Recording started? You got it. All right. So this is the talk a little bit more about ovarian cancer. This is talks in IGCS series for fellowship for the Qatar fellowship and Hiba is our star. So let's talk a little bit more about ovarian cancer. All right. The surgical option of newly diagnosed ovarian cancer. This is Moroccan objective of the study is to discuss the role of surgery in newly diagnosed ovarian cancer. And we will talk more into details about early stage and late stage. And then we'll talk a little bit more about the cytoreductive surgery and its outcome. And how do we define cytoreductive surgery? What does it entail? What are the goals? And of course, we have to always think about the collaboration with medical oncology and GYN oncology, because as you will see in the talk today Hiba, there is a lot of coordination between understanding between chemotherapy and surgery. So in a way, you know, this is just for your reference. This is nothing to spend a lot of time in. This is just basically the staging of an advanced ovarian cancer. And this, you know, as we know, stage one and two are pretty much clear, but stage three and four have changed a little bit in which in before the lymph nodes used to be in the 3C, but now they moved it to 3A. And this is just for your reference. You know, for me, I always have a slide of staging for every cancer, so I can keep an eye on things. And this is just for your reference. Now, how to approach treating ovarian cancer. And this is something that we, when you think about ovarian cancer, you always think about it as an early stage and an advanced stage. And to clarify the staging differences is the early stages, stage one and two, which I always remind myself, stage one is limited to the ovaries, stage two is limited to the pelvis. So that's how I think about things. While advanced stage is the stages that are in the abdominal cavity, in the peritoneum, which is three, and four is where deep organs, liver and spleen and beyond, diaphragm and beyond. So that's how I think about it. So let's talk a little bit more about an early stage and I have to be conscious about the time. Now, an early stage, you know, obviously this, you know, comes better when, if I am in the mode of playing. So I'll share the animation with you. So anyway, if you think about stage 1A, grade one, and I think about early stages as a stage 1A, not the grade one, and 2A. And those are the studies that we have lumped them in together. So if you think about early stages, and I want you to look at the ICON study one, action study, GOG 157 and GOG 175. Let's go line by line. If I look at ICON one, this included stage one up to 2A, in which optimal cytoreduction surgery was less than 30%. They observed versus chemotherapy, and they found that chemo is good. And we'll go through them just a little bit, you know, separately. Action trial is a stage 1A to 2A optimal cytoreduction, observations versus chemotherapy, but only four cycles, which is kind of like a little bit weird difference. And the chemo for overall survival seemed to be a better, however, that's only wins for suboptimal cytoreduction, and we'll talk a little bit in details. Then GOG 157 also included stage 1A, but grade three and stage two, and then they divided it into carbotaxel three cycles versus six, we always call it three versus six cycles chemotherapy. And then the GOG 175, which included stage 1A grade three also, to stage two, all stages, meaning all optimal, all suboptimal. And then they tried to do carbotaxel three cycles, then observation versus six months of taxol as a maintenance and there's no difference and we'll talk about that. And then we'll come back to the summary. So let's talk a little bit more about ICON one. ICON one is the study that's just rather large, included stage one and two. And this is where we say presumed stage one and two, because optimal staging was less than 30%. So we assume or presume that those are stage one and two. And they did randomize those patients after the surgery, whether it's optimal or suboptimal staging into either observation or carbotaxel for six cycles. And they found that chemotherapy actually is good for those patients. Now the five years overall survivor is 73 versus 62% without chemo. So which is clinically significant, obviously it's statistically significant. So ICON one tells us that in an early stage, chemotherapy seems to play a role, especially so if that's where you start to add the little spices on that conclusion, especially so if you only optimally stage for less than 30%. So if a patient comes in not optimally staged, presumed stage one and two, maybe chemotherapy is better for overall survival. And that's where we think optimal staging is important here. And the reason we mentioned optimal staging in ICON one being low, it's very important as we will discuss the next study. The next study is again, early ovarian cancers called the ACTION trial. Again, big number of patients, stage one A to two A, but they only included grade two and above, grade two and three and a clear cell. Now here, we said that this study included 30% optimal debulking and 60% a combination of optimal and modified optimal. And I have five slides on the ACTION trial itself in details, but let's look at the big picture. And here, this is a talk about the big picture. They did divide the cohort into two, those who are observed. So basically they did the surgery and did nothing or platen based chemotherapy for four cycles only. But when you look at the details of the study, they said four cycle plus, meaning they at least gave four cycles and they allowed patients to get more than four cycles. What the results are chemotherapy are only good for overall survival. And then we'll talk a little bit more in details. Chemotherapy are only good for suboptimal. Chemotherapy did not add anything for those patients who are optimally debulked. And when the patient does not want chemo, then you're better off with an optimal cycle reducing her. And then we'll talk a little bit, know what that means. Here are the ACTION trial outcomes. If you look at all patients, chemo versus observation, progression of free survival is no difference. Overall survival is different. So when you look at all comers, and that's where some of the most proponents arguments for chemotherapy in early stage cancer is that if you look at all comers in ACTION trials, actually chemotherapy made a difference in overall survival, 85 versus 73%. The reason is that is a little controversial. And then if you wanted to talk in more details, as we always like to discuss those in tumor board, for example, if you look at optimal cytoreduction surgery, which is a subgroup analysis of those patients, if you look at those patients in ACTION trial who had an optimal cytoreduction, actually there is no difference in the chemo versus observation. Big leap, right? Then what you are arguing saying that, hey, if it's an early stage and you optimal cytoreduce, ACTION trial actually didn't show any difference in survival, whether it's progression free and overall. And we're here, we're digging deeper into those studies. But the matter of fact, however, if you do suboptimal, if you look at the suboptimal patients, then chemotherapy did play a role, right? So that's an important thing. And that's why, you know, if you look at patients who are observed, optimal cytoreduction is the one that made a difference. Now, there's a lot of talking here, but what's the summary? If you look at ACTION trial, those patients who are stage 1A, grade 2 and above, and stage 2, those who are, you know, in ACTION trials, when they gave chemotherapy, it made a difference in overall patients. So overall survival, there is a difference. Now, on the premise for your practice, for your exam, ACTION trial big summary is the one that you, we practice. I practice that as well. Because in that sense, we are showing that when you give chemotherapy, you know, in early stage, there is a difference in overall non-progression free. The argument for the ACTION trial is that if a patient comes to you and say, hey, you removed everything, I refuse chemotherapy. Then the subgroup analysis, when they looked at optimal cytoreduction, and there is no difference in chemotherapy, then that argument holds. The argument against that is that the study is not powered to find that result. And so for that matter, when we look at ACTION trial, we say, when you do early stage of variant cancer, please give chemotherapy according to ACTION trials. And this is just the kind of like the summary of all of the study. So in a way, if I go back to the same slide that I showed you, that icon one here, icon one here, this showed that giving chemotherapy is actually better than observation, especially so if you don't optimally cytoreduce. While ACTION trial showed that chemotherapy actually makes a difference in overall survival, but not the subgroup analysis. So one can ask, give me the summary, don't give me a lot of talks. And this is where the summary here is for you. When it comes to stage one A, grade one, optimally staged, those are the patients that were excluded from all those chemotherapies. And we believe that those patients, when they optimally cytoreduce, do not need any chemotherapy. And so to take home, the take home message is the early stage grade one ovarian cancer, now tubal cancer, those are the ones when they optimally cytoreduce, we probably don't believe that they will benefit of chemotherapy. In a way, everybody else will benefit from. Whether it's six cycles or three cycles, those are the ones that is also controversial. So stage one A, grade one, no chemo. Stage one A, grade one to one C, the sum of the GOG trials, which we will talk about in the future, in the details, that there's this three cycles versus five cycles. There are 10 slides that I have on GOG 157 and the controversy around it. And so for that matter, we say, for stage one A, grade one, up to one C, when the cyst ruptures, we probably gotta give chemotherapy. A lot of physicians will give three cycles only, according the studies of 157. However, when we will discuss 157 in details, we find that it is not powered to find that result and that's why we give six cycles anyway. So the summary is, again, just back to the summary for you, Hiba, is stage one A, grade one, we don't give chemotherapy if it's optimally staged. Everybody else will get chemotherapy. Very likely that they will get up to six cycles. And that's where we will leave it like that and then we'll talk in more details when it comes to more chemotherapy in the future. Now, let's talk about the advanced cancers, so stage three and four. Now, when we look at cancer here, and this is just a chart where it looks at the number of cancer cells in the log scale versus time. And if we look, we can see that when time goes by, the cancer cells exponentially increases. If we do chemotherapy alone, there is a regression of the tumor down there, but if we do a chemo and surgery, surgery will drop the number of cells down to around 10,000 and then continues to drop with chemotherapy. This is one of the biologic arguments for us to recommend chemo and surgery as a combination for the potential cure, because each one of them is not curable. I tell my patients, if it's surgery only without chemo, it's very unlikely that we will achieve a cure. If it's chemotherapy only without surgery, also very unlikely to achieve a cure in most of the times, in rare occasions do happen. So we know the combination of surgery and chemotherapy are important. So what are the modalities of giving chemotherapies? Throughout the years, there were kind of six ways to do it. Either surgery upfront followed by chemotherapy, we call it adjuvant. There were some thoughts, which we will explore, that when we do surgery, we do chemotherapy, and then we do a second look surgery. We will talk a little bit more about the evidence behind that and what it entails. Then there is the concept of surgery, give chemo, but really go back again at the middle. They call it primary secondary chemotherapy surgery by chemotherapy, then it also fell out of favor, and we'll talk about that. And then there is a fourth one where we give chemotherapy, surgery, and chemotherapy, and that's called the new adjuvant, and then we will extensively talk about that. The other two modalities, when there's chemotherapy only followed by surgery, fell off the favor. There's not a whole lot of evidence behind it, but there's also a modality of giving chemotherapy, especially for patients who do not, who cannot go through surgery. But those are evidences that we will talk about, the evidence behind that, and then there is less likely to give you a better survival as we talked about before that, chemotherapy by itself is probably less likely to give you that overall survival. So that's less likely to be discussed. Now, in terms of the question of the role of the cytoreductive surgery, where did this concept of optimal cytoreduction come from? Did we invent it out of thin air, or there are evidence behind it? Now we go back to 1968, where the first publication came into the existence where they looked at maximum surgical effort, and they find that in 1968, they published and it'd be like, well, there seemed to be some sort of benefit to a maximum surgical effort. Then the studies started to roll in again, where Griffin in 1975 reported that surgery, probably just followed by chemotherapy, seems to improve survival. In 1978, now the concept of that optimal surgical effort starts to come to existence. Remember at that age, we didn't know if optimal cytoreductive surgery actually makes sense. In 1980s, then the ship turned around where the cisplatin came to existence, the platen-based chemotherapy, we used to give cycloagunin, well, they used to give cyclophosphamide and doxorubicin, cisplatin made a difference. And then really the first study that looked into optimal cytoreduction was published in 1992, Dr. Hoskins, where he looked at, it's a GOG52, they looked at, they said, wow, less than one centimeter is really important. And then he published another study looking at less than two centimeter. Both are studies that are done at the same time. Those are observational studies, not randomized trials. And then actually what the summary of it is that the cytoreduction, if it's less than two centimeter, remember at that time, they thought maybe two centimeter is good. So they said, referencing to anything less than two centimeter, anything more that is two to three centimeter, three to four centimeter, four to six centimeter, the risk ratio of death is higher. As a matter of fact, if you look at the first thing, you know, less than two centimeter if it's one, the risk ratio of death, if it's more than two centimeter, starts to be doubling. In a way, to summarize it, we, they used to say, hey, two centimeter is good. If it's less, if it's more than two centimeter, we have a 68% chance of more death and that's significant. So for a while, the 90s, two centimeter turns out to be the standard. Everybody used to say two centimeter, two centimeter. And that's an important thing for you to understand because when you look at studies in the 90s, they all defined optimal cytoreduction as less than two centimeter. And when you look at the progression-free and overall survival of those studies, they turn out to be less than what we see now because at that time, the optimal cytoreduction was defined differently. Now, after this, in late 90s, they compared less than two centimeter to a suboptimal. Again, same results until Dr. Bristow in 1999, that's the last study, when he pushed the envelope again and he said, no, no, no, let's push more. Let's look at less than one centimeter versus suboptimal. And then they found that if you get less than one centimeter, that is the suboptimal defined as more than one centimeter, the survival is different. So of course the study is small. That was an explorative study. And that triggered a huge sequence of events and studies to redefine optimal cytoreduction to less than one centimeter. By all means, until now, we consider less than one centimeter by most is a successful surgery. Of course, we push the envelope to less than five millimeter to complete cytoreduction surgery. And those are studies that we will discuss later, but the turnaround is Dr. Bristow's study is saying that the more the better. And then in that sense, if we combine those studies in this publication, they looked at, and this is an important for you because now we started to push the envelope. We said, if it's microscopic, look at the Kaplan-Meier curve way, way much better than less than one centimeter, which is better than less than two centimeter, which is much better than more than two centimeter. And that study, the combination of outcome from GOG 52 and 96 kind of like told us this story that a microscopic disease might be the goal. Now, how do you define microscopic disease? It's a little hard because microscopic disease is when the surgeon saw no visible disease in the peritoneum, which philosophically is a misnomer because there is a microscopic disease. There are cells in the peritoneum that we didn't reduce. So in a way, are you calling microscopic as in like there is microscopic disease or did I get to microscopic? This is a controversial thing. Nomenclature is a little bit funny, but what I want you to know that what they define microscopic as there's no visible disease. Of course, there's microscopic disease, but we went down to no visible disease. That's where the survivor really started to shine. As a matter of fact, then, you know, another publication came in, which is the GOG 104. They looked at, which is a randomized trial for IP chemotherapy, which we'll come back later. They looked at overall survival and they definitely found that microscopic disease is way, way much better than less than five millimeter and then much better than more than five millimeter. So, in a way, the overall survival for a microscopic disease turns out to be almost 72 months compared to 32 and 40 months. So, you know, that study started to show us that microscopic disease maybe is the new, is the new goal. If we look again at different studies, look at median progression-free survival and overall survival, then we can see definitely the maximum cytoreductive surgery improved the progression 20 months to 13 months and here they defined it to to be two centimeter and the overall survival is again pushed again for maximum surgical effort. So, that tells us, more studies tell us that the better, the more we remove the better it is and this is really ingrained, it should be ingrained in all of us and in your life, is that the more time we spend, the better the outcome is. As a matter of fact, Dr. Bristow also published a study and I failed to put it here but I will mention it is that he looked at all the studies of optimal debulking and they came down to a big Excel sheet and they analyzed and they found that for every one centimeter of disease you remove, the patient will gain one week of overall survival on long term. So, never the, so that tells us that the more effort you spend in the primary cytoreductive surgery or this interval cytoreduction surgery, the more time you spend to remove the disease, the better the, your outcome will be. So, now that we discuss kind of like the concept of cytoreductive surgery and then I think as I told you next time, we'll talk a little more about, you know, kind of like techniques of surgery and maybe small bowel resections and liver and spleen, kind of like highlights or a little bit of videos but here we're talking on the big picture. Now, we said okay, we did this surgery, you know, surgery is done, now what? The concept is we need to get chemotherapy. This is a slide that tells you the story of the chemotherapy right from the beginning all the way to where we are at right now. CAP used to be the chemotherapy that used to be the standard of care then and we'll go through those studies. Then GOG-52 told us that now we should do the AP, GOG-11 and 132, you know, added the Taxol and GOG-158 really started to talk a little bit more about the Carbotaxol and so GOG-158, ICON-2 and 3 and the GOG-182, those are the studies that turned around and said maybe Carbotaxol is good and then we'll talk a little bit more down the road about the dose dense chemotherapy, the IP chemotherapy, the chemo with the Bev and 218 and that's down the road but nevertheless, GOG-252, which is a randomized trial, said that you know maybe Carbotaxol is actually good and that's how, this is just a slide to tell you how the story, how we came into the Carbotaxol and I'll go through again the highlight of those studies, none in details. Now as I promised you I will just go through like all of them, this is just a slide to look at the big picture. The GOG-52 looked at cisplatin cyclophosphamide, that's the PC, cisplatin cyclophosphamide versus cisplatin cyclophosphamide and doxorubicin. Then they said well maybe cisplatin cyclophosphamide is enough. The GOG-111 looked at cyclophosphamide, I'm sorry, looked at cyclophosphamide cisplatin, the PC versus PT, which is the cistaxol. They said well you know we kind of like don't like the cyclophosphamide, how about if we replace it with taxol. So cistaxol turns out to be you know a winner and that was also replicated by the ovarian cancer-10 which is the cisplatin and cyclophosphamide versus cisplatin and taxol and that showed a difference. So at the GOG-111 and ovarian cancer-10 it seems that cisplatin and taxol are winners. Another story was told about the GOG-132 where cisplatin and taxol versus taxol again. Again all those studies for you to take home is that cisplatin and taxol became the standard of care. But the problem with the standard of care at that time was cisplatin and taxol that was a little toxic and so they started looking at the carbotaxol and then GOG-158 looked at the cisplatin and taxol versus carboplatin and taxol and they tried to like figure out if carbotaxol is not inferior can it be better and then actually they found that carbotaxol is actually non-inferior in terms of oncology and way much better side effect profile and that's a study that started to turn around. Remember ICON-2 looked at carbo versus cap, ICON-3 looked at carbo versus cap versus carbotaxol and those ICON studies looked and they said yeah carboplatin seems to be good but the 158 told us that carbotaxol is non-inferior to cistaxol and that's why we adopted the carbotaxol. Another two studies looked at the GOG-182 and the ICON-5 looked at the carbotaxol and then they definitely found that this carbotaxol seemed to be really good and then that's really better outcome for the patient. Now we say six to eight cycles because the GOG-182 and ICON-5 looked at different number of carbotaxol, the GOG-158 looked at six cycles so but by all means we always do six cycles of carbotaxol and this is just the story of how we came to understand that carbotaxol seemed to be now what we do. I'm not going to go into the details of it because we have a lot of slides but this is a slide for you this is like more into the details of the doses and then you know basically what the previous slide is and this is the again the GOG-158 and this is just something for you to for you for your reference. Now this is the summary now we will talk a little bit more about and this is again the same thing this is just for you Hiba to understand it and then to to look at it. Now the question is okay we did the surgery we did chemotherapy can we add another surgery in the middle it said maybe like that will help and actually the the summary of it is that there is no difference in outcome. There are two studies the GOG-152 and then the ORTC studies they looked at stage 2b and 4 and 3 and 4 and they what they did is surgery followed by chemotherapy then the consolidation surgery and then they found that actually there is not a whole lot of difference in progression free and overall survival. So the notion the question of can we do surgery in between chemotherapy as an adjuvant fell off the favor there are randomized trials so that's just for your reference to if a patient comes in and say hey you did surgery and the middle of the chemotherapy can you go back again and just clean up a little bit more to get more chemotherapy you I mean we tell them no those randomized trials didn't pan out to be significant so we don't do that. Now that we have done the surgery then the chemotherapy then you know people started to ask questions like okay carbotaxel is good but what about IP chemotherapy can we add IP can we get a different taxane can we get two more agents can we do consolidation after the chemotherapy why six cycles only can we do maintenance of this chemotherapy and here we're not talking maintenance as in the Bev and the Parp inhibitor that's a whole different story but really at that time in the early 2000s people started to say okay carbotaxel works can we put it in the in the IP in the in the peritoneum can we add different taxanes can we give more than six cycles can we do a maintenance chemotherapy we want it to really kill cancer and so for that matter we will discuss them in stages and then let me talk a little bit more about the IV IP chemotherapy the reason we talk about it because there are some studies that looked at the IV IP we don't practice it right now because you know as we will talk about there is another study that you know showed that there is no difference but I wanted to to talk about it because when we will talk about high-tech understanding the IP chemotherapy is important and then now there is a randomized trials looking at the IP chemotherapy back again as we as we say the IP is coming back again so for that matter let's talk a little bit more about the evidence behind the IP chemotherapy there are three GOG trials the one 104 114 and 172 and you'll see those trials when we will talk about the high-tech what the bottom line is GOG 104 looked at this cyclophosphamide cyclophosphamide and then they looked at the IP cyclophosphamide so I'm sorry IP cisplatin with cyclophosphamide versus IV only and there is a difference in overall survival so the IP chemotherapy you know made the difference in overall survival not in the progression and they said oh what else what can we do another study so GOG 114 came in and this will be the IV cisplatin versus IV taxol versus IV carbo with the IP cis a little bit you know the last four cycles for versus the IV and here when 114 told us that actually you make a difference in progression free and overall survival when with with the IP chemotherapy it is not until 172 came and that 172 and probably you know all the other faculties knows 172 became kind of like the the things that made a difference in IP everybody who loves IP chemotherapy or talk about IP chemotherapy will definitely talk about the GOG 172 where they actually did and if you look at the last slide last raw they did day one of IV taxol followed by day two of IP cisplatin and day eight of IP taxol and there was remarkable actually difference in in in overall survival as a matter of fact they always tell the story I wasn't there but they always tell the story when they presented this data at the SGO meeting and it was I think 2000 and 2001 you know there was like a silence and then there was this huge adoption of IP chemotherapy so 172 kind of like made a difference in we will talk a little bit more down the road why IP chemotherapy fell off because there was some study looking at the IV IP chemotherapy with Bev but that study kind of like showed that there's no difference between IV and IP chemotherapy and there are proponents to that study to show that well there's no difference the the the opponent of that study says that there is not a whole lot of optimal cytoreduction and Bev contaminated the data but beside the story we will leave the IP chemotherapy for another day where we will come back and talk about hyperchemotherapy and we'll talk about that study that neutralize things now that we are giving the chemotherapy carbo taxol you know four to six area under the curve and taxol every 21 days there is a big Japanese trial look at the dose dense chemotherapy and that's what the question is like hey can we give the chemotherapy differently and that's where the dose dense chemotherapy Japanese GOG trial is very very famous and you probably have to know the highlights of it because again now unfortunately it fell office of the favor again what it is is that they looked at the two two patients those who have carbo taxol every three weeks that the first column and versus the carbo taxol but the taxol were given every week so the carboplatin given every three weeks the taxol is given every every week and they have good numbers and they did show that there is a difference in progression of free survival it's 11 months statistically significant clinically meaningful but of course they failed to show a difference in overall survival whether it's two years or three years as a matter of fact just for out for the note for yourself is that the subgroup analysis showed that the really people who benefited are the young with with the pap siller cirrus not clear carcinoma and stage three not two or four so that's more of a like a academic discussion about the dose dense chemotherapy but the dose dense chemotherapy started to be again to be practiced widely in the 2010 and above I think it was published in 2010 or 2011 and then it became the thing about it does dance we will talk a little bit more about down the road when we go into details of chemotherapy why did that fell fill apart but you know I'll let you know that that kind of like fell off the favor because the GOG did replicate the study and did not find any difference although you can argue that the subgroup analysis from the Japanese GOG showed that the young the pap cirrus not the clear and stage three only the one who benefited then the question came back to be again it was like okay here's a right can we give more than two cycle consolidation and what kind and that's where some some studies have looked into this they did randomized phase 3 trials looking at surveillance versus four cycles of topotekin after that then no difference Italian study looked at observation versus topotekin no difference that's just continuation of more chemotherapy and then cisplatin also fell off there is a French and Italian investigators looked at a single high dose of carbo with cyclophosphamide with peripheral stem cells there is really no difference bottom line is after the six cycles if you consolidate with chemo we haven't seen any any benefits now that being said those are the early trials those are not the bevavizumab and the PARP inhibitors which we will talk about down the road when we'll talk more into chemotherapy I'm just giving you the big picture why do we always say yep carboplatin and tax all six cycles because the dose density didn't pan out the IP didn't pan out the consolidation didn't pan out giving more chemotherapy also didn't pan out here as maintenance chemotherapy that was a question that also was was asked and then they said I don't know if it probably doesn't work why while GOG 172 and there's a study called after six protocol in which they kind of like maintained chemotherapy to especially the tax all actually to be more than the six cycles and the summary of it is that the GOG 178 is called the maintenance tax all the after six consolidation also another tax all which is every three weeks just to give you the difference GOG 172 looked at tax all every four weeks after finishing the chemotherapy after six consolidation looked at tax all every three weeks and although 178 when GOG 178 showed a difference in progression free but the overall survival didn't difference and the biggest problem with that is that patients had a lot of side effects including neutropenia and neutropenic fever and then after six consolidation didn't show really a difference in progression and overall and that put the nail in the coffin of more chemotherapy that more tax all after so in a way a patient comes in to you or a board examiner comes and ask you to be like hey you finished six cycles of CarboTax so how about more tax all well the summary is that there are two randomized trials that one showed a difference but on the expense of a lot of side effect the other really didn't show a difference so that's why I do not and you say that I do not give more tax all after the six cycle especially if there is a response that's really now that we have bebevizumab and PARP inhibitor which we will talk about in the future. Then in that sense you know we talked about extensively talked about like okay we have surgery they have chemotherapy what about this new thing of new adjuvant chemotherapy and of course when I was a fellow it was the new thing and now it's not a new and is heavily investigated so let's talk a little bit more about the new adjuvant chemotherapy. The first trial came in I think it was 2013 New England Journal of Medicine where in in in Europe they randomized their patients into new adjuvant chemotherapy meaning CarboTax of three cycles followed by interval cytoreduction and more chemotherapy and versus primary cytoreduction. Bottom line is that they didn't find a difference in progression and overall survival. Here's what's important for us and for you to understand is that although there is no difference but obviously when you do a microscopic disease you know there is a little bit of a survival difference and when you do more than one centimeter cytoreduction there is no difference in between primary and new adjuvant so what that tells us the subgroup analysis is that whatever you do whether it's primary cytoreduction or interval cytoreduction please please please make sure that you cytoreduce down to microscopic disease coming back down to the to to that question. Other primary versus interval cytoreduction sterneries is the URTC 55971 we have the Corus, the Scorpion, the the Japanese GOG 602 they all show that there is no difference in primary cytoreductive surgery versus neoadjuvant chemotherapy in terms of survival whether it's progression free and overall survival. However all those studies show well most of the studies shows that optimal cytoreduction is important some of those studies are too small to to do subgroup analysis but definitely the New England Journal of Medicine the first neoadjuvant chemotherapy which we call the Virgo study which is Dr. Virgo is the primary author of that study showed that there is actually a difference when it comes to optimal cytoreduction there is a benefit for optimal cytoreduction. Bottom line we say when you do an interval cytoreduction make sure that you do interval and optimal cytoreduction because that will help. Now you know some of those subgroup analysis again this is just those trials where they lump them and they found that there is a difference in optimal cytoreduction and that's where the take-home message today and I wanted to wrap up so we can let you ask questions and open up for discussion is that whatever you do whether it's primary or interval cytoreduction optimal cytoreduction is really a key when we combined all those small studies the Corus and the Scorpion and the Japanese trials and they looked at the survival per cytoreduction we found that there is a difference in optimal cytoreduction. Now take-home message and here's this something for you know kind of like wrap up the first talk is that in early ovarian cancer stage 1a grade 1 really doesn't need any chemotherapy stage 1a grade 3 little controversial stage 1a grade 2 little controversial but anything more than stage 1c and 2 probably will benefit from chemotherapy we know that the as we was you looked that there's no risk clear answer to it because there's optimal there's suboptimal staging but bottom line is that we give chemotherapy and just to let you know and this is just the transparency here at the MSK we do full six cycles when indicated so we don't do the three cycles some institutions not wrong to do give three cycles or four cycles according to actual trial so that's the summary of the early the advanced you need to optimally cytoreduce and chemotherapy here's the summary if you do primary cytoreduction six cycles of chemotherapy and we'll talk a little bit more about in the future about the high-tech and the maintenance and the bath at the park but if you do neoadjuvant chemotherapy we you definitely need to optimally cytoreduce and that will be the benefit of it next time we will talk about selection between primary and interval cytoreduction surgery when do you do when you not do high-tech and then we'll talk we'll introduce the subject or the concept of secondary cytoreduction and then after that so next time we'll talk a little bit more about that then the future we'll talk we'll dig deeper into the PARP inhibitor and the bath and that's hopefully I'll ask Dr. Araui to talk more into it so I hope you find this helpful hopefully in the next talk you know it will wrap up a little bit differently and then hopefully we'll make summaries as we progress

ovarian cancer

surgical approaches

chemotherapy

staging

cytoreductive surgery

PARP inhibitors

Bevacizumab

HI-PEC