Chapters Transcript Video Multidisciplinary Treatment for Ovarian Cancer and the Role of HiPEC So speaking about the management of ovarian cancer and the role of high tech, um myself, I want to go to pretend not to understand what people really in the talk tonight. So just the objectives of the talk tonight. So we're going to review the current approaches to clinically Manager, varying cancel understand the logistics of high pick which is heated, intraperitoneal chemotherapy and its evolution as a therapeutic modality. And then we'll speak about some of the benefits of high tech in treating both primary and recurrent ovarian council. We have nothing to disclose. Yeah, I think this slide really speaks to the management of ovarian cancer patients and how important it is to really get it right with the upfront treatment and the future for these patients truly depends on what we do in the present. In their up front here next life is I speak about the burden of disease. So in 2020 is estimated that there will be about 22,000 new cases are very council and about 14,000 people will die of this disease. It's the leading cause of death among cancers and quite lethal. And the lifetime risk of developing this cancer is about 1.2%. In terms of 1.2% of women who were diagnosed at some point during their lifetime. It's a 13 leading cause of death of cancer. Death in the U. S. A. And so ovarian cancer is quite a lethal cancers. That's crazy. So my guess is cancer patients of all the age. Most of our patients are older than age, 60 patients that have a genetic mutation that puts them at risk. For example, B. R. C. A. One or two mutation and patients that have the lynch syndrome as another genetic cancer syndrome are at higher risk. Certainly certain ethnic groups or racial groups, eastern european espionage, jewish background patients are at higher risk and they are actually more likely to carry certain genetic mutations. Um Another powers patients mean that they have never had a pregnancy and childbirth are also at increased risk for this cancer. That's fine. So I speak about genetic testing and molecular profiling for this chairman. So we spoke about before there's certain cancer syndromes. Applications at higher risk. And identifying patients with these cancer syndromes may help to reduce the risk of developing cancer by during rest, reducing surgeries. And certainly if you have the cancer diagnosis, it may give us an idea of your prognosis and actually treatment options. For example, patients with BRC mutations are more likely to respond to HARP inhibitors and actually have a better prognosis overall. So about 10 to 20% of many cancers are hereditary and for varying cancel B. R. C. A one Garcia tour the two most commonly associated genes. Um And this again increase your risk of ovarian cancer. Also breast cancer. You can test with these jeans as a single gene. So if you know that particular patient has ovarian cancer and has this particular gene, you can test the family members for that particular gene mutation. Um And that would be a very directed test and is more affordable. Or you can do a multi panel testing if you're not sure that there's a particularly one mutations again increase your risk of both breast ovarian and prostate council. Similar prepares to embarrass you to actually has a higher risk of melanoma and cardiac cancer as well. Both men and next life please. So let's just look at this pie chart here and you see that mostly bears a one is the main mutation or gene mutation that puts patients at risk for hereditary ovarian cancer. But it's not only bears a one or two genes that put your risk for ovarian cancer, there are other genes. So bear say one takes a half of the price chart. They also have their say to taking a 30 and then these other gene mutations. So mutations in double strength based repair, for example, more homologous recombination efficiency genes which is A. T. M. Or red 51. And then of course your mmr gene mutations that are more common actually a part of building syndrome mutations. Other mutations are also known to cause ovarian cancer. For example A 53 and other, you know, less commonly jeans as well. So this is just the point. So it's not only only B. R. C. A. One and two. And we've learned actually through the TCG A. That there are many other genes that are associated with ovarian cancer mainly due to changes in um a DNA. Based repair. All right. So looking at the molecular data of ovarian cancer is important. So this is more looking at the semantic data from uh you're testing. So we're talking about more german line data before in terms of testing what G mutation you might have inherited. But looking at the tumor itself and looking for somatic mutation is also important. I may actually help to drive targeted therapies. Um But the two main categories overbearing cancel are based on the somatic mutations. Type one is mostly your low grade service museum Clearasil cancels. And your type two or you're more aggressive cancers are high grade service. You're hydrated and Detroit your Carson sarcomas, your undifferentiated tumors. And then the type one category, your your somatic mutations are more likely to be pr three chinese mutations, basic catholic mutations or pete and mutations. And in your type two category, which is again the most common type of ovarian cancer is going to be your high grade serious. And your high grade types is mostly p 53 mutations that identifying predominantly your brCM mutations here as well as well as um just generally mutations in All of the sweet combination deficiency jeans like 80 and my life if you are. I'm sorry. Yeah. So what's the standard approach to caring for a patient with a very canceled the standard approach is a combination of surgery and chemotherapy and what's most important is the time of surgery achieving what's called an optimal developing area or even better? Actually, no gross disease. So leaving no two minutes you can visibly see with the naked eye. And the german therapy is a platinum based therapy and also attacks all based therapist that's usually CISplatin or carbon fancy man Taxol, The median five year survival unfortunately still less than 50%. And most of our patients are diagnosed with advanced stage stage three or four and the survival drops off in less than 30%. Uh about 70% of patients will have recurrence of disease and unfortunately those patients will not be cured of their disease. Yeah. So the surgery against the foundation and the game is to remove all of the invisible disease. And we found that in patients that have no growth residual disease, they have a better five year survival. That's about 60% or more. Um patients that have less than two centimeters were greater than 0.1 centimeter residual diseases. You can see there about a 35% 5 year survival. Certainly if there's bulky disease written two centimeters of residual disease, the five year survival falls off significantly less than next time. So there was this landmark study by thomas group, it's that really showed that there is an inverse relationship between residual tumor damage on patient survival the more um are you leave at the time of side too? Reductive surgery? The worst the patient does. So this is the key. Regardless of when the surgery is done, whether it's not after chemotherapy, after new adjuvant chemotherapy or up front. Yeah. So the adjuvant chemotherapy um over the years, the G. O. G, many cooperative groups have actually looked at what's the ideal chemotherapy to get patients to the Grand Council and two minutes. That is uh looked at comparing suspecting and cyclophosphamide versus a spectacle paclitaxel and CISplatin and paclitaxel came out superior in both stories, there was a large difference in terms of the complete response rate. So you're looking at 73% versus 60% in the G 1 11 trial and in the over 10 trial is 59 versus 45%. So the standard of care became suspected and Taxol carbon Platini was looked at uh in combination with Tax law and actually showed very similar results to Cis platinum Taxol than a G O G 1 50 trial and they were compared. Um There is a difference in terms of the side effect profiles. This platform has more um new york toxicity and network toxicity. And so sometimes we use carbon platinum more often as a result. And the standard is six cycles. In terms of the human therapy. Small versus Yeah, this just shows you very nicely. The curves are separating on the left is a preparation for survival. On the right is overall survival in favor of cis platinum Taxol. So taxing based overseas platinum cyclophosphamide, cyclophosphamide really isn't used up front. Good combination with fact based therapy was taxed oil in combination with maximum is superior. So we've tried to figure out how can we improve upon the adjuvant therapy to have a better response rate for patients. And one attempt was look at boston's chemotherapy and this was giving the Taxol on a weekly basis in combination with the carbon taxes on the every three week basis. And so the japanese G. O. G. Actually looked at this and the progression free survival. Overall survival was improved with those times therapy. But this was further looked at in another clan cultural icon AIDS. That compared this dose dense, dense chemotherapy of carbon tax in every three weeks with the weekly Taxol compared to both carbon tax and and Taxol weekly compared to your usual three week regimen of carbon tax and tax of both human every three weeks. And there was no significant difference in the progression free survival. So from this icon aid study, it was then realized that this does sense. We have given tax. Oh really didn't give a survival advantage. When you looked at a wider population, you're not looking at just the japanese based population. And so given carbon platinum and tax. So whether weekly, whether those stands are every three weeks, it's similar results next, please. Okay. The question always has been um asked whether given given new adjuvant chemotherapy and then doing surgery into both sides of reduction is inferior to doing a primary site of reduction and then following an adjuvant chemotherapy. Um this is one of the things that was questioned as affecting the survival of patients. Um There is a large european study and then other studies have been done that really showed no significant difference in terms of new adjuvant chemotherapy being not inferior to primary cider reductive surgery called by chemotherapy. The most important thing actually for patients in terms of your survival. Their outcomes of prognosis is to achieve complete reception of any disease that you can see with the naked eye all microscopic disease. And that's whether you do primary surgery or you do interval surgery after. Yeah so this slide shows that this very cold study there was non inferiority. Those curves are overlapping and that's looking at primary sites or reduction followed by chemotherapy versus new. A german chemotherapy interval citing reductive surgery. And then for the chemotherapy there was no difference seen with those two groups of patients in his randomized control study. So the use of intraperitoneal chemotherapy um was looked at and thought about because of its using controlling malignant societies. And so we realized that given certain drugs for example CISplatin in the peritoneal cavity you could achieve a high concentration treating the tumor within that territorial cavity which is where a very cancer spreads on the surface of the organs within the peritoneal cavity and on the surface of the Antonio. And the principle was that the tumor and achieve potentially a better response. And so this was looked at in the G. One sent to study intraperitoneal versus ivy chemotherapy next time use and show that the I. P. Chemotherapy or intraperitoneal chemotherapy actually did an improvement in median progression free and overall survival. So it was just platinum and paclitaxel as the I. D. Chemotherapy. And that was compared to I. V. Taxol plus eyepieces platon and I. P. Taxol If you're looking at the looking at the progression free survival is there you see that five months greater progression free survival for patients that received intra peritoneal chemotherapy. It's within the peritoneal cavity and the overall survival was almost a 16 month improvement. Overall survival for I. P. Chemotherapy versus I've. This is one of the few trials and ovarian cancer that actually showed an overall survival benefit. And so really we start to think about the advantage of giving chemotherapy within the peritoneal carries are directly to the um. Uh The issue with this trial was in terms of the tolerance or actual completion of the intraperitoneal chemotherapy by the patients. Only about 40% of patients actually completed it. Um And that's because there were problems in terms of abdominal discomfort, adhesions that were farming and causing the fluid tonight diffused evenly and even more discomfort. Issues with capitals with entrepreneurial capita itself and so heated intraperitoneal chemotherapy may be a good option here. It offers a single treatment using the same intra peritoneal application of chemotherapy which is now heated. And you may avoid all these subsequent problems with the capitals in terms of giving multiple doses of introduction cemetery. Next slide please. So this event for unfortunately, a large percentage of patients with recurrent with ovarian cancer do have recurrent disease. And in these patients we wondered if picking up this recurrent disease earlier leads to improve survival. And this was looked at in a very large trial. That's your EORTC 55955 trial. And it looked at patients that were treated based on rising CEO 1 25 levels or biochemical returns versus having clinical symptoms of disease. And it really showed that there was no difference whether you treated when there was a rising CEO 1 25 or when patients became clinically symptomatic. And so this was not like a win for us in terms of figuring out how we could achieve better survival for patients. The systemic treatment recurrence has always been based on platinum sensitivity and that continues to be the main driver in terms of outcomes for these patients and next life is so this just shows again, it doesn't matter if you treat based on biochemical recurrence or clinical symptoms. There was no difference in terms of gross and thanks. So we tried to figure out what can one improve like lengthen the time for their actually to be a disease. Um, recurrence, hopefully prevent a recurrence and have long term remission. And one of these things that has become the mainstay of therapy now for ovarian cancer patients is maintenance treatment. And there are two agents that were using park inhibitors and devices. Um they're both FDA approved for maintenance therapy. Again with the hope of achieving a long term remission or even preventing recurrence altogether, achieving action. That's right. Okay. So the three part inhabitants are approved. Their limp Arzo Rebecca and Julia and limb parsa is approved for first line therapy. First line maintenance therapy after you've got your first line treatment with Carole, patton and tax or platinum based. And you have a complete or partial response. Um You have to be a patient has a somatic or germline BRCA mutation and then receiving elaborate Berlin parsa offers uh improvement in your progression free survival. It's also there's also if the approval for a new record or see Julia for maintenance after first line treatment with platinum based chemotherapy as well. But the Julia is agnostic of the BRC mutation um whether it's president or not. So it's for all comers. So again, uh limp Arza is specific locations that have a somatic or germline BRCA mutation to receive maintenance treatment after their first line chemo. And the rapper is not specific in terms of the FDA approved vote. And then uh impartial rubraca and the Jeweler are all approved maintenance therapy after two or more lines of chemotherapy for patients that have a complete or partial response to platinum based therapy. And it doesn't matter. Again your recommendation status. So this would be for a patient that has unfortunately recurrent disease treated with platinum based therapy and has a complete or partial response to platinum based therapy. Then any of these three apartment is this could be used for maintenance to hopefully prevent further recurrence Bill. This is a map is also if they are approved after first line therapy for maintenance and it's actually given up front. It's approved to be given up front with carbon tax and tax cell and then continued as maintenance therapy for 16 additional cycles. And that was based on geology to 18 study. And there's also not a study that actually led to the approval of the combination of devices, a map and limb parcel for patients that have uh August recombination deficiency after their first light therapy as well. And so we've we've tried all these ways to try and improve outcomes for patients with varying cancel because again, these patients are not having great Fire Bureau survivals. Um the different treatments that we've tried in terms of employing these different treatment strategies have pushed the bar literally each time. But still we haven't had any great games. And certainly intraperitoneal chemotherapy as its its restrictions in terms of patients being able to tolerate it. And so heated intraperitoneal chemotherapy presents a great option for patients in terms of improving their survival and their prognosis and their tolerance of this therapeutic modality. So next we'll have dr Rutherford speaking about the logistics of pipe at its evolution as a therapeutic modality. Hey Diana, why don't you come over and get me a full screen here. All right, good evening and thank you for everybody coming tonight. We appreciate your time. Mhm. Okay, we're gonna talk about high peck and how it started and I can't get that click up. Don't worry, it's gonna be hard. Hey Gretchen, can you you? There we go. Never mind. We got it. Thank you Diana. All right. Maybe we have the next slide please. Mhm. So, what is high pack Hi pack is heated, Intraperitoneal chemotherapy. It's a highly concentrated chemotherapy that's delivered into the abdomen. And the solution was sailing is heated. The theory of high peck is sort of like the interpersonal chemotherapy and that its direct treatment to the site of the cancer cells heating this solution we believe increases the absorption of the chemotherapy into the cancer cell itself. The other thing the heat does is we know that at 42° centigrade that the cancer cells should not be able to survive that heat. You have the next slide please. Hi Peck was first introduced in 1980s. It was produced, it was used for peritoneal carcinoma, ketosis which means that there's cancer all over the abdominal cavity. The hypothermia we think boosts the absorption rate of the chemotherapy into the cells and actually causes that chemotherapy to accumulate within the cell when you do um When you decide what drug do you want to use for intra peritoneal work the drugs that are really being used currently probably like the cis platinum, the mighty mice and see Dr Robinson. So what you want is a high molecular weight and a low water soluble bility drug. This platinum high molecular weight. We use that for most of the primary peritoneal cancers. We use that for like the ovarian cancer from mesothelioma is and a lot of them using his tumors so that probably those two are the most common drugs currently used. Currently a lot of people are looking at other drugs. They're looking at. The tax aims to see if there might be a survival advantage coming off of changing the chemotherapy. But we're gonna have a little conversation about that. So when should high peck be used? And that's that's a good question. So do you use it in the primary setting at the first time? You? D bulk, somebody should you use it after neologism chemo. Can you use it at the time of recurrence? Can you use it as second line treatment? So in 19 2006, Milan actually looked at hi peck and they determine that probably it's feasible at any of these time points. So the real time is nobody really knows what the right answer is to this point. So high tech was originally coined by a gentleman's um dr paul sugar baker. Dr paul. Sugar baker was used in the high peck for the nuisances, tumors and the appendices us. In fact, it's probably standard of care for anybody within appendices cancer. Today, it was originally coined the sugar baker um pro protocol. The problem is when people try to do these protocols and tried to do what he did, Nobody could reproduce it. So at first he would sort of looked at like, well maybe this isn't really true. The problem was that back when he was doing the original procedure, they did what was called an open technique. And I'll show you that in a bit. And today we're probably using we are most people using a close technique to do the procedure. The other thing that people have to realize is surgical technique has really changed over time. So today, back um when we're currently doing this, we have the body which is an electric quarterly device. We have the ligature, which is a ceiling device. When they were doing this, you have a bleeder, you're gonna you're actually going to have to tie it. So, in morbidity to the patient based on just stripping and often bleeding. So that was I think with the change of surgery and the surgical techniques, the high tech procedure. Many more people. And we can now approach the results that dr sugar baker originally had next time. The energy is high peck. Again I can have a higher dose of chemotherapy. I can concentrate that chemotherapy in the abdomen. The other thing is that minimizes the rest of the body's exposure to the chemotherapy. If you look at like intraperitoneal chemotherapy, everybody talks about abdominal pain, they talk about um some nausea with the cIS platinum. We tend not to see that in the height when we do the high pack which is important. We also have less to minimal effects of the chemotherapy of the toxicities when we do it interfered to kneel on the high pack. Yeah absorption. So you can see definitely mone marrow suppression off amid a mason. If you're using CIS platinum, there's really if I didn't tell you, we put it in you probably wouldn't know that. We even use the drug next slide. So hypothermia, we know that malignant cells are selectively destroyed and a range of 41 to 43 C. We also know that the micro circulation of most malignant tumors has decreased blood flow. And even we'll have a stasis meaning the blood is not moving. Do the hypothermic E. And that increases those cells to undergo um automatic self death. That does this by accumulating lactic acid. It lowers the ph in the environment of the malignant cells and those cells are much more fragile. And then you add the chemotherapy on top of it and then that should increase our kill rate on these cancer cells next time. The depth of penetration is 3- five. So when you look at how far that heat is going to have a benefit to you, it's going to be superficial. So if you have cancer sterilize that lymph node, the chemotherapy we're giving will not sterilize that lymph node. So what you really need is an adequate sight of reductive surgery. And that was shown originally as a doctor towards 25 mm is the largest diameter that should be considered for a residual tumor. If you're going to consider site of reductive surgery to be optimal for high peck. Well, what what we started in, what we can currently do here at Tampa General Is any tumor that you should see? You need to devote meaning removed. So any patient that we have going on for hypothermia and chemotherapy and high tech. We are reducing that patient and no residual disease. Next slide hi peck. We perform at actually that. I apologize. That should be Oh this was an open technique, open technique technique. We're getting the patient of 42 C inter abdominal since platinum 100 mg per meter squared, we get 50% of the dose Initially at zero time, 25% at 30 minutes and 25%. And that's six minutes over a total 90 minute infusion. So again, there's an open technique which basically means we have an abdomen with a midline incision and we fill that abdomen with fluid versus a closed technique means we use a temporary closure of the abdominal cavity next time. So who would be a good candidate for high peck procedure? So basically today it's being used for varying cancer, colon cancers, gastric cancers sued a maximum of parity which is using his tumors appendix, he'll tumors. And we just did a lady with mesothelioma this past week. You need a good performance status. You have to watch your other co existing comorbidities, meaning if you have somebody with minimal cardiac function. One of the things you have to be able to do, because you have to have the ability to move a lot of fluid through the kidneys to protect the kidneys from the heat. And you have somebody with cardiac significant cardiac disease or pulmonary disease because we could have fluid going into the lungs and they have decreased pulmonary function to begin little disease. We prefer to have no residual disease. And early on I had no nodal disease. The article that came out that um Dr. will talk about in January 2018 actually showed a benefit even in patients that had nodal disease. So I had to obviously rethink that thought, thanks. What does not work in for high peck is those patients we find at the time of surgery that have a secret tricks of bow, meaning all the bell is um adherent down to the root of the medicine terry. It's sort of like taking a close line, putting a sheet on it, gathering it in the center and then just crumbling all that down to the to the center where you're holding the sheep. So if you have a circuit tracks, there's no way you're getting chemotherapy or heat around that. You have the complete carcinoma ketosis. So if you put a hose in a wheelbarrow and spray it with black paint and you can't get all that black paint off, that's not, that's not going to work. I think the real question is coming down to nodal disease and I think that the papers are coming out, there's definitely benefit the high peck. And those women that have nodal disease at the time of the surgery, obviously we want the patient to have no residual disease and we still hold that pretty true here at Tampa General Next So this is a pelvis that we often get into. You can actually see like the little purplish blue, it looks like a little marble right in the center. And you can see this the structure coming down that's being the bow and a lot of the marbling in the abdomen. That's often what we get into initially. So if you go to the next slide, this is after we strip out the entire pelvic floor. So you can actually in this slide, you can see the iliac vessels, But you're coming up around 11:00 on your picture and thats futures down on the vaginal cuff and right in front of it's actually the rectum. So here we cut out part of the rectum in order to get this patient to no residual disease. We do the same kind of the bulking in the upper abdomen. Will strip out the diaphragm will take out the spleen will cut out part of the liver. If we have to cut out the diaphragm will cut out the diaphragm. We take out the fossil form ligament. We take out the globe bladder. We'll strip the entire pelvic peritoneum. If we have to take out some of the medicine, terry the balance strip the tumor off the bow, so basically again, no residual disease. Next time these are what the catheters look like. There's a total of um to leeds and four catheters. So these two catheters would go above this liver and above the spleen against the diaphragms. And then we put two catheters into the pelvis. Next slide, this is a close technique, so this is what we do here at Tampa General. The advantages as I can push the heat in the abdomen up to 42 degrees and maintain it while we circulate When we put these catheters in, we use a temporary closure. We fill the argument was somewhere between 4.5 to 6 leaders of normal sailing heated to 42° and then we put the first portion of the chemotherapy head. We add the chemotherapy, we put 2/3 up front and 1/3 at 45 minutes. Why do we do that? It's just where I was started to be trained early on and we just held to those numbers next line. So this is the actually patient here at Tampa General. You can see both catheters are in, it's actually being circulated. We actually have drapes. You gotta remember we have chemotherapy in the abdomen. So anything that's coming out of that abdomen, it will be considered a chemo spill or so. We have to handle this as a contaminant. Next slide this is actually the circulating machine that we have here at Tampa General. This will maintain our temperature somewhere between 42 and sometimes we'll sneak it up to 43°C.. We monitor lactic assets and all sugars and potassium chloride because we're pushing a lot of fluid through these patients. We want 200 ccs of urine output per hour which is a fair amount when you think about it. So and that's how we protect their kidneys. Next slide these are the mats that we put on the floor in case we spill chemotherapy. So again we handle this as a contaminant on the floor. Everything is handled as a contaminant. So the O. R. Is just not mop the floor. It's we have to clean the O. R. As it's been contaminated by chemotherapy. That doesn't mean we dump it there on purpose But it does you can get some spillage here and there. Next slide So high packed after you. I showed you the original pictures where I had the rectum resected. We do know that after high peck we will do the re anastomosis After we wash out all the chemotherapy. Because if you do the anastomosis first we have a higher rate of about perforations. Um The orders a small bowel um portions of the diaphragm are resected they repaired prior to the high peck procedure. So again the balance anastomosis are completed after the hi pecs completed. Anything else we do before If we need to take out the liver, the spleen gall bladder that's again performed all prior to the high peck procedure itself Patient we usually transferred to icu. The majority are intubated. And the big reason is fluid management for the 1st 24 hours next fine. So high pick the side effects and complications. You've got to worry about bleeding. So if you have an abdomen with five liters of sailing and you start all of a sudden that fluid turns red and you did like an IBc repair. You got a problem. We were having a fair amount of problems with aliases post um surgical. We were using some I. P. Drains. Sometimes we use it. Sometimes we don't. The big problem for the high pack as you got to worry about metro toxicity renal failure. Therefore we maintains the patient's blood pressure a little higher than baseline. We push them with Lasix and a ton of fluid surgical site infections. In theory is supposed to be higher. We have not seen that here at Tampa General Milas suppression, especially with the Mighty Mason is a real possibility that lady that had platelets after using my to mason, about 3-4 weeks out were around six for about 23 weeks next. So I'm put in 100 mg per meter squared of chemotherapy using cis platinum. You think 100 mg of chemotherapy really is going to kill cancer cells just as the one time 90 minute dose? Or is there something else that really goes on in the high tech? And I think if you start looking at it and even on the inter personal data if you go back and look at that data from Armstrong they had patients that were not treated with chemotherapy. They had courts placed and they did better than the people receiving. Uh I be chemotherapy. So the question is why So I think immunotherapy and that we cause an immunological response. Changing the micro environment is a major thing that happens. It's just my thought. I have no data to prove it. I'd like to introduce matt Anderson. Um not is probably one of the smartest scientists in ovarian cancer that I know and he will go on and discuss the clinical impact in treatment. Thank you. Well thank you for that. Hard to live up to introduction. But so uh I think what we'll do now is take a couple of minutes to kind of go back. You've heard from Dr english about our current this current standard of care for treating ovarian cancer. Um you've heard from Dr Rosa for a lot about how we actually do high peck here at Tampa general and a lot of the rationale and surgical, particularly the surgical rationale for how we perform this procedure. Um and so now that we've discussed this sort of logistics and how this treatment potentially fits into the current standard of care for treating ovarian cancer, it would be really nice to take a couple minutes to evaluate how we are actually, what data exists to support this. Um The scientific rationale for doing this um and where the field may be headed in the future and areas of active investigation that we are not only pursuing here attend translation of perspective. Next slide, please, if you go back and you pub med, high pick and ovarian cancer, you will very quickly come up with literally hundreds of articles, published manuscripts that had examined the clinical feasibility, safety and or outcomes for the use of high pack as a treatment modality for ovarian cancer and as a clinician and as a translational scientist, this technique is of great interest to me because as Dr Rutherford points out, there is this long standing history of the use of a combination I. V. I. P. Chemotherapy that suggests that outcomes are better with combined treatment. Now. Is this due to he is it due to the inflammation or inflammatory response we're inducing by adding high peck into treatment. Is it? Do? And again there's some data to suggest that this might be true but what is very clear is that ovarian cancer as a disease is somewhat unique among many of the solid uh solid tumors solid malignancies that oncologists take care of. Um And so and this is in regards to how it metastasizes. So there is a very interesting biology of ovarian cancer where the metastases of this cancer is essentially limited to within the peritoneal cavity. Do you see a lymph node metastases? Yes you do. Can you see uh solid, you know metastases to the liver Perrin comma or to the pulmonary parent comma. Yes but that's not a common occurrence and likewise, you know, you do not commonly see distant metastases, hematology has spread that goes to the C. N. S. Now. You know, if you're savvy and you spend a lot of time following the literature of the translational literature, you can say well Neil stood has this really cool model where they literally, so to mice together and show that you can get uh hematologist dissemination of cancer from one mouse to a totally separate living mouse where even asked the most uh the mice to each other from the hematologist mechanism. But again that may not be clinically relevant because that's not how we see this cancer behave in actual human patients. And those mice were immuno suppressed, they lacked an immune system, the vast majority of our patients and ovarian cancer possess. Um And so this biology, there's a unique biology that revolves around the spread of this cancer as a parent meal uh disease. There is unique aspects of that biology in terms of how the cancer survives within floating within acidic cells, how it may land and grow in the momentum, which again, I'm not sure if DR Rutherford mentioned this, but we spent a lot of time ensuring that we perform a complete romantic to me as part of our d bulking because that momentum contributes aspects to the biology of the disease. Once in ovarian cancer lands and grows and that momentum, there are multiple lines of evidence. We have, one from my lab and other labs and strangle in Chicago that show that that the fact that the tumor has landed a momentum has changed the epigenetic of that tumor in multiple ways, including the transfer of lipids directly from adipose cells uh in the momentum to the tumor cell that promote its aggressiveness. Um, and so, uh, there's a very strong biologic rationale for why high peck should be clinically not only feasible, but also attractive as a potential a tool for treating ovarian cancer. If you go back and look at the data that exists, you will see a lot of controversy because the majority of these studies are retrospective and include relatively small numbers of patients. There may be small case series, multiple issues with how some of these other studies have been uh conducted. Oftentimes subjects have been divulged to varying degrees. Um and they include diverse tumor histology ease, which becomes very quickly important because as we'll discuss a little bit as this talk goes on, um, the key cancer drivers, the underlying genetic drivers for different histology of ovarian cancers. Even the differences drivers within high grade serious carcinomas, which can differ based on the genetic background of patients is potentially very impactful for how your tumor responds to different types of treatments, including potentially high pack. Um And the other last issue is is that chemotherapy regimens have different significantly between these different studies. Um And so not all these studies have established a standard or a gold standard which which comparisons have been done. Um Different patients, different patient pools of different studies have used patients that are different context of some patients haven't received neo adjuvant chemotherapy, the numbers of cycles of chemotherapy and in addition, that vary dramatically from study to study. In addition to the types of chemotherapy that actually used to perform the high pack uh treatment itself. Not to mention some of the details that Dr Rutherford mentioned. Now people have attempted to overcome some of these limitations by doing a variety of meta analysis of this literature. Next slide, please you understand? This is question we have a question. Can high peck be performed on a re occurrence? Can you do what I'm sorry, can high peck be performed on a recurrence? Yes, we would believe it can. And there's some data to suggest that that's feasible. Again, the key, you know, and I'll get a little bit into this as we go on the key. The key questions are is that platinum, is that patient platinum sensitive? And can you achieve an optimal the bulking, which are really the key questions that you should be asking before you consider the bulking any ovarian cancer patient anyway. Okay. But in short, yes, we would believe that if the patient is platinum sensitive and we can achieve an optimal r zero to bulking, where there is no visible disease left behind, then yes, we would perform high pack for that patient. We believe that it works and there's some data to support that. Okay. Um if you look for example here one a day to uh this is a meta analysis that was published in 2015 but this actually was performed investigators. A group from uh europe actually searched five different clinical databases including Pub Med. Uh They identified a total of 37 studies, nine of which included some type of a comparison between different types of chemotherapy treatment plans, all of which. We examined retrospective data from clinical outcomes of epithelial ovarian cancer patients undergoing high peck. Okay. Um and they found in general um summarizing again, glossing over a lot of these details are trying to synthesize and integrate this detail across very disparate types of studies. They, their conclusions were that high peck plus a chemo, a surgical reductive surgery, plus chemotherapy, some type of neo adjuvant or adjuvant chemotherapy at a significantly better one year survival rate compared to patients that only went side of reductive surgery plus uh graduate or Neo Adjuvant chemotherapy. And that the odds ratio for for survival after one year was an impressive 3.76 So that means that patients four times more likely, almost four times more likely to survive, be alive and doing well one year after having undergone aipac. Um And then if you go in and then try to extend those analyses out earmarked as the 2345 and eight year survivals that were available through some of these studies. And again, this relative ratio of almost a 3 to 4 fold improvement in survival persisted across that time frame. Now. When they went back and tried to do some pooled analyses for patients looking into primary uh as a treatment tool for the primary treatment of epithelial ovarian cancer. They saw a similar improvement of survival rates. Um and the media 13 and five year survival rates for that. That pooled subset of patients undergoing high peck for the primary treatment. Ovarian cancer was 85 almost 86%. Uh 54 46.3% uh for patients. Um uh to me, it's 88, and 51 For patients undergoing high pick for the primary therapy of ovarian cancer. And when you go back and look at for patients with recurrent cancer, those survival rates are 86, So almost as good. Okay. Uh when you use and integrate high pack into part of the treatment is the current uh for the treatment of our current cancer. And given all this data, these investigators concluded particularly using um some of the analysis they were able to perform. That there is very which means the completeness of cider reduction. Are you able to get all that tumor out? Okay. And how effective high peck was going to be in terms of impacting patient survival at same point that you Tampa general makes such a big effort to try to achieve that are zero de bulking before we will put that patient through the extra potential time and some risk of undergoing high pack. Now having said that, that's just this is just one pooled analysis right there. Next slide please. There are other mount analysis. Okay. They would say that contradict this. Okay. And so this particular study is a second group of investigators who identified 22 publications solely by searching the english language on pump, it available english language, available literature and punishment data from a final group of just a limited study 11 studies, 248 patients advanced ovarian cancer stage 3248 publications. A total of sensitive ovarian cancer that included information about some type of survival and their analysis. And if you look in this analysis, so again smaller number of patients, smaller numbers of smaller number of studies, the media waited and waited. The weighted median overall survival was 37.3 months and the disease free survival was 14.4 months. The five year survival was 40%. And when you look at the subset of patients, uh had undergone high peck, this was not significantly different But yet there were some significant more did morbidity that was observed in about 20-25% of patients. And based on this, these results, this particular group of investigators did not recommend the use of high peck to treat up to Philly ovarian cancer. So clearly, just on the basis of this retrospective retrospective meta analyses which again come with all the limitations inherent to respective analyses in terms of variation and technique, variation and chemotherapy used variation, significant variation and the types of patients enrolled and most importantly, the degree to which these different cancers were debunked for the patients that were considered in these trials. Very conflicting data. Okay, so what's really slow kind of changed the field for us in terms of supporting our ability to consider high pick as a treatment for ovarian cancer patients? Well, that really came from this study, which we're going to talk about next. So the really first well defined prospective clinical trial was a group that are coming coming from Europe again, uh the data Republican in New England journal in 2018. Next slide please. And this is kind of hard to see. Um I don't know can you guys blow that slide up or increase it in size at all on. But in general they enrolled several 100 patients in high peck. And essentially I don't sorry, sorry, I didn't really kind of apologized for the difficult aspects of this to see. But the bottom line is is that these investigators enrolled several 100 patients randomised to surgery plus or minus high peck plus a standard chemo, standardized chemotherapy regimen. And I'll just next slide will kind of blow through this since I obviously didn't tell if you look the arms were relatively well balanced in terms of baseline demographics. However, there are some differences that we need to talk about the potentially skew the results. But in general, the basic fundamentals were that the the patients were relatively well balanced. They included patients with a variety of different histology ease, some of these had lived no dissections, uh and uh but and varying amounts of genetic susceptibilities to ovarian cancer, which may become important down the road. Next slide, please. And important in the meat of this study really comes here was that if you look at both progression of recurrence free survival and overall patient survival, you can see uh and like the curves on the right, there were significant improvements of almost one year in terms of both disease free interval or recurrence free survival and overall survival that was observed in patients who had undergone high pack. Next slide please. These are impressive results. It made it all the way to England Journal and it created a lot of interest. Okay. The conclusions of these investigators was clear that the addition of high pack to an interval cycle corrective surgery for patients stave stage three significant improvements without higher rate of side effects. Okay. Um, and so that's significant significantly from some of these other retrospective studies that I have mentioned for you. And in this study. Now, having said this, this study was not met with universal acceptance next slide please. So why is that? Well, there are a number of concerns raised by other european investigators are quite prominent in our field as well as some of the clinician prominent clinicians here in United States that primarily revolved around the following first is that there was actually had reduced these investigators had reduced their plan enrollment because a cruel to the study took like something like eight years Now, interestingly enough, this is not created a concern in other studies. Okay. That have been touted by some leading clinicians as speaking against high pack that had almost similarly long enrollment periods or a cruel periods. Another area of concern was the fact that the progression free survival, the expected progression free survival and overall survival in both arms was significantly less than what was anticipated by the initial statistical plan. And so this could, it's sort of a theoretical or statistical argument, but it does potentially mean that it predisposes you to observing an effect where none may actually be truthful, right? Because if it baseline, you had worse than anticipated results adding in an extra therapy might improve outcomes. You know, it's hard to really know what to make of that criticism. Whether it's truly legitimate as you might hope for. The other thing was garnered. A lot of criticism was the relatively small size of the study and there were a little bit greater number. As I mentioned, these investigators enrolled different numbers of, of different types of histology. So that's just not. This study was not confined to patients who were undergoing cider reduction, serious carcinoma, included in Detroit as well as low grade tumors, uh, low grade tumors, uh, serious tumors of the ovary, which, as we all know, behave in a very different manner and are significantly less sensitive to platinum based chemotherapy than, say, the typical high grade ovarian cancer. Now, depending on how you think Hi peck actually works. This may or may not make a big difference, but it is legitimate. And I would point out in defense of the study. These were only very small numbers of patients and potentially depending on the magnitude of the impact, not enough to account for, account for the difference in survival that was observed. Okay. So the same way that CNN tries to protect outcomes of presidential elections. Okay. And so and we all know how that turned out So legitimately, this is a question that needs to be addressed. Um And so um and then there were some questions about the timing of randomization before starting chemotherapy and how long and when people underwent surgery, lack of a clear inclusion criteria for how and when people would receive new atom in chemotherapy were allowed into the study in terms of numbers of cycles. And then some some interesting questions about heterogeneity of results with the largest effect being seen at smaller centres, which is interesting because traditionally outcomes from ovarian cancer are best at very high volume surgical centers for ovarian cancer. Okay. And so if you're getting your surgery, ovarian cancer surgery done at an institution that does maybe only six or seven ovarian cancer, the Balkans a year, that maybe is not enough because again, there is some data again, that primarily comes from here in United States. That shows that would, you know, patients who undergo the bulking surgery at low volume centers treatment at low volume centers do not do as well as those that see a lot of ovarian cancer patients and do a lot of these surgeries every single year now. Having said that. So, So how do you next slide please? How do we, how do we, how do we make sense of this and other studies that we can point to that helped to clarify some of these issues? Well, the same investigators criticizing the study like to point to this following study, which is data from a randomized trial in Korea, that it looked at 184 patients, stage three and four randomly allocated intra operatively on the base to either a trial arm that contained high peck with cis platinum, 75 mg per meter square for 90 minutes. Similar duration, but a little bit lower dose than what we're using here at Tampa general versus control arm that received no aipac. And his randomization was based on residual tumor at the outcome. After you've concluded your primary surgical too bulky. Okay, so you know, we're patients. It's just included that pool of patients for whom you could get surgical the bulking to any implant less than a centimeter. Now, I will tell you right off the bat. Okay. That we here at Tampa General Doctor rather myself under english, do not think that this is enough of the bulking for high peck to make a difference. And I can tell you even from my experience in the lab, I spent an entire a lot of time as a resident working with a gene therapist by the garden and I'll die Zaroff spending time figuring out how far agents will soak into a solid piece of tumor for the delivery of gene therapy for example. And that number is only somewhere between 3 to 6 millimeters. So if you're including tumors that are a centimeter in size, that I can tell you, I can promise you that chemotherapy is not getting to the core of that implant because it's too big. And that's part of the reason why achieving that are zero to bulking is really important. Now, conversely, you can also say, well, we know Anderson that 60% even a second look with an alcohol response was all that data from MD Anderson. And Second Look that shows that small volumes of ovarian cancer cells persist within the peritoneal cavity. But again, the vast majority of those patients, 80% of patients with residual disease are going to have microscopic only implants. And that's probably from a theoretical perspective where we're picking up gains in terms of improving outcome for these ovarian cancer patients. Ironically, if you look at the study, they took six years to enroll patients, they commonly saw problems with anemia from beside a pina, a bump and crap, knee injury, kidney injury, acute kidney injury, um as well. Um, as an uh in these patients, no differences in the rates of transfusion or neutropenia, which are not necessarily surprising because again, that's not something you would necessarily see acutely just a single dose of cis platinum. But unfortunately, these investigators did not see an improvement in either the progression free survival, the overall survival. Now, this article was widely cited in multiple write ups and including a commentary that was included in New England Journal on the study, which I just showed you. But interestingly when you pump made these authors, this study has had only by the time when it had been initially quoted as a criticism of high peck. It had only been published an abstract form. And to date this full study, I can find no evidence that this study has ever been published in its entire, I don't know if either English or Dr Rutherford ever seen it but I have never seen the article being published and I've searched these authors at length that have never been able to find this data had been published and it's been more than four years since that abstract was published, which means me to believe that perhaps there's been some other issues with finalizing the data set. So I'm very skeptical that this study is worth even really considering next slide please. So has has the next question I just want to address the brief briefly address. Is has this study that I'm citing in England Journal begun to influence care? Is it just are we the only people here at Tampa general that believe that high pick has an impact on improving over and cancer outcome? Well, the answer is actually no. Okay, interesting study that was produced by Taro and investigators collaborators who looked at the administrative claims database for ovarian cancer surgeries that covered 550 U. S. Hospitals over the time span of january 2016 to january 2020 using procedure codes and I see Ddn diagnoses limiting their case finding identification in this data. Pop search as the use of uh the hallmark of high peck as sodium sulfate administration because that had been included as a unity procedure part of the procedure in that Van Real study that came from europe. Okay. And then they compared practice patterns. They identified a total of 150 to a grand cancer patients during this time frame that had high peak at 39 hospitals. Over a total of 20,000 ovarian cancer patients that had surgery without high peak. At 258 hospitals, 90% of the seven of these cases of high pack instances where high pick had been performed Have been done after the study was published. Um and they concluded, they also found that patients undergoing hype were characterized by a longer medium of stay 8.4 versus 5.7 days. At a higher percentage of icu admissions, 63% versus 11%, and a higher rate of complications. Almost double the rate of complications. I can tell you that this length of stay is very long for us. Are typical ovarian cancer patients go home within the first or second day, typically the first day after after undergoing de bulking. They spend a day or two in the ICU. But typically the vast majority of our patients will go home within five days actually. So I can already tell you that our outcomes are better than what are quoted here. No, that's not the point. I mean you can't really compare what we're getting to what we're seeing in these publications, but nonetheless, um you know, they this is the data that was presented. So the incidence of high peck is increasing. It does have some of the adverse side effects in these cases that are found, but again, no, in patient deaths. No 30 day readmission after high peck. Um and of course high peck results in higher costs because it does cost money to give chemotherapy. And again, there are significant hospital charges, associate with longer stay and the technical components of performing the high peaks are not a surprise. Although again, I would question, I would say that this study probably under reports the incidents of hype because many of us like for example, here at Tampa General, we do not use a sodium thio sulphate infusion as a renal protected during the treatment. And so on. My suspicion is these investigators, even though this is a very recent manuscript published in the past six months are missing many of the cases and my suspicion is the incident higher than what is being reported here. Next slide please. So what questions really remain? What, how where are we going? In some ways this is really a frontier in the treatment, ovarian cancer. There is robust evidence, you know, open to become criticism that High pick improves outcomes. Um And you know, there's other mixed results with a very muddy field of medical literature behind it. So what questions really need to be remained answer before this becomes adopted as the standard of care? Well, first of all, it's simply a matter of time you need these this initial prospective study needs to be confirmed. Okay, we need to decide what that optimal chemotherapy regimen is and in what doses that should be used, inter opportunity. We really need to understand better about high peck, potentially improve the outcomes because as dr Rutherford mentioned, it's entirely possible that we don't need to add chemotherapy. It's really the heat that's working. Um And in support of this, I would cite some literature to suggest to demonstrate that cancer cells are more susceptible to high pack when they have defects in Bracha because again, it induces a shock to the system that impairs or allows that checkpoint blockade to be picked up and kill cancer cells in a way that's not possible in the absence of that intervention. Okay. There might be other interventions as well. And there's some data to suggest that survival in the retrospective literature. Again, this survival for patients undergoing high pack are much higher or better when they're cancer has a BRAC inherent Bracha mutation. Okay, and so it would be very important to define this. Okay, it's gonna be very important for us to know, as I point out in four, can we define either molecularly defined or clinically defined subset of patients that's going to be most likely to benefit from my pack. Should it really just be platinum sensitive disease? Um, you know, as we point out, one of the clear criteria that we really believe in for, which is probably the most robust evidence in literature is that, you know, it's very important to get patients down to that are zero are microscopic developing. Um and to get all the visible cancer out. And then there's a bunch of other questions about whether or not high pick that improved outcomes for other types of gynecologic cancers. Does high pack work for low grade serious cancers. It's entirely feasible that high pick as a modality may if some of the things that I mentioned to you in terms of sensitizing otherwise chemo resistant tumors to a novel way to induce the widespread cell death that's invoked by uh normal cell cycle checkpoints by, you know, by heat shocking cells that we could use this to actually treat patients with better impact who have low grade series ovarian cancers. There are not enough patients between both arms and the 2018 and real study. There are perhaps seven patients to and one arm four or five and the other that have lower rates serious ovarian cancer that were included for evaluations. And there's no detail in terms of that's no way to compare outcomes for that very small number of patients. Over the course of other retrospective article, other retrospective manuscripts that have been published, there are perhaps no more than about 20 patients with low grade serious cancers that have been included in batch data to look at whether or not this is even feasible in this patient population. Um Perhaps patients who have and Detroit cancers which have slightly different makeup of genetic drivers, are less suitable for undergoing this treatment. These are all questions that we really don't understand. And there's a whole raft of other questions are actually are still ongoing studies looking at the potential suitability of using high pack to treat metastatic and Demi troy uh carcinomas that arise in the endometrium uterine metastatic uterine cancer or serious, very serious uterine cancers as well which his velocity look like ovarian cancer. Although again, are differentiated from high grade serious carcinoma arise in the ovary by some very key differences and drivers that again have biologic impact. Next question please. Next slide please. The last thing I'm going to toss out is this very interesting paper. Again, very limited data, retrospective and nature coming out of the Cleveland Clinic which was published again in the last 3-4 months. Okay. Where investigators um Have looked at as part of a retrospective outcome looking at outcomes for a platinum resistant epithelial ovarian cancers undergoing high pack. This particular study included 13 subjects with a platinum resistant disease recurrence and they found that the media disease for uh survival for these patients who underwent an r zero result de bulking is 11 months. Now, this is one of those things that if you say you do this and clinical practice on your boards, you almost uniformly get failed. So it's kind of like a kind of a homework or something you're not supposed to be doing. But they have certain circumstances. They have done this apparently at the Cleveland clinic and uh and the disease free interval for uh for this, platinum for these patients was about 4.6 months. Okay. Overall. Um and then following high peck, 61% of these platinum resistant patients in the last line experienced a significantly longer disease free interval with an increase of approximately 10 months suggesting that high peck could even be applied to patients with platinum resistant disease. Now, there's this is the only study that raises this possibility. It's not clear. This is very scant data at best. But again, it underscores our need to better understand the clinical and molecular circumstances under which we could potentially utilize this treatment. And those are all things that we're currently working on to try to better understand next slide. So the last thing I'm going to toss out because again, you may hear people in different places depending on where runs from. May hear a lot about, Well, you know, the gynecologist colleges that my institution believe in laparoscopically de bulking ovarian cancer following new adjuvant chemotherapy. Well, I think all three of us have relatively strong feelings that this is not necessarily a great idea. This does not mean that it's not going on. And there aren't people actively studying this. But again, there may be ways to attach or apply high pack even under circumstances where you're not making a big laparotomy incision. That allows us to do the type of infusions that we typically do for high pack here at Tampa General. Um There's a treatment called pressurized intraperitoneal aerosol, chemotherapy europe I pek. It was introduced for a treatment for patients with primary peritoneal metastases back in 2011 and there's been multiple reports of its feasibility, tolerance and efficacy. There are particularly centers outside the United States that have been studying this as a tool to adopt Aipac is a novel delivery technique. Um utility of pai pec for epithelial ovarian cancers. Uh This uh this particular study identified 106 articles on pipe ac 45. Those were clinical trials that included data over almost 1800 pai pec. That first of all, not only was pai pec feasible, but it was reported, there's an adverse impact or adverse effects from hype that could be associated with the pipe back in about 12 to 15% of procedures that included things like file structure hitting abdominal pain did not negatively impact quality of life. And the data that was, they were able to ascertain in this literature search. Um And there was an objective response rate for epithelial ovarian cancer patients undergoing pai pec of 62 to 83% with the median survival of 11 to 14 months. So some suggestion that this might actually improve outcomes primarily because the mechanisms behind pai pec or thought that you're pushed under pressure. You're pushing that chemotherapy deeper into a tumor implant than would otherwise be possible in the absence of that pressure. Um And so that raises this very interesting possibility about whether or not this is something that's feasible for ovarian cancer. Um And so there actually was a recent clinical trial and open to examine this next slide please. Um That is actually open now at City of Hope in California, whose primary evaluation is to evaluate the safety of using pie pack in patients of pharyngeal carcinoma due to either uterine ovarian or gastric carcinomas, or as a separate cohort colorectal carcinomas, looking at treatment related adverse effects. Trying to kind of collect some other data in terms of preliminary data on response rates in terms of progression free survival. Also integrating the what they call a carrington to be, as well as some data on clinical regression scores about his logic basis how well they believe that tumors responding chemotherapy in the first place. Um and then begin to look at how the pie pack impacts to our micro environment and sub clonal evolution. One of the key things that we do not hi peck into a patient's pharyngeal cavity, changes the micro environment for those tumors. And as I mentioned earlier, even simple things like ovarian cancer landing on the momentum can very dramatically alter the responsiveness of that disease to chemotherapy and enhance its ability to metastasize throughout the peritoneal cavity By generating these epigenetic, we modify clones. And so it's entirely possible that by either using high pack or pie pack that we can strategies changing vascular access. Okay, so again, with another key question is can should we be doing high peck for patients that have been getting devices? Um At for example, answer is not clear yet. Okay, and again, there's some reasons why that may be good or may not be good, both from a theoretical translational perspective as well as the potential risk of side effects of visualization related to high pick not enough data for us to be able to make it away in a judgment on that. Okay, so, understanding how high tech alter that micro environment, How another question, for example, is how does high peck potentially generate neo antigens that uncovers or creates access for natural immune system that could enhance uh an endogenous immune response to improving outcomes? The doctor brotherhood mentioned earlier and I cannot stress this enough. Those patients initially, the trials who just received the apparent catheter actually have improved survival. And so it's entirely possible that altering the balance of the immune response again, keep in mind that ovarian cancer actively inhibits your body's of the patient's bodies own immune response to their cancer. And so if you can alter the balance of inhibitory and stimulatory factors around that immune response, you have a chance to actually improve that patient's outcome. And so it may be giving these occasions a good case of what you can think of as an intraperitoneal Sundberg. Okay, that's enhancing immune response. Next slide please. So in conclusion across our talks, the best available evidence that we believe support that survival. This again is controversial to some degree. Uh, and as a result as baseline, we have to say that to some degree. High pack is still considered experimental to some degree, but it's increasing becoming widely adopted. Okay. Not only are center but throughout the United States, but without question. There are any number of questions for which we need to conduct well defined clinical trials to answer some of the issues that are remaining at this point. I think I'll stop and open up the presentation James do have a couple of questions in the bank. So as of 2017, only 49% of boys and girls got HPV shots. If we increase these numbers, would we expect a decrease in a buyer? Excuse me. Ovarian cancer for HPV. HPV? I would not necessarily. Yeah, that's a great question. But that will have an impact on cervical cancer but not ovarian cancer. Yeah. You find HPV and ovarian cancers. Okay. But it's only a very small minority. Okay, now, having said that, I will tell you, I have data from my own lab, the the transcripts from the cancer genome atlas consortium that best predict ovarian cancer outcome are not human. They are all viral. Okay. However, none of them come from HPV. Okay, thank you. The next question. Atlantic health system has started a landmark study that uses blood test. See a 1 25 to screen low risk women. So what are your thoughts on this test for? But tom tom you want to try, you wanna dive in on that one or So, basically see a 125 is not a screening tool. C125 can be elevated in a multiple host of things. Everything from the and that irritates the thoracic linings, cardiac failure, endometriosis, fibroids. In fact, if you get hit in the abdomen enough You can have an elevator see you in 25. So in and of itself, it is not a screening tool. It's a better predictor if you have an ovarian mass with an ultrasound when it's combined. That being said, we're playing with some stuff and that's what this is enough. This is a real long story. But if this, combined with maybe some other um markers, it maybe have some benefit, but in and of itself it's really of no benefit. So in an effort to save time, I'm gonna stop questions here. We just have these labs to what are the side effects of high pack hair loss? What else can you list for us? No hair loss. The big one. If you use mighty mason, you're looking at bone marrow suppression. Um, you definitely like Dr Anderson said, you get a sunburn on the bow so you get, you can get fluid productions in the abdomen. Um, you get some abdominal of this conference and slowness of return of malfunction. But if you look at it probably about two, I would say by two weeks, there's really no difference in the patients that we do high pack on. I don't want to say anything. You guys can anything difference in about two weeks. I would agree with that. Yeah, no, in general, I think we've had very good success with terms of outcomes. The patients, I've, you know, we've done high paid for some patients multiple medical morbidity, these underlying hardcore and irony disease. We do have to be careful with patients with renal disease, but we have had some patients minor renal disease. We're very careful about assessing patients pre op with pulmonary function testing and but you always have to approach with caution because you want to push a lot of fluid on a patient, your heart has to be able to stand up to that. Um And so I think one of the things that goes into the consideration is patients who are going to have uh seriously. And I think one of the things that uh picked up since I've joined the group here in Tampa is, you know, tom checks the BNP for these patients as an index of heart failure. Okay, so that patients have a high BNP suggestive underlying cardiac failure. Uh Then we have to really think carefully about that. Now, having said that oedema or frank cardiac failure, we've had essentially no serious patients with renal failure. Uh Zero patients over the, almost nearly 100 patients have done in the past year and a half to two years and ended up on dialysis. Um uh so uh no significant hepatic dysfunction. Okay. Uh now bowel function maybe a little slower to return. Okay. But again, you know, even here this institution, our outcomes in terms of sending patients home are probably better than that one retrospective study I showed you were getting patients all these patients home, I've sent a patient home after high pick out the third post op day with zero problems. Okay. So uh you know and I think our medium length of stay is somewhere only in the range of about five days. Okay, So our length of stay is actually less than the one that the one arm of the study I presented to you guys that didn't receive high pack. Okay. Now, a lot of that, you can say it was due to the rest program that Dr Rutherford pioneered here in Tampa General. And we do some novel things in terms of interventions to really kind of enhanced recovery. Uh And so it may be that, you know, but again, that's another open question is how do we manage your pain? Preoperative pain around aipac? Uh We don't we don't see a lot of problems with pain. I think patients do have increased pain, but again, most of these patients get epidurals, I think most of our patients are pretty comfortable afterwards. Uh And again, this is not caused by comparison to the in delays across the board, in terms of, you know, ended up staying in the hospital for a long period of time. Excellent. Thank you so much everyone and thank you audience for your questions and comments and for joining us tonight, kinder to everyone. I will email all of y'all with directions on how to claim your cmi CPU credits with the next within the next couple of days. Thanks again, everyone for your time tonight. I hope everyone has a good rest of your evening. Thank you. Thank you so much. Published June 18, 2021 Created by
