My name is Fernando Malouf. I am an oncologist. I am in the Portuguese Beneficence in São Paulo, in Brazil, and I am also the head of the Brazilian Oncology Group. And I am very grateful to have been chosen to be one of the members of the IGCAC Board. Next slide, please. Today's webinar is being translated into Spanish, English, and Portuguese. And here are the detailed instructions that you can find in the chat, as well as in this moment in the slide that we have in English and in Portuguese and in Spanish. So you have to choose the language you want to listen to, and you can also choose the original language in which you are speaking. If you have any questions about the interpretation, please send us a note. Next slide. Well, here we have a very, very fruitful program for today. We are going to start with Cristina Fotopolo from the United Kingdom, who is going to talk to us about the clinical selection for surgery in ovarian epithelial cancer. Then Dr. Giovanni Scambia from Italy, with whom we are going to talk about laparoscopic surgery in ovarian epithelial cancer. Then we will have three interpretations in Portuguese. Dr. Michelle Zamora from Brazil, who is going to talk to us about the incorporation of PARP inhibitors. Then Georgia Sintra is going to talk about reductive cytoreduction in ovarian epithelial cancer. And our last talk will be with Dr. Carlos Eduardo Andrade from Brazil, who will also talk to us about the role of gynecological oncology in BRCA tests. Next slide. So, welcome to everyone. We are going to have the recording available on our IGSS page. And please send in the questions where we have the questions and answers session. So, the label is that only the presenters will be able to speak and the rest of the people should have their microphones in silence. Here, this webinar today is being supported by the Brazilian group of gynecological tumors, which is called EVA. Next slide. Well, without further ado, I'm going to give the microphone to Dr. Cristina for her first talk in this webinar series, which is really the last of the three series that we have had, that we have done the previous two weeks. Cristina, thank you very much for being with us. Well, it's a great pleasure for me. I'm Cristina Fotopalo from the Imperial College of London. I'm going to talk to you about the subject of interactive updates. I am very grateful to my colleague and friend, Dr. René Pareja, and I am very happy to be here taking part in this talk. We are going to talk today about the clinical selection of these ovarian epithelial cancer operations. At the moment, we see the data that we have in this meta-analysis. The more we listen to this, the more aware we will be of what they are going through. So, we want to have a better survival in terms of the progression of the disease, and this is something that we see that does not change. This is the first presentation, here the first recurrence, the second recurrence, and the third. So, that can be consistent through all the studies, all the information that we in the community of gynecologists have, and that we have implemented, and that an analysis has been carried out here, where we see tumor residues in these tertiary surgeries. So, we have to try to operate these patients. So, to be able to do that, in recent years, we have experienced an expansion or growth in the selection of what we think to do the operations on these patients, and we compare it with what is happening now and in the future. In the past, we considered something radical, like an extravaginal resection with spectrometry, and that is part of routine surgery. Nowadays, we have grown up doing other types of, doing proto-surgeries that affect less the liver and the part of the pancreas. So, we have also worked with techniques, with staplers, without the formation of the stomach. So, that is part of the routine that we do nowadays, so that the patients do not have a better quality of life, and the same thing happens with cases of metastasis in the liver or pancreas. So, we have experienced that. So, this has changed in what we can do with these patients and to what extent we can go. So, to be able to talk to the patients with the truth of what can be done and what should be done when there is a patient with an initial diagnosis of ovarian cancer, then one tells them, what do we do when this is advanced to cure it? We talk with them about the different options that tell us about those different possible surgeries. In the past, before, we depended on experience and retrospective studies, but now we have more and more prospective studies of much better quality that show us the design and the evidence. So, we can talk to the patients from a better point of view. So, the LION study that was done for these patients completely operated on these advanced diseases, and what these studies have shown us in black and white is what we have to do or what are the necessary procedures for this to be cured, this patient with an advanced cancer. So, the clinical factors are discussed with the patients. So, more or less, 55% of patients require a resection, and 20% need a splenectomy. Approximately 10% need, if they have a stomach formation, the patients. These are usually the most common procedures that need to be done for these patients. So, to be able to put all of this within a greater objectivity and have a much more objective framework, we surgeons not only have to believe and be as we have traditionally done, but we have to update ourselves in these treatments. And the European Society of Gynecology and Cancer in Gynecology has done this work in 2016, talking about these objective measurements of what is really needed and what is considered as something highly qualified to be able to say that the appropriate surgery has been done for the patients. And, of course, what can we do to select this best option? So, here we have to define these criteria. And here we see some inoperability in those patients who have advanced ovarian cancer. So, we have to send the patients to other primary therapies, those that we cannot operate on. So, we have seen that deep, diffuse infarction, when there is a part in the thin mesenteric intestine, we have also seen in the thin intestine syndrome, the tumor is made more or less, if it is greater than 1.5 millimeters. And we also see diffuse infarction when it is in the stomach and duodenum, where that cholesterol is made. And we would never go that far. In the head, where there is this pancreatic disease, really, or in the middle part of the pancreas, it is also one of the criteria for not being able to operate when the patient has other comorbidities such as diabetes, etc. Also, when we talk about the colostrumcus or the liver arteries, the part of the left gastric artery, a massive infarction is made, and then there can be a necrosis. Going further, then, when we talk about the metastases in the liver or multisegmental or central parenchyma, a transplant could be done with these patients, and they cannot be chosen to do this type of surgery. Those who have an extra-abdominal disease, neither. And here we can see some of the examples. Also those who have super large ganglions. So, these patients are not suitable for surgery. And there are other cases, as we see here, where we really prefer not to perform the surgery. So, here we have some selection criteria. And how are we going to do this in our practice today? And how do we as gynecologists, today as surgeons, what do we expect then with these images that we can have before the surgery? What do we require? Well, we talk about ultrasound, but the question is, how can a disease or a parenchyma carcinosis tell us how we can depend on these images to see if the patient cannot be operated? So, what is the state we are in at this time? Well, we have some weapons at this time. We have ultrasound, CAT scan, PET-CT, and we have magnetic resonances, all of these in a group that can assist or help us. And here we have started to think that these scans have become part of the algorithm or the tools that we have used. But the problem with CAT scans is that they are not highly accurate. In many cases, we have found out how accurate they are in some key areas of the resection. And what we have seen is that the key areas are the diaphragm, the vaso, the large intestine, the hepatopathy, and the mesenteric part. And what we have seen is that although these are considered with a high specificity and a negative predictive value, in those key areas of interest, it really shows us that it has a low sensitivity and little predictive value. So, very often we can say that maybe the mesenteric part is fine and it really is not. So, it is very difficult to be able to predict completely just using this tool. Here we see some pictures that I like to show. You may have seen them in my other talks, but I like to present photos of what I'm telling. Here we see the mesenteric part. And here we see how the cirrhosis is totally disseminated. So, you can do the complete stripping to do the complete stripping on both sides. You always have to be careful to do this carefully and not damage the mesenteric vessels, because there would be a big problem. However, imagine doing this, and it is difficult to differentiate the two photos that I showed you. Look here where you see here. An extensive carcinosis, which again in the city would be classified as carcinosis, but it is something that can be operated. So, the question is, what can we do to be able to differentiate between those cases? And I think there will be a talk after me that will refer to this. So, again, to make things more subjective and put this in each place, it is important to see the specific algorithms. And now we have taken a new consensus, which is the ESGO-ESG-IOTA, with this evaluation for before the operation. And this is a job that we have done together with the doctors that we see here, Dr. Baby. And here I have the pleasure and honor of being able to work here with Tom Bourne from the United Kingdom, Andrew Masman, Daniela, Dennis, many people who are in this group, also Maurice, where we all sit down to discuss what the imaging can show us, the images to decide if a patient is operated. And what we have seen, of course, is that there is magnetic resonance with the inclusion of functional sequences. It is important, but it is not the first, the first-line tool, but it can help us to differentiate between those masses that are malignant or enigmatic or those that are borderline. And also the PET scan, which can also have a whole body diffusion as a second step, but it should never be the first step. And especially when we talk about these borderline diseases, that is, they are not defined and are of their quantity, then it is important. What is also very important is that only the images cannot reliably detect the totality of the degree, either of a peritoneal carcinoma, or if it is a serous intestinal or mesenteric disease. So, this is in the case of carcinosis. Also very important is that only the images should not be used to make surgical decisions in terms of predicting this peritoneal tumor operability. So, in terms of these peritoneal diseases, we should not rely solely on the images. And to go a little further, we also explore the new aspects of circulating DNA, which is not used at this time in routine clinical practice, but it can be useful for algorithms in the future. So, leaving a little bit of the conventional part where we have shown patients, now we see here this study is much more advanced, also the images we have now. So, the question is how we can now, with respect to these systems, show their value and use them to say that it is much better than conventional practices. And one of the first things that has happened in many of the events is that in this study, which is called the MROC, which has been carried out in the United Kingdom, at the Imperial College, it is a study by Andrea Ruckel, and it was approved by NICE, so it is in a fundamental study at this time, where we try to see and compare the validity and the prediction or the probability of a CAT scan, making the comparison between the two with magnetic resonance. And what we try to do is not only see the probability, but also look at the economic analysis in terms of health, see all the characteristics of the patients, the need for other disciplines that participate in correlation with histology. We also did this study and we took it much further to simply look at the probability to be able to say, okay, this is what we need, these are the necessary criteria and the perspective to be able to have a good selection of our patients. So, this is regulated with multidisciplinary teams. As you know, it is not just a decision by the doctor, but it must be a decision that is made with mapping, with all the joint information, where many experts come together to make this type of decision to see the step to follow with the patients according to the images we get. So, these are the slides that I wanted to show you, because it talks about whether it can be operated in relation to age and performance. Well, it really depends on the patient too, what we have to see, not just the disease, to see if the patient should be operated or not. It requires that the whole patient is operable, and the whole patient not only has to do with the tumor in the womb. We always have to be aware of the correlation of operability in relation to age and the performance of these patients. We know from many studies that all patients can benefit from these operations, and we also know that there is a lack of proportion between the high surgical mortality when they are patients of advanced age or those who have comorbidities. Here we have the data from the GEO of Germany, where it shows the mortality rate. We see here a rate of three months, almost 30%, and six months of mortality, almost 40%. So, almost half of the patients will die. So, it's a pretty poor figure. So, for that reason, for us to be able to have a selection, or a selection algorithm that is precise and adequate, now we at HGO have done a prospective study that's a part of the famous Trust Study, which is part of the famous Trust Study, and this study we expect to be reported at the end of this year. An algorithm that consists of simple things like these that we see here, the state of the patient, all these issues that are going to give us an algorithm that we can associate with the morbidity and the mortality rate, and there we can better know who should be operated on and who should not. And of course, this is going to help us a lot. And the last part of my talk, I want to talk to you about the big elephant that we have here in the room, which is tumor biology. What about that? Because we really can't ignore that. Those patients who really have a much more unfavorable tumor biology, then they should not have a surgery or a conventional treatment. So it's important to select it, but we really don't have a reliable algorithm to select these patients. And I want to show you some data that has to do with what I'm telling you, to develop these radiomic predictors of clinical and surgical results. I think all of you have already heard about this. According to the conventional part of the CTs, we have segmentation, and this is what happens in these algorithms, in those programs, where there is going to be a factor or a vector that is going to show us the radiomic part, where we are not going to talk about predictability, but about survival. These are patients who operate. Here we see the validation data doing the segmentation, and we have seen patients who have a high-RPV group, who have a two-year survival rate. And all the patients, here we see, this was validated, and we have validated it in various parts, also in the ACE group, where we have seen that we could not validate this, but in the PFS, that is, the free survival rate of these patients. Here we see that it is much lower, but here significantly higher, if we compare it with the patients in the blue line group. So, these are great surgical efforts that in the future will also help us predict and choose the right patients to recruit. In phase 3 trials, you can choose the patients in the lower part, if they should be operated, with those who have this high figure, simply do the treatment. So, with that, you can predict the survival chances for those patients with ovarian cancer and help clinically select the patients. This will be very useful for that. So, we have made many advances in terms of how to choose and how to predict, not only the probability, but also the survival rate. So, the key is still expertise, training, the training that doctors have. And this, unfortunately, as gynecologists, sometimes we cannot implement in terms of our infrastructures. We need support. Here we see the limitations of the high quality standard, with the high variability that exists in health policies and also in resources and capacity in different countries. Maybe in high-income countries, maybe, but in low-income countries, this is not available. Maybe some of these factors are available, but others are not, as we see here. And contrary to what we believe, we simply have to adapt the patients to what we really have. So, we have to look at how important that is. And we have been aware of this in the pandemic. There are some countries with high incomes, rich countries, for example, had to stop many of these procedures for months due to the lack of training and also the importance of the infrastructure we have and the support of that infrastructure. So, in the end, when we talk about patient selection, it is not only about the nodule they have, the mesentery. No, it is much beyond what we have to observe. It is about the entire package, the entire profile of the patient that must be evaluated to know if we should operate and how to select the patients. As I say, you have to keep in mind the age and their way of life, that is, their performance. And of course, all of this has to be adapted to what we have again. Thank you very much. And I will be very happy to hear the questions. Hi, Cristina. Hi, Cristina. Very nice to hear your talk. Thank you very much. Hi, Fernando. I love to see you. You know, even being an oncologist, I was able to understand almost everything. I think it was very clear, despite not being an oncologist. Yes, yes. I'm very happy. Ready, let's go. So now let's do a survey, some questions about your talk. Here are the key factors to be able to predict a complete reduction surgery. So please choose the incorrect option. The A, where there is a high specificity and a negative predictive value. The B, when this is happening in the hepatitis and in the thin intestine, etc. The third is 19.9 MRI and is recommended as a second-line tool to detect the non-cancerous origin. And the last, only the images that can be used safely to make the surgery decision in terms of the prediction of the operability of a peritoneal tumor. Somebody says they can't see the English version. Yes, that's the message. I got it. So let's see here, you know, our voting. The most voted question, the incorrect one. The last one. The one that was incorrect was the D, that is, to use only the images. Can you then make a comment on this? Yes, what I wanted to show in my talk is that when we talk about clinical selection of patients, we talk about choosing them, not choosing the images. Because sometimes, or what catches my attention often is that patients with ovarian cancer are not presented by them. They simply go to the radiologist, and I think that looks like inoperable. So the patient never even gets to the surgeon. So it's our job, it's our task that the patient is selected by who he is, and not just by the images. The advances we have in management, we have to recognize the limitations there are. Everyone who operates knows that carcinogenesis is not the same. And a CT can report that it says that it looks like it can't be operated or that it's very advanced. It really doesn't mean that it's really advanced. And we see that when the patient itself is operated. And sometimes it's the other way around. We think there's a lot, and then there isn't, or we think there isn't, and then there is. So we see in the different cancer societies that we emphasize that using a single modality is a limitation. That's why it's very good to put together these different modalities to have an adequate algorithm. And what is also operable in a patient who is homogeneous, it's not the same when we have an older patient who has comorbidities. So that's why you can't just rely on a photograph. I think there isn't enough. So I think there is also a question that they're asking about liver nectomia. So the approach there is that I think we've solved that with the LION study. It's not very clear, but in some studies there is no therapeutic control. There is no therapeutic role, but there is in terms of the prognosis and the predictive role. So in these patients, early on you have to do a ganglion analysis to see if this is suddenly hiding a stage number three. So if we have to do a systematic anatomy or if we can deviate to do another procedure, that's another question. We've worked a lot on that in this group. So I think in the future, even in the early stages, in this systematic part, we can do the ganglion resection, but that's not yet proven. But you need to know the stages to have this in a more personalized way to adapt to each patient. That's the first thing I wanted to say. The second is the role of the laparoscopy. I think the laparoscopy definitely has a crucial role, no doubt, with those low-volume diseases. We don't know where it comes from. Suddenly the tumor profile doesn't work. There are comorbidities. So chemotherapy is not an option. All these issues have to be taken into account, and that's a fact. But a routine, a laparoscopic diagnosis for patients with ovarian cancer is not something that can be done. I think that truly inoperable patients that have an extensive disease, I don't know, the percentage is very low. And that's what I think. So putting the patient, taking another second procedure and another laparoscopy, I think it should be discussed, but it's not something that can be done in all medical centers, to be honest. Especially now with the more advanced images we have, we can really reduce the need for laparoscopies in patients because we have a clearer vision in this. But in the Trust study, we have an arm, especially with French and Italian patients, where you have this anticipated prognosis, and we can do the analysis of the value of the laparoscopy in those patients. So let me ask a question. You talk about operability according to the criteria, the role of the images, and of course the integration of tumor biology and other factors that you have also mentioned, adding it to the amount of disease there is, or the volume of disease. In Brazil, we have an experience with the PET scan in patients who have a recent diagnosis of ovarian cancer. And in my opinion, to detail this more in terms of the disease in the pelvis and in the stomach, but what is extra-abdominal. And we do have some patients where we can find, particularly in those who have a problem in the pelvis and abdomen, for example, when there is metastasis in the lung. What do you think about the PET scan for those patients who have a high volume of disease when it is being decided whether to operate on a patient or not? That is an excellent question. And in ovarian cancer, when we operate on our patients macroscopically without tumors, we cannot have the illusion that there are these microscopes. Well, all those patients, even after doing the total cytoreduction, we may find that. So, going and looking microscopically, this microscopic disease that is spread everywhere, it really has no value. So, forget it. Let's assume that we are at this moment in a science movie and we have a tumor, and the patient opens up, and we see here those who are swimming in the blood vessels. And we have seen in the LION study that even when 55% of patients had microscopic ganglion disease, removing that ganglion disease did not help the patient's survival. That means that removing these microscopes does not have a benefit either because there are millions of these. So, my response to PET scan is that if there is a node or a mass, a tumor in the medial steno or in the chest, if I don't know if it's an infection or something, I say, yes, do it. Do the PET scan. But to see if there are these in the ganglions, if it's cancer or not, it really doesn't matter. And it shouldn't affect the lives of those patients either, simply because we have seen, especially in the last study, the microscopic lesions that really don't play a role. And the patient has to be treated differently. Well, here are a lot of questions. We have more than 250 people participating and watching us. Yes, it's amazing. I can quickly answer those questions. Lymphedema, for example, definitely not. The majority of patients with ovarian cancer who have this disease of the liver are going to be parotids. It is simply because of the vascular part of the ovaries where there is circulation that goes to the renal vessels. So, here is the question, how far can we go? Well, if we can make it completely clear, or if it tolerates it, we can do it. But we should not do this lymphedema to those patients who are operating and who are free of tumors. This is obsolete. And we have shown that it has nothing positive for survival. Let me ask you about lymphedema. We have three random trials, and the last one is LIONS. And this was three years ago, which shows that it has no role in a systematic lymphedema. And on the other hand, the mortality is high. So, you need to be in the ICU. That is to say, everything is put at higher percentages in this case. But we are talking about ovarian cancer for those who are endometrium, for example, those of this type. So, we have some data, some publications. The first in 2011, and the second is a systematic meta-analysis in 2017 that shows that for metastatic carcinomas, it was stage 1, and the article was for an advanced disease. So, both articles show us a benefit to do this both in early diseases as well as those that are advanced. So, what do you think about that? Well, in the study, we added, I don't remember the percentage, but we have to differentiate this. In the LIONS study, for advanced disease patients, not for those early. So, if we have this, presumably, we have to look if we give chemotherapy, and we should give that patient chemotherapy, but if there is an advanced cancer to remove those nodules involved microscopically, it does not have, but those that are bulky, yes, those that are larger. So, the patients have a higher risk of having those, and of course, they will have to be operated, but not if we are talking about microscopic ganglions, and there are many oncologists who say, okay, a patient who has clear cell because it does not respond to chemotherapy, so we simply operate, and we do not give chemotherapy to those patients, but if they have these positive ganglions, they need something else, so it is not the battery that really made the difference, but the addition of the other treatment, that is, chemotherapy, but we cannot say that removing microscopically those involved ganglions is going to be a benefit. No. I don't know if that makes sense. Yes, yes. I think that again, we are going to look at this disease more and more, and now with molecular biology, yes, of course, we treat it as something of the endometrium, and it does not make the profile of those patients, but we see that every time we do more and more. Yes, I think we have come to time. We have so many questions for your talk, so what I'm going to ask is that we're going to continue with our next presentation, and I will be working on the chat. Thank you very, very much, and we'll see you soon in New York. Exactly, I hope to do so, and thank you very much for having me. Okay, so the next speaker now is Dr. Giovanni Scandia. The next talk is by Dr. Giovanni Scandia, who is going to give us a very good talk about parascopic surgery selection. First of all, let me thank the organizers for inviting me to discuss with you the laparoscopic selection for surgery in this type of cancer, to be able to provide a comprehensive review of the laparoscopic selection for surgery in epithelial ovarian cancer. I would like to first discuss the different stages, starting with the disease in the first stage. Although laparoscopy in the early stage has been proposed for many years, in current literature there is evidence in relation to the oncological result of the early stage disease. Treated in this way has been controversial, despite the survival of patients treated laparoscopically compared to a similar group of women treated through laparotomy. A recent review on this topic said that so far there is no real evidence available to quantify the benefit of laparoscopy for the early stage management of these patients. The main concern of this issue is the association that exists between laparoscopic surgery and the intraoperative viability of cancer cells that can suddenly negatively affect patient prognosis. A very large, recent retrospective study analyzed more than 8,000 women who were in stage number 1. And in this large study, in this broad cohort of patients, they analyzed the trends that occurred in minimally invasive surgery and capsule rupture over time, along with the association between minimally invasive surgery used, the rate of rupture and survival. And in their document they showed that 22.5%, a rate of 22.5% of capsule rupture, and more importantly, they showed that capsule rupture had a negative effect on survival and also that the use of this along with other elements was associated with the risk of capsule rupture in a multivariate analysis. Therefore, patient selection is much more important, mainly in relation to the choice of surgical approach. In fact, patient selection and survival results seem to be related to each other. To provide an objective method of selection on the preferred surgical method in this group of patients, we recently designed a retrospective study to identify preoperative and intraoperative patients and their associated tumor characteristics with an increased risk of tumor rupture during surgery in early stage ovarian cancer. And the secondary point was the creation of a score system that could predict the probability of that rupture. This is a retrospective study that was carried out at the Augustino G. Marley Polyclinic University and in patients with early stage disease. And also all the characteristics of the preoperative tumors were reclassified according to the IOTA classification. A multivariate analysis showed us the diameter of the tumor and the ovarian peritoneal fossa were independent of the rupture and therefore were included in this score system. Based on this data, we develop the score associated with specific rupture rates. Therefore, professionals will be able to identify which patients were guided with minimally invasive surgery and this could be a reasonable option and those in which allopatomy should be used. So, we can therefore conclude that in the case of early stage disease, the selection of the surgical strategy is necessary to prevent intraoperative problems and affect the survival results. And the application of a laparoscopic score system could be a useful tool to select patients that are suitable for laparoscopic surgery. Moving the discussion to advanced disease, both in the last conference, ESMOSGO, and in the NCCN guides, the laparoscopy can be useful to evaluate if the optimal reduction in the site can be achieved with a recent diagnosis of an advanced disease. In our institute, more than 10 years ago, we identified a PIV score system that has been externally validated and this laparoscopic score system includes six variables that have been shown in our study that the PIV score scale greater than or equal to 10 was associated with a low probability of achieving a complete site reduction at the end of the first surgical procedure to reduce the volume. Regardless of the score system, the presence of carcinosis and mesentery retraction were identified as absolute criteria for non-operability. The concordance of this score did not coincide with some main results found and this was validated by other authors, confirming that the laparoscopy can predict the complete site reduction in advanced ovarian cancer. Other predictive laparoscopic models have also been designed and validated. The R3 and R4 models associated a computerized tomography and laparoscopic data to determine the cancer index along with the lesion site score. And in this document, it has been shown that all three predictive models worked very well, but the study also confirmed that the efficacy of laparoscopic evaluation of the disease and the study concluded that all models could predict site reduction surgery, even if they were more reliable to predict complete site reduction surgery. We also have positive data on the effectiveness of laparoscopic evaluation of the disease in primary treatment. And in this document, we have a clear demonstration that laparoscopy is a cost-effective way to improve primary treatment because the benefit of laparoscopy was influenced by the mitigation of severe complications and their associated costs. It is also very interesting to consider that laparoscopy could also be a good way to assess or predict complications in primary treatment and using this method that is now available, which combines four different variables, including performance data, CA-195, and tumor load evaluated through the PIB score through laparoscopy, we are able to calculate the risk of major complications for each individual patient. According to this, we clearly see that there is an increase in the risk of complications with an increase in the risk score. So, using this method, we can calculate the individual risk of each patient for complications in the main site reduction surgery. The same selection process can be applied to the other site reduction surgery scenario. In 2010, a modified PIB scale was created in a prospective and published way to be able to identify patients that were suitable for a complete site reduction. And in this study, four of the previously mentioned variables of the PIB were included in the final calculation, each with two score points. So, this article really showed that laparoscopy can discriminate against patients with partially stable disease after site reduction chemotherapy, which can be susceptible to having a successful IDS. Preoperative selection, laparoscopy has been shown to be a key tool to determine the primary treatment for all site reduction surgeries. But it is also important to consider that in some cases, starting the procedure with laparoscopy can also give us the opportunity to use minimally invasive surgery to do all the site reduction surgeries, all the site reduction surgery procedures in patients with an optimal response to the auxiliary chemotherapy. And this trial was the feasibility study that showed that minimally invasive surgery can be used successfully in patients who are having an optimal response to the auxiliary chemotherapy. And after this study, several of the other articles were published on this topic. And what we did very recently was to develop a homogram that could predict the feasibility of minimally invasive surgery that was obtained through a retrospective analysis of more than 300 patients who were being subjected to minimally invasive surgery or an open approach. And again, the preoperative variables were used to predict the probability of minimally invasive site reduction surgery using multivariable models and the probability of minimally invasive surgery according to the identified variables that we have here in this homogram, in this slide, which are the sum of the points associated with the probability of success in minimally invasive site reduction surgery. And so, therefore, it provided us with the need to choose the surgical method. After the encouraging results of this trial, which has been confirmed by several other documents, now we are participating in this randomized study of international phase 3, in which patients with an optimal response to non-assistive chemotherapy are randomized to experimental site reduction surgery versus open site reduction surgery. And this is controlled in terms of the survival rate of the disease. So, as far as the disease, we can say that the laparoscopic evaluation of the tumors in the recent diagnoses in the advanced disease can predict complete site reduction. And the laparoscopic score system can be reproduced, validated and cost-effective, and can help clinicians and professionals in the selection of treatment for patients, both in surgery of both types. Now we move on to recurrent disease. And in what has to do with the recurrent scenario, laparoscopy is again accepted by the NSCN guides as an adequate strategy to evaluate if optimal site reduction can be achieved during secondary site reduction surgery. And with respect to laparoscopic selection for secondary site reduction surgery in our institution, here we can see the GMELI algorithm to manage patients with recurrent ovarian cancer. All patients are subject to a PET scan, which is discussed in a multidisciplinary scenario. And those who have an extra-abdominal metastasis are sent to chemotherapy. And those who have intra-abdominal, inguinal, and cardioplankton recurrence are evaluated for a secondary site reduction. And in the case of recurrence that is not acceptable, for example, intraparenchymal, liver, which involves specific volumes, or those that are not optimal for surgery due to performance standards, then they are sent to chemotherapy. The rest of the patients receive surgery that always starts with the diagnostic laparoscopy. And secondary site reduction surgery is done either openly or with a minimally invasive approach according to the location of the disease. The figures refer to the period between 2012 and 2020, in which we have evaluated almost 450 patients. Based on this data that we show in this slide, the performance in terms of the Yameli algorithm compared to other methods that are used to evaluate and select patients for surgery after recurrence according to the TIAM model and the ALGO score. As you can see, the algorithm has better accuracy than the other models. In addition, this slide shows us data from a preliminary analysis that was carried out in our institution and that has not yet been published, which is demonstrating an oncological security of doing secondary site reduction surgery with a minimally invasive approach in certain selected patients. In general, in our institute, we test the viability and security of secondary laparoscopic site reduction surgery. And this was done in 58 cases where multiple procedures through minimally invasive surgery have shown the results that we have in this slide along with other interpretive results. A low rate of complications was also detected, confirming that in certain patients, secondary laparoscopic site reduction surgery can be done successfully through minimally invasive surgery. So, according to recurrent disease, we can say that laparoscopic evaluation of tumors to be able to predict operability is effective only or also in this recurrence. And in minimally invasive surgery, in recurrent cancer, we have promising results, but we surely have to develop the laparoscopic model to be able to prevent and achieve the complete reduction in secondary cases. So, in conclusion, I think that laparoscopy is very useful, a very useful tool in ovarian cancer, both as a diagnostic method for selecting patients for open surgery, but also as a starting procedure in ovarian cancer, and it can also give us the opportunity to do surgery through minimally invasive procedure in certain selected cases. So, my advice and our policy at Gemelli Hospital is to start each procedure for ovarian cancer through minimally invasive surgery and then decide if laparoscopy is needed or not. Muchas gracias por su atención. Thank you very much for your talk. Buongiorno. It's a real pleasure to have you here in this webinar that has been planned. First of all, we have a survey to read and then we will have the questions. The question is, which of the next laparoscopic results constitutes an absolute contraindication to try to resist the procedure? Number two, mesenteric root retraction. Number three, diaphragmatic carcinomatosis. Number four, need of bowel resection. Number five, superficial liver metastatic disease. Now people are voting. We'll wait a few more seconds to go. Why are people voting, Professor Escambia? I'm really sorry that Italy is not going to play in the World Cup. I am a soccer fan. I'm going to go to Qatar, but without Italy, it's not going to be the same, you know? So, I'm really sorry. It's difficult for us to understand how it was possible. Unfortunately, it was. We have the answers and the most voted is the mesenteric root retraction. Can you comment on that? Yes, I think the comment is very clear. Because I understand that almost 80% of the people answered the correct answer. And I think that now we have very, very few situations in which ovarian cancer can be completely eliminated. And one is mesenteric retraction. As for the others, we can do almost everything. So, I'm really happy that I see that most people have identified mesenteric root retraction as the only contraindication for ovarian cancer surgery. So, it's very good. There is a question. Which is, if you find in laparoscopy a score of 6 or 4, do you proceed with cytoreduction surgery by laparoscopy or do you prefer to go to laparotomy? We do laparotomy because in the present we feel that cytoreductive surgery in ovarian cancer must be done by laparotomy. But we are open to designing clinical trials, I believe. This could probably be done within clinical trials, but currently we do not have a clinical trial on this topic. So, we do laparotomy. So, those are some questions that I would like to ask you. So, the first question is, what is the care? What are the precautions that you have to take in a laparoscopic procedure to not have an implant? Well, I think you have to be very careful when you do this selection because you have to do this to eliminate the CO2 tumor in the peritoneum. And we also pay a lot of attention to closing the hole very well. And I should say that in our experience, which is now very, very vast, the metastasis or the location after the diagnostic laparoscopy is very rare. And in any case, this would not change the patient's prognosis. Okay, so that's a question from Dr. Farnesati. Do you believe that intraoperative spilling in a patient with a negative wash has a negative effect on survival? Yes, I believe so. And to avoid spilling, obviously in early stage disease, that's why we're giving some rules about it. So now we utilize this score, which is based on the combination of the tumor mass diameter and additionally the mass, the effect of the mass on the pelvic peritoneum. So I think I'm a person who strongly supports laparoscopic use in all stages of the disease. And in any case, we have to be careful to be able to do the proper management. The second point that Christina also mentioned just a few moments ago was that in early stage disease, we are working a lot on laparoscopic detection of the ovarian cancer ganglions. And this could be the opportunity to do an evaluation of the state with the reduction of the complication of other surgical methods in this stage of the disease. Okay, another question is from Dr. Miguel Quijotoque Correa. What is the percentage of conversion to laparoscopic surgery? What I mean is, I understand, not in the early stage, but in cases in which we are doing, I imagine for a patient in which we are thinking of doing resection. So just to clarify the answer, in early stage disease, we do almost 90% laparoscopy. It's very rare that we do something different. In advanced disease, we have to make a conversion to assess operability in very few patients, but I would say about 10%, because there are cases in which laparoscopic evaluation is not good for various reasons. It could be additions or difficulty in entering the peritoneum. I would say about 10% conversion. Another question for you, Professor. Do you do laparoscopy and laparoscopy on the same day? How long does the diagnostic laparoscopy take for advanced cancer? I imagine the question is, if you think the patient has to be converted to laparoscopy, do you wait for pathology or something else, or do you do the conversion at the same time, with the same anesthesia and just move forward? Yes, in routine clinical practices, we do it immediately. So we do the laparoscopy and then we decide immediately if the patient can be cytoreduced. But also during the last two years, we had two clinical trials in which we did laparoscopy and then laparotomy, because we did a clinical trial in which the treatment was different according to the BACR state. So the biopsies, the BACR evaluation, and then in 10 days we decided the second step of the surgery. But in routine treatment, in routine clinical practice, we do it at the same time, laparoscopy and then laparotomy. What we are doing now, and this could be something that we could discuss, is that we are increasingly using ultrasound biopsies in patients in which we feel that the patient is not suitable for surgery. We did some ultrasound biopsies instead of laparoscopy. One more question. What are the tips from Dr. Luis Puentes? What are the tips to involve the retraction of the intestine in a laparoscopy? Well, here we have to use at least two instruments to have some experience in moving the intestine to be able to understand if there is a retraction or not. And considering that when we validated our PI score, we did a multicenter study in which different centers in Italy sent us their evaluation with the video and we reviewed their evaluation. And there was a strong behavior. So the learning curve to do such a laparoscopy is fast. So after 10 procedures, you can do a correct evaluation. Okay, and from Dr. Patricia Paturi, during the laparoscopy, where does the tumor come from? Where does the tumor come from in the laparoscopy? Well, we prefer to do biopsies in the peritoneum to be able to do the diagnosis. And if we do large biopsies, we can put them in a plastic bag and remove them in this way. Okay, and my last question is from my part. We have seen robotic surgery that has advanced in many, many areas. So far in UIN oncology, you know, most of the information is about this type of cancer. Do you see any role or any advantage so far for robotic surgery in the laparoscopic part? Any specific indication? Yes, if we talk about gynecological oncology in general, I believe that in obese patients, robotic surgery is better than laparoscopy. And I also believe that one of the advantages of robotic surgery is that it is easier to do some difficult procedures, minimally invasive, which are then easier. So I think that in the future, most of the minimally invasive gynecological surgery will be done through robotics. And this is also why we now have more than one robotic platform available. So the future of minimally invasive surgery is probably robotics. Okay, so I have been receiving a lot of good feedback from everyone in your talk, particularly from Dr. Ine Pareja. And I hope that Brazil does very well in the World Cup because Brazil and Italy are good friends. Yes, yes, of course. Professor, thank you very much for your participation. Have a very good Saturday. And we will continue with the program. Thank you very much, thank you very much. Okay, so now we are going to our third lecture. Thank you very much for the invitation IGSS to be here today. We will talk about how to incorporate PARP inhibitors in clinical practice. So the studies that supported the use of PARP inhibitors in the first line are only one, Prima and Paola. In these studies, we noticed a certain difference with respect to the design, the drugs, the population. But in general, all of them show that the use of PARP inhibitor in the first line in BR patients has mutated. It has a survival gain, free-of-progress survival, which is statistically significant and important. It is therapy alone for PARP inhibitor, a double therapy with anti-angiogenic. When I talk about patients who have homologous recombination deficiency, we see that benefit of the use of PARP inhibitor, either again alone or in therapy combined with evasizumab. But when I look at those patients who are proficient in homologous recombination, I see a gain in the use of niraparib. But this gain is not expressive when I associate the double anti-angiogenic. With respect to global survival, we still do not have the results. They are a little mature, but we use the data of EPFS2 free-of-progress survival. And we already see a gain in EPFS2 free-of-progress survival in an important way. The importance of evaluating it is that when I do an assessment of the gynecological tumors and then enter the ovary, we see that there is a correlation between winning EPFS2 free-of-progress survival and winning global survival. The advantage is that we are facing a shorter follow-up time of these patients. So the question is, what influences the selection of the PARP inhibitor? Well, in theory, this decision should include the differences of the preclinical models of the PARP inhibitors and ideally a study that compares these drugs directly. Today, we know that there are differences in preclinical studies, both in the inhibition of the catalytic site and in the ability to do PARP trapping. There is a difference in which PARPs are preferred by each drug. But we do not have clinical data that shows in the literature that one PARP inhibitor is better or worse than another. So, from a practical point of view, the choice today, according to the guidelines based on clinical data that are available in each scenario, that is, in each design of study, in this need to combine or not with Bebacizumab, with the consideration of access to medication, pathology, and toxicity. So, as for the clinical data available from the studies, unfortunately, we lost the audio. Paola includes all the new patients and 70% of these patients do not have a racial disease. But Paola has the issue of adding Bebacizumab. So, I'm not giving more passive, I'm giving an active control arm. And I'm allowing this drug to enter neo-adjuvancy, even, suddenly, in some way, altering what we consider the response to neo-adjuvant treatment. Very good. The prime study, on the other hand, is the opposite. I have around 70% of patients with racial disease who have a worse prognosis and here they are really sensitive to platinum. There is no use of Bebacizumab in this neo-adjuvant process. Today, one of the parameters we use to choose the treatment we will do with the PARP inhibitor is to know if I'm going to give or not Bebacizumab. Bebacizumab, in this process, has become increasingly important. We know that it increases the response rate, so when I look, for example, at the results of the Antalya study, I see that I even have a higher rate of complete reception of these patients who do neo-adjuvancy with Bebacizumab. But if we look at other studies like the NOVA, I see that there is an increase in surgical capacity, but not necessarily this translates into a complete reception. The fact is that we have security to use Bebacizumab today and that it has been widely used in this neo-adjuvancy process with a differential that we still do not have the information so concrete about how the relationship of Bebacizumab with respect to the status of BRCA. This was evaluated in the GEOG 2018. Apparently, we see that those patients who do not have a mutation in BRCA get a greater benefit from the use of anti-angiogenic, and this was reviewed in the Italian Retrospective Study. And again, we see that those patients that are BRCA wild-type tend to have a higher BVAC use gain, possibly this is because it has some relationship with the molecular subtypes of CGA, and they will fit very well with those active and immune-reactive genes. And this may not have much to do with angiogenesis and VEGF. In addition to this, what will influence our choice with respect to a PARP unit or another are the considerations, let's say, of access, what is authorized by the FDA. For example, here in Brazil, by Anvisa, that changes a little from one place to another, and just to tell you that here in Brazil, for example, we can use combination therapy with an anti-angiogenic PARP inhibitor for any recently diagnosed patient with ovarian cancer. So there are these regional singularities. And there is also the issue of toxicity. So NIRA-PAR-IV has a very specific toxicity, which is thrombocytopenia and hypertension, while OLA-PAR-IV usually gives more anemia and fatigue. They are different toxicities, and that can sometimes motivate us to choose one treatment or another. So it is difficult to make an algorithm that looks at all the information. We still have a lot of nuances that we need to understand better with respect to first-line treatment. But in general, when I am in front of a BRCA-muted patient or with positive HRD, I can do chemotherapy and, depending on the response, I can continue with some PARP inhibitor. And I can also do chemotherapy with anti-angiogenic and define if I will continue only with anti-angiogenic or I will associate the Bebasisumab. In this slide, we can see the negative homologous recommendation, which is negative HRD. In Brazil, specifically, this arm that can make BFMAS or LARAPIPE can be present in all groups. There are questions today that involve the incorporation of PARP inhibitors. So in that patient who is BRCA-muted, we know that all of them need to receive maintenance. Before, it was questioned about whether those patients who are at lower risk, who can do a primary cytoreduction without residual disease, if they could have a good benefit. And the evaluation of this study alone is very clear. When we do not face patients who do not perform maintenance, even if they are BRCA-muted and completely cytoreducted, around 60% will recur until the second year. So they all benefit. But the question is, when do I need to offer a double block for those BRCA-muted patients? Or how much should I save from Bebasisumab for a recurrence? Especially considering the sensitivity that exists in this group of patients with Bebasisumab. So the idea is not to compare the study with the study, but the source that financed these two studies, both Paola and Solo, have the data of the patients. And when we compare them with each other, we see that the use of Bebasisumab along with PARP inhibitor, apparently adds some free-of-progress survival. I'm not going to talk about the statistical meanings. I think it doesn't make any sense. But when I see all these data and look retrospectively at what was in Bebasisumab, when here with or without Bebasisumab, I reduced the risk of progression by 30%. So when I compare these two arms, the two PARP inhibitors, one with Bebasisumab and the other without Bebasisumab, I still see a similar risk relationship. The reasoning here is much more speculative, but it would be in the sense that maybe if it had a synergistic effect of these two drugs, I would expect to find a reasonable minimum with a higher risk reduction for patients that I don't see. So maybe think of a more adjective effect that is synergistic in these patients with BRCA mutants. In those patients that have positive HRD tests but don't have BRCA mutation, we don't have an answer to what needs to be done. If I need to do a double block or if I can only continue with PARP inhibitor as a single agent, if it's enough for those patients or not. Now, where there are more questions is in the negative HRD disease. So, given that the benefit is lower in this subgroup, we are talking about the order of two months, would it be worth leaving the PARP inhibitor only for the progression of these patients when there was a recurrence? This has been highly questioned because we don't really know what the benefit would be that we would stop giving these patients. Because when we look at the data alone, especially the first, where half of these patients did not receive a second line of treatment, well, we were afraid of saving a treatment for a second line that we may not even be able to offer. So, given all these questions, I think we should talk about the future, how to improve the selection of patients and then look for the study. We need HRD studies that are more reliable. We have to look specifically at the primary study because in this primary study I have all the patients selected that respond exclusively with platinum. So, I'm talking about patients that, from the point of view of the information we have today, when responding to platinum, will have a potential response to the PARP inhibitor. And even in this group of patients so selected, I have a negative HRD still in a third of the patients, 34%. Now, if we think that this may be a flaw in this study to detect these HRD patients, well, it makes sense to find a benefit, even in a group that does not have a biomarker within the study. And in addition to not being able to see these 34% who benefited from the drug, I still have a 15% that the test is unknown because I do not have tissue or because it is not conclusive or because the sample is not suitable to be evaluated. So, we need to improve the development of this study and how we can do the HRD evaluation. In recurrent disease, it is simple. I have platinum sensitivity, but the first line, I do not have that information. So, we really have to improve this situation and bring a high percentage of false negatives and start moving forward for a test where I reduce the number of false negatives and increase the positive predictive value of the test. In recurrent ovarian cancer, we have the development of drugs that are in the second line and go to the first line. So, when it comes to the first line, the patients who used treatment were virgins. But when it comes to the second line, here for the HRD evaluation, these patients may not have received it either. So, all these studies, in all of them, we have patients who were not exposed in the first line to the PARP inhibitor. When I look at all these patients who respond to chemotherapy in recurrence, all of them benefit from the use of PARP inhibitors. And it's interesting because when I compare them to each other, I don't see any difference. So, whatever the drug or the study, the risk reduction is very similar between the drugs in this patient profile. So, in recurrent ovarian cancer, we would use as options or platen-based chemotherapy with bevacizumab or platen-based chemotherapy followed by PARP inhibitor as long as it has not previously administered this to these patients. Well, how is all of this going to evolve? Looking at the data of only two, when we look at these patients who received maintenance with PARP inhibitor, they show a response to platen-based chemotherapy and have a tendency to respond less than those patients who have not received maintenance with the PARP inhibitor. So, this is extremely important when thinking about subsequent therapies. But when these patients respond to platen-based chemotherapy, we have the data, for example, of Oreo, which was previously presented. These patients again benefit from the PARP inhibitor when they have a response to platen-based chemotherapy, regardless of the state of the HRD. Emphasizing that the HRD study probably does not reflect a current tumor situation. It may mean that at some point there was a homologous recombination deficiency, but we do not know exactly when, and that platen sensitivity is still a marker. Obviously, with a slightly lower response than what occurs in the initial lines, but the benefit and the drug still exist. So, this is a general view of how we can incorporate PARP inhibitors into our clinical practice, and I am here to answer any questions. Thank you very much. Michelle, excellent. Excellent, Dr. Michelle, wonderful. Excellent presentation. And I think these are really very, very important topics. And these are the topics that really changed the topic of ovarian cancer. And I would believe that there are, well, there are many questions here with these paradigm shifts. Well, an important message that you convey in the presentation is that if we had access to these drugs, I mean, it is important to use them in the first place, up front, because we really do not know, in fact, if patients who are going to have a recurrence, if they are going to have a recurrence with platen sensitivity, or number two, if they are going to respond to platen treatment. So, we know, many were approved in the first line, but really many are exposed to this, and this does not happen in a large number of patients. So, using them initially is possibly going to be better. Very good. Let's go to our third question. I'm going to read it in English. What would be the incorrect alternative to PARP inhibitors? PARP inhibitors, here we can see the answers, A, B, C, D. It's increase, increase. Look here, it's reading the question number, the answer, A, B, C, or D. PARP inhibitors, here we can see that PARP inhibitors can rarely cause myelodysplastic syndrome. C, there is clear evidence that some PARP inhibitors are superior to others in first-line maintenance therapy. Here, therefore, we have four questions. Michelle, people are voting here, and let's wait a little longer. Increase, not decrease. It was a type error. Yes, here was an error. I would like to thank you for the invitation again, and congratulate you and Audrey for being our representatives here in Brazil, in the IGCs. We are really proud. We are very proud that you are there. Thank you very much. It is a pleasure to be here and very happy. Well, we see the vote. Very good. Do you want to make a comment, Dr. Michelle? We can speak in Portuguese, our native language. Would you like to discuss the alternatives? Yes. Well, I don't know if those people who voted, voted before the questions were corrected. Well, it's actually going to increase PFS. The question, let's see, with regard to the letter C, 34% vote. Unfortunately, we have no data comparing the PARP inhibitor directly with another so that we could really choose a reference point. The toxicity is this, gastrointestinal, and that's what we're most concerned about. But what would be around 1% of patients? That happens in that low percentage. Well, do we have any other questions? Because I have several questions for Professor Michelle. Well, the first question, Doctor, is in the randomized studies, we included patients with 3 and 4 state who had treatment with platinum and did not really have a progression. They had a disease control. We know that stage 2 has a recurrence possibility of around 50%, more or less. So, it's a high percentage. And we work with treatment that helps with much smaller recurrent numbers in other gynecological tumors. My question is the following. Outside of recording, in closed rooms, patients 55 years old, ovarian cancer, high degree of state 2, very well operated, with ischemia. Do we recommend PARP inhibitor for that patient? I think the following. We're talking about 2B small and 2B large. A small implant in the pelvis would be, let's say, more comfortable to offer to the patient. If I had a 2B with a large volume, it would be the option to offer PARP inhibitor. Now, the big problem is the restriction that we're going to have on authorization on the part of the plan. And unfortunately, we can't justify it because it's not represented in the health plan. Now, the other question is that we know that the PARP inhibitors, there is no evidence that one is better than the other. But the toxicity standard is different, clearly. I have a patient, for example, in stage 3, operated, treated with chemotherapy. We prefer, in that patient, if it has a mutation, BRS1, BRS2, or choose, let's say, the medicine that is available at that time. What would you do? Well, I see with respect to the PARP inhibitors, that conversation directly with the patient is important because we have, in the question of, in the pathology, we have toxicity that are different. I like to let the patient understand the two options and that there is that difference in the pathology, in the administration. And that a NERAPARIB, even though it doesn't give nausea and fatigue, we invent problems, many times with the plaque, that can limit and that we have to hospitalize that patient. So, normally, I participate in the decision, but I don't have a selection before talking to that patient, actually. It is important to remember that NERAPARIB has two doses, higher and lower dose according to weight, and with the base of plaquettes. Obviously, that is in the PRI study. Another question, and in which I have many doubts in my history, in my clinical practice, we know that Bebacizumab, according to the GEOG 218 and Icon 7, does not increase survival, and PFS is maintained in the positive update with 218. But in the Icon 7 it was positive. The question is the following. With these data from PRIMA, Paola and Solo, when should we think about using Bebacizumab? Especially looking at the load, disease and performance status. Well, the first point, in the past, before the results would be in the first line, we were a little more permissive with Bebacizumab, neoadjuvant. Now that we know what to put in the neoadjuvant, we can make a sequence in the treatment, and there is a tendency to prescribe much less as a neoadjuvant. In general, if we had to say, well, the clinical response is very important, let's say, to platinum. I'm going to start by not giving Bebacizumab, and the clinical response will guide me the indication. PRIMA patients, for example, are super responsive. Now, if I already started, I had a very large load of disease, and I needed to give Bebacizumab as a neoadjuvant, the idea is to add or not a PARP inhibitor. Now, if I did not start, if I'm just going to put a PARP inhibitor, I also have a tendency to give only in the case of neraparib. Because in the same way, as we see an effect in the mutated PBCC, I really think that HRD has a biological justification so that I can have a synergy effect. So there is a tendency to use Bebacizumab later. Yes, I agree with you. The use is gradually decreasing with the PARP inhibitors. We have two questions. I'm going to ask you, Doctor, to answer Dr. Vicuna in the chat, a question she has about pathological anatomy, and also Dr. Saber Akatu, what would be the type of ovarian cancer that responds more to Bebacizumab? She would like to know if it is serous, endometriotic. Yes, please, you can answer in the chat for these two colleagues who are also congratulating your presentation. A quick answer. To this day, we are looking for my markers with Bebacizumab. The day we find it, it will be wonderful. I agree. Yes, I agree with you. Thank you very much, Michelle. You are a person I love very much and I congratulate you on your excellent presentation. We are going to introduce the next speaker, Dr. Georgia Sintra. A very important topic with relevant updates in the last two years, which is the role of resuscitation surgery. Welcome, Georgia. Ah, we have a break now. Sorry, guys. We have a 5-minute break and we'll be right back. Okay, we're coming back. This webinar is going so well that I almost forgot the break for the interpreters who need those 5 minutes. So I apologize to them. Now we're back. We have two more talks and the first one is by Dr. Georgia Sindra, who is a surgeon in Brazil. She's part of the EVA group, the gynecological oncology group in Brazil, and she's going to talk about a very, very important topic, a very important team. So, Georgia, thank you so much for being here. After your talk, you're going to speak in Portuguese. I hope that their lecture is great, and I'm sure it's going to be. And I'm sure it's going to go very well. Thank you so much for your participation. Hello, I'm Georgia Sindra. I'd like to thank the IGCS organizing committee for the invitation. I'm going to talk about secondary site reduction in ovarian cancer. I don't have any conflicts of interest. In the context of primary treatment, no one has any doubts about the great importance of surgery in treatment and in the possibilities of treating patients with ovarian cancer. But we know that despite the appropriate treatment, most of these patients will relapse. And it's a controversy in the context of recurrence, if surgery would continue to have an impact. Several observational studies on this topic were published. And in such a way that it was possible to do a meta-analysis in 2009, in which the conclusion was that among the patients subjected to surgery for recurrent ovarian cancer, complete site reduction is associated independently with global survival. And for this group of patients selected, the surgical goal must be the resection of the entire macroscopic disease, that is, complete site reduction. This same meta-analysis showed us that the rate of complete site reduction is very heterogeneous among the studies, and that the majority is below 60%, showing us that there is a lack of selection criteria for these patients, to know, in fact, in which of them we managed to achieve complete site reduction. Finally, prospective studies began to come, where two were completed in advance due to the lack of recruitment. We have two favoring surgery, which is Desktop 3 and SOC 1, and for now we only have a free-of-progression survival publication, and one that has not shown any benefit of surgery, which is ROR 2.13. We will talk about each of these. We will start by talking about Desktop studies, which are a series of studies that were taught and developed, as should be the whole study, starting with a retrospective analysis of recurrent ovarian cancer cases, operated in order to generate hypotheses, and the hypotheses generated were that surgery would have an impact, but when complete site reduction had been achieved, and that they would have a subgroup of patients, it would be possible to anticipate this possibility of complete site reduction, which were patients who met some of the criteria we will talk about. And then came Desktop 2, which served to validate this score, which anticipates the possibilities of complete site reduction. And finally, the randomized prospective, which is Desktop 3, which served to evaluate whether or not there were benefits of surgery in these patients. So Desktop 1, the first of this line of studies, was a retrospective analysis of several German and Swiss centers of these recurrent ovarian cancer patients subjected to surgery. And it is important to know which patients were analyzed, why they were excluded, non-epithelial histology, borderline tumors, and patients who were subjected to interval neo-adjuvant chemotherapy. So they were only analyzed patients who performed primary site reduction. And what did this study find? This study found that only patients in which all macroscopic disease was removed, that is, in which complete site reduction was performed, had a survival rate, leaving the disease up to a centimeter or more than that, nothing has changed, the survival curve is identical, showing, then, the hypothesis of what should be achieved, complete site reduction with the reception of all macroscopic disease. And the other hypothesis that was generated is that some patients who met specific criteria were more likely to achieve complete site reduction. These criteria are status 0 performance, sites with less than 500 milliliters, and complete site reduction in the first surgery. These three variables together were called the AGO score. And then the second study came up, which is DESKTOP2, which was used to evaluate this finding. If this AGO score was really able to predict the patients to whom it would be possible to achieve complete site reduction, which was seen in DESKTOP2, it was found that 51% of patients met these AGO score criteria and that it was possible to achieve complete site reduction in 76% of these patients. Therefore, concluding that it is a criterion, an adequate score to anticipate which patients can really benefit from surgery because complete site reduction can be achieved, we finally reached DESKTOP3, in which an electrified prospective analysis was carried out with 408 patients in the first platinum-sensitive recurrence and who met and had the positive AGO score. These patients were allocated to surgery, whose goal was complete site reduction without residual disease, followed by chemotherapy, or immediate start of chemotherapy. In this study, 80 centers from 12 different countries participated, and reference centers with quality criteria for treating ovarian cancer. These are the same centers that participated in the LION study. To consider an adequate center, it was necessary for this center to have quality research criteria, clinical history information, and obviously surgical quality. This was analyzed by the surgical volume of this center and by which surgeries were performed within site reduction. So it was large volume centers with trained surgeons, the same from the LION study. What did the survival curves show? They showed that there was a benefit from surgery, both free from progression and global survival. But when we do the analysis of patients who were subjected to complete site reduction, compared to those who were left with residual disease, what was verified is that for patients who had residual disease, in fact, a damage was caused during surgery, because survival was less than in the control group, which was chemotherapy alone. In patients where complete site reduction was achieved, a gain of almost 16 months arose, compared to patients in which surgery was not performed. The conclusion of the study is that patients with recurrent ovarian cancer, platinum sensitive, subjected to surgery, had a gain of global survival and free from progression, compared to patients who were only subjected to chemotherapy. However, this gain occurred only in patients in which complete site reduction was achieved, without residual disease, thus demonstrating the importance, reinforcing the importance of the correct selection of patients and the center in which these patients will be operated. To decide to perform surgery, you have to achieve complete site reduction, otherwise we will only harm this patient. The SOC1 study had a methodology, a design very similar to Desktop 3, but the inclusion criterion is the iModel, associated with the PET-CT. The iModel includes some criteria similar to the Agile Score, but it also includes the FIGO study, the CA-125, and the free progression interval up to recurrence. This is associated with PET-CT, so this is how patients were selected for this study. What we have for publication is for free progression survival, and there is a benefit in performing surgery on these patients for free progression survival. And finally, then, we have the GOR213 study, which has not shown benefits for surgery, but the design of this study was different from other studies. They were the same patients with recurrent ovarian cancer, platelet-sensitive. However, for them to be included, it was enough for the surgeon to consider that the disease was resectable. There were no clear objective criteria, as in Desktop 3 and SOC1. So it's a study that is not purely surgical. It is surgical and also with drug analysis. The number one goal, in fact, was to verify whether to add bevacizumab to chemotherapy, and then, as maintenance, it would bring survival benefits. And goal number two would be if surgery would also bring some benefit to these patients. The number of patients included was also high. There were more than 400 patients, and half of these patients were Asian. The progression-free survival curve was very similar between the group that was subjected to surgery and the group that was not subjected to surgery, and global survival, thus showing a benefit trend for the group that was not subjected to surgery, although this is not statistically significant. Here is a table that shows the main characteristics of the three studies to help us understand the reason for this difference in the results. So, as has already been said, the inclusion criterion of Desktop 3, the patients had to have a positive IGO score. In SOC1, they had to have an I-model with PET-CT, and in GOR-213, it was enough for the surgeon to consider that patient viable for cytoreduction, and this is reflected in the complete reception rate, which in GOR-213 was lower, 67%, compared to almost 77% in SOC1, and 74% in Desktop 3. Another very important difference is the number of patients receiving the B-vaccine. In Desktop 3, it was 23%, and in GOR-213, 84%. We also see an important difference in the survival rate and the results of the study according to the group. The group that had the best survival rate was GOR-213, which was not subjected to surgery for 64 months. The group with the worst result was Desktop 3, which was not subjected to surgery with a difference of almost 19 months with the same type of patients not subjected to surgery, however, with a difference in GOR-213 with the addition of B-vacizumab. So, B-vacizumab could be the explanation for this difference in the results. In the appendices of the articles of the supplementary material, there are graphs of survival according to the use of B-vacizumab. In the study, GOR-213 shows that the curves are very similar in the patients who used B-vacizumab, but in the patients who did not use B-vacizumab, there is a very important difference between the patients who were subjected only to chemotherapy and those who were subjected to surgery, but the unexpected result is that the best survival curve in GOR-213 was in the patients who were subjected to chemotherapy and did not receive B-vacizumab with an average survival of 67 months and this has not been observed in the Desktop 3 study, in which the appendices have the survival curve and that surgery continues to show a benefit in relation to the realization of chemotherapy alone. So, with these very different results and even with the unexpected result of the group without B-vacizumab of GOR-213, I apologize, I ran out of audio. Well, some considerations If you are convinced that secondary cytoreduction brings benefits, to ask what our behavior would be with patients who were subjected to neoadjuvant chemotherapy after the interval cytoreduction and with patients who were badly altered at first because they were in centers that are not reference centers and were evaluated in the Desktop 1 study. Therefore, we cannot use a Joe score in these patients. So, we do not have the answer about what to do and which are the candidates in this context. At least in Brazil, it is the majority of patients. If you are convinced that there is no role for surgery when B-vacizumab is available, what explanation can we give for the survival of patients in the non-surgical group that has not received the drug in GOR-213, showing again this graph, since it is a double study, which is not pure surgical. We can not separate what is in fact the impact of the drug and what is the impact of surgery and draw conclusions about it. In this way, there are still many doubts, so what are the conclusions that we can actually get? There are two studies with mature and discordant results, however they have different designs, different inclusion criteria, and since the pure surgical study, which is the Desktop 3 study, favored surgery. So the trend of the scientific community is that the results of the Desktop 3 study in relation to GOR-213, but what is consensual, in fact, is that R2 surgery in a recurrence scenario is deleterious. The proper selection of these patients and surgery being performed in a reference center is important, fundamental. It is important to emphasize that although with strict criteria, a quarter of these patients, 25% of them, will not be able to reach full cytoreduction. And this should be evaluated along with the patient and informed with the risk of surgery. I apologize, there is an open audio. I apologize, there is someone with an open audio and the translation interferes. Well, I am here available to answer your questions. Thank you very much. Very good, says Fernando. Georgia, excellent presentation. And now, says Dr. Fernando, that we will move on to the survey. I will read in English. Desktop 3 favors surgery, GOG 2.13, systemic therapy, and SOC 1, SOC, is pain-in-survival analysis. Number 2, good PS, complete initial surgery, ascites less than 500 milliliters and are some of the AGO criteria. Number 3, surgery is better indicated when systemic therapy fails for recurrent epithelial variant cancer. And number 4, a complete cytoreductive surgery is a significant prognostic factor for epithelial variant recurrence. Well, first of all, thank you very much for this opportunity, it is an honor to be participating. I want to thank you for the opportunity. It is an honor to be participating in this event with such important people in the world of research and dedication to patients with ovarian cancer. I will give a few minutes for everyone to respond to the survey. Excellent presentation, says Dr. Fernando. I think the questions are coming in. I have some questions as well. Questions that will help me to think of a way of handling, of treatment for these patients. Let's wait a few more seconds. I think the alternative that people are incorrect with is C. Do you want to comment on something, Dr. Giorgi, before we start with the questions? Of course. I would like to respond that all these works, as well as the doubt that we have, as well as what we are dedicated to, is to understand if the surgery of the cytoreduction has a role in the sensitive platelet patients. In platinum-resistant patients, as Dr. Cristina commented in her class, tumor biology is not favorable. And the therapeutic options are still much more limited. And considering all the morbidities that we know are related to ovarian cancer surgery, it is not, in principle, a patient candidate. There are reports, several series of strict cases. The last one was in 2015, trying to see if there was a benefit of the secondary cytoreduction for platinum-resistant patients. But we still don't have that answer. And in principle, this answer is no, to dedicate surgery, a surgery that, with the relevant morbidity in patients, where we have a better option of healing, a better perspective of disease control, which are platinum-sensitive. In this space of the platinum-sensitive, we know that one of the points that is still open is the role of chemotherapy with hyperthermia. We have two studies in the first line, a Korean study that was negative, a positive Dutch study where patients have been operated on in intervals, or hyperthermia chemotherapy. That is, the patients did chemo, cytoreduction in intervals, with or without hyperthermia. In this alleotarization, all the statuses have been controversial. We must consider, in some scenario, chemotherapy with hyperthermia with recurrent platinum. And I'm going to address two different spaces, platinum-sensitive and platinum-resistant as well. I would like you to talk a little bit about these two groups of patients, the role of chemotherapy with hyperthermia. HIPEC data with the recurrence scenario. We have a Zidanovit study that was published last year with the memory team, and at first there was no benefit compared to patients who have not received HIPEC. HIPEC in ovarian cancer is very controversial. The Dutch study on cytoreduction in intervals, including the DS team that published Desktop 3, understand that everything that was involved in this study does not allow for a positive response from HIPEC to indicate this treatment. And, in fact, there is a discussion, precisely in platinum-resistant patients, that the use of HIPEC could improve the response. And then, in these patients, to suddenly have a selection of patients for this treatment. In the literature, we will not have an answer. They are only studies that were not published. They are stories, a series of cases. But, in principle, in the recurrence scenario, what we have from the negative study is from the memory, which was published last year, but without an adequate indication based on the literature. And a practical question for you. Some cases that we have seen, the disease is platinum-sensitive, but it may present itself with some points of carcinoma. And, generally, that is, my interpretation is that the great benefit of surgery comes for people who respond to chemotherapy. That is, here the question is that surgery alone precedes chemotherapy. It may not be. And, suddenly, the group that benefits the most would be the group that is still sensitive. If you operate on the patient and do chemo later, we cannot calculate whether the patient will respond or not. Because here, in the case of complete cytoreduction, you have cured the disease. My question is, in some cases of ours, the option is to do two or three cycles before the treatment and operate later, and follow chemotherapy as if it were a cytoreduction of interval rescue. Of course, none of the three studies did that. Only three studies operated and treated later. How do you, doctor, see this strategy? It is a strategy that has not been studied in these main studies. I believe that, as any, it is one of the main advantages of neoadjuvance, to evaluate what type of tumor we are dealing with, the sensitivity to the drug, and the question of when there is the discussion of the reason why surgery would be good in these recurrent patients. One of the discussions is that by reducing the volume of the disease and reducing it to a microscopic level, which is our goal, to remove all macroscopic disease, if that would have any impact. And micro-tumoral environment and even immunological response is one of the discussions of the reason why you do cytoreduction if this would improve the survival of these patients. By exposing, and one of the discussions of neoadjuvance in the primary scenario, is if these patients, we will be increasing in them the opportunity, the possibility of a possible resistance to platinum. There is no answer, but it is one of the discussions of neoadjuvance with primary cytoreduction, if neoadjuvance could promote a decrease to become platinum resistant. I believe that this strategy is very valuable, valid, when in the evaluation of the patient, we do not anticipate that we will remove all the disease or achieve a complete cytoreduction. In a scenario that you anticipate that will achieve the complete cytoreduction, and then we have the ideal score for the patients that had complete cytoreduction in the primary scenario, a non-neoadjuvance and a good performance, we can offer. In the patients in which this is not possible, we will not achieve the complete cytoreduction. Does this strategy of a new neoadjuvance make sense, then, in these patients? Dr. Gheorghe, I have other questions, and I ask you to answer the chat later. I want to thank you, you are very important in our country, in the surgical area. The class was fantastic, and now we are moving on to the last class. Unfortunately, the last one, because it is a fantastic seminar. In the last class, we will talk about the BRCA test and other biomarkers in advanced ovarian cancer, with Carlos Eduardo Andrade. Mr. Carlos, welcome. It is a pleasure to have you in this third IGCS webinar. It is a pleasure to be here in this excellent IGCS initiative for all gynecologists and oncologists around the world. I will talk about the role of the BRCA currently in our treatment of advanced ovarian cancer. I have no conflicts of interest for this specific presentation, and we will talk about the incidence, the difference between the BRCA mutation, the role of this BRCA in the decision of the treatment of ovarian cancer, both in the initial diagnosis and the recurrence, both from the point of view of systemic treatment. Initially, the decision before about the role of surgery and chemotherapy in the treatment of ovarian cancer was much simpler. We had to choose between primary site reduction and neoadjuvant chemotherapy, and the patient was subsequently subjected to chemotherapy based on platen. In the recurrence, the only decision we had was whether we did a secondary site reduction or not, and these patients went to chemotherapy based on platen. These decisions were based on clinical questions of the patient and on some models that added imaging tests. Nothing very complex, but medicine has evolved, and we have white therapies based on precision medicine, which uses, for example, patients with genomic stability due to the deficiency of the recommendation pathway. In this group of patients, PARP inhibitors are apparently very efficient drugs to make a white therapy for these patients. The tests to detect the homologous recombination deficiency can be done both in the tumor and in the blood. If done in the tumor, we are only evaluating the germinal mutations as well as the somatic mutations. If we do the blood test, in this case, if we do the leukocytes, the DNA of the leukocytes in this blood, we will only have the detection of the germinal mutations. If we find circulating DNA in a tumor, it could still detect both germinal and somatic mutations, because the germinal mutations are present in all the cells of this patient's body, and the somatic mutations are present in the tumor cells. In the normal cells of this body, there are no such mutations. Regarding the frequency of BRCA mutations, we know that these mutations are quite frequent in ovarian cancer, especially in the serous epithelial cells, and the frequency of these mutations is around 18% of germinal mutations for BRCA, 7% for somatic mutations, other mutations related to repair genes and homologous recombination deficiency, which make up 8%, and 17% we find a homologous recombination deficiency through genomic or functional tests, but we do not find a mutation in these patients. So, the tests to detect homologous recombination deficiency have characteristics that… there is a difference between them. There are tests that will detect many gene mutations that are related to the homologous recombination pathway, and the main gene in this case is BRCA1 and 2. There are tests that will evaluate alterations in the genome that occur due to a deficiency in the homologous recombination pathway. These are the genomic tests. It is as if we found the effect, the mark, the scar that the mutation causes in the genome, and these are the functional tests that look for products that are accumulated or produced from the homologous recombination deficiency. So, in the first class, we will see the cause, we will look for the cause, the second, the effect, and the third will be a real-time test to evaluate if there is a homologous recombination deficiency. However, these tests have problems, a series of problems that interfere with their specificity, that is, in the ability to truly… When I find an alteration in the genomic tests, it often happens, it often doesn't, but it happens that sometimes this test reflects something that happened in the past and that now the homologous recombination deficiency no longer happens. In other situations, we have, for example, the test of loss of sensitivity. How does it happen with a patient when we do the test? We don't detect repair gene mutations, but other cell groups of these patients do have a homologous recombination deficiency. And they would benefit from white therapies for this type of problem. There are also tests that are not validated. So, why discover mutations in BRCA and homologous recombination deficiency? Several studies have already shown the role of the class of PARP inhibitors in this group of patients. In this way, these groups had very important methodological differences. The groups of patients are different, but in general, all these studies, here in the case of patients initially diagnosed with ovarian cancer, showed significant benefits for patients who had BRCA-homologous recombination deficiency with greater progression-free survival in recurrent disease. Also, PARP inhibitors have shown a lot of efficiency in these groups of patients with ovarian cancer, especially in patients who had BRCA or homologous recombination deficiency, showing in this way that there is a significantly greater progression-free survival in patients who use PARP inhibitors. And analyzing these studies, which group of patients had the most benefit from the use of PARP inhibitors, we found that patients with tumor mutations, sorry, somatic or germinal, found in the tumor for BRCA are the patients who benefited the most from the use of PARP inhibitors. Secondly, we would have patients who do not have a BRCA mutation, but have a homologous recombination deficiency or mutations in other genes. These patients also have a significantly higher benefit in the use of PARP inhibitors. In some studies, these patients showed a benefit in the use of PARP inhibitors, and this may be due to some deficiency of the tests in detecting patients that are not actually viable patients that have a homologous recombination deficiency. Or it means that the patients were classified with a homologous recombination deficiency, but did not have this homologous recombination deficiency yet. Already related to the presence of BRCA mutation or homologous recombination deficiency with surgery, we still have few studies. This Italian study is very interesting, with a large number of patients, and it was able to identify that patients who have a BRCA mutation, despite having, in general, the same FIGO status, the same BRCA presence or no BRCA, did not show a significant difference. Patients with a BRCA mutation had a much higher tumor load. Along with that, it is important to realize that in this study, unlike other results that we have, that we presented before, patients who had BRCA gene mutations did not have a free survival of higher progression compared to patients who have BRCA wild-type or without mutations, at least not statistically significant. Wild-type. But when we analyze the subgroup of patients, patients only without BRCA mutations, we can see that for these patients we have interesting information. The realization of primary cytoreduction brought a better free survival of statistically significant progression compared to patients who submitted to neoadjuvance. And in the group of patients who had a BRCA mutation, the survival, despite being numerically superior in patients who performed primary cytoreduction, was not statistically superior to patients who did neoadjuvance chemotherapy. There are also studies about patients in recurrence who presented a BRCA mutation or not. And if we analyze patients who had BRCA mutations, those who performed a secondary cytoreduction had a survival rate of 78% in 5 years. Those patients who did not perform a secondary cytoreduction had a survival rate of 73% in 5 years. This has not been statistically superior to patients who did not have a BRCA mutation. They were wild-type. When they performed a secondary cytoreduction, they had a survival rate of 1 year and 54%. If they did not perform a secondary cytoreduction, the survival rate was 52% in 5 years, and this has been statistically significant. And there is a controversy, a different study, the SOLOWAN study. Do you remember that SOLOWAN evaluated only patients with BRCA mutations? So, we have a group selected from patients with PARP inhibitors, only those patients who have a better response to PARP inhibitors. And if we realize, the patients who have the most benefits are those who have a higher survival rate, in cooperation with patients who did not have residual disease after surgery, the front surgery. We realized that the patients who did OLAPARIB and UPFRONT, is the group that has the best results in terms of free progression survival. It is the group that has not reached the free progression average, which is achieved both in the group that did OLAPARIB, and in the placebo group, they had a worse free progression survival. So, this indication of primary surgery, or if we indicate neoadjuvant for patients with BRCA, there is still a lack of studies as a way for us to decide and select patients who have benefited from one type or another of patients. Another good point that we have of advantages of recognizing patients with ovarian cancer, who have BRCA mutations, is the possibility of doing a follow-up with the family. This is recommended to the entire society with guidelines, and this has a very important implication for the relatives of these patients. If we discover relatives who have a BRCA mutation, based on the case we are dealing with, we will discover women who do not have ovarian cancer yet, but have a risk, if it is BRCA 1, around 39 to 59%. If it is BRCA 2, between 13 and 29%, they have the possibility, as well as the high risk of detecting ovarian cancer throughout life. We can offer these women risk-reduction surgery, remove this cancer before something happens, and for that I need to recognize in my patients who have a BRCA mutation, and from then on I recognize their relatives who have that, I can prevent ovarian cancer from cancer-producing surgeries. So, if I don't try, I can't prevent it, and if I don't prevent it, I'm going to kill these patients in an unnecessary way, and not forget that in addition to BRCA, other genes have indications of risk-reduction surgery that have been found in their relatives, such as HATS, RAD51, both BC and D. As a final message, now in the era of precision medicine, it is very important that we select patients who will truly benefit much more from these new therapies, mainly in a context of resource limitation. It is important that we identify BRCA mutations, homologous recombination deficiency in patients with ovarian cancer, and thus select in a better way patients who will benefit in a better way from PARP inhibitors. Current trials present significant limitations, and there are spaces to develop new trials with lower cost and confidence that still have to be validated. In addition, to recognize patients who have hereditary signs in order to avoid unnecessary deaths among the relatives of these patients. That's all, thank you very much. I am here to discuss and answer your questions. Carlos, thank you very much. You are wearing the Brazilian shirt. Carlos, thank you very much. You are wearing the Brazilian shirt, right? Yes, I took the opportunity to wear it here because it is very cold. Excellent presentation. Well, here we have a question from multiple choice. What would be the incorrect alternative to the following question about genetic tests in patients with ovarian cancer? Only women. Here we have the questions. Here we have the pathogenic variations. We see here only the diagnostic women, the women who do not have a mutation variant. Then the genetic evaluations. Number four is the first or relatives of the first or second line, the patients who have ovarian cancer with a known pathogenic cancer susceptibility. So, let's see if we have to offer a specific genetic risk assessment. Very good. When people respond, in the meantime, I would like to thank you for the invitation. Thank you very much and congratulate you for this wonderful event. These three days of presentations were excellent, excellent. It is an honor to be here. This is a very special moment in my career and thank you very much for the invitation. It is really very important that you are here with us on this last day of this webinar. And thank you very much for being here. Well, let's save a few minutes. Well, I think we already have the option. Very good. It would be the option. Would you like to make a comment quickly, Carlos? Actually, two comments about this. I agree with the response of the majority. That's it, actually. Not only is it serous, but there is also a benefit when non-mucinous epithelial and light cells that have to be differentiated, you have to do those tests for BRCA. The second point is the sequence for that test, which is very important. That is, a blood test is going to be done in the tumor. The advantage of one like another, well, when we do it in blood, the germinal test is really discovered, the germinal test. So you can orient a way, in a genetic way, all the relatives of that patient. So when it is negative, you have a tumor and you do a test to evaluate if there is not, let's say, the somatic, but the germinal of the BRCA, unlike other genes that are related to the tumor. If this tumor is negative, we know that it does not have germinal, but if it is positive, you have to do a blood test again, and there you can do both tests. Actually, you have to start doing it again in blood to see if it is germinal or somatic, and if it is in blood, it would be germinal, and in that case, the whole family is oriented. That is the process that should be obtained Many times we have to do a blood test, and tumor, and take, and blood, in different situations, obviously. Excellent. A question, Carlos. We have MyChoice, it is a test used in Paola, Villa, and Prima, right? Do you think that other tests, for example, LOH or Foundation One, which is one of the markers, that MyChoice uses, apart from Transition Lack Scale, and Allergic Telomere, only LOH, is it really enough to discriminate between HIV present or absent, or should we really use MyChoice? Excellent question. Your questions are always excellent, Fernando. Thank you very much. We have problems, the tests were studied in clinical texts, MyChoice was the most studied, and it is the most used and most recommended, to be used, because it has a validity of the tissue used in clinical trials with respect to PARP inhibitors, at least it was the most used, in these clinical studies, but we have to recognize also the limitations, I have already commented this with several people, that it may be that that SIG3 that was left, the homologous combination was reversed, and you really do not see an adequate specificity, and a question of sensitivity also, which is very important in this test, which is not so adequate. Now, it is important to verify more the sensitivity, to really be able to detect more patients, because despite being the best point of research, the stability is very important, and also brings a greater sensitivity to the test. Foundation, my impression is that it is more complete, and should be superior, but there are still missing more tests, that are much more real, and that better separate these patients, that there is going to be a separation of these patients. It is something subjective, but they are being done, which are functional tests, to really understand the mutations. They are being studied, but they have not yet been validated in clinical studies, to be able to say if they are better to discriminate in a patient with homologous discrimination. Well, excellent, thank you very much. Thank you very much, Carlos, for your participation. I would like first to thank all the speakers. Thank you, Audrey Tesonoda, also for organizing this incredible program that we have had during these three series. I would also like to thank the EVA group, which is the Brazilian group of inecological tumors, who have sponsored this talk, and all of you who attended our meeting this Saturday. I know that we are going to record these presentations, and they will be available on our portal next week. But no less important, we as a group are participating, not only in the country, but in Latin America and in other developing countries, with many academic initiatives. So, if you are interested in any of these educational initiatives that we have, please send us an email to be able to collaborate a little more and give you more data, and also talk about consensus in many developing countries in Latin America, countries in Africa, the Middle East, Asia, and in some parts of Europe as well. So, my email is maluf, M-A-L-U-F, and then another F, at uol.org. So, please send me an email, and I hope that we can do wonderful things together, and I hope that we can help other developing countries, which, as we all know, need a lot of collaboration and a lot of integration. Again, thank you very much to everyone for the great support. I hope that you have a wonderful Saturday, and Sunday, a good weekend, so that you can rest and be healthy. Thank you very much again. I will try to answer all the questions that I have seen here in the chat, so that I can answer them. Bye-bye. Thank you. Thank you all very much. Thank you, Renee and Audra. Thank you for the wonderful work of organizing this webinar, and very grateful to be able to participate with you in this. Bye to you all. See you. Bye.

genetic testing

ovarian cancer

treatment decisions

BRCA mutations

prevalence

guiding treatment choices

homologous recombination deficiency

detecting mutations

benefits

identifying mutations

hereditary factors

family members

implications

ovarian cancer patients