Okay, fine. Okay, Dr. Malouf, I'm going to hit start webinar. So good luck everyone and thank you. And if you have any questions, put them in the WhatsApp chat. Thank you. Good luck. Okay, guys. You guys just let me know when I can start, okay? Yes, we will. Hello, everybody. Welcome to the interactive updates on selected topics in gynecology oncology. Today's the third webinar series and we're going to discuss ovarian cancer. This webinar is supported by IGCS, it's an international initiative, really, really important. My name is Fernando Maluf. I'm a medical oncology at Beneficência Portuguesa de São Paulo and also Albert Einstein Hostel. I'm also the president of the Brazilian Gynecology Oncology Group and very grateful to be elected to be one of the board members of IGCS. Next slide, please. So today's webinar is being provided in Spanish, English, Portuguese, and a handout with detailed instructions may be found in the chat, as well as on the slide in Portuguese and the slide in Spanish. Select, please, the interpretation icon, then select the language you would like to hear. You may also mute original audio to hear interpreted language only. If you have any questions, please, regarding interpretation, let the IGCS education knows. Next slide. So we have a very productive program today. We are going to start with Cristina Fotopolo from UK. She's going to talk about the clinical selection for surgery in epithelial ovarian cancer. This will be followed by Dr. Giovanni Scambia from Italy that will talk about laparoscopic selection for surgery in epithelial ovarian cancer. Then we'll have three Brazilian IGCS members, Dr. Michele Samora from Brazil is going to talk about the incorporation of PARP inhibitors in our practice, followed by Dr. Georgia Sintra that will talk about secondary cytoreduction in epithelial ovarian cancer. And our last talk will be provided by Dr. Carlos Eduardo Andrade from Brazil as well about the role of gynecology oncology in BRC1 and 2 testing. Next. So welcome everybody. The recording will be available in the IGCS education. Please submit the questions via Q&A feature and the webinar etiquette fit to window. Presenters will be the only ones able to speak and attendee microphones are muted. So without further ado, this is provided and supported by the EVA, the Brazilian Gynecology Group. Next. So without further ado, I'm going to invite Dr. Cristina for our first talk in this really, really interesting webinar series. Our last one from the three series you're talking from the past two weeks. Cristina, thank you very much to be with us. From Imperial College in London. It's my great pleasure and honor to be here with you today and discuss in the form of interactive updates on selected topics in gynecology. I'm very grateful to IGCS and also to my friend and colleague, René Pareja, who allowed me to be part of this team today. So we're going to discuss about the clinical selection for surgery in epithelial ovarian cancer. We all know that in ovarian cancer, there is an ongoing surgical paradigm that the more we remove, the better we operate those patients, the more we can alter their journey. Patients who are operated to more free will have a significantly better survival, both progression and overall survival. And this is something that does not change in the first presentation, in the first relapse, in the second relapse and in the third relapse. And that will be consistent throughout all studies, throughout all years that we as gynecology community have implemented and have conducted analysis. The survival benefit is massive, is huge, between the tumor-free and not tumor-free operated patients, giving a clear signal to us that we need as gynecologists to strive to operate those patients better. So in order to do that, we have in the last years experienced a massive and constant expansion of the limitations of what we thought to be doable in the past, compared to now and in the future. In the past, we used to consider something radical, like, I don't know, pelvic resection with bowel and the splenectomy. All this is part of the routine surgery now, and we have expanded our limits towards operating in the chest, removing paracardiac lymph nodes, doing mediastinaloscopies and removing mediastinal lymph nodes, regularly open up and routinely open up, opening up less sac, celiac, trunk, and diaphragmatic acura and removing lesions from there. It's part of routine now to do multiple bowel resections with staplers, without anastoma or without stoma, so that the patients do not have an altered quality of life. And the same is with a true distant metastasis, like liver meds, where patients are now being fully operated. So we have experienced a massive change of what we can do on those patients and how far we can go. In order to be able to talk to the patients through what is able to be done and what probably will be needed to be done when you have a patient with the first diagnosis for ovarian cancer that comes to you and says, okay, I have now an advanced ovarian cancer, what do we do to get this cleared? You discuss with them, of course, all the options, and the options include primary versus interval-dividing surgery. In the past, we used to rely on experience and on retrospective studies. Now we have the increasingly more prospective phase three high-quality surgical studies that show us objectively data within a prospective randomized design and the qualified evidence, so that we can talk to our patients from a better perspective. The line was a study, a phase three surgical study of completely operated patients in advanced disease. And what this study has shown is black and white, what we need to do in order, what procedures need to be done in order to get somebody with advanced disease, tumor-free ovarian cancer. And this is a table that I personally use a lot in clinics in order to discuss with the patients, listen, this is what needs to be done. So approximately 55% of the patients will need some type of bowel resection, and 20% will need a splenectomy, approximately 10% will need a stoma formation. So the patient's concern of having a stoma is actually less than 10%. And patients will need around 60% diaphragmatic resection. So these are usually the most common procedures that need to be done in those patients. So in order to put all that into a higher degree of objectivity and into a more objective framework, and we are surgeons, we are not alchemists, we're not just belief, but we're not just traditioners and believers, but we now have actually objective evidence that we need to follow equally with systemic treatment. We have, within the European Society of Gynecology, identified and developed a program since 2016 of a quality assurance in advanced ovarian cancer surgery. So some objective measurements, what is needed and what is considered as highly qualified and as correct and accurate in order to be able to say, okay, I've done a correct surgery for those patients. And of course, what can we do in order to select centers and select patients? So we have defined in those quality assurance criteria, some criteria of inoperability in advanced ovarian cancer, that will help us as clinicians select those patients who are not suitable for primary bulking, but we have to divert them to either primary chemotherapy or neoadjuvant chemotherapy. So we have seen that diffused deep infiltration of the mesenteric root with retraction, so that a very large parts of the bowel and of the small bowel ending in small bowel syndrome would need to be removed. Diffuse carcinosis of the bowel parts, diffuse involvement and infiltration of the stomach into adenine would never in ovarian cancer remove the entire stomach and do an esophageal genostomy. Yeah, we would never go that far. And disease in the head or middle of the pancreas, we're not talking about this pancreatic disease, we're talking about really head and middle of the pancreas so that a complete pancreatectomy or large parts of the pancreas resulting in diabetes, et cetera, would need to be done. Involvement of the celiac trunk, hepatic arteries, left gastric arteries, we're not talking again about solitary lymph nodes of the celiac trunk. These are easily removable. We're talking about massive infiltration resulting in cholestasis, resulting in frozen lesser sac. Going further, central or multi-segmental parenchyma liver meds, patients who come to us primarily with diffused liver meds so that a single segmentectomy would not be able to deal with that, these patients should not and cannot be selected for primary surgery. Patients with irresistible extra-abdominal disease like mediastinal lymph nodes, multiple mediastinal lymph nodes, lung meds. I had a patient once who couldn't have her necklace on because she had big lymph nodes on superclavicularly so that she couldn't actually even wear a tight T-shirt. So these patients are not suitable for surgery. And of course, in more rare cases, brain meds that we actually rather see more rarely. So these are some selection criteria. The question is how can we implement it into surgical practice and daily practice? And what do we as gynecologists, surgeons expect from preoperative imaging? There is no discussion that multiple liver meds are easily seen even in an ultrasound. The question is how can a disease of peritoneal carcinosis that reaches the limit of non-receptability, how can we reliably detect that? Same with lymph nodes, same with mesenteric root retraction. So what is the status and what is the status quo currently of preoperative imaging? We have some weapons in our armamentarium. We have CT, we have ultrasound, we have MRI and we have PET-CT. All this in one group that help us. We have started since years and the conventional CT has been part of the game and of the algorithm of preoperative imaging since years. The problem with CT is that this is not highly accurate. We have in many studies, but also in Imperial, we have explored how accurate preoperative CT can be in key areas of resection. And what we have seen is that if we take key areas of resection like the diaphragm, the spleen, carcinosis of the large bowel, carcinosis of the small bowel, and rectum, porta hepatis, mesenteric lymph nodes, what we have seen is that even though preoperative CT can show a very high specificity and negative predictive value in those key areas of interest, it actually shows a rather low sensitivity and actually low positive predictive value. So very often it might say the mesentery is cleared. Actually you go in and you saw five nodule carcinosis everywhere, et cetera. So it is very tricky to be able to completely predict operability with conventional CT. You see here some pictures that I like to show and probably I've shown them in the past. We have seen them perhaps in my other talks, but they're very good representative pictures of what I want to say. You see here carcinosis of the entire mesentery, yeah. But you see here how the cirrhosis is completely spared. So we can actually strip that completely so that you can have a completely stripping of the mesentery, both sides. You always need to be careful not to work always tangentially and not to injure the mesenteric vessels because then you end up in a bowel ischemia. Same here. However, it's very tricky from preoperative imaging alone to differentiate between those pictures I showed you and those pictures, yeah. Well, you see here again, extensive carcinosis, which again in the CT would be classified as carcinosis, but these are completely resectable pictures. So the question is what can we do in order to be able to differentiate between those? I'm not going to go into laparoscopy because Giovanni Scambias is going, I believe, to talk about that after me. So in order, again, to make things more objective and to put imaging into boxes and see how can we have specific algorithms, we have now taken the new ESCO-ISOC-ESSEC consensus guidelines on preoperative assessment. This is a team, a walk that we have done together with Dirk Timmerman. It's actually Dirk Timmerman's baby, this, where I just had the pleasure and honor to help. Giovanni Scambia was part of it, Tom Bourne from the UK, Andres de Boas, many key opinion leaders, Daniela, Dennis, Ignace, many people, Philip, Maurice, where we all sat together and we said, okay, what can imaging show us? How can imaging help us in order to preoperatively select patients for surgery? And what we have seen is that, of course, tumor markers is important. MRI with the inclusion of the functional sequences is important. It's not the first tool, but can be used as a second line to differentiate between benign, malignant, and borderline masses after the ultrasound. That was a very high consensus. Apexity can detect between non-ovarian cancer origin and second metastatic tumors, but it's never the first step, apexity in ovarian cancer, especially when you talk about low-grade disease, borderline disease, it's very tricky to use and to reliably rely on apexity. What was very, very important was that imaging alone cannot and should not detect reliably the entire extent of either peritoneal carcinosis or the entire small bowel or mesentery. It was very important to us to notice that there is no single modality, imaging modality, that can tell you, hey, this is inoperable in terms of mesentery disease or carcinosis disease. Also very important, it was that imaging alone should not be used for surgical decision-making in terms of prediction of peritoneal tumor susceptibility. Again, when we have somebody with diffuse liver, lung, brain meds, that's another story, but in terms of peritoneal disease, we should not rely on imaging alone. And we went a bit further and we went and explored the new aspect of circulating DNA, which is not yet part of routine practice, but shows promising results. And I think in the future, will be implemented into future algorithms. So going away from the conventional CTs where we have clearly shown its limitations, we now have diffusion rate MR and much more advanced imaging than we had in the past. And the question is, how can we now, especially in restricted systems, prove its value and actually use it and say this is much better than conventional imaging? And one of the first attempts that are happening, or one of the many attempts that are happening, is the MROC study, which is a study that we have performed in the UK, starting from Imperial College. It's a study from Andrea Rocca and was approved by NICE. So it's a government-funded study where we try to see and compare the validity and prediction of a probability of CT between conventional CT and diffusion rate MR. So what we have seen, what we try to do is we see not just the probability, but also time in theatre, health economic analysis, and follow-up visits of the patients, and blood transfusion, need of ITU, need of other disciplines, a correlation with histology, correlation with stage. So we have brought this study much further than just mere operability in order to be able to say, okay, this is what we need. These are the criteria that we need from an imaging perspective in order to safely and accurately select patients. And this has happened in regulated, the multidisciplinary teams and tumour boards in the UK. Everything's very centralised, as you well know. So it's not just a decision of the study team. I think this is what the operable was or not, whatever. It's all done with maps, with the sugar baker maps. We think tumour boards where many experts sit together and discuss all the patient's journey in relation to how they were predicted from imaging. So it will be a very interesting study where I hope we can have the results shown to you in the next few years. Okay, so we have now predicted the operability from an anatomical perspective. The question is, is actually the patient operable? It's not just the disease operable. We can't forget, we're not operating a disease. We're operating the patient. So it's not the disease that needs to be operable. It needs the whole patient to be operable. And the whole patient is not just tumour living in the mesentery that needs to be stripped. We need to always have a real correlation of the probability in relation to age and performance of patients. We know from many studies that all the patients fit, all the patients will benefit from our debugging and maximal effort surgery like all the other patients would do. However, we also know that there is a disproportionate high surgical mortality and morbidity in advanced stage, in advanced disease patients with multiple comorbidities. We have here the data from the German AGO that show that patients who are older than 75 years and have advanced comorbidities, they actually will have a three months mortality rate of almost 30% from primary debugging and six months mortality of almost 40%. So almost half of your patients will be dead after half a year, which of course is something detrimental. For that reason, we have, in order to have a very specific and accurate and reliable selection algorithm of who would belong into this very, this small category. We have now, we think the AGO, we have done the FRAGILE study. The FRAGILE study is the, a sub part of the famous STRESS study, which is a study of primary versus end-of-life dividing surgery. And this study will hopefully give us, I think it will be reported end of this year or by this year, an algorithm consisting of simple things. Like a scientist, pleurofusion, albumin, age of the patient, performance status, that will give us a specific algorithm that will be associated with her mortality and morbidity from surgery. And will then give us like a recipe of who should be operated and who not. So bear with us. This data will come soon. And will of course help us further. And then the end part, the last part of my talk, I want to talk about the big elephant in the room, which is human biology. When we select patients, we cannot in this time and age, ignore tumor biology. There will be patients who will have a more unfavorable tumor biology compared to the others that should actually, should not be selected for conventional treatment, like conventional surgery and conventional chemo. And the question is, how do we select them? The answer is we don't really have anything reliable to select them yet. And I want to show you some data beyond conventional imaging, which we have developed in Imperial and also similar attempts have been done in many countries. This is the new aspect of radiomics. I'm sure you have all heard about it. The radiomics is an effort where according to conventional, from conventional CTs, we will have segmentation of conventional CTs that is happening in very complicated algorithms in programs where there will be a factor, a vector. We call it an Imperial radiomic prognostic vector that will predict not operability, but outcome and survival. So these are patients only who are operated to more free patients with an RPV high versus RPV low, according to the radiomics analysis and segmentation of conventional imaging. And we have seen that patients with a high RPV have a very, have a median overall survival less than two years as opposed to more than four years, five years in the RPV low group. All patients operate tumor free, all of them, yeah. And this was validated in an Imperial data set in the TCGA data set. And we also validated it in the group of SN in, by Andreas de Bois and Philippe Parter. What we have seen that we couldn't show, we couldn't validate it in the overall survival, but we could validate it in the PFS. And we have seen here that patients tumor free operated patients who had an RPV low had a significantly higher PFS compared to patients with an RPV high. So very clear signal, independent of surgical effort, independent of residual disease that will in the future also help us predict a select patients. For example, we could, in a phase three trial, select and see whether patients with an RPV low should be operated with an RPV high, should just be diverted to other techniques. And this is something that when we first published it in 2019 in London, it was even in the mail online, which is very, yeah, not very high quality surgery. It said that artificial intelligence can now predict chances of survival for varying cancer patients and help clinically select patients for surgery. So we have done many, many advances in varying cancer, how to select and how to predict, not just the probability, but also survival of our variant cancer patients. Key remains the training, the expertise and the infrastructure. And this is something that we, unfortunately, as gynecologists can often not influence in terms of infrastructure, yeah. We need ITU support. We need blood pump. We need world bed availability. We need see at a time. We need health. We need government funding. And this is something that is not a given in all countries. It may be given in very some high income countries, but it is not given in all countries. And the fact that I need five hours to do a debunking and then ITU bed and blood is fine, but it's not always available. So we very often have to divert our practice. And against our beliefs and against what we think is the right thing to do, we just have to adopt the patient's care to what we have. And of course, how important those things are, we have seen it in the pandemic, yeah. Even in countries like the UK, which are highly civilized and highly rich countries otherwise, we had to stop the primary device for at least a few months across many gynecology cancer centers in the UK. Showing how important the factor of infrastructure and support of infrastructure is. So at the end, when we talk about selecting patients, it's not just about a mesenteric node or peritoneal carcinosis, whether it's operable or not. It's much more beyond that. Yeah, it's about the selection of package of care and the whole patient's profile that needs to be evaluated. Whether we have, how we select the patient's age, patient's performance status, patient's wishes, yeah. Correlation of all that to the disease load. And of course, all this adapted to environment and infrastructure. Thank you very much. And we'll be very happy to receive your questions. Hi, Cristina. Very nice talk. Hello. Hello, Fernando. So nice to see you. So nice to see you. You know, even being a medical oncologist, I couldn't understand almost everything. So it was very, very clear. No, then I'm very happy. I'm very happy. So we are going to answer a question regarding the lecture from Cristina. So these are the key factors to predict a complete cytoreductive surgery. Choose the incorrect option. So not the correct, the incorrect. Pre-op imaging has high specificity and negative predictive value. Critical areas of interest are the diaphragm, small bowel, orthopedics, mesentery, spleen, large bowel, rectum, lymph nodes. CA-99 MRI PET CT recommended a second line tool to detect a non-ovarian origin. Imaging alone can be safely used for surgical decision-making in terms of prediction of peritoneal tumor resecability. Somebody says they can't see the English version. Yes. Yeah, that's the message. I got it here. So let's see here, you know, our voting. So the most voted question, the most voted question, the incorrect one was the last one. Cristina, can you comment briefly on the options here from A to D? Exactly. So I think what I wanted to show in my talk is that it's not, when we talk about clinical selection of patients, we talk about selection of patients, not about selection of pictures in a tumor board. Because sometimes people, what strikes me very often is that ovarian cancer patients are never even presented from the medical oncologist to the gynecologist, just because a radiologist has said to the medical oncologist that looks inoperable. So the patient never even reaches a surgeon. So at the end, it's our job and our task that it's the patient who needs to be selected for treatment, not just the picture. So on the other hand, we also, despite the advances we are experiencing in imaging, we have to really acknowledge the limitations. And all of you who operate know very well that mesenteric carcinosis doesn't equal mesenteric carcinosis. And a CT report that says, oh, this looks inoperable or it's very advanced, it doesn't really mean it will be advanced and inoperable when we open up. But also the other way around, how often do we have operable patients or we think operable and then we open up and it's a completely different picture. So that is why in all work and guidelines work that we have done within the different societies and also IGCS, it was very important that we emphasize the limitations of any single modality. And at the end, it's the different various modalities that we need to put together to have an algorithm. It's a combination of the, and what also is operable in a patient who is young and fit is not necessarily operable in an older patient with multi-morbidities. So it's an algorithm of clinical selection, not just one picture. And that is why, for example, just a tumor marker or just a picture are not enough. I think there is a question about lymphadenectomy, if I may reply, Fernando. Yeah. So the approach regarding lymphadenectomy, I think we have solved this question with the Lyons study. It is now clear that we, in all in early and in advanced stages, there is no therapeutic role of staging lymphadenectomy. There is no therapeutic role. There is a role, however, in terms of a predictive and prognostic role. So in early patients, we need to do a lymph node staging in order to be able to know whether this is an occult, so a hidden stage three disease, so that we give this patient PARPs, we give this patient Avastin. So whether we need to do a full systematic lymphadenectomy or whether we can now deviate to a sentinel lymphadenectomy, that's another question. Yeah. And we have Giovanni Scambia here who has done a very big work in that. So I think in the future, we will replace, even in ovarian cancer, in early stages, full systematic lymphadenectomies with sentinel node. It's not yet established and we need to prove the oncologic safety, but fact is we need lymph node staging in early stages to tailor adjuvant treatment, not to make the patient live longer from the actual lymphadenectomy. So that is the first. And the second is about the role of laparoscopy. The laparoscopy has definitely a very crucial role in patients with low volume disease, ascites. We don't really know where the cancer is. Is it a colorectal cancer? Is it an ovarian cancer? The tumor profile doesn't fit. We want to give a chemo because of morbidities and we can't because we don't have a biopsy that can be done imagically guided. That is a fact. So to do routinely a diagnostic laparoscopy in all patients with ovarian cancer, that's not something that I would personally support. I think to, I mean, the truly inoperable inoperable patients with extensive disease everywhere, how many, five, 10%, the rest you can really get them at least a centimeter. So to put the patient to an extra laparoscopy and the second procedure in all of the cases, I think needs discussion. And it's also not feasible in all centers to be honest. Yeah. And especially now with the more advanced imaging that we have, we can perhaps reduce need of laparoscopy in patients where we have a more clear picture in the imaging. However, in the TRUST study, we have a arm, not an arm, but there will be a population, especially the French and Italian patients who had a diagnostic laparoscopy in advance. So we can then see, we will have a subpopulation analysis where we will see the value of laparoscopy in those patients. So let me ask a question. You talk about recyclability by the criteria, you know, the role of imaging, and of course the role of the integration of molecular biology and other factors added to the volume of the disease. Yes. We have some experience in Brazil with the PET-CT in patients with a recent diagnosis of ovarian cancer, and not in my opinion to detail more regarding the disease in the abdomen and pelvis, but the extra abdominal disease. Yeah, it's a very good question. Yeah. And we do have some, you know, some patients where we can find particular in those with lymph node involvement in the abdomen, pelvis, medastinal lymphadenopathy, and even a lung metastasis. So what do you think about the PET-CT for the patients with, you know, high volume disease when you are, you know, deciding to get an operation to do upfront or not? Yeah, that is a very, very good question. In ovarian cancer, even though we operate our patients macroscopically tumor-free, we don't and we can't have the illusion that they are microscopically tumor-free. All those patients have, even after completely bulking, disease everywhere. And that's why they need chemo. Okay. So to go and chase microscopically, microscopic disease and microscopic cells that are scattered around doesn't really have value. So forget the PET-CT. Let's assume we are in Star Trek, yeah, in a science movie, and we have like a tool that could scan the patient and see the little cells swimming in the blood vessels. They would be everywhere. And we have seen in the LION study that even though 55% of the patients, 56% of the patients had microscopic lymph node disease in the lymph node anectomy arm, by removing those lymph node disease, it wasn't any benefit in survival. This means that by removing microscopic disease, it doesn't really have any benefit just because there is tons of microscopic disease everywhere. So my answer to PET-CT is that if I have a node, if I have a mass in the mediastinum or in the chest that I don't know is it infection or is it cancer, yes, do a PET-CT. But to do a PET-CT to see whether a 3-millimeter suspicious lymph node is cancer or not, it doesn't really matter. And it shouldn't also dictate the music and the journey of those patients, just because we have seen that, especially through the LION study, that these microscopic lesions do not really play their role and the patient should be treated more according to the bulk of the disease. There are many questions here. We have almost more than 250 people seeing us. It's amazing. I can go very quickly through them, very quickly, a quick answer that I can give in terms of lymphadenectomy staging, definitely not just pelvic. The majority of patients in ovarian cancer who will have a lymph node disease will be paraortic and not pelvic. It's just because of the vasculature of the ovaries, the circulation which goes to the renal vessels and not in the pelvis. If no macroscopic disease intraoperative, how far do we go in terms of radicality? Well, if we can achieve complete clearance, then we should do that if the patient can tolerate it. We should not do a full systematic lymphadenectomy in patients who are operated tumor-free. This is obsolete and we have proven that it's of no survival benefit. Cristina, let me ask a question here about the lymphadenectomy. We have three randomized trials. The last one is the LIONS trials in New England three years ago that show no role of systematic lymphadenectomy. On the other hand, it's worse because the mortality is high, precision, need for ICU, rate of infection. Everything was higher in the lymphadenectomy. But we are talking about epithelial variant cancer, particularly the serous and endometrioid types. We have some data published in International Journal of Gynecology and Oncology. First, I think, 2011. The second one, it's a systematic meta-analysis in 2017 showed that for clear cell carcinoma, the meta-analysis was stage one and the paper from 2011 was advanced disease. So both papers show a benefit in clear cell carcinoma lymphadenectomy for advanced disease and for early stage disease. So what's your take about the clear cell? Okay, so in the LIONS study, we included clear cell patients. I don't remember how high it was. We need to differentiate. So LIONS study was for advanced ovarian cancer patients, not for early ones. So if we have a clear cell with an early, presumed early clear cell, we have to do a lymph node staging to see whether we give chemo and what chemotherapy to give. Now, if there is a clear cell, advanced clear cell ovarian cancer, to remove microscopically involved nodes has absolutely no benefit. However, to remove bulky nodes, we know that there is a benefit in that. So it's, and clear cell patients have a higher risk of bulky nodes. And yes, they need, they have a higher need of lymph node dissection, but not of microscopically involved nodes. And if you turn it, and there are many oncologists who say, okay, a patient who is clear cell, because it's not a very highly responsive chemo cancer, we just operate and don't give chemo. Whereas if they have positive lymph nodes, they have a reason more to give chemotherapy. So it wasn't really the actual lymphadenectomy that made the difference, but the addition of chemotherapy, the removal of bulky nodes, but we can't say that removing microscopically involved nodes will have a benefit apart from tailoring adjuvant treatment. I don't know if it makes sense, but. Yeah, yeah, yeah. I think we, again, we are going to detail the disease more and more. And now with molecular biology, I think we're going to. Even more. Even more. And clear cell. We treat it like endometria. I mean, we do not do MMR profiling in those patients. We go even more and more, of course. So I think we are ahead of time. Cristina, we have so many questions regarding our lecture. So what I'm going to ask is, we are going to move to the next presenter. I can reply on the chat. Exactly, exactly. So thank you very, very much. And we see each other in New York, okay? Exactly. Looking forward to it. Thank you so much for having me. Thank you so much for having me. Bye-bye. Thank you so much. Thank you. Okay. So the next speaker now is Dr. Giovanni Scandia, who is going to present. It's a very nice talk about the laparoscopic selection for surgery. First of all, let me thank the organizing committee for inviting me to discuss with you the laparoscopic selection for surgery in epithelial ovarian cancer. In order to provide a comprehensive review of laparoscopic selection for surgery in epithelial ovarian cancer, I would like to divide the discussion in relation to the treatment setting, starting with the early stage disease. Even though laparoscopy in early stage ovarian cancer has been proposed since many years ago in the current literature, evidence in relation to the oncological outcome of early stage ovarian cancer treated with minimal invasive surgery have been controversial. Despite the superimposable survival outcomes of laparoscopically treated patients compared to a similar group of women treated via laparotomy, a recent Cochrane review on this topic stated that so far, no good quality evidence are available to help quantify the benefit of laparoscopy for management of early stage ovarian cancer patients. The main concern on this subject is the association between laparoscopic surgery and the intraoperative spillage of cancer cells, which can therefore negatively affects patient's prognosis. A very recent, very large retrospective study analyzed over 8,000 women with stage one epithelial ovarian cancer. And in this large cohort of patients, these authors analyzed the trends in minimal invasive surgery use and capsule rupture over time, together with the association between minimal invasive surgery use, rupture rate, and survival. In their paper, they demonstrated a 22.5% rate of capsule rupture. And more importantly, they demonstrated that capsule rupture had a detrimental effect on survival, but also that the use of mists together with larger tumor sites were independently associated with the risk of capsule disruption on multivariate analysis. Therefore, patient selection is of utmost importance, mostly in relation to the choice of surgical approach. Indeed, patient selection and survival outcomes appear to be related one to the other. To provide an objective selection method on preferred surgical approach 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 surgery through mists for early stage ovarian cancer. And the second end point was the creation of a score system able to predict the likelihood of capsule rupture. This is a retrospective single center observational course study, which was performed in the Policlinico Universitario Agostino Gemelli and in patients with early stage disease. And we also, all the preoperative ultrasound tumor characteristics were reclassified according to the IOTA classification. At multivariate analysis, only tumor largest diameter and additions to ovarian fossa peritoneum were independently associated with tumor rupture and therefore included in the scoring system. Based on this data, we developed the score associated to a specific rupture rate. Therefore, clinicians will be able to identify in which patients continuing with minimal invasive surgery may represent a reasonable option or patients in which laparotomy should be performed. So we can therefore conclude that in case of early stage disease, selection of surgical strategy is necessary to prevent intraoperative spillage and affect survival outcomes. Moreover, the application of a laparoscopic scoring system may represent a useful tool to select patients suitable for laparoscopic surgery. Moving the discussion to advanced disease, both in the last ESMO-ESGO consensus conference and in the NCCN guidelines, laparoscopy may be useful to evaluate whether optimal cytoreduction can be achieved in patients with newly diagnosed advanced disease. In our institution, more than 10 years ago, we identified a PI score which have been subsequently internally and externally validated. The laparoscopic scoring system included the six variables and it has been demonstrated in our paper that a PIV score equal or greater to 10 was associated with a low likelihood of achieving a complete cytoreduction at the end of the primary debulking surgery procedure. Independently from the scoring system, the presence of carcinosis on small bowel mesentery and mesenteric root retraction were identified as absolute criteria of inoperability. The concordance of the scoring algorithm with primary debulking surgery findings identified that primary debulking surgery was validated by other authors, confirming that laparoscopy is able to predict complete cytoreduction in advanced ovarian cancer. Other laparoscopic predictive models have been designed and validated. The R3 and R4 model scores associated computed tomographic and laparoscopic data to determine peritoneal cancer index together with lesion size score. In this paper, it has been demonstrated that all the three predictive model worked very well but the paper also confirmed the efficacy of the laparoscopic assessment of the disease. And the study concluded that all the three models were able to predict the suboptimal cytoreductive surgery even if they were more reliable for predicting complete cytoreductive surgery. Also, we have positive data or cost effectiveness of laparoscopic assessment of disease burden in primary treatment planning. In this paper, there is a clear demonstration that performing laparoscopy is a cost effective way to improve primary treatment planning and that because the benefit of laparoscopy was influenced by mitigation of serious complications and their associated costs. It is also very interesting to consider that laparoscopy could be also a good way to assess or to predict major complications in primary debulking surgery. By using this app that is now available which combines four different variables including performance status, ascites, CI125 and tumor load evaluated through the PIV score by laparoscopy, we are being able to calculate the risk of major complications for each individual patient. In this slide, you clearly see that there is an increasing risk of complications with an increase of the risk score. So by using this simple method, you can have the possibility to calculate the individual risk of the single patients for major complications at primary debulking surgery. The same selection process can be applied to the interval debulking surgery setting. Indeed, in 2010, a modified PIV score was prospectively created and published to help identifying patients suitable for complete cytoreduction after neoadjuvant chemotherapy. In this study, four of the already mentioned variables of the PIV score were included in the final calculation, each of them scoring two points. So this paper clearly demonstrated that staging that laparoscopy can discriminate patients with partially stable disease after neoadjuvant chemotherapy which can be susceptible of successful IDS. Preoperative laparoscopic selection has therefore been demonstrated to be an effective tool to plan adequate primary treatment for both primary and interval debulking surgery. But it is also important to consider that in some cases, starting the procedure by laparoscopy can also give us the opportunity to use minimal invasive surgery to perform all the interval debulking surgery procedure in patients with an optimal response to neoadjuvant chemotherapy. This mission trial was our feasibility study demonstrating that minimal invasive surgery can be used successfully in patients undergoing an optimal response to neoadjuvant chemotherapy. After this study, several other paper were published on this topic. And what we did very recently was the development of a nomogram able to predict the feasibility of minimal invasive IDS which was obtained by a retrospective analysis of over 300 patients undergoing surgery through either minimal invasive surgery or open approach. Again, preoperative variables were used to predict the likelihood of minimal invasive interval debulking surgery using multivariable models and the probability of minimal invasive surgery IDS according to the identified variable is depicted in the nomogram of this slide being the sum of the point associated with the probability of successful minimal invasive IDS. Therefore providing an assistance in choosing surgical strategy. After the encouraging result of the mission trial which has been confirmed by several other papers, we are now participating to this international prospective multicenter randomized non-inferiority phase three trial, the LANS trial in which patients with optimal response to neoadjuvant chemotherapy are randomized to minimal invasive cytoreductive surgery, the experimental arm versus open cytoreductive surgery, the control arm in terms of disease-free survival. So as far as advanced disease, we can say that the laparoscopic assessment of tumor burden in newly diagnosis advanced stage disease is able to predict the complete cytoreduction. Moreover, a laparoscopic scoring system is a reproducible, validated and cost-effective tool able to assist clinicians in patient's treatment selection in both upfront and interval debulking surgery. Now we move to recurrent disease and for what concerns the recurrent setting, again, laparoscopy is accepted by the NCCN guidelines as an adequate strategy to assess if optimal cytoreduction can be achieved during secondary cytoreductive surgery. Regarding laparoscopic selection for secondary cytoreductive surgery in our institution, here you can see the GEMELLIS algorithm to manage patients with platinum-sensitive recurrent ovarian cancer. All patients undergo PET scan, which is discussed within a multidisciplinary setting. Those with extra abdominal metastasis are sent to chemotherapy. Those with the intra-abdominal, inguinal or cardiophrenic recurrence are evaluated for secondary cytoreduction. In case of unresectable recurrence, for example, intraparenchymal liver involving both lobes or patients not fit for surgery according to performance status, they are offered chemotherapy. The remaining patients are offered surgery which always start with the diagnostic laparoscopy in order to exclude unresectable miliary disease. Secondary cytoreductive surgeries performed by open or minimally invasive approach according to the site of disease. Numbers refer to the period between 2012 and 2020 in which we have evaluated almost 450 patients. Based on this data, we show in this slide the performance and in terms of accuracy of our Gemelli algorithm compared to older methods to evaluate, to select patients for surgery at recurrence, including the AGOS-Core and the TIAN model. As you can see, probably the Gemelli algorithm has a better accuracy than the other two models. In addition, this slide shows data from a preliminary analysis carried out in our institution and not published yet, which are demonstrating an oncological safety of performing secondary cytoreductive surgery with minimally invasive approach in highly selected patients. Overall, in our institute, we test the feasibility and safety of laparoscopic secondary cytoreductive surgery. And this was done in 58 cases when there went multiple procedures via minimally invasive surgery, as shown in this slide. In this population, alongside with good intraoperative outcomes, a low complication rate was detected, confirming that in selected patients, secondary laparoscopic cytoreduction can be successfully done by minimally invasive surgery. So as far as recurrent disease, we can say that laparoscopic assessment of tumor burden to predict operability is effective also in disease recurrence. As data on minimally invasive surgery and recurrent ovarian cancer are promising, probably we need to develop a laparoscopic standardized model to predict complete cytoreduction in recurrent disease. In conclusion, I think that laparoscopy 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 laparoscopy could also give us the opportunity to perform surgery by minimally invasive surgery in selected cases. So my advice and our policy as in the Gemelli Hospital is to start every procedure for ovarian cancer by minimally invasive surgery, and then decide if laparotomy is needed or not. Thank you very much for your attention. Professor Iscambia, thank you very much for your lecture. Buongiorno. Buongiorno. It's a really pleasure to have you in this webinar that has been, you know, planned with Dr. Regia, others to other health. And we have first a poll to read and then we go over the questions, okay? So the question is, which of the next laparoscopic findings constitutes an absolute contraindication for going away with cytoreductive surgery? Number one, large omental cake. Number two, mesenteric root retraction. Number three, diaphragmatic carcinomatosis. Number four, need of bowel resection. Number five, superficial liver metastatic disease. Now people are voting. We wait a few more seconds to go. While people are voting, Professor Iscambia, I really regret that Italy is not going to play in the World Cup, you know? Yes, I know. And I'm really, I don't know how it happens. I am such a soccer fan and I go every World Cup. I'm going to Qatar, but without Italy it's not going to be the same, you know? So I really regret. Yes, thank you for your comprehension, but it's difficult to us to understand how it was possible, but unfortunately it was. Oh my God, so we have the answers and the most voted option here is the mesenteric root retraction. Professor, can you comment on that? Yes, I think that the comment is very clear because I understand that almost 80% of people answered the right answer. And I think that now we have very, very few situations in which ovarian cancer cannot be completely resected. And one is the mesenteric root retraction. As far as the others, we can do almost everything. And so I'm really happy that most of the people did the, identified the mesenteric root retraction as the only contraindications to surgery in ovarian cancer. So it's a very good answer. Okay, there is one question that is, if you found at laparoscopy a score of six or four, do you proceed with cytoreductive surgery by laparoscopic or you'd prefer to convert for a laparotomy? We do laparotomy because at present we feel that the cytoreductive surgery in advanced disease should be done by laparotomy. But we are open to design clinical trials. I think that this could be done probably within clinical trials, but at present, we do not have a clinical trial on this topic. So we do laparotomy. Okay, so that's two questions for myself that I'd like to go over with you for a medical oncologist, okay? So the first question is, what is the care? I mean, what's the precaution you do have to do in the laparoscopic procedure to not have an implant? Yeah, so you have to be very careful when you make desufflation because you need to do this to remove the trochars without CO2 in the peritoneum. And we also are very, we paid attention to closing the trochar hole very well. And I should say that in our experience, with now very, very large trochar metastasis or localization after diagnostic laparoscopy are very rare. And in any case, this do not change the prognosis of the patient. Okay, so that's a question from Dr. Farnesati. If you think that interoperative spillage in a patient with a negative peritoneal washing and had a full staging has a negative effect on survival? Yes, I think so. And so we have to avoid tumor spillage in obviously in early stage disease. And this is why we are giving us some rules about this. So we now utilize this score that is based on the combination of the tumor mass diameter and additions of the mass to the pelvic peritoneum. So I think that's this, I am a really strong supporter of the laparoscopic use in early stage disease. And, but we have to be careful in order not to have spillage. The second point that Christina was talking about just a few minutes ago was that in early stage disease, we are working a lot on the laparoscopic detection of sentinel node in ovarian cancer. This could be a good opportunity to have an assessment of the lymphologist status and with the reduction of the complications of the ectomy in early stage disease. Okay. Another question is from Dr. Miguel Erique Matute Correa is what's your percentage of conversion when you do a laparoscopic surgery? You mean in, I understand not in early stage, but in cases in which we are doing, I mean, probably. I imagine for a patient that you are thinking about resect, you know? Okay. So, please just to clarify the answer. In early stage disease, we do almost 90% by laparoscopy. It's very rare for us to convert. In advanced disease, we have to make a conversion in order to assess operability in very few patients, but they should say about 10%, because there are cases in which the laparoscopic evaluation is not good for several reasons. That could be additions or difficulty to enter into the peritoneum. I should say about 10% in which we need to convert. Okay. Another question for you, Professor Iscambia, is do you do laparoscopic and laparotomy at the same day? How long it takes the diagnostic laparoscopic for advanced? So, I imagine that the question is, if you think that the patient has to be converted to a laparotomy, do you wait for pathology or other features, or you do the conversion at the same anesthesia and just go forward? Yes. In the routine clinical practice, we do immediately. So, we do laparoscopy, and then we decide immediately if we have to convert and to do open surgery, if the patient can decide to reduce. But we have also, during the last two years, we had two clinical trials in which we did the laparoscopy and then a laparotomy, because we had a clinical trial in which the treatment was different according to BRCA status. So, we did the biopsies and BRCA evaluation in 10 days, and then we will decide the second step of surgery. But in routine clinical practice, we do at the same moment, laparoscopy and then laparotomy. What we are doing now, and this could be something to be discussed, is that we are more and more using ultrasound biopsies in patients in which we feel that the patient is not suitable for surgery. We perform ultrasound biopsies instead of laparoscopy. Okay. One more question. What are the tips from Dr. Luis Puentes, the tips to evaluate the retraction of the mesentery in a staging laparoscopy? The tips is, we have to use at least two instruments and to have a little bit experience in moving the bowel and to understand whether or not there is a retraction. But consider that when we validated our PI score, we did a multi-center study in which different centers in Italy sent us their evaluation with the video and we checked their evaluation. And there was a strong concordance. So, the learning curve to perform such kind of laparoscopy is rapid. So, after 10 procedures, we are able to make a correct evaluation. Okay. And from Dr. Patricia Paturi, during laparoscopy, from where do you take the tumor out? So, where do you take the tumor out in the laparoscopy? We prefer to do biopsies in the paracolic gutters or in the peritoneum in order to have the diagnosis. And if we do large biopsies, we put this into a plastic bag and put it out through the plastic bag. Okay. And my last question is for myself. Yeah. We have seen the robotic surgery advances in many, many, many areas. Yeah. So far in GYN oncology, you know, most of the data is in endometrial cancer. Do you see any role or an advantage so far for robotic surgery over laparoscopic? Any specific indications? Yes. If we talk about gynecological oncology in general, I think that in obese patients, robotics is better than laparoscopy. And I think also that one of the advantages of robotics is to make easier some difficult, minimal invasive procedure. So this is, I think that in the future, most of the minimal invasive surgery in gynecology will be done by robotics. And this is also why we have now more than one robotic platform available. So the future of minimal invasive surgery probably is robotics. Okay. So I have been receiving many good feedbacks from everybody, from your lecture. Thank you. Particularly from Dr. René Pareja and Aldrei Tissonoda. I hope that you cheers for Brazil in the World Cup because Brazil and Italy are good friends. Yes. And- Be sure, I will do. Okay. Professor Escambia, thank you very much for your participation. Have a super nice Saturday and you move the program. Thank you very much. Grazie mille. Grazie mille. Grazie. Okay. So now we are going to our third lecture from Dr. Michele Samora. She's a medical oncologist. She's my colleague at the AgarCore Hospital Cancer Institute. And she'll talk about how to incorporate PARP inhibitors in our practice. So I'd like to thank the GCS invitation to be here. and we're going to talk a little bit about how to incorporate PARP inhibitors in clinical practice. The studies that supported this are only one, which is PRIMA and PAOLA. In these studies, we notice that there is a difference in the size of the drugs in the population. But in general, they are a multi-use of the IV inhibitor, especially in the first line, in those patients that have the disease. And the rate of arrival is higher, and the statistics show us that it is significant. Whether it's a person that has the IPARP with that therapy, when I talk about the patients that have deficiencies or comorbidities, then we see that benefit of using that IPARP in a first-line treatment to combine this with the medication. But when I see that the patients that have ophthalmologists, I think I see a gain when we use NICAPADI, and this is more expressive when we have this with antigenic. With respect to the global survival, we see the results that are quite mature here, but we see where we see the DFS of FS2, and we see, again, also in terms of how they can survive. And it's important to evaluate this, because when I do a resection of the gynecologist's tumors in the ovary, we see that there's a great relationship between cortisol 2 and canard survival in terms of the global survival. So the thing is that we have a shorter follow-up time for these patients. So the question is, what influences when you choose the inhibitor, the IPARP inhibitor? Well, this decision tells us about the differences of the potentials of the models that are preclinical and comparing directly with drugs. Today, we know that there are differences in the studies that are done preclinically, both in terms of the power of the punnet as well as doing the PARP trapping. So there is a difference between what are the PARPs that are preferably located for each medication. But we have clinical data in the literature that shows that the PARP inhibitor is better or worse. So from the standpoint that is practical in the election today, we do this according to the guidelines in the clinical data that we have. In other words, in a study. And this decision of combining or not with the consideration of the medication, the pathology as well as the toxicity of the drug. So in terms of the clinical data that is available in the studies, unfortunately, we lost the audio. We apologize. So the Paola has all the new patients and 70% of those patients do not have a residual disease. But in Paola, we see that it aggregates. So that is why I'm not giving all that because I have an active arm and I'm allowing that this medication enters in the new adjuvants even earlier in what we consider a response to residual adjuvant treatment. So the PARP study, on the other hand, is on the contrary. I have 70% of the patients with residual disease that have the worst prognosis and here they are really sensitive to platinum. There is no use of metformin in this process of coagulants. So today, all of the parameters that we use for the treatment that we do with the PARP is whether I can provide the drug or not. And that process has become more and more important every time because we know that it increases the response rate. So, for instance, when we look at the results of the study that was done in Italia, I see that the resection is completing those patients that do this with amazocystoma. If we look at other studies like the NOVA, we can see that it increases the surgical operability, but that does not necessarily translate into a complete resection. The thing is that we're sure when we use or safe when we use comizumab and it has been broadly used in this process of no adjuvants with a differential, which is that we still do not have the information as comprehensive to see how the relationship is between the drug and the status of the PRCA. So this was evaluated in this study in the GOG 218 when we see that we can obtain over here a bigger benefit with the use of antiogenic. And this was made in the retrospective study made in Italy. And again, we see those patients that are PRC-type. They're prone to have a better gain of amizomab. So probably this is because it has a certain relationship with the molecular subtypes of TCA, and they are going to match very well with this active gel that we have here and also the immunoreactive. And it's because I do not have probably a lot of relationship with the angiogenesis and the PCR path. So what influences the choosing of the IPAR are the considerations of access. In other words, what is authorized by FDA in the United States and here in Brazil, for instance, by UNICEF. So that changes a little bit from one place to another. So I want to let you know that here in Brazil, for instance, we can use a combined therapy with antigenic and an inhibitor of PARP for those patients that are recently diagnosed with ovarian cancer. And these are the special attributes in this talk. So we see here also the different relevant toxicities between Olaparibe and Niroparibe, which is the thrombocytopenia, for instance, and the neutropenia. Olaparibe gives you more, for example, the toxicity that both medications are different. Maybe that is how we choose one treatment or another. So it's difficult to make an algorithm that includes all the information, that we still have a lot of different factors that we need to understand in a better way with this treatment of first line. But in general, we can say that when I am before a patient that has mutation or ACR positive, then we do the chemotherapy, and according to the results, we continue with a PARP inhibitor. We can also do a chemotherapy with antigenic and see if we continue only with the antigenic or maybe we associate it with the inhibitor. So in this slide, we can see the recommendation that is homologous and negative, which is the HRD negative. Specifically in Brazil, this arm probably tells us that it can be present in all the groups. So we asked today, what is it that involves the incorporation of the IV? Well, in those patients that are BRCA with a mutation there, we see that there's no doubt that all those patients should receive the PARP inhibitor. But what happens with those that have a lower risk? Well, they can do it if they don't have a residual disease, and maybe they could have a benefit. So we have to assess this. And the study is very clear where we do not apply to patients that do this maintenance with BRCA that is mutated. Approximately 60% will recur to the second year, so they all benefit. The question is, when do I need to do the blockage in those patients that is double for those that have the mutated PCRC, or how much should I keep in order to avoid a recurrence? Well, especially when it's BRCA homologous isomab. So the idea is not to compare the study with another study, but the source that financed this, both Paola as well as Solo, have the data of patients. And when we compare them between them, we see that the use of methamisomab along with the PARP is going to add some survival to free of disease. So I'm going to be talking about the statistic indicators. I don't think it has any sense. But when I look at all this data, and I look retrospectively what we had before methamisomab, if I reduce this risk in 30%, but if I compare the two arms, one with methamisomab and another one without it, then I can see a risk relationship that is similar. So what we have two here is much more speculative, but maybe it could have a synergy effect when we use these two drugs. So I would expect to find a minimum that is reasonable with a higher reduction of risk for patients. I do not see it here. So we have to think of having a test with HRG that is positive in the administration with BRC. We must offer a double blockage in this as an agent that is the sole one to use. If it is sufficient, well, I have to see if I can do the blockage, if I should use it. And if it's sufficient for those patients or not. Now, where we have more questions in terms of our HRD negative in the test. So, well, we have to see in those groups if it's worth to leave the inhibitor just for the progression of these patients when there is recurrence. So this has been highly questioned because we really do not know which is the benefit that we would be able to get or what would be the benefit to the patient. So we have to look at the data by itself. We see that half of them did not receive the second line of treatment. So, well, we were afraid of having a treatment for a second line that probably we would not be able to offer to these patients. So, during all these questions that we were making, I think we need to think about the future and how to select better. And then look at the study because we're going to need studies of HRDs that are more reliable and measure specifically what is going to happen. So, I'm talking about, because from the standpoint of the information that we have available right now to respond to platinum, there is a potential response to the iPARP, especially in this group of patients that are so selected. I have an HRD negative where we see that 34% of the patients are there. If this is a failure or a fault of our study in these HRD patients, it makes sense then to find a benefit, even in a group that doesn't have a biomarker within the study. And also, if we cannot see these 34% that had a benefit with a drug, I still have 15% that shows that the test is a no because we don't have the tissue or because it's not concluded, or it's not efficient to be evaluated. So, we need to improve the development of the study. And how can we make this assessment of HRD in a recurrent disease? Well, that's important. I have a sensitivity to platinum, but in the first line, I do not have that information. So, we have to really improve the situation and that it brings a high percentage of false negatives and starts advancing for a test where I can reduce the amount of false negatives and I can increase the positive predictive value of the test. In the recurrence of ovarian cancer, we have the development of second-line drugs that go to first line. But when we're talking about the first line, the patients that use this treatment were virgin. But when they give the second line of treatment for the evaluation of the algorithm, these patients could not have received it. So, all these studies, we have some patients that were not exposed to the first line of the PARP inhibitor. But when I look at all these patients that respond to the chemotherapy, the recurrence, all of them benefited from the use of IPARPs. So, it is interesting because when I compare them among themselves, I don't see any difference. So, therefore, whichever medication or the study we see, the reduction of risk is very similar between these drugs in this profile of patients. So, in the recurrence of ovarian cancer, we would use these options, either the platinum-based chemotherapy with resisumab or the one that is followed also with the inhibitor if there is not administration of this previously to the patients. So, how are we going to relate all this? Well, looking at the data of only two of them, when we observe the patients that receive the maintenance with the IPARP, we see that they show a response to the treatment with platinum, and they have a trend to respond less than those patients that have not received maintenance with the IPARP. So, this is extremely important to have in mind in these therapies that are made afterwards. But when these patients respond to the platinum treatment, we have the data, for instance, of Oreo, which was presented before. And these patients can benefit from the IPARP when they have a response to platinum independently from the status of HRD, highlighting that the HRD study does not reflect probably the situation of the tumor. Maybe it means that at a certain time, there was a deficiency or the homologous of resistance, but we don't know when. And the sensitivity to platinum continues being platinum. Obviously, in a lower response, we see that this is a little bit lower than what happened initially, but the benefit of the drug still exists. So, here we have a general vision of how we can include this in our clinical practice of the IPARPs, and I'm here available to answer any question. Again, thank you so much. Excellent. Excellent. I think that these are very important topics, and these are the topics that really change the ovarian cancer, and there's a lot of people, and we have a lot of questions over here with these changes. An important message that we have to transmit through the presentation is if we had access to these medications that you've mentioned, I think it's important to use them at the early moment, in other words, up front, because we don't know in reality if the patients that are going to have a recurrence, if they're going to have that recurrence with the sensitive platinum, or number two, if they're going to be responding to the platinum treatment. So we do know that a lot of them were approved for first line, but there's also a lot of questions. So this does not happen in all the patients that we treat. So using this initially, possibly, is going to be better. So very good. Let's go on with our third poll of the day. I'm going to read it in English. Parp inhibitors have been shown to decrease PFS. What is the incorrect alternative of the following questions about the parp inhibitors? A is parp inhibitors have been shown to decrease the PFS. It should be increased. Parp inhibitors can cause rare myelodioplastic syndrome. C is there is a clear evidence that some parp inhibitors are superior than others in the first line maintenance therapy. And here, therefore, we have a fourth one that says the most common side effects with parp inhibitors are fatigue, anemia, and GI symptoms. So let's wait a few more seconds. While we wait, Maluf, I would like to thank you again for the invitation and congratulate you and Audrey, who are our consultants, representatives of Brazil at GCS. Great pride, right? I would like to make a comment. Maybe, Michelle, in Portuguese you can speak, because that's our native language. I don't know if the people that voted before making the correction of the increase and the decrease, if it's going to increase the PFS with regards to that of 34%. Unfortunately, we do not have any data to compare this with the IPARP with another so that we can really choose. So the toxicity in the GI is something that is a matter of concern for us, but it would be like a procedure in our patients, and that occurs in that low percentage. Okay, do we have another question? Because I do have several questions for Professor Michelle. Okay, the first question for Dr. Michelle is in the studies that we have seen that are randomized. We included patients with stage 3 and 4 of cancer who had treatment with platinum and did not really have a progression. In other words, there was a control of the disease. And we know that the stage 2 has a possibility of recurrence of approximately 50%, pretty much. So it is quite a high percentage. So we work with treatments that are adjuvant with recurrent numbers that are much lower in other gynecologists' tumors. So my question is the following. Out of recording in a closed door, for those patients, a 55-year-old patient with ovarian cancer of high degree of stage 2, very well operated with ischemia, do we indicate the IPARP for that patient or not? I think the following. Speaking about the V2 and V large, an implant in the pelvis probably would be more comfortable to offer to the patient. If I have a 2V with a large volume, that would be the option to be offered with adjuvants with inhibitor PARP. So the big problem is the restriction that we're going to have of authorization by the plan. Unfortunately, we are not able to justify this because it's not actually represented in the health care plan. We know that IPARPs, there is no evidence absolutely of one being better than the other, but the standard of toxicity is different between them, and this is clear. So I have a patient in stage 3 of cancer that has been operated, treated with chemotherapy, and we prefer in that type of patient to see if it has a BRC1 or BRC2 mutation, or should we choose the medication that we have available at that moment. So what would you do? Well, I see with respect to the IPARP inhibitors that it's important to have that conversation directly with the patient because we have to look at the pathology, and we see that there is toxicities that are different. So I like to let the patient understand the two options and that there is that difference in the pathology when you administer the drug, in spite of the fact that it can have some side effects like fatigue, et cetera, but many times we try to do this with the chitopenia that can limit us, and maybe we have to put that patient in the hospital. So normally I participate in the decision, but I do not have a selection previously to speaking to the patient. So it's important to remember that this dosis, maybe with a higher dosis, is going to be according to the weight of the patient based on the platelets, of course, and that is in the print study. Another question in which I have a lot of doubts with regards to my clinical practice because we know that Bebacizumab, according to the JOC218 and ICON7, does not increase the rate of survival in the PFS. The disease-free survival is 218, and it maintains positive. So in the ICON7, it was positive. So my question is the following. With this data of prima paola in solo, when is it that we should think about using Bebacizumab, especially observing the load or the burden of the disease and the status of the performance? Well, before having these results of the first line in the study, we were a little bit more permissive with this adjuvant disease, but now that we know that giving this in the new adjuvants, we can do the sequencing of the treatment, and there is a trend to prescribe much less as an adjuvant. But in general, we can say that if we had to say, okay, the clinical response is very important with regards to platinum, I'm going to be starting by giving Bebacizumab, and then I'm going to have the indication according to the clinical response of the patients. And the patients, for instance, in prima, they respond very much. But if I started, I had a burden of disease that was very high, and I had to give Bebacizumab as a new adjuvant, then the idea is to include an iPARP. If I didn't start, and if I'm only going to place this iPARP, I also have a trend of giving only in the case of metamaribe, because a way or another, as we see an effect in the PVCC mutated, I think that HRD has a biological justification so I can have a synergy effect. So, there is a trend of using metamizumab, and I agree with you in this in terms of the use that is lower little by little when we use the iPARP. We have two questions. Doctor, I'm going to ask you to answer to Dr. Vicunha in the chat a question that he has about the pathological anatomy, and also Dr. Savera Taku to see which would be the type of ovarian cancer that responds better to amizumab. She wants to know if it's a serous or then the one of the endometrium, or maybe you can answer those couple questions on the chat for these two colleagues that are also congratulating your excellent presentation. You can give him a quick answer. Well, we're looking for biomarkers with amizumab. The day that we find it, it's going to be marvelous. I agree with you. Thank you so much, Dr. Michel. You are a person that I really appreciate, and I really want to congratulate you for your excellent presentation. So, now we're going to introduce Dr. Jorge Assintes. We have a 5-minute break and we'll be right back. You Okay, so everybody, we're coming back. You know, this webinar is going so well that I almost forgot the break, but the interpreters need a break, the five-minute break, so sorry for them. So now we are back. We have two more lecturers, and the first one is from Dr. Georgia Sintra, which is outstanding surgeon in Brazil. She is part of the EVA group, the Gynecology Brazilian Oncology Group, and she will talk about, you know, a very, very, you know, important team that is the role of cytoreductive surgery in the salvage setting. So, Georgia, thank you very much. After your lecture, you're going to talk in Portuguese, our native language, and I hope that their lecture is great, and I'm sure it's going to be. Thank you very much for your participation. Hello, I'm Georgia Sintra. I would like to thank the organizing committee for the invitation, and I will talk about secondary cytoreduction. I have no disclosures, conflict of interest, and in the context of primary treatment, nobody has any questions about the great importance of surgery in the treatment and the possibilities for care for the patient with ovarian cancer, but we know that despite the proper treatment, most of these patients will relapse, and it is a controversy even in the context of recurrence if surgery will continue to have an impact. Several studies talk about this topic, and they were published, and it is possible to do a meta-analysis in 2009, and the conclusion was that in the patients that were subject to surgical treatment because of recurrent ovarian cancer, complete cytoreduction is associated to the global survival, and for the selected group of patients, the surgical objective has to be the resection of all of the macroscopic disease, so a complete cytoreduction. This meta-analysis also showed us that the rate of complete cytoreduction is very heterogeneous in the studies, and that the majority is below 100%, showing for us that there is still a selection criteria lacking for these patients to know, in fact, which of them actually achieve full cytoreduction. And finally, we had the prospective studies where both were finalized in an anticipated manner because of the lack of recruitment. We have two that favor surgery that Desktop 3 and SOC 1, and now we only have the publication of Survival 3, a progression, and it hasn't shown any benefits of surgery. We will talk about each one of these, and we will be talking about Desktop Studies, which is a series of studies that were designed and developed as all studies should be, starting with an analysis that is retrospective of the cases of ovarian cancer that are recurrent that have had surgery with the purpose of generating hypothesis, and the generated hypothesis were that surgery would have an impact, but when we had reached full debulking, and that they would have a subgroup of patients in which it would be possible to anticipate this possibility of full debulking, and patients that met some criteria, of which we will now talk. And then we had Desktop 2 in 2011 that was done to validate the score if it anticipated the possibilities of full debulking. And finally, the perspective randomized, which is the Desktop 3, which was useful to assess if in fact there is or not any benefit of the surgery in these patients. So Desktop 1, the first of this study line was an analysis that was retrospective of several Swiss and German centers of patients with recurrent ovarian cancer subject to surgery. And it is important to know which patients were analyzed, why they were excluded, and which type of tumors were excluded as well according to different criteria. So we only analyzed patients that had primary debulking. And what did the study find? Well, the study found that only the patients in which all of the macroscopic disease was removed, so those in which there was full debulking, had a gain in survival, leaving the disease in one centimeter or not. But the curve of survival has not changed, it is identical. Therefore, the hypothesis of what has to be reached is full debulking with the resection of all the macroscopic disease. And the other hypothesis that was generated is that some patients that met the criteria, the specific criteria, had a higher probability of achieving full debulking. These criteria are performance at a zero, site of less than 500 milliliters, and full debulking in the first surgery. These three variables together were called the AGO score, AGO score. And so then we had the second study, which is the desktop two, that was given to validate this finding. If this AGO score was really capable of predicting the patients in which it would be possible to reach full debulking, that happened in desktop two. We found that 51% of the patients comply with this criteria of the AGO score, and that it was possible to reach full debulking in 76% of these patients. Therefore, concluding that it is a criteria that has a correct score to anticipate which patients really can be benefited from the surgery because it is able to achieve full debulking. And finally, we reached desktop three, in which we performed an analysis that was prospective and randomized with 408 patients, the first recurrence, platinum sensitive, and that complied with the AGO score and had an AGO score that was positive. These patients were randomized into surgery, which objective was to achieve full debulking without any residual disease, followed by chemotherapy, or the immediate beginning of chemotherapy. In this study, there was a participation of 80 centers in 12 different countries, centers of reference with quality criteria for the treatment of ovarian cancer. They are the same centers that participated in the LION study. To consider a center to be adequate, it is necessary for the center to have quality criteria in terms of investigation, information of clinical charts, and obviously, surgical quality. This was analyzed according to the surgical volume of this center, and according to which surgeries were performed and the debulking. So it was about centers of great volume with surgeons that were trained. The same of the LION study. So what did the curves of survival show? They showed that there was a benefit of the surgery, both in terms of survival, free of progression, as well as global survival. And when we do the analysis of the patients that were subject to full debulking, according to those that had residual disease, what was verified is that for patients that had residual disease, in fact, there was a damage caused when performing the surgery because survival was lower than in the control group, which was just chemotherapy. In the patients where there was full debulking achieved, there was a gain of almost 16 months in comparison to those patients in which the surgery was not done. The conclusion of the study is that patients with ovarian cancer that is recurrent, that is platinum sensitive, subject to surgery had a gain in global survival free of progression in comparison to the patients who were only subject to chemotherapy. However, this gain was only gotten in patients in which it was possible to achieve full debulking without residual disease, showing this way the importance, reinforcing the importance of the correct selection of the patients and the centers in which those patients were operated on. To decide to perform the surgery, there has to be full debulking because, on the contrary, we will only be causing problems for this patient. The SOC study, SOC 1 study, had a methodology and design that was very similar to desktop 3, but the inclusion criteria is the eye model associated to PCT. The eye model included some criteria similar to the AGO score, but also the FIGO stage, the CAI 125, and the free of progression interval until recurrence. This associated to PCT, so it was the way how the patients were selected for this study. What we have of publications is survival free of progression, and there is a benefit in performing surgery in these patients for survival free of progression. And finally, we have the DOG 213 study, which showed benefits for the surgery, but the design of the study was different from other studies. It was the same patients, but for them to be included, it was enough for the surgeon to consider that it was a respectable disease. There was no clear and objective criteria like in desktop 3 and SOC 1. So this is a study that is not surgically promising. The objective number one was, in fact, to verify if adding Vepsimab to chemotherapy and then as maintenance would bring benefits of survival. And objective number two would be if the surgery would also bring any benefit for these patients. The number of patients included as well was high. It was more than 400 patients, and half of these patients were Asian. The curve of survival, progression-free survival, was very similar between the group that was subject to surgery and the one that was not. And global survival showed, so far, a trend of benefit to the groups that were not subject to surgery, even though it is not statistically significant. Here we have a chart that shows the main characteristics of the three studies to help us understand the reason for this difference in the results. So as we already mentioned, the inclusion criteria of desktop 3, patients had to have AGO score positive. In SOC 1, they had to have eye model with PET CT. And in GOG 213, it was enough for the surgeon to consider that that patient was viable for debulking. And this is reflected in the full resection rate, which in GOG 213 was lower, 67%, in comparison to almost 77% in SOC 1, and 74% in desktop 3. Another very important difference is the number of patients that received the evasive smaps. In desktop 3, it was 23%, and in GOG 213, 84%. We also see a significant difference in the survival rate in the results of the study, according to the group. The group that had the best survival was group GOG 213, that was not subject to the surgery with 64 months. The group with the worst result was the group of desktop 3, that was not subject to the surgery with a difference of almost 19 months, with the same type of patients, not subject to the surgery. However, a difference in GOG 213 with the addition of bevacizumab. So bevacizumab could be the explanation for that difference in the results. In the appendices of the articles of the supplementary material, there are graphs of survival according to the use of bevacizumab. In the GOG 213 study, it shows that the curves are very similar in the patients that used bevacizumab. But the patient that did not use it, there is a very important difference in the patients that were subject only to chemotherapy and those that have been subject to surgery. But the unexpected result is that the best survival curve in GOG 213 was in the patients who were subject to chemotherapy and did not receive bevacizumab, an average of survival of 67 months. And this has not been observed in the desktop 3 study, in which the patients have a survival curve of the patients that did not use bevacizumab. And in regards to the benefit of only chemotherapy, so these results, they're different. According to the unexpected result of the group without bevacizumab of GOG 123, I apologize. There is no audio. Now it is back. Some considerations that we have to have until after all this information is transmitted. If you're convinced that secondary debunking brings benefits, you should ask what would be our conduct with those patients who were subject to neoadjuvant chemotherapy after the interval debunking and with those patients that were more altered initially because they were in centers that were not referenced. Points it is about patients who have not been assessed in the desktop 1 study, therefore we cannot use the AGO score in these patients. So we do not have the answer about what to do and what are the priorities in this context. At least in Brazil, it is the majority of the patients. So in case that you're convinced that there is no role for the surgery with bevacizumab is available, then what explanation can we provide for the 67-month survival in the non-surgical group that has not received the medication? Showing this graph once again, there is a double study that is not purely surgical. We're not able to separate which impact is the impact of the drug and which is the impact of surgery and be able to extract conclusions about this. This way, there is still a lot of questions, doubts, and open points to be able to determine the survival of these patients. So which are the conclusions that we can, in fact, obtain? There are some results, but they have different designs, different criterias for inclusion. And Desktop 3 favored surgery, so the trend of the scientific community is to consider more the Desktop 3 studies results with related to AGO. But, in fact, R2 surgery in a recurrent scenario, the proper selection of these patients and the surgery being done in reference centers is very important, it's fundamental. It is important to highlight that even though with inscribed or with properly described criteria, a fourth part of these patients, 25% of them, will not be able to achieve full debulking. And this should be assessed together with the patient and informed with the risk of the surgeries. I apologize, there is no audio. I apologize. There's somebody that has an open mic and it interferes with translation. Thank you very much. Hello, I'm Georgia Sintra. I'm here for your questions. Thank you so much. Very well, Georgia, excellent presentation. And now, we're going on to the poll. Correct option. Desktop three favors surgery, DOG 213, systemic therapy, and SOC 1, the SOC, is pain and survival analysis. Number two, good PS, complete initial surgery, ascites, less than 500 milliliters, and are some of the AGO criteria. Number C, surgery is better indicated when systemic therapy failed for recurrent epithelial ovarian cancer. And number four, a complete cytoreductive surgery is a significant prognostic factor for epithelial ovarian recurrence. Thank you very much for listening to me. And in this case, with patients with ovarian cancer, I'm going to give a few minutes so everybody can answer the poll. Excellent presentation, Dr. Fernando says. I think that the questions are coming in, and I have some questions as well. Questions that will help me to decide the best treatment for these patients. I think that the alternative that patients are choosing as incorrect is C. Would you like to mention something about this, Dr. Giorgia, before we begin with the questions? Yes, of course. I would like to answer that all of this work, as well as the question that we have, as well as what we dedicate ourselves to, is understanding if surgery of secondary cytoreduction, secondary debulking has a role in platinum-sensitive patients. And platinum-resistant patients, such as Professor Christina mentioned in her class, tumor biology is not favorable. And the therapeutic options are still much more limited. And considering all of the morbidities that we know are related to the ovarian cancer surgery, it is not initially a candidate patient. There are several cases written down. The latest one was 2015, trying to see if there was a benefit of secondary debulking for platinum-resistant patients. But we still don't have this answer. And initially, this answer is no. Dedicating a surgery, a surgery that with relevant comorbidities in the patients, there is a better option and a better perspective of control of the disease, which are platinum-sensitive. So in this space of the platinum-sensitive, we know that one of the points that is still open is the role of chemotherapy with hyperthemia. We have two studies in the first line, a Korean study that was negative, a Dutch study positive, where patients have been operated in interval or chemotherapy hyperthemia. So in this randomization, all of the status have been controversial. We have to consider in some scenario hyperthemia with platinum recurrent. We have to have, I would like for you to talk about these two groups of patients, the role of chemotherapy with hyperthemia, high-tech data in the scenario of recurrence. We have a study that was published last year with the team. And initially, it showed it's very controversial, this topic, actually. The Dutch study about the interval debulking, the DS study that published desktop three, entails that everything that was in the study did not allow to have a positive response of high-tech to indicate that treatment. And in fact, there is a Dutch study and in fact, there is a discussion precisely in the platinum resistant that the use of high-tech could improve their response. So in those patients, could have perhaps a selection of patients for this treatment. Literature does not have any answers yet. It is just studies that were not published, a series of cases. But initially, in the scenario of recurrence, what we have of negative study is the memoir study that was published last year, but without a proper indication based on literature and a practical question for you. Some cases that we have seen, the disease is platinum sensitive. But there is eventually some carcinomatosis points. And generally, my interpretation is that the great benefit of surgery comes for people who respond to chemotherapy. So that matter of patients where chemotherapy proceeds, maybe it's not the group that is most benefited from this. If you operate the patient and do chemo afterwards, we're not able to calculate if the patient will respond or not, because in those cases of full debulking, you've resuscitated the disease. So my question is, in some cases of ours, the option is to have two or three cycles before the treatment and have surgery afterwards, follow chemotherapy as if it were a debulking rescue of interval. Of course, none of the three studies did that. How do you, doctors, see? I think that as any, you have to assess what type of tumor we're seeing and what is the sensitivity to the drug. And the question of when we have the discussion of the reason why surgery would be a good option in these patients as a recurrence, one of the discussions is if when decreasing the volume of the disease to a microscopic level, which is our objective, to remove all the macroscopic disease, if that would have some sort of impact in the tumoral environment. And the immunological response is one of the discussions and the reasons why you do this cytoreduction. And if this would remove, that was improved, the survival of these patients with the debulking. And one of the questions is, if in these patients we would be increasing the opportunity or the possibility of likely resistance to platinum. So it is one of the discussions of the neoadjuvants with primary debulking, if this could really promote a discussion until becoming platinum resistant. I think that this strategy is very valuable and valid when the assessment of the patient, we don't assess that we will, or we don't think that we will achieve full debulking. In a scenario where you anticipate that you will be able to achieve full debulking, then we have the AGO scores for those patients that had full debulking in a primary scenario and non-neoadjuvants. And a good performance, we can offer the patients in which this is not possible, we will not be able to achieve full side toe, full debulking. So it makes sense in those patients. Dr. Jorge, I have another question. But for you to afterwards respond in the chat, I would like to thank you. You're very important in our country and the surgical area. And your presentation was fantastic. And now we're going on to the last one. Unfortunately, the last one, because it is a fantastic seminar. And the last presentation we will talk about different biomarkers in ovarian cancer that is advanced with Carlos Eduardo Andrade. Welcome, Carlos. It is a pleasure to have you here. It is a pleasure to be here in this wonderful initiative of IGCS for all the gynecologists and oncologists around the world. I will talk about the role of BRCA currently in our treatment of advanced ovarian cancer. I do not have any conflict of interest for this specific presentation. And we will be talking about the incidence, the difference between the mutation of BRCA, the role of this BRCA in the decision of the treatment of advanced ovarian cancer, both in the initial diagnosis and recurrence, both from the point of view of systemic treatment. Initially, the decision with regards to the role of the surgeon and chemotherapy in the treatment of ovarian cancer was much simpler. We had to choose between primary debulking and neojuventara therapy. And as a sequence, patients were subject to chemotherapy based on platinum. And the only decision that we have with chemotherapy was if we would do secondary debulking or not. And these patients would go into chemotherapy based on platinum. These decisions were based on clinical matters of the patient and some models that added imaging. Nothing too complex. But medicine has evolved. And we are having different therapies based on precision medicine that uses, for example, patients that have this genomic zone according to the deficiency and some recommendations. So in this group of patients, the inhibitors to have a therapy for this type of patients. The tests to detect the recombination deficiency, homologous recombination deficiency can be done in the tumor and in blood. If it's tested in the tumor, we're just assessing the germinal mutations as well as the somatic mutations. If we do blood testing, in this case, if we see the leukocytes in the blood, we will only have the detection of the germinal mutations. And if we have the possibility to detect both somatic or gremlin, because germline mutations are present in all of the cells of the patient's body and the somatic are present in the tumoral cells, not in the normal cells of that body. With regards to the frequency of the mutations of the BRCA, we know that these mutations are very frequent in ovarian cancer, especially in the epithelial cells. And the frequency of these mutations are at around 18% of germinal mutations for BRCA, 17% for somatic, and other mutations related to the homologous recombination index form 18% through genomic or functional tests. But we do not find a mutation in those patients. So the test to detect the efficiency of homologous recombination presented characteristics that have a difference between them. There's assays that will detect many mutations in genes that are related to the HRR pathway. And the main gene in this case is BRCA1 and 2. There are some assays that will assess alterations in the genome that happen due to a deficiency in the homologous recombination pathway. So it's as if we found the effect, the scar that the mutation is causing in the genome, which are the functional tests that look for products that are accumulated or produced from the deficiency, the HR deficiency. So in the first case, we will see the cause. We can, in the second, the effect. And in the third, we would have an assay in real test, a test in real time to assess if the HR deficiency is occurring. However, these assay have problems, a series of problems that interfere in the specificity or the capacity to really see when I find an alteration in the genome assays. Many times, it happens. Many times, it doesn't. But it happens that sometimes this has to reflect something that happened in the past and that now doesn't happen anymore in terms of the HR deficiency. In other situations, we have the test of losing sensitivity, as is the case of a patient when we do the test and we detect mutations of certain genes. But other groups of cells do not have that deficiency of HR. There is also some tests that are not validated. So to discover mutations in BRCA and HR deficiency, several studies already showed the role of these type of inhibitors in this group of patients. So this way, these groups had differences in terms of methodology that were very important. The groups of patients are different. But in general, all of these studies, here in the case of patients that were diagnosed initially with the OC, showed benefits that were significant for those patients that had HR deficiency of BRCA with a higher survival free of progression. And the recurrent disease also, the inhibitors have shown a lot of efficiencies. And these patient groups with EOC, especially patients that have BRCA mutation or HR deficiency, showing this way that there is progression free survival that is significantly higher in patients with these inhibitors. And analyzing these studies, which would be the group of patients that have the most benefit from the use of these inhibitors, we found that the patients that had mutations, whether tumoral, sorry, somatic or germinal, found in the tumor for BRCA are the patients that obtained the higher benefits from the use of these inhibitors. So these are the patients had a deficiency in mutations of other genes. These patients had significant benefit that was higher in this use. And patients that had HR deficiencies, in some cases, these patients showed benefit in the use of these inhibitors. And this might be because of some deficiencies in the tests and being able to detect patients that are not really viable and have the deficiency, the HR deficiency. Or it means that the patients were classified with HR deficiency, but did not have that HR deficiency actually yet. And related to the BRCA mutation, we still have a few studies. This Italian study is very interesting with a great number of patients. And it was able to identify that the patients that had BRCA mutation, despite having, in general, the same status, the same BRCA presence or not, did not show any significant difference of the patients that had BRCA, had a tumor load that was much higher. Together with this, it is important to perceive that in this study, unlike other results that we presented before, patients that had mutations of the BRCA gene did not have a regression-free survival that was higher in comparison to patients that present BRCA wild type or without mutations, at least not statistically meaningful wild type. But when we analyze a subgroup of patients, patients that did not have any BRCA mutation, we see that for these patients, we have interesting information. The primary debulking had a better progression-free survival, statistically significant, with regards to patients that were subject to neoadjuvant. And in the group of patients that had BRCA survival, despite that it was significantly higher numerically speaking in the patients that had primary debulking, it was not statistically higher than the patients that did neoadjuvant chemotherapy. Also, there are studies about patients and recurrence that had mutation or not. And if we analyze the patients that had mutations in BRCA and those that had secondary debulking was different than those patients with the other scenario, and this has not been statistically higher than the patients that did not have any BRCA mutation that were wild type, when they did secondary debulking, there was a survival of one year and 54%. If they did not do the secondary debulking, the number was significantly different statistically speaking. And there is a controversy, a different study. The study SOLO1, if you recall SOLO1, it says just patients with BRCA mutations. So we have a selected group of patients, just those patients that have a better response to these inhibitors. And if we see, the patients that have the most benefit are those that have a better survival, free of progression, and those that had, sorry, I lost my audio for a second. The patients that upfront was a group that had the best results in terms of free of progression survival was a group that has not reached the average of the free of progression that was achieved. And the group that had the interval surgery, the non-adjuvant chemotherapy of the placebo group, there was a higher survival free of progression. So this indication of primary surgery, or if we indicate neoadjuvant for patients with BRCA, there is still more studies missing as a way for us to be able to decide and select the patients that have benefited from one type or the other of patients. Another point that we have as an advantage is to recognize the patients that can have a benefit from this. It's the possibility of doing follow up with the family. It is recommended to all the society through guidelines. And this has a very important application for the relatives of this patient that we discover relatives that have BRCA mutation, starting from the case that we are treating. And we will discover women that do not have ovarian cancer yet, but have a risk. So if it's BRCA1, around 39% to 59%. If it's BRCA2, from 13% to 29% have the possibility. So there is a very high risk of detecting ovarian cancer throughout life. And we can then offer these women surgery for the risk reduction, removing that cancer before something happens. And for this, I need to recognize my patients, which have the BRCA mutation. And from then, I recognize those family members that have that as well. And I can prevent ovarian cancer from surgeries that are cancer reducing. So if I can't prevent, I'm going to kill those patients in an unnecessary manner. And we shouldn't forget that other genes have also have indication of risk reduction when found in relatives using certain type of genes. So as a take-home message, it is very important that we select patients that really will be benefited much more from these new therapies, mainly in a context of limited resources. It is important that we can identify BRCA mutations, HR deficiency in patients with ovarian cancer. And that way, we can select, in a better way, the patients who will be benefited from a better way from those inhibitors. Current tests have important indications, and there are spaces to develop new tests at a lower cost, and knowing that they still have to be validated. And also recognizing the patients that have hereditary signs to be able to avoid unnecessary deaths. And the relatives of these patients, that is all. Thank you very much. I'm here to be able to talk to you and answer your questions. Thank you very, very much. You're wearing the Brazilian jersey, is that it? That's it. I'm taking advantage of the cold. Thank you so much. I'm going to take advantage. It's so cold over here. Your presentation has been excellent. And here we have our poll, our questions for now, with the criteria of selection. It's what would be the incorrect alternative of the following questions about genetic testing in ovarian cancer patients? OK, here we have A, B, C, and D. In women who don't care a germline pathogenic or likely pathogenic BRC1 and 2 variants, somatic tumor testing for BRC1 and 2 pathogenic or likely pathogenic variants should be performed if available. Number three, genetic evaluation should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer. Number four, first or second degree blood relatives of a patient with ovarian cancer with a no germline pathogenic cancer susceptibility gene variant should be offered individualized genetic risk evaluation. Excellent. While people are answering, I also would like to thank the commission. We want to see how many people answer. I want to really thank the persons that organized this because I think that all the presentations have been great and very enriching. So I want to thank you especially. This is great. Thank you. Yes. This is fantastic. This is a fantastic presentation about ovarian cancer. OK, here we have the answers. I have two comments with respect to this. I agree with the answer that most of you gave with the number eight, which is actually the correct answer. Only women diagnosed with serious papillary ovarian cancer. But there's also benefit when the epithelial and the ocular cells have to be differentiated. In other words, you have to make those tests for BRCA. And the second point is a sequence for that test. That is very important. We're going to be making this test in blood. And the advantage, if we compare both of them, when you do this in blood, we really are able to discover the germ test. So you can do this to guide in a genetic way all the relatives of the patient that has ovarian cancer. So that is a test actually to assess if there is the existence of the somatic or if it's germinal. It's a germ. And we make the differentiation with other that have to do with this homologous path. If this is negative, then we know that it's not going to be a germ. But if it is positive, you have to do the test again in blood. And there is when you need to make both tests. You have to start again the test in blood to see what kind of cancer it is. If it is in blood, it will be gem. And if not, it will be doing the orientation for all the family. That is actually the process that should be held. Many times, we have to make tests in blood and also doing it in a tumor. So these, of course, are different situations in which you have to see case by case. Carlos, excellent. We have a question. We have a method that has been used in Paola and Prima and several of our studies. Do you think that other tests, for instance, the LOH, the Low Foundation of One? Which is one of the markers that my choice use apart from transition lab scale and the malary larynx. So only the AOH, is that sufficient to be able to discriminate between if it is present or absent? Or should we actually need that choice? Yes, that's an excellent question also. Questions are always excellent, Fernando. Thank you so much. We have problems. The tests were analyzed in clinical context. That was the one that was studied the most. And it's the one we use the most and we recommend the most to use because it has the tissue that is used as valid. And we have some clinics that have analyzed the eye part. But at least it is the one that is most used in these clinical trials. But we have to recognize also the limitations that this has. I already talked about this with several people and several colleagues. Maybe those, the secreto, I've already reverted. There's no specificity that is appropriate. And also, the sensitivity test is also very important. Maybe it's not so appropriate. Now, it is important to verify the sensitivity a little bit more to be able to detect more patients. Because in spite of being the best point of research, the stability is extremely important and also gives us more sensitivity when we look at the foundation test. So my impression is that it's more thorough and it should be better. But we still need more tests that actually give us a better information to be able to separate these patients. I know that this is subjective. And I know that there are some tests now that are functional tests and studies in order to really understand the mutations. These are being studied, actually. But there's no clinical trials to be able to establish if they're better in order to discriminate a patient that has homologous discrimination. So, OK. Thank you. Excellent. Thank you so much, Carlos, for your participation. I'd like first to thank all the speakers, Dr. Cristina Fotopolo, Dr. Giovanni Scambia, Dr. Carlos Andrade that gave a fantastic, our last lecture for the day, and also Dr. Jorge Acintra and Dr. Michele Samora. I'd like to thank my co-chairs, which are not my colleagues only, but my friends, Dr. René Pareja and Dr. Audrey Tissonoda for putting this incredible program for the three series. I'd also like to thank the EVA group, our Brazilian Gynecology Oncology Group, that sponsored this webinar series. And of course, all of you who attended this meeting on a Saturday. You're going to record today's sessions. And this will be available in the IGCES members education portal next week. And last but not least, we are involved as a group, not only in the country, but in Latin America and in other places, such as developing countries, in a lot of academic initiatives. So if you'd like and be interested in doing some academic initiatives with us, please send us an email so we can collaborate more and have more data, such as consensus and real-world data for developing countries in Latin America, countries in Africa, Middle East, Asia, and some parts of Europe as well. My personal email is maluf, M-A-L-U-F, followed by another F-C, at uol.com.br. So please send us an email, and hopefully we can do good things together as a whole group, particularly in the developing countries, which needs a lot of integration and collaboration. So thanks again for IGCES for the whole support. I hope you guys have an incredible Saturday and Sunday. Get rest and be healthy, you and your family. Thank you very, very much. I will try to answer all questions at the Q&A. Or send an email for me, mdcarlosandrade, arroba de email, dot com. Bye-bye. Thank you very much. Thanks again, René and Audrey, for the incredible job to put all this program together. Thank you very, very much. I'm very grateful to be with you within this program. Thank you very much all. Bye-bye. I see you.

PARP inhibitors

ovarian cancer

PRIMA study

PAOLA study

efficacy

first-line setting

BRCA mutation

biomarker deficiencies

improved outcomes

chemotherapy

bevacizumab

progression-free survival

homologous recombination deficiency

platinum-sensitive disease

pathology