I'm Fernando Maluf, I'm an Oncologist in Portuguese Beneficence in Brazil and I'm also the President of the Brazilian Oncology and Gynecology Group. It's a pleasure to be here with all of you at this IGCS event. Next slide. So, today's webinar is being provided in English, Portuguese and Spanish. And you can find all the instructors in the chat to listen to the interpretation. We have the Spanish information, Portuguese, English. Please select the interpretation icon and you can choose the interpretation of your preference. You can also change the original audio, if you prefer. If you have any questions about the interpretation, please let us know at IGCS. We will send you all the data. We have a very productive program today, very interesting. We start with Dr. Cristina Fotoporo from the United Kingdom. She will talk about clinical selection for surgery in epithelial ovarian cancer. Then we will have the participation of Dr. Giovanni Scambia from Italy, where he will talk about laparoscopic selection for surgery in ovarian cancer. Then we have three members of the Brazilian IGCS, Michele Samora from Brazil, who will talk about the incorporation of PARP in our practice. Then we have Dr. Georgia Sintra on secondary cytoreduction in ovarian cancer. And the last lecture will be by Dr. Carlos Eduardo Andrade from Brazil on the role of gynecology and oncology in BRCA trials. So, welcome everybody. You have the recording available in case you need it. Please send all your questions in the chat. The speakers are the ones who will be able to speak. Please, you must have the microphones off. Those who are not doing any presentation. Also supported by EVA, the Brazilian Group of Gynecological Tumors. So, without further ado, I would like to invite Dr. Cristina for our first lecture, which is very, very interesting. This is the last webinar of this series that we started a few weeks ago. Cristina, thank you very much for being with us. Hello, I am Cristina Fotopolo from the London College of Surgeons. It is a pleasure to be here with you to discuss the updates in gynecology, oncology. Thank you to the IGC, my friend, dear colleague, René Pareja, for allowing me to be part of this event. Let's discuss the clinical selection for ovarian epithelial cancer surgery. We all know that in ovarian cancer there is a surgical paradigm that the more we remove, the better the patients will have. Patients without tumors will have a significantly better survival, both in terms of progression and global survival. This does not change in the first presentation, in the first recidivism, in the second recidivism, and in the third. It is consistent in all studies that we, as a community of gynecology and oncology, every year we have implemented and we have done an analysis of the enormous survival benefit between patients operated with and without tumors, giving us a clear sign that we need to make an effort to better operate those patients. In recent years, we have experienced a massive and constant expansion of the limitations of what we thought was viable in the past, compared to today and the future. In the past, we thought that a pelvic recession, with testosterone and spectrometry, was very radical. All of this is part of the surgical routine today, and we have expanded our limits to operate on the thorax, remove parathyroid lymph nodes, do mediastinoscopies, remove lymph nodes, and routinely open the anterior mesentery, the celiac trunk, the diaphragmatic pillar, to remove all these injuries. It is also part of the routine today to do multiple intestinal recessions with grampians, without stomach, so that the patient does not have an altered quality of life. And the same thing happens with the true metastasis, such as the hepatic metastasis, where patients are now being fully operated. So we are experiencing a change in what these patients do and how we can move forward. To be able to talk to patients about what can be done and what will probably be necessary to do, when you have a patient with a first cancer diagnosis that says, well, I now have an advanced variant case. What can we do? So you talk about all the options that include primary cytoreduction versus interval cytoreduction. In the past, we used to rely on experience and retrospective studies. Now we have more and more high-quality phase 3 surgical prospective studies that objectively show us the data within a randomized prospective study and the qualified evidence so that we can talk to patients. Leon Lyon is a phase 3 surgical study with patients fully operated in advanced disease. What the study showed is what we need to do in advanced disease of ovarian cancer. This is a table that I personally use a lot in my clinical practice to discuss with patients what needs to be done. Approximately 55% of patients will need some type of intestinal section and 20% will need a splenectomy. Approximately 10% will need a stomach formation, but in fact patients concerned about having a stomach are less than 10%. And 60% of patients will need about a diaphragmatic recession. These are the most common procedures that need to be done in these patients. So, in order to put all that into a more objective and into a more prospective framework, and we are surgeons, not alchemists, not just nurses and believers, but we now have objective evidence that we need to follow together with systemic treatment in the European Society of Gynecology and Oncology. We have identified and developed the Programme since 2016 of Quality Guarantee in Advanced Surgery of Ovarian Cancer. These are objective measures on what is necessary and what is considered as currently qualified. What is right and necessary to be able to say, I did a right surgery in these patients and what can we do? In these patients, some patients selected, we defined in those quality guarantee criteria, some criteria of inoperability in advanced ovarian cancer that help us as a clinic to select those patients that are not suitable for a primary reduction and we need to direct them to primary chemotherapy or neoadjuvant. We saw a deep infiltration of PUSA, a very large part of the small intestine would lead to a short intestine syndrome needing to be removed. Diffuse carcinosis of the intestine parts, diffuse involvement in stomach infiltration, ovarian cancer, having to remove the entire stomach to do an esophagostomy, we would never go so far. Disease in the head or in the middle of the pancreas, we are not talking about pancreatic disease, we are really talking about the head and the middle of the pancreas so that a pancreatomy would need to be done by diabetes. Involvement of the celiac trunk, hepatic arteries, left gastric arteries again, we are not talking about the solitary lymph of the celiac trunk. These are easily removable. We are talking about massive infiltration resulting in cholestasis, resulting in a frozen mesenteric. Talking now about hepatic metastasis of the central parenchyma or multi-segmental, patients look for us mainly with diffuse hepatic metastasis. We could not do a single segmentectomy on these patients. They should not and cannot be selected for a primary surgery. Patients with extrabdominal disease, such as lymph nodes, mediastinal, metastasis and pulmonary. I had a patient who could not even wear a necklace because he had large superclavicular lymph nodes. He could not even wear a proper shirt. These patients are not suitable for surgery. And in rare cases of cerebral metastasis, which we actually see less often. So, we have some selection criteria. The question is how we can implement in the surgical practice and in the daily practice what we, as surgeons, expect from the preoperative image. It is not a discussion that multiple hepatic metastasis are easily seen even in ultrasound. The question is how we can detect safely a peritoneal carcinogen disease that reaches the non-resection limit. How can we detect it? The same with lymph nodes and mesenteric retractions. So, what is the current status quo of the preoperative image? We have some tools. We have tomography, ultrasonography, magnetic resonance and PET scan. All available. The conventional tomography is part of the algorithm in the preoperative image. But the problem with tomography is that it is not very precise. In many studies and also in Imperial College, we study the precision of preoperative tomography in key areas of resection. What we have seen is that if we take these key areas of resection, such as diaphragm, spleen, thick intestinal carcinogen, thin and straight intestinal carcinogen, hepatic system, lymph nodes, mesenteric retractions, what we are seeing is that it shows a very high sensitivity and a very low predictive value in these areas of interest. In fact, it is a very low predictive value. So, possibly, we can show a clean mesentery, right? In fact, you find carcinogens everywhere. So, it is very difficult to fully predict the operability with conventional tomography. We see here some pictures that I like to share. You've probably seen them in other lectures, but they are very good and representative images of what I want to talk about. We see here a carcinogen all over the mesentery. But we see how this part is completely covered. We can open it, open it completely and lose a total view of the mesentery on both sides. But you have to be very careful not to work always tangentially and not injure the mesenteric vessels because it can have an intestinal ischemia. However, it is very complicated with the preparatory images to differentiate between these images that I showed you and these here. We see here an extensive carcinogen, which again in the tomography is classified as a carcinogen, but they are completely dry images. So, the question is, what can we do to differentiate between them? I'm not going to talk about laparoscopy because Giovanni Scambia will talk about that later. So, in order to be more objective and to be able to classify the images and see how we can have specific algorithms, we have now adopted the new guidelines of the ESGO-ESG Consensus on Preparatory Evaluation. This is a work that we did together with Dick Timmerman. It's his idea. I only had the pleasure and the honor of helping. Giovanni Scambia was part of the team. He was born in the United Kingdom and many important opinion leaders, Daniela, Denis, Ignace, Philippe Maurice, among others. We met to think about how imaging could help us select patients for surgery. What we saw is that, of course, the tumor markers are important. The magnetic resonance with the inclusion of functional sequences is important. It would not be the first option, but it can be used as a second line to differentiate between benign, malignant, and limitrophic masses after the ultrasound. A PET scan can detect between the origin of the ovarian cancer and the second metastatic tumors, but it is never the first option. And especially when we talk about these low-degree diseases, limitrophic diseases, it is very difficult to use and totally depend on them. What is very important is that the image alone cannot or should not detect, in a reliable way, the entire extension of the perineal carcinoma, the thin intestine, or the mesentery. It was very important for us to understand all this, that there is no single modality, that can say that this is inoperable in terms of mesenteric disease or carcinoma. It was also very important to know that the image itself should not be used to make the surgical decision in terms of the prediction of the peritoneal tumor. When we have a metastasis in the lung, the servo, this is another story, but in terms of peritoneal disease, we should not rely on imaging only. Let's go a little further. We studied the new aspect of circulating DNA, which is still not part of the routine practice, but shows promising results, and I think it will be implemented in the algorithms in the future. Very well. Leaving aside conventional tomographies, where we clearly show its limitations, now we have magnetic resonance with diffusion rate in much more advanced images than we had in the past. The question now is how we can, especially in restrictive systems, prove its value and really use it to be able to say that it is much better than a conventional image. One of the attempts for this to happen is the MROC study, a study carried out in the United Kingdom from the Imperial College. It is a study by Andrea Hocan and approved by the UNAI. Therefore, it is a study funded by the government, where we try to compare the validity and the probability prediction between conventional tomography and magnetic resonance with diffusion rate. What we try to do is to see not only the probability, but also the time in the theater, economic health analysis, and visits to accompany patients, blood transfusion, needs of the ICU, need for other disciplines in relation to histology, stage. So we took the study much further than just operability to be able to say if it is what we need. These are the criteria that we need from the point of view of the image to select patients with safety and precision. And all this will happen in regulated, multidisciplinary teams and tumor councils in the United Kingdom, as you know very well. Therefore, it is not just a decision of the study team. Everything is done with this team. It is done with maps, with the entire group, specialists, with the tumor council, where many specialists participate on the patient's journey according to how they were predicted from the image. It will be a very interesting study and I hope we can have results in the coming years. Okay, so we have now predicted operability from an anatomical perspective. The question is, is the patient operable? It is not just a disease. We cannot forget that we are not operating a disease, we are operating a patient. So we need the total patient, because we need this patient to be operable. We need to have a correlation of operability in relation to the age and status of the patient's performance. We know from many studies that all patients will benefit from all cytoreduction surgeries. However, we also know that there is disproportionately high surgical mortality in patients with multiple comorbidities in the advanced stage of the disease. We have here the data from the German AGO that shows that patients over the age of 75 and with advanced comorbidities will have a mortality rate of 3 months of almost 30% due to primary cytoreduction and a mortality rate of 6 months of almost 40%. So almost half of the patients will die after six months, which is detrimental. Therefore, in order to have a very specific, precise and reliable data of who would belong to this very small category, the AGO did a project study, which is part of the famous Trust study, and we hope that by the end of the year we will have an algorithm consisting of simple things, such as sinusitis, pleural sputum, albumin, patient's age, performance status, which will give us a specific algorithm that would be associated with a higher mortality, comorbidity of the surgery. And then it will give us, let's say, a recipe of who we should operate on or not. So these data will arrive shortly and will certainly help us even more. In the last part of my talk, I would like to talk about the big elephant in the room, which is tumor biology. When we select patients, we cannot ignore tumor biology. There will be patients who will have a more unfavorable tumor biology in comparison to others, which in fact should not be selected for conventional treatment as conventional surgery or conventional chemotherapy. So the question is how we select. We don't have anything at the moment. And I would like to show you some data, in addition to the conventional image we developed at Imperial College, and similar attempts were made in many countries. This is the new aspect of radiomics. I'm sure you've heard of it. Radiomics is an effort where, from conventional tomographies, we have segmentation of conventional tomography, which is happening in very complicated algorithms, very complex, in programs where there will be a factor or a vector. We call it the Imperial Radiomic Prognostic Vector, which will predict not the operability, but the outcome and survival. So these are patients operated free of tumor with high RPV versus low RBPV, according to a radiomic analysis and segmentation of the conventional image. And we saw that patients with high RPV have an average global survival of less than two years, in opposition to more than five years in the group of low RPV, all patients operated free of tumor, all of them. This was validated in our set of data from Imperial, from TCGI, and what we saw in this group is that we were unable to validate the overall survival, but we were able to validate PFS. And we saw that patients operated free of tumor with low RPV had a significantly higher PFS compared to patients with high RPV. So a very clear sign, regardless of the surgical effort, regardless of the disease, is that in the future it will also help us to select patients. For example, we could, in a Phase III study, select patients with low RPV that should be operated and with high RPV that should only be used for other techniques. And when we published it for the first time in 2019 in London, it was even published in an online e-mail that is not of high quality, but it said that artificial intelligence could predict the chance of survival for patients with liver cancer and help clinically select patients for surgery. So we made a lot of advances in liver cancer, how to select and how to predict not only the operability, but also the survival of our patients with liver cancer. The key is still training, experience and infrastructure. But we, unfortunately, as gynecologists and oncologists, often fail to influence in terms of infrastructure. We need the support of the ICU, we need blood banks, we need availability of nursing beds, we need time for theater. And this does not happen in all countries. We can have it in some very high-income countries, but not in all countries. And the fact that I need five hours to do a cytoreduction, and then a bed and blood, I have it. And it's okay, but it's not always available. So, many times, what we try to do is to direct our practice to other beliefs. Patients are very important. We have seen this a lot during the pandemic, even in countries like the United Kingdom, which are highly civilized and rich countries. We had to stop a primary cytoreduction for a few months in many oncological cancer centers in the United Kingdom. Therefore, the infrastructure and support of this infrastructure is very, very important. Finally, when we talk about selecting patients, it's not just a mesenteric nodule or peritoneal carcinoma that is operable. It's much more than that. It's about selecting the care package and all the patient profile that needs to be evaluated, how we select the patients, age, performance status, the patients' wishes in relation to all of this, all of this with the load of the disease. Of course, all of this is adapted to the infrastructure environment. Thank you very much, and I will be very happy to answer your questions. Hello, Dr. Cristina, very nice talk, excellent presentation, thank you very much. Well, I'm not an oncologist, but I understood everything, everything is perfect, I'm happy. Let's answer a poll about Dr. Cristina's presentation. These are the key factors to predict a complete cytoreductive surgery. Choose the wrong option. Here we have all the questions. We have A, B, C and D here on the screen, you can answer the four options. You can choose the one that is the incorrect answer. Only the image can be used safely to make a surgical decision in terms of prediction. Well, there you can read all the options, just choose the wrong option. Somebody says they can't see the English version. Yeah, that's the message, I got it. So, let's see here, you know, our voting. The most voted question, the incorrect one was the last one. Cristina, could you comment briefly on the options we have here? From A to D? Yes, exactly. What I wanted to show in my talk is that when we talk about clinical patient selection, we are talking about patient selection, not selection, for example, of the images. Many times, it strikes me very often that patients with ovarian cancer are not being presented because a radiologist simply saw an option. No, the patient does not even come to surgery until the end of the day. Our role is to take care of patient selection, not only through the image. So, we have many limitations. Many of you who are surgeons, you know that ovarian cancer is complex. And, for example, a tomography shows that it is very advanced, not necessarily, it can be said that it is advanced, and also the opposite. Now, we have many patients that many times we study and are not consistent with the images. There are many things we have done, and I think that in society it is very important that we emphasize the limitations on a single modality. That is, there are several modalities that we need to put together to generate an algorithm, a mixture. That is, what is operable with a patient is not necessarily operable with another patient, with an older patient or a younger patient. So, in fact, the algorithms, we need to depend on that. For example, the markers in the images are not enough. I think we have a question about lymphadenectomy. Could you answer, Fernando? So, the approach regarding lymphadenectomy, with the study of Lyon, it became clear that in the advanced and initial stages there is no therapeutic role of lymphadenectomy. There is no role. However, there is a role in that prognostic and predictive role. So, we need to do an input stage, a staging that does not reach stage 3. We give all the options to the patient. Now, we need to do a complete lymphadenectomy. Another thing, I know that Giovanni Scambia will talk about this, but I think that in the future we will replace in ovarian cancer, with initial stages with sentinel nodules. It is not yet established, but we need to confirm the oncological safety. But we need to generate an assisting treatment. And the second question is about the role of laparoscopy. Laparoscopy definitely has a fundamental role in patients who have a low-volume disease. Be it colorectal or tumor profile, it does not fit. We will give chemotherapy for comorbidities, and we cannot because of something else. To make a diagnosis in ovarian cancer, in fact, those patients who cannot be operated and have a very advanced disease, the percentage is low. I think we cannot expose the patient to get a second treatment, a second laparoscopy, and we cannot do all this in medical centers. Especially now, with the most advanced images we have, we can reduce the need for laparoscopy in patients because we have a much clearer vision in this regard. The TRUST study, for example, with patients from France and Italy, where there is this early diagnosis, we can make the value of laparoscopy in these patients. So, I would like to ask you a question. You talk about the operability, according to the criteria, and the role of the images, and obviously the integration of tumor biology, among other factors that you have already mentioned. According to the amount, the load of the disease, in Brazil we have an experience with PET scans in patients with a recent ovarian cancer diagnosis. In my opinion, to make a detection beyond the pelvic and intra, but we have some patients, we can find specifically in those who have pelvic and abdominal problems, and when they have pulmonary metastasis. What is your opinion about PET scans for those patients who have a high load of disease, when you are making the decision whether it is operable or not? That would be an excellent question to answer. And in ovarian cancer, although we evaluate the patients microscopically, we can not have ... Well, all these patients, after making a complete reduction, we can find all this that you are mentioning, and find microscopically the diseases, which are spread everywhere. This has no value, so let's forget it. Let's assume that we are, for example, we have a tumor, we open the patient, and we see those who are in the blood vessels. We see in the study that although 55% of the patients had a microscopic ganglion disease, apart from this disease, it did not help the patient's survival. This means that, apart from all this, there is no benefit, because there are thousands. So, my answer with respect to PET scans, if there is a nodule, a tumor in the intestine, in the chest, well, I say yes, let's do the PET scans, but to see if we have problems in the ganglions, or if it is cancer, it does not matter, actually. And it should not affect the patient's life, because, in fact, we have seen, especially in the last study, microscopic lesions that really do not have a fundamental role, and the patient has to be treated in a different way. We have many questions here in the chat. We have more than 250 people participating, and it's amazing to have this call. I would like to quickly answer the questions. Lymphedectomy, for example, effectively most patients with ovarian cancer, this is due to the vascular part of the ovaries, where the circulation will pass through the renal vessels. So, the question is, can we remove everything? It would be very good, but we can't do sterectomy in those patients who are free of tumors. This does not work. We have shown that there is nothing positive for survival. Regarding lymphadenectomy, we have three randomized studies, the last one, Lyme, which was three years ago, which shows that there is no systematic process. On the other hand, high risk, therefore, needs to be in the ICU. So, they are increasing the percentages, but we are talking about ovarian cancer. For example, we have some data in some publications. The first was in 2011. The second was a systematic meta-analysis in 2017, which shows that for osteoarthritis, the meta-analysis of stage 1, and this was for an advanced disease. The two articles show a benefit, actually. Now, what would be your opinion on the clear cell? In the Lyons study, we need to make a difference. The Lyons study, for patients with advanced disease, to see whether we give chemotherapy, and what can therapy do. Now, we need to see if we provide chemotherapy, and what would be the chemotherapy, if we have an advanced cancer, to remove those nodules, microscopically involved, but others that are larger, yes. So, patients are more likely to have these, and they need to be operated. But we are not talking about microscopic ganglions. There are many oncologists who say that if you have a clear cell, and you do not respond to chemotherapy, then we simply go into surgery, and if you have these positive ganglions, you need many more options. So, all of this makes a difference. In other words, chemotherapy, but we cannot say that microscopically removing those involved ganglions will be a benefit, no. I do not know if that answers your question. Yes, again, let's look at this disease more and more, and now we treat it as... We need to get into these patients even more, actually. I think we have no more time. Cristina, we have a lot of questions, according to your lecture. What I'm going to do is this. Let's do a translation of the next speaker, and I'm answering the questions in the chat. Thank you very much. And we are in New York. It's a pleasure to be here. Thank you very, very much. Okay, so the next speaker now is Dr. Giovanni Scambia, who will present something very good about laparoscopic surgery. First of all, let me thank the organizing committee for inviting me to discuss with all of you the laparoscopic surgery, in epithelial ovarian cancer, to be able to provide a comprehensive review of laparoscopic selection for surgery in epithelial ovarian cancer. I would like to discuss the different stages, starting with the disease in the first stage, although the laparoscopy in the initial stage of ovarian cancer has been proposed for many years. In the current literature, there is evidence in relation to the oncological state of ovarian cancer in the initial stage, treated with minimally invasive surgery, has been controversial. Despite the impossible survival results of patients treated with laparoscopy, in comparison with a similar group of women treated via laparotomy, a recent review by Cochrane on this topic stated that, until now, there is no evidence of good quality available to quantify the benefit of laparoscopy for the management of the previous stage of these patients. The main concern on this subject is the association between laparoscopic surgery and intraoperative spilling of cancer cells, which can, therefore, negatively affect the patient's prognosis. A large retrospective study, recently carried out, analyzed more than 8,000 women with stage 1 epithelial ovarian cancer. And in this court of patients, the trends that occurred in minimally invasive surgery and the rupture of the capsule over time, along with the association between the use of minimally invasive surgery, using the rupture rate and the survival rate. In this article, they demonstrated that a rupture rate of almost 22.5%, and even more importantly, they demonstrated that the rupture of the capsule has a detrimental effect on survival, and also that the use of minimally invasive surgery, along with other elements, would be associated with the risk that these capsules would be ruptured in an analysis. Therefore, the selection of patients is much more important, mainly related to the choice of surgical approach. In fact, the selection of patients and the survival results seem to be related to each other. To provide the objective selection method on the preferred surgical method in this group of patients, we recently designed a retrospective study to identify preoperative and intraoperative patients and tumor characteristics associated with an increased risk of tumor rupture during minimally invasive surgery at the initial stage of ovarian cancer. And the secondary point was the creation of a scoring system capable of predicting the probability that this rupture of the capsule existed. It is an observational court study, a retrospective study of a single center that was carried out at the Agostino Jemeli University Polyclinic in patients with an initial stage disease. And all the characteristics of the preoperative ultrasound tumor were classified according to the IOTA classification. A multivariate analysis only showed the diameter of the tumor and the addition to the ovarian fossa peritoneum were independently associated with the tumor rupture and therefore included in the scoring system. Based on this data, we developed the scoring associated with the specific rupture rate. Therefore, doctors could identify which patients could continue with minimally invasive surgery and this could be a reasonable option and assess those patients in which laparotomy should be performed. Thus, we can conclude that in the case of an initial stage disease, the selection of the surgical strategy is necessary to prevent intraoperative spilling and affect the survival rates. In addition, the application of a laparoscopic scoring system can represent a useful tool to select the right patients for laparoscopic surgery. Moving the discussion to advanced diseases, talking now about advanced disease, in the last ESMO ESCO conference and in the guidelines of the NCCN, laparoscopy can be useful to assess if the ideal site reduction can be achieved in patients with a new diagnosis of advanced disease. In our institution, more than 10 years ago, we identified a PIV score that was later validated internally and externally. The laparoscopic scoring system includes six variables and it was shown in our article that the PIV score equal or greater than 10 was associated with a low probability of achieving a total site reduction at the end of the primary surgical procedure of site reduction. Regardless of the scoring system, the presence of carcinogen or retraction of the delgado-mesenteric and mesenteric root intestine were identified as absolute criteria of operability. The concordance of the scoring algorithm with the primary findings of site reduction surgery identified that the primary site reduction surgery, once validated by other authors, which confirms that laparoscopy, it is able to predict the complete site reduction in advanced ovarian cancer. All predictive laparoscopic models were projected and validated. The R3 and R4 models of the model were associated with computerized tomography and laparoscopic data to determine the peritoneal cancer index along with the injury size score. This article showed that the three predictive models worked very well, but the article also confirmed that the effectiveness of laparoscopic evaluation of the disease and the study then concluded that all three models were able to predict the great vision of site reduction surgery, even if they were more reliable to predict complete site reduction surgery. We have positive data on the cost-effectiveness of laparoscopic evaluation of disease load in primary treatment. In this article, we have a clear demonstration that laparoscopy is an economic and effective way to improve the main treatment because the benefit of laparoscopy was influenced by the mitigation of serious complications and their associated costs. It is also very interesting to consider that laparoscopy could be a good way to evaluate, to predict major complications in primary and site reduction surgery. And using this app, which is already available, which combines four different variables, including performance data, CITI CA-125 and tumor load. Evaluated through the PIV score, through laparoscopy, we were able to calculate the risk of major complications for each patient individually. In this slide, we can clearly see that there is an increase in the risk of complications with an increase in the risk score. In this way, using this method, we have the possibility to calculate the individual risk of patients for major complications in primary site reduction surgery. The same selection process can be applied to another configuration of the interval site reduction surgery. In 2010, a modified PIV score was created and published prospectively to help identify patients that would be suitable for complete site reduction. In this study, four of the variables already mentioned in the PIV score were included in the final calculation, each of them scoring two points. In this way, this article clearly demonstrated that laparoscopy can discriminate patients with a particularly stable disease after non-adjuvant chemotherapy of site reduction, which can be susceptible to having an adverse effect after a successful IDS. The laparoscopic selection has therefore been demonstrated to be an effective tool to plan the appropriate primary treatment for primary and interval site reduction surgery. But it is also important to consider that, in some cases, starting the procedure with laparoscopy can give us the opportunity to do minimally invasive surgery. In this way, we can perform all interval site reduction surgery on patients with an ideal response to non-adjuvant chemotherapy. This study, MISSION, demonstrated that minimally invasive surgery, it was a feasibility study, demonstrated that minimally invasive surgery can be successfully used on patients subject to an ideal response to non-adjuvant chemotherapy. After this study, several other articles were published on this topic, and what we did recently was develop a monogram, which would be able to predict the viability of minimally invasive IDS, which was obtained by a retrospective analysis with more than 300 patients who were subjected to minimally invasive surgery or open approach. Again, the pre-operative variables were used to predict the probability of minimally invasive surgery and the probability of minimally invasive surgery using multivariable models, and the probability of minimally invasive surgery according to the identified variable. We see here in the monogram of this slide. The sum of the associated points, successful, minimally invasive, and IDS probability, thus providing assistance in the choice of surgical strategy. After the encouraging results of this MISSION study, which was confirmed by several other works, by several other documents, we are now participating in this random study of international phase III, where patients with a great response to neoadjuvant chemotherapy are randomized for minimally invasive IDS surgery. An experimental arm versus elective surgery in an open location, and the control arm in terms of survival, free of disease. In terms of advanced disease, we can say that laparoscopic evaluation of tumor load in disease, in advanced stage, recently diagnosed, is able to predict a complete cytoreduction. In addition, the laparoscopic punctuation system is a productive tool, validated and economical, able to help doctors in the selection of treatment for patients in initial cytoreduction surgery, and also in intervals. Now, let's move on to recurrent disease. And for what concerns the recurrent environment, again, laparoscopy, it is accepted by the NCCN directors as a suitable strategy to evaluate whether the ideal cytoreduction can be achieved during secondary cytoreduction surgery. In relation to laparoscopic selection for secondary cytoreduction surgery in our institution, we can see here the GML algorithm to treat patients with recurrent ovarian cancer sensitive to platinum. Platinum. All patients are subject to PET scan, which is discussed in a multidisciplinary environment. Those with metastases and abdominal are sent for chemotherapy. Those with intra-abdominal, inguinal, or cardiophrenic residue are evaluated for secondary cytoreduction. In the case of non-resistant residue, for example, intraperigonal liver, involving specific volumes, or those that are not great for surgery due to performance standards, are sent for chemotherapy. The other patients are subjected to surgery, which always starts with a diagnostic laparoscopy, in order to exclude the non-resistant miliatric disease. Secondary cytoreduction surgery is performed by open or minimally invasive approach, according to the location of the disease. The numbers refer to the period of 2012 and 2020, where we evaluated almost 450 patients. Based on this data, which we are showing here on the slide, the performance of one algorithm compared to the other in terms of precision of the twin algorithm with other methods used to evaluate and select the patients for surgery after the residue. According to the model, with the AGO score and the TIAN model, as you can see, probably the twin algorithm has better accuracy compared to the other models. In addition, this slide shows that we have preliminary analysis that was carried out in our institution and has not yet been published, which demonstrates an oncological security of secondary cytoreduction surgery with a minimally invasive approach in certain selected patients. In general, in our institute, we test the viability and security of secondary cytoreduction by laparoscopy. This was done in 58 cases that were subjected to multiple procedures through minimally invasive surgery, as we show here on this slide. In this population, a low rate of complications was detected, thus confirming that in certain selected patients, a laparoscopic secondary cytoreduction can be done successfully through minimally invasive surgery. In this way, according to the recurring disease, we can say that the laparoscopic evaluation of the tumor load to be able to predict the efficacy of the surgery is also in the recurrence of the disease. In minimally invasive surgery and in recurring ovarian cancer, we have promising results, but we probably need to develop a standardized laparoscopic model to be able to predict the complete cytoreduction in the recurring disease. The laparoscopic method is a very useful tool in ovarian cancer, both as a diagnostic method to select patients for open surgery, but also by starting a procedure in advanced ovarian cancer by an initial procedure in ovarian cancer to perform surgery through a minimally invasive procedure in certain selected cases. In this way, my advice and our policy at Gemelli Hospital is to start with all the procedures for ovarian cancer by minimally invasive surgery and then decide if laparotomy is necessary or not. Thank you very much for your attention. Thank you very much, Professor Scambia, for your presentation. Buongiorno! It is a great pleasure to have you with us in this conference, a conference that was planned. First of all, we have a poll for you to read and answer and then we will move on to the questions. So, the question of this poll is which of the laparoscopic results is an absolute contraindication to perform cytoreductive surgery? I apologize, I ran out of audio. We wait a few more seconds to go. While people are voting, I really regret that I'm not going to play in the World Cup. You know? Yes, I know and I'm really... It's sad that Italy is not going to play in the World Cup. I know, but in reality, I don't know what to do. I'm a big football fan, but without Italy playing, I'm going to Qatar, but without Italy playing, it won't be the same, right? I'm really sorry. It's difficult for us to understand how it was possible. It's difficult for us to understand how it happened, but, well, that's what happened. We have the answers, and the answer people have chosen is the Mesentery Retraction. Can you comment on that? Of course, I think the comment is very clear. The answer is clear, because I understand that almost 80% of the people answered. I understand the reason why they answered the right answer. I think that now we have few situations where ovarian cancer can be completely eliminated, and one of them is the Mesentery Retraction. Regarding the others, we can do almost everything. In this way, in reality, I see that most people identified the Mesentery Retraction as the only contraindication for ovarian cancer surgery, so it's very good. We have a question here from the audience, which is, if you find in the laparoscopy a score of 6 or 4, do you proceed with the laparoscopic cytoreduction surgery, or do you prefer to go to a laparotomy? Because at present, we feel that the advanced disease cytoreduction surgery should be done through a laparotomy, but we are open to clinical trials. We could do this within clinical trials, but we don't have a clinical trial on this topic yet. In this way, we do the laparotomy. These are some questions that I would like to address, to comment with you. I think the first question is, what is the care, what are the precautions that you must take in a laparoscopic procedure so that you don't use an implant, for example? Look, I think we should be very careful, we should be cautious when performing this patient selection, because we must do this to eliminate the tumor in the peritoneum and also, we pay a lot of attention at the time of closing the hole. It must be closed very well, and I should say that with our experience, our experience is very large, the metastasis or the location after the diagnostic laparoscopy is very rare, and in any case, this would not change the diagnosis of this patient. Okay, so this is a question from Dr. Farner Satti. Do you believe that the intraoperative flow in a patient with a negative peritoneal wash causes a negative effect on survival? Yes, I believe so. And to avoid spilling, obviously the disease must be diagnosed in the previous stage, that's why we give some rules regarding this. As soon as we use this score, which is based on the combination of tumor mass diameter and addition of tumor mass diameter, and in addition to that, the mass, the effect of the mass on the pelvic peritoneum. I think that a person who supports the use of laparoscopy in all stages of the disease, and in the same way, we must be very careful, we must be cautious, and in this way we can make the right management. And the second point that Cristina mentioned very well a few moments ago, was that in the previous stage disease, we are working a lot to detect laparoscopically, laparoscopic detection of the ganglions in the ovarian cancer, and this could be an opportunity for us to make an assessment about the stage and the status, with the reduction of the complications of other surgical methods in this stage of the disease. Another question from Dr. Miguel Correa, what would be the conversion percentage when a laparoscopic surgery is done? Well, according to what I understand, not in the previous stage, but in cases where we are doing it, I imagine that for a patient where we are thinking of doing the resection, to do the resection, just to clarify this answer, in the previous stage disease, we do almost 90% through laparoscopy. It is very rare that we do something different to that, okay? In the advanced disease, we must make a conversion, so that in this way we can assess the operability, in a few patients, but I would say that approximately 10%, because there are cases where laparoscopic assessment is not good due to various reasons. It could be addition or difficulty getting into the peritoneum. I would say that approximately 10% conversion. Another question for you, Professor. Do you do laparotomy and laparoscopy at the same day? How long does laparoscopy take, if you think that the patient is diagnosed for cancer? The question, I think it goes more in the sense that if the patient must be converted to laparotomy, do you wait for the pathology, or do you wait for something else to convert this, or do you do the conversion at the same time, with the same anesthesia, and just move on? Yes, in routine clinical practices, we do it immediately. As soon as we do laparoscopy, and after that we decide immediately if we should convert to open surgery. If the patient can be reduced, but also during the last two years. We had two clinical tests, where we did laparoscopy and then laparotomy. Because we did a clinical test, where the treatment was different, according to BRCA status. As soon as the autopsies, the evaluation, we did that, and after 10 days, we decided the second step of the surgery. But in routine clinical practice, in the day-to-day, 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, what we are doing is that we are increasingly using ultrasound biopsies on patients in which we believe, we feel that the patient is not suitable for this surgery. We did ultrasound biopsies, and instead of laparoscopy. Another question, what are the tips, from Dr. Luis Puentes? The tips for resection of the brain is a laparoscopy, this is the tip. So he answers that here we should use at least two instruments to have some experience in moving the intestine so that we can understand if there is a retraction or not. And taking into consideration the fact that when we validate our TI score, we did a multicentric study where different clinical centers in Italy sent us their evaluation with video, and we reviewed the evaluations and there was a strong agreement between them. In this way, the learning curve to hit the laparoscopy is fast, as soon as after 10 procedures we can then perform an adequate evaluation. Well, and from Dr. Patricia Batturi, during the laparoscopy, where does the tumor come from? From where does the tumor come from in the laparoscopy? It's a question, it's here. He answers that we prefer to do biopsies in the peritoneal part, so that we can do the diagnosis, be able to do the diagnosis. And if we do large biopsies, we can, in this way, put it in a plastic bag and remove it in this way. And the last question is mine, my question. We saw robotic surgery that has advanced in many sectors, until now, GYN oncology, most of them address this type of cancer. Do you see any role, any advantage so far for robotic surgery in the laparoscopic part? Any specific indication about that, doctor? He says yes. If we talk about gynecological oncology in a general way, I believe that in obese patients, robotic surgery works better than laparoscopy. I also believe that one of the advantages of robotic surgery is that it's easier to do some difficult procedures, minimally invasive, which is much easier. I think that for the future, most minimally invasive surgeries, gynecological, will be done through robots. And this is also the reason that we currently have more than one robotic platform available. This is the reason, as soon as the future of minimally invasive surgery is probably robotic. Okay, Steve. Wow, I have received an excellent feedback from everyone from your presentation, particularly from Dr. René Pareja, and I hope that Brazil plays very well in the World Cup, that it goes very well because Italy and Brazil are good friends. So I wish good luck for Brazil in the World Cup. Professor, thank you very much for your participation. I wish you a fantastic Saturday and we will continue with the program. Thank you very much to all of you. Okay, so now we are going to our third lecturer from Dr. Michelle Zamora. And she will talk about how to incorporate in our practice all the processes mentioned here. So the studies that based the use of PARP inhibitors in the first line were SOLU1, PRIMA and PAOLA. In these studies, we notice some differentiation regarding the design, drugs, population, but in general, what they all show us is that the use of PARP inhibitors in the first line in BRCA patients has a progression-free survival gain that is statistically significant, clinically important, either in isolated therapy of the PARP inhibitor or in double therapy with an antigen. When I talk about patients who have homologous recombination deficiency, we still see this benefit of the use of the PARP inhibitor, or in combined therapy with bevacizumab, but when I go to those patients who have proficiency in homologous recombination, I see a gain in the use of niraparib, but this gain is not expressive when I associate the double blockade with the anti-angiogenic. Regarding global survival, we do not have the results, they are not mature yet, but we use the data from PFS2. We already start to see a significant gain in progression-free survival 2, and the importance of evaluating it is that when I do an evaluation in the gynecological tumors and then in the ovary, we see that there is a correlation between gaining progression-free survival 2 and gaining global survival. The advantage is that we are facing a shorter time for patients. So the question is, what influences the choice of the PARP inhibitor? In theory, this decision should include the differences in the preclinical models of the PARP inhibitors and ideally a study that compared these drugs directly. Today we know that there are differences in preclinical studies, both in potency in the inhibition of the catalytic site and in the potency of doing the PARP trap, that there is a difference in which PARPs are preferentially blocked by each medication, but we do not have any clinical data that shows in the literature that a PARP inhibitor is better or worse than the other. So, from a practical point of view, the choice today in a guideline is based on clinical data, which are available in each scenario, that is, in each study, in this need to combine or not combine the CISUMAB with the consideration of access to medication, posology and toxicity. So, in relation to the clinical data... Paola involves all comers, so mutated and non-mutated, and 70% of these patients do not have a residual disease, but Paola has the issue of adding Bevacizumab, so I'm not giving more placebo, I'm giving an active control arm, and I'm allowing this medication to enter neoadjuvants, perhaps even altering what we consider a response to neoadjuvant treatment. And Prima, on the other hand, is the opposite, I have 70% of patients with a residual disease, patients who have a worse prognosis, and here they are really sensitive to platen, there is no use of Bevacizumab in neoadjuvants. Today, one of the parameters that we use to choose the treatment that we are going to do with paracetamol is to know if I'm going to give or not Bevacizumab. And Bevacizumab in neoadjuvants has become increasingly important. We know that it increases the response rate, so when I look at, for example, Antalya, I see that I even have a higher complete reception rate of these patients who do neoadjuvants with Bevacizumab, but if I look at other studies, for example, like this one, I realize that I increase the surgical capacity, but not necessarily that translates into complete reception. So we are sure to use Bevacizumab today and that it has been widely used in neoadjuvants. With a differential that we do not yet have such concrete information about the relationship of Bevacizumab with the status of BRCA. This was evaluated in Georgia 2018. Apparently, we see that those patients who do not have BRCA mutation derive a greater benefit from the use of anti-angiogenics. This was revisited in an Italian study, retrospective, and again we see that those patients who are BRCA-wild tend to have a greater gain from the use of Bevacizumab. Why is this? It is possible that it has to do with some molecular subtypes of OCDA. We know that BRCA, normally mutated, will fit into the immunoreactive subtype and that this pattern of genes activated in the immune-reactive may not have much to do with angiogenesis and the VGF pathway. In addition, what will influence our choice in relation to UNI, Bird Park, or others, are the considerations of access. So what is authorized by the FDA, by EMAI, for example, here in Brazil, by the VISA. This differs a little from place to place, and just so we can describe it, in Brazil, for example, I can do the use of therapy combined with anti-angiogenic, Park inhibitor, for any patient recently diagnosed with thyroid cancer. So there are these regional particularities. There is the question of toxicity. Negaparib has a very specific toxicity, which is platyopenia and hypertension, while Olaparib usually gives more anemia and fatigue. These are different toxicities that can sometimes motivate us to select one treatment or another. So it is difficult to make an algorithm that contemplates all the information. We still have a lot of nuances that we need to understand better in relation to the first treatment. But in general, when I'm dealing with a BRCA-mutated patient with positive HRD, I can do chemotherapy, and then, in the absence of an answer, I follow up with some Park inhibitor, or I can do chemotherapy with anti-angiogenic, and then define if I'm going to follow up only with anti-angiogenic or associate with Sizumab. And here in the corner, there is the negative homologous recombination, which is negative HRD. In Brazil, specifically, this arm that can make Olaparib can be present in all groups. There are questions today that involve this incorporation of the birth inhibitors. So in that patient who is BRCA-muted, we know that all of them need to receive maintenance. In the past, there was a question about whether those patients who are less at risk, who can do a primary situation without residual disease, if they would be beneficial. And the soil evaluation is very clear. When we are dealing with patients who do not do maintenance, even BRCA-muted and completely reduced sites, around 60% will be residual until the second year. So everyone benefits. But the question is, how much do I need to offer a double blockade for these BRCA-muted patients, or how much can I keep Bevacizumab for a relapse? Mainly thinking about that sensitivity that exists in this group of patients with Bevacizumab. So the idea is not to compare studies with studies, but the source that financed these two studies, São Paulo and Solo, has the data of the patients. And when we compare one with the other, we see that the use of Bevacizumab together with the birth inhibitor, it apparently adds something to the survival rate, the progression rate. We're not going to talk about statistical significance, it doesn't even make sense to do that, but when I take this data and look retrospectively at what existed of Bevacizumab, when I did chemo with or without Bevacizumab, I reduced the risk of progression by 30%. So when I compare these two arms, the two birth inhibitors, with or without Bevacizumab, I still see a similar risk ratio. The reasoning here is much more speculative, but it would be in the sense that maybe if I had a synergistic effect of these two drugs, I would expect to find a lower ratio, with a higher risk reduction for these patients, which I don't see. So maybe think of a more additive than synergistic effect in these patients who are BRCA-muted. In those patients who have the positive HRD test, but who don't have a BRCA mutation, we don't have the answer of what I should do, if I should do a double blockade, or if I can only follow with a birth inhibitor as a single agent, if that's enough for these patients. And where there are more questions than in the negative HRD disease, so, given the benefit of being smaller in this subgroup, we're talking about a two-month test, would it be worth leaving the birth inhibitor only for the progression of these patients when they recur? This is very questionable, we don't know how much we would stop giving benefit to these patients, but when we look at the soil data, and especially of the cousin, around half of these patients received a second line of treatment, we are reluctant to keep a treatment for the second line, which we may not be able to offer. So, in the face of all these questions, I think we need to talk about the future, how to improve the selection of these patients, and then I think we need to look at the test. We need to look for a more reliable HRD test, and then we need to look specifically at the cousin, because in the cousin I have all the patients selected, responding exclusively with platin. So, I'm talking about patients that, from the point of view that we have until today of information, when responding to platin, are potentially responsive to the birth inhibitor. And even in this group of patients so selected, I still have a negative HRD in a third of the patients, 34%. And then if we think that this can be a flaw in this test to detect these HRD patients, it makes sense to find a benefit, even in a group that does not have a biomarker in the study. And besides that, besides not being able to see this 34% that had benefit with the drug, I still have 15% of patients that the test is unknown because I don't have a tissue, or because it is inconclusive, or because the sample is not suitable to be evaluated. So, we need to improve the development of this test, and how we are going to evaluate the HRD. In the disease, this divide is simple, I have the sensitivity to platin, but in the first line I don't have this information. So, what we need to do is improve this distribution. I need to leave an HRD test that comes to me with a high percentage of false negative, I start to move forward with a test where I reduce the amount of false negative and increase the positive predictive value of my test. In recidivated ovarian cancer, we have a drug development that is from the second line to the first. So, when it got to the first line, those patients who used the treatment were virgin, but when I tested the second line here for algorithm evaluation, those patients also couldn't have received it. So, in all these studies, we have a patient who was not exposed in the first line to parp inhibitor. And when I look at all these patients who respond to chemotherapy in recidivism, all of them benefit from the use of parp inhibitors. And it's interesting because when I compare one with the other, I don't see a difference. So, whatever the drug or the study, the risk reduction is very similar between drugs in this same patient profile. So, in recidivated ovarian cancer, we would use chemotherapy based on platen with bivacizumab or chemotherapy based on platen followed by parp inhibitor, as long as I haven't previously administered this to these patients. How will this evolve? So, looking at the data from SOLU2, when we look at these patients who received maintenance with parp inhibitor and they are exposed to chemotherapy with platen, they have a tendency to respond less than those patients who didn't receive maintenance with parp inhibitor. So, this is extremely important when thinking about subsequent therapies. But once these patients respond to platen, we have the ORIO data that was presented, these patients return to benefit from the parp inhibitor when they have a platen response, regardless of the HRD status. Reinforcing the fact that the HRD test probably doesn't reflect a present situation of the tumor. Maybe it means that at some point there is a tumor recombination deficiency, but we don't know exactly when and that the sensitivity to platen is still a marker. Obviously, with a slightly lower response than what happens in the initial lines, but the benefit of the drug exists there. So, I think this is a general overview of how we will incorporate parp inhibitors in our clinical practice, and I'll be available for us to talk. Thank you very much. Michel, excellent. Excellent lecture. And I think this is a theme that has changed the history of ovarian cancer. I'm speaking in Portuguese now. And I think there are still many questions to be asked about this paradigm shift. I think an important message that you pass on is that if we have access to these medications and indication, it is important to use them up front, at the first moment. Because we don't know, in fact, if the patients that will recidivate, if they will recidivate first as a sensitive platen and second, if they will respond to the treatment with platen. And we know that parp inhibitors were approved not only in the first line, but for sensitive platen with response to resposition. And obviously, this is not the case for the vast majority of patients. So, using it up front is apparently much better. Let's go to our question. I'm going to read in English. What's the incorrect alternative of the following questions about parp inhibitors? Parp inhibitors have been shown to decrease PFS. Sorry, it's increase. Particularly BRC1 in two mutated patients as well as HRD. So, increase, not decrease. Parp inhibitors can cause rarely myelodysplastic syndrome. There is clear evidence that some parp inhibitors are superior than others in first-line maintenance therapy. And the most common side effects of parp inhibitors are fatigue, anemia, and GI symptoms. So, here we have four questions. Michele, people are voting. Let's wait for people to vote a little longer. So, people are voting. We're waiting for a few more seconds. So, the first question is increase, not decrease. The first question would be increase. No, here we have an error. Congratulations to you and to Audrey. You are our representatives of Brazil at IGCES. I'm very proud of you. Thank you. We are very grateful to have been chosen for the IGCES board. People are voting. Let's go. Do you want to comment, Michele? We are now speaking in Portuguese, our native language. The alternatives. Yes, I think the first people who voted may have voted before the correction. So, we know that the parp inhibitor will actually increase PFS. And the letter C, 34% voted. Unfortunately, we have no data comparing a parp inhibitor with another so that we could choose one preferentially. And this is toxicity. Intestinal gastrointestinal toxicity. And what we are most concerned about is splasic myelitis. But it happens in around 1% of patients. Perfect. Let's see if we have any questions here. Let's see here. If not, I have several questions for Professor Michele. Let's see. I don't think there are any questions from the audience yet. My first question for you. In randomized studies, we included patients with stage 3 and 4 who had treatment with platelets. And they had, or actually did not have progression. They had disease control. We know that stage 2 has a chance of recidivism of around 50%, at least. That is, it is very high. And we work with adjuvant treatments with much lower recidivism numbers in other gynecological tumors. So, my question is, off record, in closed rooms, a 55-year-old patient, ovarian cancer, high-degree papillomavirus, with stage 2, perfectly operated. Does chemo? Do we recommend the PARP inhibitor for this patient? What I think is this. We have, sometimes I joke, the 2B and the 2B. So, I think a small implant on the skin, maybe I would be more comfortable not offering it to the patient. If I had a 2B with a large volume of skin, it would be totally rational for us to offer this adjuvant also with the PARP inhibitor. The big problem is the restriction that we will have authorization for the plan and that, unfortunately, we cannot justify because it is not represented. The other question is, we know that the PARP inhibitors, we have no evidence that one is better than the other. But the toxicity standard is clearly different. I have a patient with stage 3, operated, treated with chemotherapy. Do we prefer olaparib or niraparib if this patient has a BRCA1 or BRCA2 mutation? Or pick your choice, choose the drug that is available at the moment? I think that more and more with regard to PARP inhibitors, this conversation with the patient is very important. Because we have the issue of posology and toxicities that are initially very different. I like to let the patient also understand that there are both options and that there is this difference in posology. And that niraparib, although it does not give nausea and does not give that significant fatigue as olaparib, we face problems with the plaquitopenia, which can be limiting. We may need to hospitalize the patient, transfuse, or go to the emergency room. I usually participate in the patient's decision. I don't have a pre-made choice before I talk to them, you know? It is important to remember that niraparibia has two doses, the higher dose and the lower dose, according to the weight and the basal level of platelets. This was an amendment to the prior study. Another question that I have doubts about in my day-to-day life, I would like to hear your opinion. We know that Bebacizumab, according to the GOG 218 and the Icon 7, does not increase survival, and PFS remained only positive in the 218, but in the Icon 7, in the re-update, it was lost. The question is, with these data from Prima, Paola and Solo, when should we think about using Bebacizumab? Particularly looking at the volume of disease and BRCA status. The first point, I think that in the past, before the results came out in the first line of PARP inhibitors, we had a tendency to be more permissive with Bebacizumab, including neoadjuvant. And now, as we know that putting it in neoadjuvant will be digital, which I will be able to do in the treatment sequence, I have tended to prescribe less in neoadjuvant. So, in general, if we had to say, I think the clinical response is very important, the platinum. So, if I'm going to start by not giving Bebacizumab, this clinical response will dictate the indication a lot. I think it's the patients from Prima who are very responsive. If I already started, if I had a very large volume of disease and I needed Bebacizumab in neoadjuvant, the sequence is to add or not the PARP inhibitor. In the rest, if I didn't start, my tendency is that if it's BRCA mutated, only the PARP inhibitor, and if it's HRD, I've also had a tendency to give only the PARP inhibitor, in this case, nigaparib. Because, in the same way we didn't see an additive effect in the BRCA mutated, and we couldn't see it in the proficient, I don't think HRD has a biological justification for me to have a synergistic effect there. So, there's a tendency to give Bebacizumab more to the later line. I agree 100% with you. I think the use has been gradually decreasing with the PARP inhibitors. Well, we have two questions here. We're already a little over time. I'll ask you later to answer for Macon de Vicunha in the chat. Michele, a question about what molecular study we should ask in pathological anatomy. I'll ask you to answer for Dr. Sabera Khatun, what is the type of ovarian cancer that is more responsive to Bebacizumab? I think she wants to know if it's serous, endometriotic, light cells, or mucinous. You can answer in the chat for our two colleagues who are prestiging this event. Malu, a quick answer, until today we are looking for a biomarker for Bebacizumab. The day we find it, it will be wonderful. I agree. Michele, thank you very much. You are a dear colleague. I thank you for the excellent lecture. We will now move on to another colleague who is also a member of the EVA group, Dr. Georgia Sintra, a surgeon. This is a very important topic that has had relevant updates in the last two years, which is the role of resuscitation surgery. Welcome, Georgia. Everybody, we are coming back. This webinar is going so well that I almost forgot the break. Five minutes. Now we are back. We have two more presentations. The first is by Ms. Georgia Sintra. This is a Brazilian surgery that is part of the EVA group, the Brazilian oncological and gynecological group, and will talk about a very important theme, a very important team. Georgia, thank you very much for being here. Your presentation will be in Portuguese. I am sure it will be fantastic. Thank you very much for your participation. Hello, I am Georgia Sintra. I would like to thank the organizing committee and GCS for the invitation. I am going to talk about site and secondary reduction In the context of primary treatment, there is no doubt about the great importance of surgery in the treatment and healing chances of the patient with ovarian cancer. But we know that despite the adequate treatment, most of these patients will recede and it is a controversy in the context of the receding if the surgery would continue to have an impact. Several observational studies were published on this subject and it was possible to make a meta-analysis in 2009 in which the conclusion was that among the patients subjected to surgery for receding ovarian cancer, the complete situation is associated independently with global survival. For this select group of patients, the complete surgical situation must be the receding of the entire macroscopic disease, that is, a complete situation. This same meta-analysis showed us that the complete situation rate is very heterogeneous among the studies and that the majority is below 60%, showing us that there is a lack of a criterion for selecting these patients so that we can achieve the complete situation. Finally, then, the prospective studies began to come, two were previously closed due to the lack of recruitment, we have two favoring surgery, Desktop 3 and SOC 1, which at the moment only have a publication on free survival and progression and one that did not show any benefit Let's start by talking about Desktop studies, which is a series of studies that were designed and developed as every study should be, starting with a retrospective analysis of the cases of receding ovarian cancer in order to generate hypotheses and the hypotheses generated were that surgery would have an impact on the complete situation and that there would be a subgroup of patients in which it would be possible to anticipate this chance of complete situation, which were patients who met some criteria. Then came Desktop 2, which served to validate this score that anticipates the chances of complete situation and finally the randomized prospective, which served to evaluate whether there was any benefit or not from surgery in these patients. So Desktop 1, the first of this series of studies was a retrospective analysis of several German and Swiss centers of these patients with receding ovarian cancer subjected to surgery and it is important to know that there were borderline tumors and patients who were subjected to Neurodegenerative Interval Surgery. So only the patients who did the primary situation were analyzed. And what did this study find? That only the patients in which all macroscopic disease was resected, that is, the complete situation was performed, that is, leaving the disease up to 1 cm or more than that, nothing changed, the identical survival curve. So showing the hypothesis that what should be achieved is the complete situation with resection of all macroscopic disease. And the other hypothesis that was generated is that some patients who met specific criteria had a greater chance of reaching These criteria are These three variables together were then called AGO score. And then came the second study, which is Desktop 2, which served to validate this finding, if this AGO score was able to predict patients in which it would be possible to reach the complete situation. And what was seen in Desktop 2? That 51% of patients meet these criteria of the AGO score and that it was possible to reach the complete situation in 76% of patients. Therefore concluding that it is a criterion, it is an adequate score to anticipate that patients can actually benefit from surgery because it is possible to reach the complete situation. And then finally we arrived at Desktop 3 in which a randomized prospective study was done with 408 patients in the first sensitive platinum recidiva and that met the positive AGO score. These patients were randomized for surgery whose goal was the complete situation without residual disease, followed by chemotherapy or immediate start of chemotherapy. From this study, 80 centers from 12 different countries participated and reference centers with quality criteria for the treatment of ovarian cancer. These are the same centers that participated In order to be considered an adequate center it was necessary to have research quality criteria, appointment information and obviously surgical quality. This was analyzed by the surgical volume of the center and by which surgeries were performed within the site reduction. They were large volume centers And what did the survival curves show? That there was a benefit of surgery both of free progression survival and of global survival. But when we do the analysis of patients who were submitted to the complete situation compared to those who were left with residual disease what was verified is that in patients who had residual disease there was a malefiction to perform the surgery because the survival was less than the control group which was to do the isolated chemotherapy. In patients who reached the complete situation there was a gain of almost 16 months compared to those who did not perform the surgery. The conclusion of the study is that patients with residual ovarian cancer submitted to surgery had a gain of global survival and free progression compared to patients who only performed chemotherapy. However, this gain occurred only in patients who reached the complete situation without residual disease demonstrating the importance of the center in which these patients will be operated. To decide to do surgery you have to reach the complete situation otherwise we are only harming this patient. The SOC1 study had a methodology a very similar drawing to Desktop 3 but the inclusion criterion is the iModel associated with PET-CT. The SOC1 study has similar criteria but it also includes STADIU-FI, CA-125 and the free progression interval up to the residual ovarian cancer. This is associated with PET-CT and how the patients were selected to enter this study. What we have in the publication is the free progression survival and there is a benefit of surgery in these patients for free progression survival. Finally, we have the GOG-213 study that did not show any benefit for surgery but the design of this study was different from the other studies. They were the same patients with residual ovarian cancer, platin-sensitive and it was enough for the surgeon to consider that disease as resectable. There were no objective and clear criteria as in Desktop 3 and SOC1. And this is a study that is not purely surgical it is surgical and also with medication analysis. The number one goal was if the addition of Bevacizumab to chemotherapy and after as maintenance and the second goal would be if surgery would also bring some benefit to these patients. The number of patients included is also high, more than 400 patients and most of these patients were Asian. The free progression survival curve was very similar to the group that was subjected to surgery and the group that was not subjected to surgery and of global survival showing a benefit for the group that did not undergo surgery despite this not being 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. In the inclusion study of Desktop 3 the patients had to have the ADO score positive in SOC1 they had to have the IMODEL with the PET-CT and in GEOG213 it was enough for the surgeon to consider that patient as a possible site reduction. This is reflected in the complete resection rate which in GEOG213 was the lowest 67% compared to almost 77% in SOC1 and 74% in Desktop 3. Another very important difference is the number of patients receiving Bevacizumab in Desktop 3 it was 23% and in GEOG213 it was 84%. We also see an important difference in the survival rate in the number of studies according to the group. The best survival rate was in GEOG213 that did not have surgery with 64 months. The group with the worst survival rate was in Desktop 3 that did not have surgery with a difference of almost 19 months with the same type of patients not having surgery but with the difference in GEOG213 with the addition of Bevacizumab. Could Bevacizumab be the explanation for this difference in the outbreaks? In the appendices of the articles in the supplementary material there are the survival charts according to the use of Bevacizumab. In GEOG213 the patients who used Bevacizumab the curves are very similar but in the patients who did not use Bevacizumab there is a very important difference from those who only did chemotherapy and those who did surgery. But an unexpected result is that the best survival curve in GEOG213 is in the patients who did chemotherapy and did not receive Bevacizumab for 67 months. This was not observed in Desktop 3 where in the appendices there is the survival curve of patients who did not use Bevacizumab and that surgery continued to show a benefit in relation to chemotherapy. With these very different results and even with the unexpected result of the group without Bevacizumab and GeoG200 Some considerations that we have to make after all this information If you are convinced that the secondary situation brings benefits What will be our behavior with the patients who were submitted to neoadjuvant chemotherapy and then to the interval situation and with the patients who were poorly operated in the beginning because they were in centers that are not reference centers for ovarian cancer treatment They are patients who were not evaluated on Desktop 1 therefore we cannot use the Age-O-Score in these patients So we do not have the answer of what to do and which are the candidates in this context that at least in Brazil is the majority of patients And if you are convinced that there is no role for surgery when Bevacizumab is available What explanation can we give for the survival of 67 months in the non-surgical group who did not receive the drug in GeoG213 As it is a dual study, which is not a pure surgery we cannot separate what is the impact of the drug and what is the impact of surgery and draw any conclusion in relation to this So we still have many doubts and open points to decide in these patients So what are the conclusions that we can actually reach? There are two studies with mature and discordant results but that have different drawings, different inclusion criteria and the pure surgical study, which is Desktop 3, favored surgery So the tendency of the scientific community is to consider more the results of Desktop 3 in relation to GeoG213 But what is actually consensual is that R2 surgery in the relapse scenario is deleterious The adequate selection of these patients and the surgery being performed in a reference center is fundamental And it is important to emphasize that even with rigorous criteria a quarter of these patients, 25%, will not be able to reach full substitution And this must be evaluated along with the patient, informed of the risk of this surgery As we have already reinforced several times, operating and leaving the disease is worse for this patient I thank you very much again for your attention And here is my email for future questions Thank you very much Hello, I am Georgia Sintra I would like to thank you for your question Thank you, Georgia Sintra Very good, Georgia, excellent presentation Now we will go to the question for people to vote I will read it in English Epithelial ovarian cancer recurrence is a challenging and common scenario Choose the incorrect or incorrect option Desktop 3 favors surgery, GOG 213, systemic therapy, and SOC 1, the SOC, is pain and survival analysis Number 2, good PS, complete initial surgery, ascites, less than 500 milliliters, are some of the AGO criteria Number C, surgery is better indicated when systemic therapy fails for recurrent epithelial ovarian cancer And number 4, a complete cytoreductive surgery is a significant prognostic factor for epithelial ovarian recurrence I will give some time for people to answer It was excellent, excellent presentation I think the questions are coming I have some questions that will elucidate some ways of handling these patients Let's see here, let's wait a little longer for the vote, a few more seconds I think the alternative that people are voting as incorrect is option C Would you like to comment, Jorge, before we ask the questions? Perfect, I would answer too All these works, and the doubt we have, and what we dedicate ourselves to, is to understand if surgery, in the secondary institution, has a role in sensitive platelet patients In platelet-resistant patients, as Professor Cristina commented in her class, tumor biology is very unfavorable And really, the therapeutic options are much more limited And considering all the morbidities that we know are related to ovarian cancer surgery, it is not, at first, a candidate patient There are reports of cases, there are a series of very restricted cases The last one I reviewed is from 2015 Trying to see if there was any benefit of the secondary institution in platelet-resistant patients But we don't have that answer, and at first the answer is no To dedicate, to consider surgery, surgery with relevant morbidity in patients In which we have a better option of healing, a better perspective of disease control, which are sensitive platelets In this space of sensitive platelets, 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 Dutch study that was positive, where patients were operated in intervals with chemotherapy and hyperthermia Then, the patients did chemotherapy first, with or without hyperthermia, it was this randomization, followed by chemotherapy So the results were controversial We should consider in some scenario, chemotherapy with hyperthermia in recurrent platelet disease And then I will touch on two different spaces, in sensitive platelets and in resistant platelets as well So I would like you to comment on these two groups of patients, the role of chemotherapy with hyperthermia In high-pec data, in the recidivism scenario, we have a study by Zivanovich, which was published last year by the staff of the Memorial, and at first had no benefit compared to patients who did not receive high-pec High-pec in ovarian cancer is very controversial So even in the Dutch study, and in the interval situation, many, including Dubois and the staff of Essien, who published Desktop 3, understand that the biases that were involved in this study still do not allow a positive response from high-pec, from indicating this treatment And in fact there is a discussion, precisely in the resistant platelets, if the use of high-pec could improve the response and then in these patients have some, perhaps a selection of patients for this treatment Also in the literature we will not have answers, we do not have quality studies, we also have case reports, a series of cases So, in principle, in the recurrence scenario, what we have of a negative study is that of the Memorial, which was published last year, the individualization, but without a precise indication, based on the literature. Perfect. And a practical question here. Some cases that we see, the disease is platinosensitive, but it eventually presents itself with some points of carcinomatosis. And generally, my interpretation is that the great benefit of surgery comes to those who are still responsive to chemotherapy. That is, that question that surgery alone dispenses with chemotherapy is not correct. And perhaps the group that benefits the most is the group that is still sensitive. If you operate on the patient and do chemotherapy later, we cannot estimate whether the patient responds or not, because in those cases of complete cytoreduction, you have cured the disease. My question is, some of our cases, we choose to do two or three cycles before treatment, and operate later and continue chemotherapy, as if it were a cytoreduction of interval rescue. Obviously, none of the three studies did this. The three studies operated and treated later. How do you see this strategy? This is a strategy that has not really been studied in these main studies. I think it is one of the main advantages of neoadjuvance, you evaluate what type of tumor you are dealing with, so the drug sensitivity, and even the question of, when there is a discussion about why surgery would be beneficial in these patients with residue, one of the discussions is really if, by reducing the volume of the disease and reducing it to a microscopic level, which is our goal, to remove all macroscopic disease, if this would have any impact on the tumor microenvironment and even immune response. It is one of the discussions about why, if you actually reduce it, it would improve the survival of these patients. One of the discussions about neoadjuvance in the primary scenario is whether we would be increasing the chance of a possible platinum resistance. This has no answer, but it is one of the discussions about the difference between the primary situation and neoadjuvance, and whether neoadjuvance could promote a decrease in the interval until it becomes platinum resistant. I think this strategy is valid when, in the patient evaluation, you do not anticipate that it will remove all the disease or reach a complete situation. In a scenario where you anticipate that you will be able to achieve a complete situation, and then we have the Agile score for patients who had a complete situation in the primary scenario, so not in neoadjuvance, and with the CITV-500 ML and good performance, you offer. In patients where this is not possible, you will not reach the complete situation, this strategy of a new neoadjuvance makes sense. Excellent. Jorge, I have a few more questions for you. I will ask you to answer in the chat later. I thank you very much. Thank you very much for being here in our country, in this surgical area. The class was exceptional, and we will now move on to our last class, unfortunately, because this is a fantastic webinar. This class is a very important topic, in which we will talk about the testing of BRCA and possibly other markers in advanced ovarian cancer, or in ovarian cancer without sulatus, with Carlos Eduardo Andrade. Carlos, welcome. It is a pleasure to have you here in this webinar, the third webinar of the IGC-S series. Carlos Andrade, it is a pleasure to be here, in this excellent initiative of the IGC-S, for our education, and for all the ecological gynecology in the world. I will comment on the role of BRCA currently in our treatment of advanced ovarian cancer. I have no conflict of interest for this specific presentation. We will comment on the incidence, the difference between the germinative and somatic mutation of BRCA, the role of this BRCA in the decision of treatment of ovarian cancer, both in the diagnostic part and in the recurrence, both from the point of view of systemic treatment and surgery. Initially, the decision, in the past, on the role of surgery and chemotherapy in the treatment of ovarian cancer, was simpler. We had to choose between primary circulation or neoadjuvant chemotherapy. Subsequently, the patient was subjected to platelet-based chemotherapy. In the recurrence, the only decision we had was whether we would do a secondary circulation or not, and this patient would go back to chemotherapy, if possible, if it was sensitive. If possible, platelet-based again. These decisions were based on clinical issues of the patient and some models that added image examinations and CA 125 value. Nothing too complex. But medicine has evolved, and today we have advanced therapies, based on precision medicine, which use, for example, patients with genomic instability due to the deficiency of the recommendation pathway. In this group of patients, the PAP inhibitors are apparently a very efficient class of medication in being a therapy for some of these patients. Well, the tests to detect moderate recommendation deficiencies can be done both in tumors and in blood. If they are done in tumors, we are only evaluating both germinative mutations and somatic mutations. If we do the blood test, in this case, if we do the blood test in the leukocytes, we extract the DNA from the leukocytes of this blood, we will only have the detection of germinative mutations. If we find circulating tumor DNA, we could still detect both germinative and somatic mutations, because germinative mutations are present in all cells of the patient's body. Somatic mutations are present only in tumor cells. The normal cells of this body do not present these mutations. About the frequency of BRCA mutation, we know that these mutations are quite frequent in ovarian cancers, especially in serous epithelial cells. And the frequency of these mutations is around 18% for BRCA germinative mutations, 7% for somatic mutations, 8% for other mutations related to homologous recombinant genes, and 17% we even find a homologous recombinant deficiency through genomic or functional tests, but we do not find a mutation in these patients. So the tests for us to detect homologous recombinant deficiency show some characteristics that differentiate them. Well, there are tests that will detect mutations, mutations in genes that are related to the homologous recombinant pathway, and the main gene in this case is BRCA1 and BRCA2. There are tests that will evaluate changes in the genome that occur due to a deficiency in the homologous recombinant pathway. These are genomic tests. It is as if we found the effect, the scar that the mutation causes in the genome. There are functional tests that look for products that are accumulated or produced from the homologous recombinant deficiency. So in the first class we will see the cause, we go after the cause, in the second the effect, and the third would be a real-time test, to evaluate whether the homologous recombinant deficiency is occurring. However, these tests present problems, a series of problems that interfere with their specificity, that is, in the ability to really, when I find a change in the genomic tests, many times it can occur, many times not, but sometimes this test reflects something that happened in the past and that now no longer occurs, the homologous recombinant deficiency. In other situations, we have, for example, the test of loss of sensitivity, as it happens when a patient, when we do the test, does not detect mutations in the repair gene, but other cell groups of this patient do present the homologous recombinant deficiency and would be benefited with target therapy for this type of problem. There are also tests that have not yet been validated. So, why discover mutations in BRCA and homologous recombinant deficiency? Several studies have already shown the role of the park inhibitor class in this group of patients. So, these groups had important methodological differences, the groups of patients are different, but in general, all these studies, here in the case of patients with initial diagnosis of liver cancer, showed a significant benefit for patients who had a homologous recommendation deficiency or BRCA mutation, with a better progression-free survival. In the recurrent disease, also the inhibitors of PARP showed to be quite efficient in groups of patients with liver cancer, especially those who had a BRCA mutation or homologous recommendation deficiency, showing that there is a significantly greater progression-free survival in patients who use PARP inhibitors. Already analyzing in these studies which group of patients benefits the most from the use of PARP inhibitors, we find that patients with a mutation, whether it is somatic or germinative, found in the tumor, for the BRCA, are the patients who benefit the most from the use of PARP inhibitors. Secondly, we would have patients who do not have the BRCA mutation, but have a homologous recommendation deficiency with mutations in other genes. These patients also have a significantly higher benefit in the use of PARP inhibitors. In patients who have a proficiency in the homologous recommendation pathway, these patients, in some studies, showed benefit in the use of PARP inhibitors. This may be due to a deficiency in the tests, in detecting patients who are not proficient, have a homologous recommendation deficiency, or in the deficiency of the test to say that the patients who were classified with a homologous recommendation deficiency did not have this homologous recommendation deficiency. In relation to the presence of a BRCA mutation or homologous recommendation deficiency in surgery, we have very few studies. This Italian study is very interesting, with a large number of patients. It was able to identify that patients who have a BRCA mutation, despite having the same FIGO stadium, the same similar CS25 value, and the presence or absence of ASCID, did not show significant difference. These patients who had a BRCA mutation had a higher tumor load. Along with this, it is interesting to realize that in this study, among other results that we had previously presented, patients who had mutations in the BRCA gene did not have a higher free progression survival than patients who have a BRCA white target, or without mutations, at least not statistically significant. But when we analyze the subgroup of patients with or without a BRCA mutation, we see that for these patients we have interesting information. The implementation of primary cytoreduction brought a better statistically significant free progression survival in relation to patients who were subjected to neoadjuvance. In the group of patients who had a BRCA mutation, the survival, despite being numerically superior in the patients who did the primary cytoreduction, was not statistically superior to the patients who did the neoadjuvance chemotherapy. This subgroup also studied patients in recurrence who had a BRCA mutation or not. If we analyze patients who had a BRCA mutation, those who performed a secondary cytoreduction had a survival rate of 78% in 5 years. Those who did not perform the secondary cytoreduction had a survival rate of 73% in 5 years. This was not statistically superior. In the group of patients who did not have a BRCA mutation, those who performed the secondary cytoreduction had a survival rate of 54%. Those who did not perform the secondary cytoreduction had a survival rate of 42% in 5 years. This was statistically significant. And then I put a controversy, a different study that showed a different result. In the first study, only patients with a BRCA mutation were evaluated. Here we have a select group of patients who used a PATH inhibitor, only those who supposedly have the best response to PATH inhibitors. And if we notice, the patients who benefited the most, those who had a higher survival rate of progression, were the patients who did not have residual disease after surgery, but those who did the upfront surgery. Putting this in graphs, we realize that the group that did OLAPARIB and did the upfront surgery, is actually the group that has the best outcome in relation to the survival rate of progression. It is the group that did not reach the median survival rate of progression. It was achieved by the group that did OLAPARIB and did the upfront surgery, that is, adjuvant chemotherapy. And in those placebo groups, they also had a worse survival rate of progression. So this indication of primary surgery, or neoadjuvant surgery for patients with BRCA, still lacks more studies as a way for us to choose and select patients who will benefit from one type or another of treatment. Another beneficial point that we have as an advantage, of recognizing patients with BRCA mutations, is the possibility of making genetic counseling for this family. This is recommended by all societies in their guidelines, and this has a very important implication for relatives. If we find relatives who have a BRCA mutation, based on the index case, the case we are dealing with, we will find women who do not yet have ovarian cancer, but have a risk during life of, if it is BRCA 1, around 39 to 58% of ovarian cancer during their life. If it is BRCA 2, between 13 and 29%. So with such a high risk of having ovarian cancer during life, we can offer these women risk-reducing surgeries, removing ovarian and uterine tubes before something happens. To do this, I need to recognize in my patients who have a BRCA mutation. From there, I recognize who are the relatives who have it, preventing them from having ovarian cancer from risk-reducing surgeries. If I don't recognize it, I don't detect it. If I don't detect it, I don't prevent it. If I don't prevent it, I end up killing these patients unnecessarily. And let's not forget that in addition to BRCA, other genes also have indications of risk-reducing surgeries that were found in relatives, such as BRIP1, genes related to lynch, PALP-B2, RAD51C and RAD51D. As a final message, I would like to say that now, in the era of precision medicine, it is very important to select patients who will really benefit more from these new therapies, especially in the context of resource limitation. It is therefore important to identify BRCA mutations and homologous recommendation deficiency in patients with ovarian cancer, and therefore select patients who will benefit the most from PALP inhibitors. Current tests have important limitations and there is room for the development of new tests with lower cost and more reliability, and that need to be validated. In addition, recognizing patients with hereditary genetic signs has the power to avoid unnecessary deaths in their relatives. That's it. Thank you very much. We will be ready to discuss it soon. Carlos, thank you very much. Are you wearing the Brazilian jersey? That's right. Taking advantage of the cold. The class was exceptional. We will have a question here with multiple choices. I will read it to people. Are you wearing BRCA variant, pathogen, or probably pathogen of the germ line? For BRCA1 and 2, that would be the second question, the second option. Number 3, genetic evaluations must be done in conjunction with medical care providers familiar with the diagnosis and management of hereditary cancer. And the fourth option, relatives with blood from first and second degree, a patient with case of ovarian, genetic variant, susceptibility, should be offered genetic evaluation. Please choose your answer. I would also like to thank the organizing committee. Congratulations, it was fantastic. All three days of presentations were wonderful and very enriching. Finishing this was a great honor and a very special moment in my career. Thank you, Saúde. You are a national hero. It is absolutely worthy that you are here with us and closing this third fantastic webinar on ovarian cancer. Very good. Let's wait a little longer. I think we already have option number 1 as incorrect. Do you want to comment quickly, Carlos? Two comments about that. I agree with the majority's answer. For me, that's right. Not only ovarian, but there is also a benefit, especially for non-mucinous epithelial cells, so for endometriosis of light cells, and for those indifferent, also test for VRSA. The second point is the sequence of this test, which I find interesting. If you are going to test in the tumor, you are going to test in the blood. The advantage of one and the advantage of the other. In the blood, when you test, you already discover, in general, a germinative test. So you can already make a genetic advice from the entire family of this patient. But when the test comes negative, you have to go to the tumor and test to evaluate if there is no somatic. It will no longer be the germinative, but it would be the somatic mutation of the BRCA, preferably of other genes that are related to the hormone recombination pathway. If you start in the tumor and it comes negative, you already know that there is no germinative also. But if it comes positive, you have to go back to the blood. So you always have a chance to do both tests. You have to go back to the blood and see if, in fact, this mutation is somatic or germinative, because if it is in the blood, it would be germinative, and you make the advice of the entire family. So just this detail of the sequence, of the results, which often requires testing the blood and the tumor, and the tumor and the blood in different situations. Excellent. One question. We have the Myriad-MyChoice as a test used in Velia, Paola and Prima. Do you think that other tests, such as LOH in Foundation 1, which takes the Laws of Arteriosclerosis, which is also one of the markers that Myriad-MyChoice uses, in addition to the Transition Like Scale, and also the imbalance of the alleric telomere. Is LOH enough to be able to discriminate between present or absent HRD, or should we force to use Myriad-MyChoice? Excellent question. Your questions are always very good, Fernando. We have problems. The tests were studied in a clinical context, Myriad-MyChoice was the most studied, so it ends up being more used and more recommended to be used, because it has the validity of having been used in clinical trials regarding PARP inhibitors. It was the most used, at least in these clinical trials. But we have to recognize limitations. Limitations that I have already started to comment on, which may be that the scar that was left has already been reversed due to the homologous recommendation deficiency and does not have the appropriate specificity. And a matter of sensitivity, which is very important in these tests, which is also not so adequate. If you only do LOH, you would lose even more sensitivity. Certainly, you would fail to detect more patients, because despite being the best research point, stability and allele are also important and bring better sensitivity to the test. So, comparing Foundation and Myriad, my impression, although there is no study comparing, but for being more complete, I believe Myriad would be superior. But we still lack a more reliable test that better separates these patients. It is still a subjective thing and it is coming. There are tests that are being developed, mainly functional and better understanding of mutations, which are coming, being studied, but have not yet been validated in clinical trials. Unfortunately, we cannot say if they are better discriminators for patients with homologous recommendation deficiency. Excellent. We are now close to the end. I thank you very much for your participation. I am going now to turn out in English. So, I would like first to thank all the speakers, Dr. Cristina, Dr. Giovanni Scambia, Dr. Carlos Andrade, who gave a fantastic, our last lecture for today, due to your excellent lectures, presentations, Dr. Jordi Acintra, Michele Samora. I would like to thank my co-presidents, not only my colleagues, but also my friends, Dr. René Pareja, Dr. Audrey Tsunoda, for putting this incredible program during these three days. I would like to thank our EVA group, the Brazilian Oncology Group, and all of you who participated in this session this Saturday. You will receive the recordings, you can find this on the portal next week. And finally, I would like to say that we are involved as a group, not only as a country, but in Latin America as well, in a lot of academic initiatives. Now, if you would like to have some work on academic initiatives, please send an email. And we will collaborate together to have more data, consensus for developing countries in Latin America, China, Africa, Asia, Middle East, and other parts of the world. My email is maluf, at uffc, uol.br. Please send an email, and we hope that we can work together as a group, especially in developing countries, because we certainly need a lot of collaboration and integration. Again, thank you very much, EGCS, for your support. I hope you have a great weekend, get plenty of rest, and be healthy. You and all your family, thank you very much. I will try to answer all the questions that came in the chat. Or you can also send me an email. Bye-bye, EGCS. Thank you very much. Thank you again, René and Audrey, for the wonderful work that you have done with this program. Thank you very much. I am very grateful to be here with all of you and in this program. Thank you very much. See you.

PARP inhibitors

ovarian cancer

BRCA-positive patients

clinical data

medication accessibility

dosing

toxicity

bevazizumab

anti-angiogenic drug

BRCA mutation status

histological subtyping

surgery

chemotherapy

homologous recombination deficiencies

precision medicine approaches