we're going to briefly discuss some studies, right?

[00:37:18]I separated the best ones as I considered them suitable for this class.

[00:37:22]Modern evidence suggests the effectiveness of low-dose radiotherapy in osteoarthritis, right?

[00:37:27]Basically, if we look at the literature, I think 70% of the studies are German, right? So, in 2021, right, this 2021 study, 970 patients were treated, right, a prospective study.

[00:37:42]Unfortunately, some of these studies followed the patients for a very short time, right? This study, for example, followed patients for 2 months and the response rate was 66%.

[00:37:53]But the problem with this study here is that, well, it used too much of a gray drug. The maximum effective dose, which we will confirm throughout this discussion, is 0.5, and even with this less effective dose, the responses are good, right? This other study is more interesting, okay? I ranked them from least interesting to most interesting, scaling the discussion. This study is more interesting, although the sample size is smaller, 159 patients, but the follow-up period was longer, at 2 years, right?

[00:38:22]So he showed that there was a sustained response, right? The patients who entered this study had an average pain level of 0 to 10, and after just one fraction, one session, one course of six- fraction radiotherapy, they experienced a significant drop in their pain from seven to three, and it was a sustained response for 24 months. That other study, it was more interesting because it compared the 0.5 dose and the dose of one grey, right? So it was also a German prospective study, right? 2020, quite an interesting number, 480 patients, right? And the conclusion of this study is that he saw a much better response with 0.5 gre, right?

[00:39:08]Versus a grey. Better for everyone, right?

[00:39:10]Better for the patient, less exposure, better for the radiation therapist who is more comfortable, right? Less doses, right?

[00:39:17]For a benign condition. So, this study was very interesting. This other study, it's also different from what we see in radiotherapy, where we always think, "less is more," right? The less healthy patient structure I have to treat in order to treat that disease, the better. But here, less is less, right? So this study showed that in smaller, limited fields, only within the joint, the response will be worse.

[00:39:46]So, ideal fields are fields that are more comprehensive, right? Including related muscle structures, tendons, and joints that are a little closer, right? If possible, an adjacent joint, right? If it's allowed, like here in my hand, for example. So, you just need to increase the field a little, right? You already have a 70% reduction in pain and a 30% greater response, which is the complete response you can give your patient, right? And remember that this study here, look, wasn't a recent study, right? A 2016 study they were doing was still using grayscale, right? It's not the ideal dose, and the responses are still coming back good, right?

[00:40:31]This other [clearing throat] study, I thought it was really cool. It's a study where he's already addressing re-irradiation, right?

[00:40:37]The aim of this study is to confront re-irradiation. It is also a German study.

[00:40:42]So he conducted a course of radiotherapy on patients who started this treatment with a pain level of seven out of 10. So the improvement six to eight weeks after radiotherapy was very minimal, right? Around a point. The patient's pain went from a seven to a six.

[00:41:00][snoring] still using this dose here, right, of a grey, right, most patients, but this study, its objective was to show the benefit of re-irradiation. So, when he re-irradiated the patient, that is, repeating the initial procedure— in this case, if he is treated with three doses of GRs during re-irradiation, he has to administer three doses of GRs again—he provided an additional 50% control of the patient's pain.

[00:41:26]So, the patients who were re-irradiated, well, they went from pain level six to pain level three, and the response was sustained over 24 months, right? So this study here is encouraging, right? It gives us the basis to re-irradiate the patients, right?

[00:41:45]This Iranian study, which is a bit more recent, from 2025, is a small study, but a good study because it was more organized than the other studies. It was a randomized, double-blind study with a very small sample size of 60 patients. So he put 30 patients in the radiotherapy group that received the treatment and 30 patients who did not. It was a simulation, a simulated placebo, right? The patient would get into the machine, lie down, the machine would spin, perform all the necessary treatment, the technician would enter the room, and everything would be fine.

[00:42:15]And in the end he saw that the study patients started with a pain score of nine, and the patients who were irradiated saw their pain drop to three [clearing throat], while those who were not irradiated maintained the same pain level. Unfortunately, this study didn't re-irradiate the patients, did it? It could have been re-broadcast so we could have that confirmation and follow up. Well, the study was very short, it was only six months of follow-up, right? We saw that the response has two phases, and the other phase of improvement is after a few months, right, of radiotherapy. So, the study didn't capture the full benefit of radiotherapy, right? But it was a study that proved the effectiveness of that dose.

[00:42:56]They've already started standardizing this 0.5 gray since 2023, right?

[00:43:04]This study is different from the others; it was the longest study, a Russian follow-up study, right? It was a nine-year follow-up.

[00:43:15]And this study was interesting because it showed, throughout this entire period, a sustained response in patients who underwent radiotherapy and in patients in the control group who did not. And what was most incredible about this study was that there was a reduction in the need for arthroplasty in patients who underwent radiotherapy, right? Something around 50%. Are there any oncologist colleagues here? It's a benign illness, and psychologists are always on the lookout. But some people have read it, some residents have it. Boss, if there were a vaccine here that reduced the number of patients needing surgery by 50%, how many millions of dollars do you think the labs would charge? About 300 million, 30. Yeah, he still doesn't know, he still doesn't know. Ah, because they haven't joined yet [laughs] I'm just kidding, okay? Laboratories are also important because they conduct research, right? You have to have something in return from them, you know. But that's it, okay?

[00:44:12]So, we're getting some accelerated responses. Uh, [clearing throat] so, what's the ideal patient like? The ideal patient is one with grades one and three, according to the Kelgren Lauriscy staging system, with refractory pain and active inflammation. So, where does radiotherapy fit into this pyramid?

[00:44:31]For the patient to be eligible for the most ethical and correct indication for radiotherapy, in my opinion, they need to undergo initially non-invasive procedures, more conservative, non-pharmacological approaches, and physiotherapy. Then something pharmacological can be tried, even if the pain persists, something around six months of trying, three to six months, six months of trying, the study shows six months of trying. Then you can consider the possibility of radiotherapy, right?

[00:45:08]Studies show that before a surgical procedure, this attempt is valid, yes, okay? So you can postpone or even prevent that patient from undergoing surgery, right?

[00:45:19][Clearing throat] We're almost at the end of the class, but whenever we talk about radiotherapy, we have to talk about safety profiles, right? Regarding the risks associated with radiotherapy, we bring up the non- carcinogenic risks, right? And carcinogenic risks. What is that?

[00:45:34]Non-carcinogenic risks are the acute toxicities that we see, right? Well, many studies, many articles, they state that there is no toxicity to the treatment. No toxicity to the treatment, but pushing it quite a bit. There's a German study that followed 1000 patients and only one had mild radiodermatitis, which is that inflammation of the skin, right? That resolves itself there. If you want to optimize the results, you can hydrate the patient's skin, you can use a topical corticosteroid, right? But overall, it's such a mild toxicity that time will resolve it, right? And no, it's not an acute toxicity, let's say, that can occur in around 25% of patients; they experience a worsening of pain during radiotherapy, right? Patients experience a worsening of pain, which would be a toxicity, I would classify it as acute toxicity, right, the worsening of pain, but the pain tends to stabilize and then, right, tends to improve, right, there is a higher percentage chance of that happening.

[00:46:35]And the carcinogenic risk, that's the big elephant in the room, isn't it? Every time we think about undergoing radiation therapy for benign conditions, the concern that arises is the risk of developing cancer, right? We know that radiotherapy has two effects: the deterministic effect and the stochastic effect. The deterministic effect, as the name suggests, is an effect that is already determined. Determined by what? based on the tolerance dose of the structure you're irradiating. One example here is the optic nerve; it can tolerate up to 54 or 55 degrees Celsius, right?

[00:47:07]So he is determined. The bone marrow, for example, depending on the level you're treating, tolerates 45 to 50. So this effect is already known, we can already estimate it accurately.

[00:47:19]As for the stochastic effect, we don't have a mathematically defined model for it.

[00:47:27]We don't know, oh, from so many greens will cancer develop.

[00:47:31]Unfortunately, we don't have that information. What we know is that the stochastic effect, that is, the effect of developing a second neoplasm, is more related to the dose. The higher the dose, the greater the effect. The lower the dose, the less effect. It's related to the volume treated. It's related to the location, an abdominal region. For example, you're going to expose the patient to a greater stochastic effect than a joint, for example, which has a slower replicative process, right?

[00:48:00]So, and young patients, right?

[00:48:02]The older the patient, the lower the risk of this, this stochastic effect, this radiation-induced neoplasm, right? Studies estimate that radiation-induced cancer wo n't appear today or tomorrow if the patient is properly staged; it takes decades, one, two decades, 15 years, there's a divergence in the literature. But if you put me against the wall and said, "I want to know the risk." An estimated risk, calculated mathematically, based on the likelihood of nuclear accidents. They found that three out of every 10,000 patients, in men over 70 who underwent knee treatment, have a risk of developing a neoplasm. But that risk is theoretical, right?

[00:48:44]In practice, according to the German guidelines, the German Society for Radiation Therapy, which has been treating these patients for longer, there are no reports of this, right? So this provides more safety for both professionals and patients, right?

[00:49:00]The United States is starting to get involved, it's starting to get involved, right? The United States was kind of absent, and the American Society of Radiation Therapy, through Astro, right? He already wrote a paper about it last year, right? A review of benign diseases, with particular emphasis on the issue of arthritis. So I've become suspicious because I've noticed they're starting to show interest. Why do I say "ears perked up"? I took the time to leaf through Peres, which is like the Bible of radiotherapy worldwide, written by American authors, and believe it or not, out of 12,000 pages there are n't even three paragraphs talking about radiotherapy, right? Well, of course, when we study a book, no matter how new it is, it's a reflection of the times. Medicine advances very quickly, and nowadays we don't give books as much importance as we do to papers, which are something that's becoming more prevalent today. I don't know if Dr. Renato is watching this class, send him my regards, okay? He's recovering from surgery, but he [clearing his throat] was kind enough to send me this super recent article, you know, in the red journal Astronomy, a leading evidence-based radiotherapy journal, meaning he's already preparing the ground for the Americans to do, look, showing it as if it were a consensus, a very recent contour atlas, right, April 4, 2026, right? The United Kingdom is not far behind either. The United Kingdom has a consensus on benign diseases. This is the most recent one I've seen, the most recent one I've found. March 2023. The United Kingdom, it's already focused on working with the most evidence available, right? In this case, he doesn't mention joint treatments, but he does mention plantar fasciitis, right? He brings up here that it 's also a very old treatment, dating back to 1924, a giant German study with 8,000 patients, showing a 70% improvement in pain within 3 months. This other study here, another study in Germany, although with a smaller sample size of 130 patients, but only patients with intense pain, 90% presented with intense pain, polypharmacy, and 10% with moderate pain. And in those patients with severe pain, after radiotherapy, 80% had a very satisfactory response, right? And these patients experienced acute toxicity. 28% of patients experienced a worsening of pain during radiotherapy, okay?

[00:51:20]So here he treats plantar fasciitis, right, as level A evidence, right, the highest degree, so patients should be treated with radiotherapy, right, uh, effective, safe, at a dose of 0.5 GHz, right, but he states here over three weeks in these cases.

[00:51:42][Clearing my throat] two to three weeks, right? It also brings other benign diseases, but our focus is on level A and others at levels B and C.

[00:51:50]The German guideline from 2022, the most recent one, also speaks very well about plantar fasciitis, the answer, right? He already sets a range here of 0.3 to 0.7, right? And he indicates that this treatment should only be done when conservative measures have been exhausted, right? He also outlines it as level A evidence, and there are different levels of evidence, right? Plantar fasciitis, prophylaxis of heterotopic ossifications, epicondylitis, he treats as level B evidence, and arthritis, in general, the German guideline treats as level C evidence. Level C evidence is bad, it doesn't have the same scientific impact as level A evidence, for example. But Germany does a lot. And why isn't it evidence A?

[00:52:39]Because we lack a study like this one here, which is in phase three, right? This South Korean study, from what I 've read, I found it to be an excellent study because it includes, for the first time, the participation of an orthopedist in designing the study along with a radiation therapist, because until then, other studies treated the radiation therapist as if they were a doctor specializing in joint disease. And we're not, you know, even though we're doctors, we have a somewhat more limited knowledge, not as in-depth as an orthopedist.

[00:53:08]So, the orthopedist actively participated in the design of this study.

[00:53:12]These patients, initially there were 1000 patients undergoing treatment with physiotherapists and orthopedists, right?

[00:53:19]So, it was a screening, just two minutes, professor, it was a screening, right, of these patients, and so far the patients who did not respond to this therapy with orthopedists and physiotherapists will be exposed to radiotherapy with a dose of 0.5 mg/dL in a blinded, randomized, multicenter group, right? The famous beard and mustache hairstyle, right? Perfect. Here, the study involved a 24-month follow-up.

[00:53:45]This study is what I think will ensure my auditor friend doesn't have any headaches when it comes time for him.

[00:53:50]Just send the little pit, and that's it, right? You don't even need to read anything else. And how is radiotherapy done, Dr. Fernando?

[00:53:57]Just 60 more seconds. And how is radiotherapy done? It's a relatively straightforward treatment, isn't it?

[00:54:02]The patient comes in and has a CT scan without contrast. The structure to be treated must be mobilized appropriately.

[00:54:11]We're using a very low dose, so the precision has to be perfect, right?

[00:54:18]Uh, here's a drawing of a plantar fasciitis treatment plan, right? Well, the patient is located after treatment and has completed the course of radiotherapy. Just to wrap up the lesson, I had, well, there are coincidences in life, right? I was even starting to lose hope of returning to Fortaleza.

[00:54:35]My mother stayed there, she was right there, she stayed behind the scenes, chasing opportunities as they arose, I had kind of switched off, you know? Yeah, she was experiencing a lot of joint pain. Then I said, "Mom, come get a plane here to do this treatment with me."

[00:54:50]I was in Vitória da Conquista, Bahia, at the time, right? She said, "I'm not going to get treatment when you get back." So I said, "Okay." Then she came, I went back, treated her—I had already treated a friend of mine in Vitória da Conquista, and the response was spectacular.

[00:55:03]And the medical physicist and my mother, uh, when I arrived here, she was limping; she was an extremely active person. If you get to know her a little here, if you let her, she'll talk until tomorrow morning without stopping; she has so much to talk about, right?

[00:55:16]And what she likes to do most is wander around the mall. Not to buy anything, Mom, right?

[00:55:22]Just wandering around, going into the stores, meeting the shopkeepers. When there's a sale, people call even knowing she won't charge, right, Mom? Just kidding, but she goes there, talks to people and everything, and she stopped doing that, she stopped completely. At home, she started to get depressed. My sister, who is also a doctor, already wanted to start a... She was given an antidepressant. And she had this radiotherapy. Today she's eight weeks along, she's having an incredible response, and she sent me this picture from yesterday, doing what she loves most.

[00:55:53]Going to the mall. Going to the mall [laughs] is R. It has to be Rio Mar, right? No.

[00:55:59]It has to be Rio Marceal from Rio Mar. And coincidentally, I brought her here today because of her silly son. He's always with his mom. No, because today she's going to have her first dose of re-irradiation. It's today at 9:30 in the morning. 9:30 in the morning, Dr. Fernando. So, we took advantage of it, we came together, right? And today she's going to have her first one. Why is she going to have it? Because she had a pain level of eight and now it's a pain level of one to two, right? And it's worth reinforcing this for the sake of the studies.

[00:56:30]Okay? Thank you very much.

[00:56:31]Thank you, sir. [applause] Well, folks, the class is really long, isn't it?

[00:56:37]We'll have another moment here.

[00:56:38]This is a This is an extremely current and initial topic. I wanted to call André, I wanted to call Carlos Eli, Marcelo. Thank you, Marcelo, for accepting even at the last minute. We couldn't, you know, expedite this process, but the rheumatologist, orthopedist, let's sit down here. It's very important. I also wanted the moderators to be very objective, because Thiago took up a lot of the class. You can sit down, Thiago, right? And then I wanted to start with André, so he can get together to try to get this audit approved quickly, right, André?

[00:57:15]Here, here.

[00:57:16]Good morning everyone. Congratulations to Thiago for the [clearing throat] presentation.

[00:57:23]Some aspects that we noted here from his presentation, although it was very good, I think it's worth mentioning.

[00:57:35]In reality, as was said in his class, it's a new but old subject.

[00:57:41]Normally, three years after the discovery of the RIS, good results began to be seen in the treatment of joint diseases.

[00:57:53]When you talk about joint diseases, we have to think not only about osteoarthritis where He focused on it, but we also have some other aspects that are worth touching on. So, for example, for enthesitis, it shows a good response.

[00:58:11]Now, we have to remember that, unlike in the United States, and perhaps because of this, it hasn't evolved as much, unlike the reality, low-dose radiotherapy treatment is a slow treatment. So, it's not a treatment for the acute phase. It improves over the weeks that follow.

[00:58:34]When you talk about enthesitis, I even missed the work. At last year's conference, a study was presented precisely on knee enthesitis, done by a South Korean group led by Dr. [Name].

[00:58:49]And it was the first study done with placebo control, because until then all the other studies had weak evidence, no control, there were margins to cause doubt about the real use of low- dose radiotherapy. When we talk about plantar facetitis, we have to remember that the degree of improvement in plantar facetitis is equal to the degree of improvement when you treat cheilitis with low- dose radiotherapy. Why did I mention it here now?

[00:59:27]Okay?

[00:59:28]When you look at what's covered by health insurance plans and the Unified Health System (SUS), the Unified Health System admits to discussing low-dose radiotherapy for cheilitis and gynecomastia post-treatment, uh, prior to prostate cancer treatment. So, before treating the patient with hormones, they suggest preventive radiotherapy to avoid gynecomastia.

[01:00:03]Logically, it can also be done during treatment, but the expected result is better when done beforehand.

[01:00:12]Moving beyond the SUS, we get to the main problem we have, which is health insurance companies. Today, health insurance companies only discuss low-dose radiotherapy for cheilitis. All other treatments are not yet approved by the National Health Agency.

[01:00:35]When you talk about benign tumor lesions, which is the area Roberto and I normally work in, what do we have?

[01:00:46]We have work that... This is from the German group, which is for cysts.

[01:00:54]The work wasn't small, partly because there aren't many; there were 10 patients, and of those 10 patients, seven had a response, that is, 70%, which would be the same as for cheilitis.

[01:01:11]There's a disease within orthopedics, a knee disease, that's very difficult to treat, which is nodular synovitis. In the College of Surgeons in London, UK, there's a study showing that those patients who had already been treated, who had already had surgery, had a good response when they underwent low-dose radiotherapy.

[01:01:41]When Thiago spoke about knee osteoarthritis, is that correct? What do we have in relation to Kel's classification?

[01:01:55]Why is there no effect when you do low-dose radiotherapy in advanced stages of knee osteoarthritis?

[01:02:03]Because the cartilage has died. So the chondrocytes are gone. It's bone on bone. So if you do it there, maybe there will only be pain relief, but no benefit. No air. So, that's why in the studies, okay? Normally it's done for moderate cases, which is ideal.

[01:02:27]Radiotherapy restrictions are absolutely not applied to children or adolescents. This is completely postponed, nor to pregnant women. The ideal age is over 60 years old. When you consider the 40-60 age range, this range needs to be very well discussed and well explained to the patient so that we can make it very clear what risks may occur in the future, that we are still in the study phase and we don't yet have, let's say, 100% certainty. A pathology in the area of ​​rheumatology mixed with orthopedics, which has a good effect and is proven by several studies, is palmar fibromatosis, which is the Double Item type, and plantar fibromatosis, which is the LED Roxo type. So, for these two fibromatoses, we have studies that really prove that low-dose radiotherapy has very good scientific evidence.

[01:03:35]The great challenge is trying to get it incorporated into the SUS (Brazilian Public Health System). It's more complicated. Why? Because through the SUS (Brazilian Public Health System) we haven't had adjustments or improvements in coverage for years, but through the SUS we already know that for gynecology and KOID (Kelodystrophy) there is coverage for the supplementary health system. So, societies can start demonstrating the effectiveness and thus encourage public consultations to try to expand coverage for low- dose radiotherapy, which today is only covered for part of KOID. Thank you.

[01:04:23]Good morning.

[01:04:25]You can speak, Dr. André, it's because KOID is no longer considered low-dose, it's considered high-dose. The most current fractions of KOID, they use three fractions of six grams. That's a lot of dose, right? Right?

[01:04:41]I think you confused low- dose with benign disease, you see? Okay.

[01:04:49]Good morning, everyone. I wanted to thank you for the invitation regarding osteoarthritis in rheumatology. I would like to comment first that I think it's the first time many people have heard about this disease, known as arthrosis. But as time goes on... Over time, due to robust evidence of an inflammatory microenvironment in the joints associated with osteoarthritis—which is why it evolved from arthrosis to osteoarthritis—there's a lot of research, and the pharmaceutical industry spends billions searching for therapeutic targets against matrix metalloproteinases, against the stimulation of anti-inflammatory cytokine profiles like TGF beta, IL10, decreased L1, IL6, and TNF-α. However, phase two studies, which I've been following at every congress since 2020, show promising future therapies for osteoarthritis.

[01:05:42]When it reaches phase three, it's a disaster; there's no biological treatment for osteoarthritis.

[01:05:48]Regarding oncology, rheumatology already uses a medication that I think most people should know about: a low-dose oncology treatment, methotrexate. Metathoraxate, I explain to the residents. We use LD MTX, we use low-dose methotrexate.

[01:06:06]We don't produce a side effect. His treatment is oncological, I would say ablative, which is a term from radiotherapy. We use an anti-inflammatory dose, which is the same rationale behind low-dose radiotherapy, as he explained excellently. It reduces neutrophil adhesion, changes the cytokine profile, and shifts macrophage subtypes.

[01:06:28]So, it has an excellent anti-inflammatory effect. Regarding why this is important, what is the relevance, I would say it's enormous. I treat diseases related to muscle stress linked to innate immunity, which is autoinflammatory, autoimmune diseases like rheumatoid arthritis, psoriasis, even oncological conditions, like a patient with lumbar pain who has multiple myeloma.

[01:06:49]Regarding all of this, I have good answers, because it's the most frustrating disease to treat in the office, osteoarthritis, all that stuff that's in every textbook, Rockberg, any book, including, sharing the frustration, Rockberg doesn't even mention low-dose radiotherapy. I learned about it because at conferences, every now and then, when an international speaker comes to talk about osteoarthritis, mainly If it's from a Germanic country, he mentions, I only know the theory, I've never seen a patient who has done this, but all that has been mentioned, anti-inflammatory, uh, intra-articular corticosteroids, it works, but it works for a maximum of 14 weeks. After that, the return, viscosupplementation had a huge impact, which was trying to stimulate the cartilage, using a very expensive corticosteroid stimulator, the response was extremely frustrating.

[01:07:43]And surgery, right, when the patient reaches stage 4, it's surgical, there's nothing else to do.

[01:07:50]However, it's frustrating because many patients arrive in the initial phase. We have many patients in their 60s, remembering that osteoarthritis of all causes, all of them, all ages combined, is the most common cause of arthritis. So, what we see every day is that the most common disease we have is one that basically has no specific response. We have, right, biologics, advanced therapies for other diseases, but for osteoarthritis there is no treatment. Those who, forgive me, the industry... But those chondroprotective agents, hyaluronic acid, collagen, they're absolutely useless.

[01:08:24]There's no evidence. The clinical practice with them is awful, and some even take up to 360 months. The effect is 3, I'd say, and the effect is terrible. So even we at HGF, where I'm a preceptor, have many patients, including those with plantar fasciitis, which, as mentioned in international recommendations, has the strongest evidence. People say it's very well indicated, right? It should be used for other things, but the greatest excitement and level of evidence is actually for plantar fasciitis, but you have a case in your own home, right? Anyway, I don't even need to convince you of that.

[01:08:57]But I appreciate the invitation because knowing that there's an initiative like this here in the city is excellent because it generates hope for patients.

[01:09:06]Honestly, I have a patient I started treating at 88 years old for rheumatoid arthritis. In 8 months he was in remission from rheumatoid arthritis. Nowadays I'm racking my brain. Regarding him, I'm racking his brain, sorry, racking his brain with him because of the osteoarthritis he has. It's preventing him from walking, from ambulating, and consequently generating a terrible psychological effect, because the patient has completely preserved cognition.

[01:09:31]It's the osteoarthritis, the gonarthrosis, the knee orthosis that I've already injected with corticosteroids, I've injected with viscoelastic fluid, supplementation, I 'm doing injections, doloxetine, I've done everything you can imagine, and the response is bad, which is normal, usual, unfortunately.

[01:09:47]Marcelo, we're even, I'm really encouraging Thaago a lot, and he's well on his way to his master's degree and a scientific initiation project where we're going to partner with you, right, to have the patients, we're also going to put the pharmacology lab there, you know. I told him exactly that yesterday, when he showed me this work yesterday, I said, we have to talk to Roberto and Dais so we can also try to reproduce this, and maybe not. In terms of pre-clinical work, the work is actually clinical, right? So this will progress.

[01:10:24]Let's go, Carlos.

[01:10:25]Good morning. Thank you for the invitation.

[01:10:27]Congratulations, Thaago. And I think this is one of the radiotherapy classes that has captured the audience's attention the most. It's a topic that I think many people didn't know existed for benign diseases. Radiotherapy for benign diseases has treatments, right? There are several indications, from seizures, arteriovenous formations, pterygium, Graves' ophthalmopathy, and cardiac arrhythmias, right? Arterial tachycardia, atrial fibrillation, in short, it's a world of possibilities.

[01:10:55]And whenever I present the department to some students, the people from the multidisciplinary department, sometimes I say there is radiotherapy for benign diseases, but some time ago I used to say this more forcefully, but we barely have space for cancer, right?

[01:11:07]We're going to be occupying the equipment with benign diseases, but I think that's changing thanks to hypofractionation, you know? Hypofractionation in cancer is... We're starting to free up more slots. So much so that before, departments would work past midnight; there are departments out there that ran 24 hours non-stop when we didn't have hypofractionation.

[01:11:28]We noticed this was very noticeable with the arrival of hypofractionation and the reduction in shifts. And then you have the availability of a linear accelerator to treat a condition that has such a strong impact, right? In relation to the world population, and you're not going to force the machine. A machine like that to do a treatment like this, which is a dose that I call anecdotal in relation to the dose for cancer, really the machine will say: "Oh, you're kidding me, you're just tickling me, you're not going to force it almost at all, right?"

[01:12:04]So here's a tip, Dr. Sérgio, not to negotiate another one of these machines to get rid of it. When the new one arrives, give away the old one, leave the old one there for us to do, because it's a very simple treatment, it's an extremely simple treatment, it makes you very comfortable, you know? In terms of doing the treatment, and it's a straightforward technique. Right?

[01:12:21]Very calm too. Yes. Uh, so, regarding the anatomical dose, Thagão, you did exactly the calculation I was doing. The mathematician, people have an idea of ​​this difference between the dose of 70 grams and the dose of 3 grams for osteoarthritis. The mathematician gives 20- something times greater than the cancer dose, right? But that doesn't count. What counts is the radiobiological calculation. And you were generous, you used, I saw there, you used alpha 3, right? If you put alpha 2 or 1.5, the difference is even greater. I did the calculation, it's more than 40 times smaller than the dose for cancer treatment. This alpha, in this characteristic, considering the slower-responding tissues, right?

[01:13:02]So I think it's something promising.

[01:13:04]I think the bottleneck there will be the regulatory issue, right? And nothing that prevents, seeing, I don't know if there is this dialogue between institutions and operators individually regarding packages, right? Institutions starting to see some... uh... Values ​​for those who want to do it privately. And what I also wanted to say in relation to the audience, both because of the topic and Thiago's ease with the subject matter. And I also believe that many people in the audience have close people who identify with the topic. Everyone has their grandmother there who has gone through this, who is there going to physiotherapy sessions, having intra-articular treatments, right? Sometimes there is a surgical risk, the surgeon says: "Look, surgery is indicated, but the surgical risk is very high."

[01:13:50]So I think this impact is very significant. I imagine the impact on a country's economy when a young person stops working to accompany their grandmother, their father, their mother, and these treatments. Not to mention the issue of the toxicities of anti-inflammatories, gastric ulcers, right, kidney infections, isn't that right? So I think it's something very promising and once again, congratulations. There's a lot to cover, Thiago. I'll share it with the audience, but... So, in your mother's case, you're actually not doing re-irradiation, but rather complementing an initial treatment. Comment on something, for example, if you've seen patients who actually need to be re-irradiated during the course of their lives. I don't know if you've seen this work. Note, Mr. Fernando, re-irradiation is indicated eight weeks after the end of the first course. This re-irradiation is nothing more than a repetition of what was done in the first course. That is, your mother will receive the first dose of 0.5 C GRES today; she will receive six doses distributed over two to three weeks, exactly as we did initially. There's even a Spanish study that says : "When the patient has that mold, that mask, preserve it when they finish the first course, because they have a 30 to 50% chance of needing re-irradiation, right?" So, it serves as a warning, in this case, the mother dealt with her health insurance plan, it took me 4 months to send articles, PPs, discussing with the auditor, then it went to the medical board, it resulted in a tie, two auditors were in favor, two auditors were against. Then I asked, but isn't there a single radiation oncologist auditor?

[01:15:35]My questioning led me to choose a radiation oncologist in Brazil; it couldn't be someone from Ceará due to a conflict of interest, but I might know someone who could be there, right? right? They imagined that.

[01:15:46]So I made my choice, they were even ethical, they gave me five names, I chose one, then this radiotherapist broke the tie in my favor, and I was able to get treatment for my mother through the health insurance plan. The second course of re-irradiation went smoothly because I had already submitted so many papers that I think the CFA is already aware of the issue.

[01:16:02]Then, regarding re-irradiation, if they authorize the radiation, they have to pre-authorize a re-irradiation session. Let's say openness, without a doubt, right? So, just to conclude Dr. Fernando's question, this part is important. If the patient has a complete response, meaning they don't feel any pain and don't want to have re-irradiation, then you don't recommend it. But if, months or years later, that pain returns, you can re-radiate it, right? No, not good.

[01:16:26]Yeah, I'm pretty relaxed about the dosage, you know? Primarily, you select the patient's age range, right? I also believe that at 40 years old and everything, I'm putting it in the paper, but I think that in an older age group, I believe that the only case of grade one radiodermatitis with that dose [laughs] was reported, right?

[01:16:46]I don't think there should even be radiation dermatitis with that dose.

[01:16:51]That was contact dermatitis. Let's go here, Sara, it 's just a request for Montago. Mrs. Dora, please don't sue your doctor for breach of medical confidentiality, okay?

[01:17:05]Yeah, that 's right, it was a very secretive situation.

[01:17:08]Good morning, good morning everyone. Hey, my name is Ismael, for those who don't know me, I'm a radiotherapy resident. Well, it's interesting to bring up a point you made, Dr. Thiago, the direct relationship between these diseases that will cause a limitation of the patient's movement and a reduction in their quality of life, and cardiovascular diseases. If we consider our aging population, one of our biggest concerns is cardiovascular disease; these are the diseases that will cause the most morbidity and ultimately lead to an increase in mortality. So, if we have this secondary beneficial gain, let's say, because the primary one would be the control of pain and the initial symptoms of the patient, the complaint they present, but from the moment we improve all of that, we improve the patient's mobility, the patient starts to move, returns to doing physical activity.

[01:17:57]Physical activity will also bring other secondary benefits for controlling other conditions, both cardiovascular and osteoarticular diseases in the patient. So, with a treatment that, technically speaking in terms of dose quantity and treatment time on the machine, is all very simple, relative for us in radiotherapy in relation to other treatments we perform, the gain we can achieve for these patients. And I think that further encourages us to start thinking about the benefit of fighting harder for this type of treatment and not just looking at radiotherapy as a treatment for oncological diseases, because I think we've been gaining more and more ground in treating benign diseases as well, and we need to start expanding that perspective.

[01:18:42]Yeah, that's what Germany is all about, right? 40% of the volume, sorry, 1/3 of the total volume of radiotherapy for benign disease, right? That 's a lot, isn't it? Yes, you have an economic factor, right? Europeans always think about spending less, right? Because it's a state-run medicine, right?

[01:19:04]Yes, you can.

[01:19:10]Well, good morning everyone. Look, I'm 73 years old, right? I'm a professor at UFC, I'm still a native speaker to this day, right? I've always been very dynamic, as he said, very busy during the day at work, and at night strolling along the river or somewhere like that, more or less. But I gradually lost a lot of my quality of life. Over the past year, I've started to realize that I 've aged, and I thought I still was. I used to tell my daughter, who 's also a doctor, Juliana, "I think old age arrived this year," and she started laughing, " Now that you're noticing this." Then I realized that I had aged precisely because of this knee problem. I have it, and when it's level four, I've never been sedentary. I've always been a swimmer, I've walked, I've done a lot of things for my health, you know? Ah, quality of life.

[01:19:56]And then I noticed that I was getting older, I was really getting sad, I didn't want to go out anymore, I didn't want to have a group of friends from UFC, I didn't want to meet anyone anymore. That's when I started to feel sad. That's when he suggested to me: "Mom, let's do it." I was already on my way to getting a prosthesis. I would never do it because I'd get so nervous thinking that everything might go wrong and I might suddenly not be able to walk anymore. I was terrified of finding myself in a wheelchair in the future, that whole story, you know? So this treatment was excellent for me because it helped me overcome my sadness. I'm not going to tell you that I'm 100% sure, that's impossible. I'm not going to say this, but I think I'm about 80%, 70%, 80% okay. And here I say, Thiago, I arrived, how are things today?

[01:20:44]He lives in the same building as me, coincidentally keeping me company morning, noon, and night. How are things going, two of us? I'd say that's okay too, right? It's not 100%.

[01:20:52]I woke up feeling a bit like this today, I think a knee of mine told me it existed. The culá appears like that, small, it's a feeling like that, he sent that one lightly. Then the next day I feel great, so the effect is excellent. I'm doing great, I've started smiling again, I've started going out again, I've started taking walks again, and that's how it is. I didn't want him to post that photo anymore. I sent it to him the day before yesterday.

[01:21:17]So, thank you very much.

[01:21:19]The treatment is excellent. I came here today to do that. Do you want to do it again? He wants? Yes, I want to. So I'm all set, I'm confident, I know I won't be 100% because of my age, because of my other experiences. I have arthritis, it's due to age and arthritis, that whole story, but just knowing that I wake up happy is already a very good story, it's already a very good result.

[01:21:42]Thank you very much, and I don't think I'll sue the doctor if things don't work out. [laughs] I, I, I have one once and another thing, today I also noticed that physical activity complements that. Swimming, which I started last week, is excellent alongside this treatment, and I also do weight training every day afterward. So this is also super important. And then suddenly I think I'd become his poster girl, right? I said that the day, in fact, we already have the spokesperson for the health insurance companies, to convince the health insurance companies. You can't say you 're Thago's mother, you know, [laughs] right? Anyone else? We're going to have another event here, right?

[01:22:28]Does anyone else have any questions? Just one thing, I also think the point of the presentation is important, because if you look at all the studies, the outcome evaluated was always pain relief, but with that Korean study in vitro and viv, showing restructuring and regeneration of the protein, I think that also sparks good hope, right? To perhaps reverse structural damage, right?

[01:22:52]Yes, maybe joining forces with Reio Mato, you could have some kind of association between you and radiotherapy, right? Well, so I think this is going to generate a lot of things to see, and Marcelo, in our conversation yesterday, became totally open to us forming this partnership. We'll do the same here with the college. I tried to see someone from the Faculty's Reato as well, I think it's okay, right? Hey, doctor, right?

[01:23:22]So, there you go, you're going to do this channeling for us because Joério is with you too, right? No, no, no, HGF, right?

[01:23:30]Working, and we also made contact with him. Well, then we'll consider it, right? Congratulations, Thago, right?

[01:23:39]Congratulations, now consider the session closed. Next week is Nursing Month, right? So we're going to have a nursing theme here, like we do every year, bringing in a guest speaker, either from outside or from here, with an important and very current topic, okay? So, good morning everyone, and have a good weekend. Let's just take a picture here, Thago.