No, this is so exciting. Welcome, everybody. Welcome to IGCS 2022, our first annual meeting, as you just heard, in person for 1,104 days. It's great to see you all. I think everything's been taking longer because everybody's like, I got to hug you. I just got to be in person with somebody. So it's been great. So it is beautiful. It's great to be here. This center is amazing. I hope you get a chance to go around outside and look at where you're going to be getting your food from, which is right outside the roof on both sides of us. There's even bees out there. They have hives outside. We have the river that we can see from the backside of this room up here. It's wonderful. We've got some great events planned for us. It feels great to be here. So thank you all for being here. We have an unbelievable program. I think I'm just so excited. It's all packed with science and education. Thank you to all who submitted abstracts and to this huge faculty. We have over 210 experts, speakers, moderators, and co-chairs that will be presenting live, of course, for the next three days. Before I move on, though, I just cannot go any further without recognizing the immediate past president, Dr. Roberto Angioli, to come up on stage here and help us recognize the 2020 and the 2021 Scientific Committee co-chairs. Roberto? Actually, before you get going, you're on. I do want to thank Roberto for his service. Now, remember, this is a guy who served two years as the president and had no meeting, as you just heard. And Dr. Ognin reminded me that somehow we're going to have to make it up to her. We'll give that meeting in Rome. Actually, we had a meeting. It was just a different one. Exactly. Thank you, Rob. IGCS would like to recognize the 2020 Scientific Program chairs, because we were unable to recognize them in person due to the pandemic. So please join me in welcoming Dr. Rainer Kimming and Thomas Herzog. Give me a second. And then I want to invite Dr. Anna Wagner and Matt Powell to the stage. These are the 2021 program chairs. Thank you. Well, Rainer and Tom fearlessly led the IGCS to our first virtual meeting ever in 2020, in a time where things were very uncertain. It was an outstanding meeting and very successful at a time when many societies struggled. So we really like to thank Rainer and Tom for their excellent work. IGCS is very grateful to them. And just when we thought we just might make it to Rome, we didn't. However, Anna and Matt provided the IGCS 2021 delegates with a virtual platform unlike anything we'd seen before. So I think you guys remember just how we switched in 2020 immediately to a virtual platform. And we amped it up for 2021 and made a great opportunity for us. Unfortunately, we had to be flexible. We had to pivot. We had to provide science for our global audience. But it came off with fantastic and excellent exceptional education. So on behalf of the society, I want to honor you with this token of appreciation. Thank you so much for your hard work. Mm-hmm. Thank you. Thank you. Thanks, bud. Thank you so much. Thanks, bud. All right. OK. I would now like to give a shout out to those participating virtually. We are sorry for those of you who couldn't make it here in person. We know that there are over 175 people who had issues with visas, which was really unfortunate. So we're so sorry you couldn't participate in person here in New York City, but so glad that you can participate via the live stream and the on-demand. We are reaching over 2,000 gyn-oncology professionals here at IGCS. This is the largest international meeting of its kind. Audrey and Brian, there you are. Why don't you come on up? Now I'd like to welcome our 2022 program chairs, Audrey Sinoda from Brazil and Dr. Brian Slomovitz here from the United States. They have worked tirelessly to ensure IGCS 2022 is a success, and we cannot thank them enough for all their hard work. Audrey, come on over here. So you know, last night, if you weren't aware, good morning, and thank you for being here. Last night, if you weren't aware, Aaron Judge hit number 61. So it was an exciting time. I've been a Yankee fan for a long, long time. You know, after the game, he was interviewed, obviously. He said, I was just trying to go up there and start a rally and get something going. And then he went on saying, it's an incredible honor. So I think Audrey and I really feel the same way. It's been a fun year, and we're really honored that you're all here. We first wanted to start off thanking the entire program committee. If you are a member of the 2022 program committee, please stand up to be recognized. We are so proud of the meaning we have planned, and we'd like to thank you all for all of your efforts. We've enjoyed working with every one of you, and you all played a role in the success of the final program, from grading abstracts to chairing sessions and securing expert speakers to join us. Thank you for your commitment to women's cancers and giving so freely of your time. Thank you for your commitment to women's cancer And we also would like to thank all the entire IGCS team, everyone behind the scenes at Keen's group, and the amazing staff here at the Javits Center. Lastly, we would like to thank our industry partners and sponsors for their support. Thank you for your commitment to women's cancers, and thank you for your commitment to women's cancer and giving so freely of your time. for their commitment to IGCS and our educational mission. Make sure to give our sponsors some attention and visit them in the innovative conversation hubs at the exhibit hall. We will be using social media and especially Twitter to amplify the thoughts of our delegates. If you tweet, please include hashtag IGCS 2022 in your post. If you hear something interesting, we encourage you to take a fun photo and share your thoughts and the more you tweet, the more your likely chance you win a prize. With the lights out, I can't really read my notes very well. Oh, please. I'll just wing it. Consistent with all IGCS meetings, this year we'll hear about the latest clinical advances and international developments in research, practice and treatment for the care of women affected by gynecologic cancers. A few numbers to share. There are 51 surgical films, 13 debates, 536 accepted digital posters, four amazing master sessions, nine industry symposia and we really have in our plenary sessions, we have a lot of great plenaries, some of them practice changing and we're really honored that they were submitted to this meeting and it's really a pleasure. You won't wanna miss plenary session four tomorrow as we hash out the opinions and facts about PARPs. Also tomorrow is an invited guest lecturer, Tal Zaks, really the key figure behind the COVID vaccine while he was then the CMO at Moderna. And IGCS 2022 will be a productive three days of education, networking and reconnecting with our colleagues. For those participating virtually, thank you for joining us. I would like to point out all sessions in hall 501 will be broadcasted live to our virtual audience and the other sessions will be available within 24 hours. Everyone here today participating in person also has access to the virtual platform. You may download the APP, the app, IGCS 2022. Thank you for being with us virtually and here in beautiful New York City right now. Let's get started, Brian. I would like now to introduce our moderators for this session, Dr. Larry Copeland and Dr. Alex Olloway. Thank you. It's a pleasure and honor to be here today, moderating this session with Alex Olaweya. Alex, we have an incredible lineup of abstract presentations for this session. We strongly encourage interaction and conversations with all of you in the audience. So please use the floor mics during the Q&A. Those joining us virtually may ask questions, as well, using the Q&A section virtually. First up, we'll hear from Dr. Bradley Monk, one of the directors of GOG Partners. Dr. Monk, the stage is yours. I want to thank Dr. Slomavits and the program committee for having me, President Coleman, thank you. It's my pleasure to present to you the results of CALA, if I could get my confidence monitor here to work, I'd appreciate it, Dervalumab in combination with and following chemo radiation and locally advanced cervical cancer. These are my disclosures. It's been more than 22 years, 23 years to be exact, that the standard of care locally advanced cervical cancer was defined as weakly cisplatin pelvic radiation and brachytherapy and it's unchanged. It's estimated that 67% of those patients remain progression free if they're low risk. Now immune checkpoint inhibitors have transformed the therapeutic landscape in cervical cancer being approved as single agents in second line and being approved with chemotherapy with or without Bevacizumab in persistent recurrent or newly diagnosed stage IV B cancer. The idea with CALA is that we can add immune therapy to chemotherapy and radiation and promote a more immunogenic tumor microenvironment leading to enhanced cures. And that certainly was shown in the non-small cell lung cancer trial known as Pacific with Dervalumab as maintenance after chemotherapy and radiation. So now this is the first phase three trial adding to chemotherapy and radiation and in maintenance in high risk locally advanced cervical cancer. So you, 120 sites, 15 countries, enrolled 770 high risk patients with histologically confirmed cervical cancer is defined as, now we use the 2009 FIGO staging system. So that would be high risk defined as 1B2 to 2B with at least one positive node based on imaging greater than 1 centimeter in short axis or any stage 3 or 4A cancer. Stratification factors are as you see there, 770 patients randomized one-to-one, standard of care chemotherapy radiation placebo was the control and fixed dose Dervalumab, a human anti-PD-L1 antibody at a fixed dose of 1,500 milligrams every four weeks. Primary endpoint was investigative progression free survival with overall survival response and duration and local and regional control as well as distant control and safety being secondary endpoints. Now we needed 246 events, 246 deaths or progression to achieve a hazard ratio of 0.65 to have this be a positive trial with a two-sided P-value of 0.05. And if we hit that statistical significance, the alpha would be carried forward in a hierarchical fashion. FIGO screened over a thousand patients to enroll 770 patients and follow those patients during COVID with a very low dropout rate, a very low discontinuation rate. Now it took 22 months to enroll this trial. We then followed them for 11, 13 months and here the data cut was in January earlier this year. You can see that some patients were still getting the Dervalumab at the time of the analysis, about 35% and about 33% were getting placebo. I want you to note during COVID the dropout rate was only three patients in the Dervalumab arm and only one patient lost a follow-up I mean in the placebo group. And I want to thank the world for enrolling, a substantial Latin American enrollment with a 46%, Asian enrollment 39%, 10% United States and 4% in Russia. Most patients had ECOG status of 0 and were squamous tumors but this was a high-risk group of patients with 66% of the patients having stage 3 or 4A cancer and 64% having positive pelvic nodes and even 12% having positive aortic nodes. We evaluated the PD-L1 status using a combined tumor and immune cell area score using the sp263 antibody. So at a 1% threshold, 92.5% were positive. At a 5% threshold, again tumor and immune score, 80.8% were positive. And patients received full dose on time. So 100% of patients were treated, 96.4% of the patients completed radiation as per protocol audited by a Radiation Oncology Steering Committee chaired by Joe DiMaiadeff, 94% of the patients got brachytherapy, the radiation pelvic dose was 5400 centigrade and with brachytherapy at the meeting it was 8337 centigrade. And most patients were treated on time less than 60 days. This is the primary endpoint. Hazard ratio is 0.84. There was a numerical superiority at one year of 3% in progression-free survival and at two years, 4% did not reach statistical significance. These are the hypothesis generating subgroups. You can see the confidence intervals are broad. But the patients at highest risk of progression and death, specifically the lymph node positive stage 3 group had a hazard ratio of 0.71, still not reaching the 0.65 target hazard ratio. In the aortic node subset, the hazard ratio was 0.60. Overall survival is not mature, 17%. Hazard ratio is 0.78, did not reach statistical significance. Secondary endpoints included response rate, local and distant control. You can see there was a 3% improvement in response rate. Again these p-values are nominal. There was no improvement in local control. In fact, the hazard ratio is directionally opposite. There was a trend towards better control distantly, hazard ratio 0.75 with a 3-4 month improvement at one year and a 5% improvement at two years. You can conclude that Dervalumab did not interfere with the delivering of chemotherapy and radiation at full dose and on time, meaning that the adverse reactions were similar. There was a discontinuation rate that was higher of any treatment in the Dervalumab arm, 3.9% difference, almost a 3% difference in any Dervalumab discontinuation and a 1% difference in radiation discontinuation. Adverse events are here. There were no new safety signals. The dark color, of course, is the grades 3 and 4 adverse events. The most common immune-related adverse events was hypothyroidism, but there was no grade 3 or 4. So in conclusion, Dervalumab in combination with and following chemotherapy and radiation did not statistically improve progression-free survival in patients with high-risk locally advanced cervical cancer compared to standard of care chemotherapy and radiation. Safety was similar, but I showed or we showed that we got work to do in trying to cure more patients with locally advanced cervical cancer. It begs the question now. This is the fifth randomized trial when immune therapy is added to chemotherapy and radiation four times in head and neck and now cervix and continued maintenance does not improve progression-free survival five times. Thank you to all for enrolling in this trial. Thank you for answering this question in a definitive way. I'd like to acknowledge the sponsor, AstraZeneca, and thank you for having me. Brad, congratulations on your work and your excellent presentation. Up next, we will hear Dr. Keta Larusso, distillation, and we will take some questions after that. Feel free to, if you're virtual, get your questions in now. Thank you. Thank you so much. It's my great pleasure and honor to be here to discuss this very, very important trial. My disclosure. So, cervical cancer still remains an international health concern with more than 500 patients with disease every year and more than 300 deaths due to this disease. Age of disease is the most important prognostic factor, and locally advanced disease is diagnosed in more than 65% of our patients, and this patient experienced 5-year PFS of around 60% and 5-year overall survival of about 60%. Chemoradiation, concomitant chemoradiation, became the standard of care in 1999 after the publication of five randomized trials reporting an increase in overall survival when we combine chemo plus radiation. But if we look at the granularity of stage, the overall survival gain for stage 2b was 7%, and for stage 3, only 3%, thus suggesting that there is still a great room of improvement for this patient. And we tried to improve, but unfortunately, new adjuvant chemo followed by surgery or adjuvant systemic chemo after chemoradiation did not report an increase of overall survival with respect to chemoradiation alone. In this scenario arrived immunotherapy. Immunotherapy has reported compelling activity in second and third line cervical cancer either alone or in combination with chemo, and we know that radiation may induce immunomodulatory effect by increasing antigen presentation, by activating a pathway of immune response like Gart's sting, by modulating the tumor microenvironment, and regulating immune checkpoint expression. So there was a strong rationale in combining immunotherapy plus radiation therapy, and also we have a trial in lung cancer suggesting an increase of overall survival when we use immunotherapy as maintenance after chemoradiation in lung cancer. Dr. Monk, a colleague, has provided that the great merit to have produced the first randomized trial exploring the rule of immunotherapy in combination with chemoradiation in locally advanced cervical cancer. In their trial, high-risk locally advanced cervical cancer were randomized to receive concurrent chemoradiation plus BRCA, or concurrent chemoradiation plus Durvalumab in combination and maintenance for two years. But unfortunately, the primary endpoint of the trial, progression-free survival, was not positive. And a no significant trend toward a reduced, distant progression to here was reported. Why a trial with a so strong biological rationale failed to demonstrate benefit? It's a matter of the strategy, or it's a matter of the trial? As Brad anticipate, this is the fourth negative randomized phase three trial combining immunotherapy plus concurrent chemoradiation. And the difference with respect to Pacific trial is that in this trial, immunotherapy was given in combination with chemoradiation. So one hypothesis is that when we provide concurrent administration of immunotherapy to radiation, this may have impaired the immunotherapy efficacy. There are two proposed mechanisms with which immunotherapy works in combination with radiation. The first one suggests that only immunotherapy is able to reinvigorate exhausted T-cell, intratumoral T-cell. If this is true, it's evident that the close sequencing of treatment is not necessary, and probably new adjuvant setting is the best way to combine immuno plus radiation. There is a second proposed mechanism according to which radiotherapy may stimulate the proliferation and differentiation of naive T-cell and immune checkpoint contribute to this stimulation. In this second scenario, the close sequencing is necessary and preclinical data suggests that this second mechanism is dominant in the combination. So that if we want to take advantage of the peak of tumor T-cell, which occur five to eight days post-radiation, we need to combine immunotherapy or either the first or the last day of radiation treatment. Two years ago, Dr. Duska and colleagues published this very interesting preliminary trial. It's a randomized phase two trial combining pembrolizumab with chemoradiation or pembrolizumab after chemoradiation in locally advanced disease. The final results of this trial will be presented very soon, but the preliminary publication and the author do not suggest nor anticipate any issue in terms of safety, but also on efficacy when pembro was combined to chemoradiation. The second hypothesis, in my view, more interesting is that radiotherapy is a double-edged sword regarding immune effect. It can work both as an immunostimulatory effect, but also it can be immunosuppressive according to the dose we use. So in this scenario, the elective irradiation of draining lymph node may end T-cell priming. And this preclinical data suggests that conventionally fractionated radiotherapy schedule may be suppressive. And this is exactly the schedule we use in cervical and the neck cancer. And that in order to provide better tumor control, immunotherapy should be combined with hypo-fractionated schedule. So that in this scenario, if we want to increase our efficacy, we need to design different trial adapting the radiotherapy treatment plan in terms of timing, fields, dose, and fractioning. But we need to be careful because radiotherapy is a crucial component of the treatment and up to 75% of patients are cured, so we cannot change this scenario. Moreover, the scanty clinical data we have suggests that on tumor biopsy taken before and after chemoradiation, both in lung and then the neck cancer, there is no decrease in tumor infiltrated lymphocyte. Let's move very quickly to the trial. I was surprised when I received the slide for the first time, I want to thank the author for providing me the slide in advance. I was surprised that this trial was planned with a 32% maturity for the primary endpoint. This means that a larger number of patients should be enrolled in order to get, as soon as possible, the number of events for the primary endpoint. And in fact, in this trial, according to the statistical plan written in the protocol, 770 patients were enrolled in order to achieve 227 PFS events with a median follow-up of 18 months. So the question for the author is why this strategy was adopted, also considering that when we decide this trial, we have several theoretical suggestions that we will succeed, but we do not have any early preliminary data on this strategy in cervical cancer. Probably this is a lesson that we have to get for the future. Looking at the enrolled population, this is a huge global trial, and up to 40% of patients were Athean. What we know is that this patient may present prognosis, different prognosis, and potentially also different treatment outcome. So region of the world was a stratification factor of the study. Do we have evidence suggesting that the treatment performed differently according to the race? The primary endpoint was progression-free survival. According to the statistical plan, the trial was designed to demonstrate a three-year progression-free survival from 65 to 76%. But at the two-year in the control arm, the PFS was 62%, thus suggesting a clear overestimation of the control arm. Why the control arm underperformed? Because we enrolled an high-risk population or because the quality of treatment was not so good? Gillian Thomas usually said that if you want to demonstrate a positive trial, you have to have a good quality of chemoradiation, and look at the quality of the treatment. 13% in the Durvalum ab arm did not complete chemotherapy treatment, and 28% of patients overread the overall treatment time, which may have impaired the efficacy of treatment. Looking at radiotherapy, the compliance and the global dose seems very, very good. But in order to evaluate the quality of radiotherapy, we need more information. What was the total dose on the cervix? And also, what was the boost on the lymph node in the pelvis? And also, what were the radiotherapy techniques used? I'm sure we will find all this information in the paper. The end point, what we know is that immunotherapy may impact on overall survival much more sometimes than in progression-free survival. And this separation of the curve, really preliminary 17% maturity, represent possibly a signals of overall survival in ovarian, in Calatria. I would suggest to continue to follow this patient to get overall survival events. And now I want to close with an optimistic message. Looking at this forest plot, it seems that high-risk patient, parahortic node-positive patient, may gain a benefit. For sure, this patient represent only 12% of the population and forest plot are only hypothesis-generating. But probably there are some patient that can gain benefit. For all this reason, I think it is too early to put the tombstone on this strategy in locally advanced cervical cancer. I use suggest to wait for the results of a Knot A18 trial, NGOT611, GOG3047, which is identical in the trial design with some key difference. The primary endpoint in Knot trial is progression-free, but also overall survival. The agent uses an anti-PD-1 inhibitor and non-anti-PD-1 inhibitor. We have evidence in other tumor, not in cervical cancer, that this can make a difference. And also the population enroll is an higher risk with at least two positive pelvic lymph nodes. So in conclusion, immunotherapy is practice changing in cervical cancer, but in advanced disease, alone or with chemo. Unfortunately for our patient, KALLA trial failed to demonstrate the benefit when we combine immunotherapy with chemoradiation. And until today, concurrent chemoradiation remain the standard of care for this patient. And lastly, I want to sincerely congratulate to the authors for their continuous effort in ameliorating treatment and cure strategies for our patient. Thank you. Thank you, Dr. LaRusso, for that great distillation. Are there any questions? Now we have Dr. Rita Ribeiro present his abstract titled, Uterine Transposition, Feasibility Study, followed by some thoughts from Dr. Mario Lataio. Thank you so much. It's an honor and a pleasure to be here today to present the results of the Uterine Transposition Feasibility Study. Those are my disclosures. Around 2,000 women every year in America will need pelvic radiation for non-gynecological cancers. It increases their chance of survival, but it also causes infertility in women with healthy pelvic and reproductive organs. There are different mechanisms related to this, and one of them is that radiation causes ovarian failure even in low doses. So at the age of 30, 14 grades are enough to cause complete and definitive ovarian failure. But just not just ovarian failure, it also reduces uterine volume, impairs uterine distensibility due to the myometrial fibrosis, causes uterine vascular damage, and causes endometrial injury. So those patients cannot get pregnant. What options do those patients have? They can have a frozen embryo. They can do a site vitrification, ovarian cryopreservation, ovarian transposition, and even in the future, uterine transplant. Well, the problem is all those treatments have a high cost. They cause some treatment delay, not a big issue, but it's still an issue. Some patients will lose their partners due to many, many different things related to their relationships, and all those patients need a surrogacy uterus, which we all know it's very difficult to do, especially in some countries. Or they will need a transplant with all the problems related to transplants. So what we have hypothesized is instead of performing the radiation with the uterus in pelvis, we could mobilize the uterus along ovaries and tubes to the upper abdomen and keep it supplied by the ovarian vessels, perform the radiation, and then place it back to the pelvis. What's the primary objective of the trial? It's to preserve the uterus and ovaries with normal function in six months. And what's the criteria for feasibility? Well, those patients need to have normal menses, normal hormonal levels, and also normal endometrium. It also needs to be safe. So no surgical-related deaths, no major complication with significant sequel, and the cancer recurrence rate lowered in 30% in two years. The secondary objectives were to evaluate the associated morbidity of the procedure, evaluate the cancer recurrence in two years, and also evaluate the pregnancy rate in five years. This is a prospective, non-randomized study. The sample size was defined as 10 cases or two years of recruitment, and the inclusion criteria was women with 18 to 40 years old, non-gynecological pelvic cancer who required pelvic radiation, and desire to carry pregnancy. The exclusion criteria were infertility, previous ophorectomy, tumor-infiltrating uterus, ovaries, or tubes, distant metastasis, previous pelvic radiation or paralytic radiation, and any patient who needed chemotherapy with more than 30% of gonadal toxicity. Well, how the procedure is performed. First, we have to mobilize the uterus, tubes, and ovaries to the upper abdomen, and it's pretty much like in a simple hiss. So we section the round ligament. We open the broad ligaments, dissect the bladder, and we section the uterine vessels, and then we just section the vagina. So it will free the uterus from the pelvis and allow its mobilization to the upper abdomen. But we also need to dissect the gonadal vessels up to their origin level to allow proper mobilization to the upper abdomen. So we start dissecting the column, mobilize the column, and here you can see the dissection of the right gonadal vessels up to their origin to allow this mobilization that has to be done carefully, obviously, and you can see the uterus being placed in the upper abdomen. Then we suture the uterus to the anterior abdominal wall, so it will not mobilize during the treatment, and suture the cervix to the umbilicus, so those patients can be exempt in the post-operatory, and they also can have regular menses through the umbilicus, and that's how they look like after surgery. We check the blood supply of ovaries and uterus two days after surgery, and we usually perform an MRI 15 days after surgery, too, so the patients have regular menses. And after radiation, we place the uterus back to the pelvis in two to four weeks if they don't need a retrospectomy, for instance, or we do it with the cancer surgery related to it. So those are the adhesions you find before placing it back, so you just have to release all the adhesions, and then the uterus can be mobilized back to the pelvis. Once it's in the pelvis, we suture the cervix to the vagina, and then we start suturing all the ligaments, round ligament, broad ligaments, to make sure it looks pretty much as in normal women, and that's the final aspect after re-implanting the uterus in the pelvis. What are the results? So from June 2017 to June 2019, eight patients were included with a mean age of 30 years, a median follow-up of 30.6 months. And regarding the primary outcome, which is uterine preservation in six months, one patient was excluded because she died four months after uterine transposition, so she didn't reach the six-month period for evaluation. One patient had a uterine necrosis, so she needed a hysterectomy, which was converting the ovarian transposition on the fourth post-operatory day, and six patients kept the normal menses, normal hormonal levels, and the domitrile after the treatment. Regarding the secondary outcomes, especially surgical complication, the most common complication was cervical ischemia, especially in the first case where we were ligating the paracervical vessels too close to the cervix. But then after the initial learning curve, those patients are having better results. Most of the patients had rectal cancer, but one patient also with a pelvic sarcoma. What are the outcomes related to fertility? Of the six patients who managed to preserve their uterine function, three did not try to get pregnant so far, and three patients tried and two patients got spontaneously pregnant. And when this abstract was sent to the IGCS, the first baby was born in February after 37 weeks of pregnancy, and the other patient was pregnant, 20 weeks pregnant, and this baby was delivered like two months ago after 38 weeks of normal pregnancy. So in conclusion, uterine transposition, it's a feasible procedure. There is surgical morbidity that has to be considered. Spontaneous pregnancy is possible, but we need more studies to evaluate long-term pregnancy and oncological safety. And I want to deeply thank all these patients, brave women who accepted to join this trial. Thank you so much. Excellent presentation, Dr. Ribeiro. Dr. Letaio, please begin your distillation. Well, as the first New Yorker, I want to thank you all to the city that I love and hate many times. So it's a wonderful time to be in the city in September. So enjoy the city. All right. So I was asked to give a distillation on this abstract by Dr. Raytime Ribeiro. This to me is kind of akin to the Big Pen. It's a simple concept. It just took somebody to think of it. And you have to compare, you know, the baseline rate is 0% fertility for these patients. So that's the baseline rate you're comparing it to, okay. These are my disclosures. We've done ovarian transpositions for a long time. You know, there's been different ways described with different success rates. I know many places have gone away from doing this because they feel the success rate is low and they figure let's just cure these women with rectal cancer who cares about their hormones and their fertility. Their primary goal should be cure of their cancer. But we are curing these women and many women are being diagnosed young and they're living from their treatments. And then when they realize that they have to take these hormones for the rest of life and cannot have a child themselves, that creates a lot of anxiety and secondary problems. We've been doing ovarian transpositions for these patients for a very long time at our institution and we transect the tubes so we can get them completely out of the radiation field for rectal cancer, which is a slightly lower field. And you can see they're usually placed at the level L4-5, but the tubes are transected and removed actually. We published our outcome with one of our prior international fellows in 22 patients with anal rectal cancers, basically showing that we could do this without interfering with their needed rectal cancer therapy. And our outcomes were that two-thirds of women retained hormonal function either based on hormonal levels and or resumption of menses after radiation. But we also noticed that women less than 40 had the highest rate, and it's not 100%. It's 90% retention of ovarian function, and those over 40, only 40% retained ovarian function. So again, this is a comparison to zero. So I don't think you need fancy statistics to say that zero versus 90 is probably significant. So there is limitations to this, though. These women cannot get pregnant on their own. There has been no, obviously, no spontaneous pregnancy, especially if the tubes are transected and removed. And there's been no live pregnancy in women who've been radiated as an adult for a pelvic cancer. The concern is not that they probably won't be able to get pregnant from REI or IVF. It's the concern is that the distensibility of the uterus and the complications from a pregnancy that has delivered severely premature. So we've had not a single patient of ours ever get pregnant after radiation for rectal or anal cancer or the pelvic tumors that are non-gynecologic. In 2017, Dr. Raytan actually presented this at another meeting, which I will not mention the name. The first thing I said was, why didn't I think of it? So and here you see one of our cases now. The uterus sits nicely above the umbilicus, well away from the radiation field. We don't bring it through the umbilicus, though, and I'll have some questions for Dr. Raytan about that. Dr. Raytan now did a feasibility study, which he's just presented with these eight patients enrolled. Of course, you see one uterine necrosis is removed. But again, if you don't move the uterus up, it's basically necrosed anyway, essentially, in all practical purposes. It's a nonfunctional uterus. So that's your comparator. One patient died from carcinomatosis at four months, which is unfortunate, of course, for a young patient. The most exciting thing is this, and I have to give him a huge congratulations. I haven't had anybody have a pregnancy yet, and I keep asking them to get pregnant ASAP, but they refuse to listen to me. So, I mean, three patients tried to get pregnant. They both got pregnant on their own and delivered full term. I mean, again, you don't need fancy statistics to tell us that this is something of probably great interest and value to these women. And there will never be a randomized trial, for those of you who want to call for randomized trials. No one's going to do a randomized trial in this area, right? So I have a few questions for Dr. Raton to sort of teach us a little more. And I have lots of questions. He and I talk all the time about this. In the study, you mentioned that uterus was placed back two to four weeks after radiation or at the time of colorectal procedure. I asked how many of these patients were replaced at two to four weeks after radiation. How did you make that decision? Since often nowadays with anal rectal cancers, they wait three months to see what the responses to radiation decide on the rectal procedure. Would you ever convert to laparotomy? This has all been done MIS so far. Would you ever convert your patient to a laparotomy at the time of moving up to do this procedure, which obviously would add more potential risks and maybe delays to the radiation treatment? What do you do for perioperative considerations such as the use of antibiotics, anticoagulation to try to hopefully avoid vascular events? Now, I saw that you bring the cervix to the umbilicus. What are your thoughts on not bringing the cervix to the umbilicus? And what is your guidance that you would have for surgeons who are thinking of offering this at their own institutions? And if maybe we keep that slide out for Dr. Ribeiro because he's got a great memory, but I don't know if I'll remember all. Thank you all for allowing me to do this. And a huge congratulations to Dr. Ribeiro. Thank you. Thank you, Mario, for all your support and all the things you have done for it. And I think we are usually replacing the uterus two to four weeks on those patients that don't need another surgery for any other reason. So for pelvic sarcomas. But because we want to place the uterus back as fast as we can to, because it's obviously awkward to have menses through the umbilicus, right? So we want to place back. But we, six of the eight patients, they replaced the uterus at the time of the retrosymoidectomy, something like three months after the chemoradiation. I would love to see the questions. What are your thoughts about not bringing the cervix through the umbilicus? Yeah, I think that's a great option. We are moving towards that now. But in the beginning, we were very concerned about the uterine necrosis. So we want to be able to check the perfusion daily, sometimes three or four times daily. And the best way to check a flap vascularization is by looking at it. So that was the reason. And also because we knew that if the patients have menses through the umbilicus, it means the surgery was working. So that's what we are doing. But now we are moving towards leaving the cervix inside the abdomen and just suppressing menses. I think it was something that we needed to do in the beginning, because it was something new. And we want to be on the safe side. Your perioperative considerations regarding antibiotics, anticoagulation. We now are, when we leave the cervix inside the abdomen, we are keeping them for five days on antibiotics, because we were concerned about endometriosis and some peritoneal infection in the beginning. Because those patients, they do not have innervation of the uterus. So would they feel pain if they have a necrosis? And actually, they don't have pain. So we would not be able to know if they are having a complication sometimes. So that's why we kept those on antibiotics now. And we use anticoagulation for 30 days for those patients. But as we do in most of the cancer cases, gyne cancer cases, so we use the same protocol. And that's what we do. Great. Thank you both. We're running about 15 minutes behind. I don't see any questions from the audience. The audience is either stunned or asleep. I suggest the performer. So we're going to move on. Thank you both. Thank you. Up next, we will hear from Dr. Trey Leith, followed by Dr. Robert Coleman, and followed by a distillation by Dr. Konstantinopoulos. On behalf of my co-authors, I will be presenting a post-talk subgroup analysis of overall survival by number of prior lines of chemotherapy in the SOLO3 trial, which compared Olaparib as a line of treatment versus non-platinum chemotherapy in patients with BRCA-mutated, platinum-sensitive relapsed ovarian cancer. These are my disclosures. The PARP inhibitor Olaparib was approved by the U.S. FDA as a monotherapy treatment based on promising anti-cancer activity in a subgroup of patients with ovarian cancer. And Study 42, a single-arm, Phase II study of Olaparib treatment in patients with germline BRCA-mutated advanced cancer who had received three or more prior lines of chemotherapy. SOLO3 was a confirmatory study conducted at the request of the FDA. SOLO3 was an open-label Phase III trial which assessed the efficacy and safety of treatment with Olaparib as a non-chemotherapy option in patients with germline BRCA-mutated, platinum-sensitive relapsed ovarian cancer who had received two or more prior lines of platinum-based chemotherapy. At the primary readout in 2018, SOLO3 met its primary endpoint. In light of emerging data suggesting a potential survival detriment with PARP inhibitors as a monotherapy treatment line in relapsed ovarian cancer, this post-hoc subgroup analysis of overall survival by number of prior lines of chemotherapy was recently conducted. In total, 266 women were enrolled and randomized in a two-to-one fashion to receive either Olaparib treatment or single-agent non-platinum chemotherapy consisting of either pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topatecan. Patients were treated until disease progression and the primary endpoint was objective response rate or ORR. As previously noted, the primary readout in 2018, SOLO3 met its primary endpoint and demonstrated statistically significant and clinically meaningful improvement in ORR for Olaparib versus non-platinum chemotherapy. It also demonstrated a significant improvement in the secondary endpoint of PFS for Olaparib versus chemotherapy. At the final overall survival analysis in April of 2021 with 61% data maturity, the overall survival results suggested no differences between Olaparib and chemotherapy. However, it should be noted that the study was not powered for overall survival. And given the potential confounding of overall survival data due to the use of PARP inhibitors as a subsequent therapy for patients in the chemotherapy arm and the higher number of withdrawals prior to death in the chemotherapy versus Olaparib arm. This descriptive post hoc subgroup analysis of efficacy by number of prior lines of chemotherapy was not powered for formal significance testing. Here are the patient baseline demographics. Of note, 28% of patients in the Olaparib group with three or more prior lines of chemotherapy had progressed more than 12 months after the last platinum therapy versus 43% in the chemotherapy group. Most patients in both arms had a BRCA1 mutation, although slightly more patients in the chemotherapy group had a BRCA2 mutation. Most patients in both arms had metastatic disease, although in patients with three or more prior lines of chemotherapy, slightly more patients in the Olaparib group had metastatic disease than the chemotherapy group. Here's a reminder of the results in the full analysis set as previously noted. A quarter of chemotherapy patients versus 11% of Olaparib patients withdrew from the study prior to death, which may have confounded the overall survival results. It's also noteworthy that 61% of the chemotherapy patients who received subsequent therapy crossed over to a PARP inhibitor with a subsequent line of therapy. In patients with two prior lines of chemotherapy, PFS numerically favored Olaparib over chemotherapy with a hazard ratio of 0.46. Overall survival also numerically favored Olaparib over chemotherapy with a hazard ratio of 0.83, although the confidence interval crossed one. In patients with three or more prior lines of chemotherapy, PFS numerically favored Olaparib over chemotherapy with a hazard ratio of 0.87. Conversely, overall survival numerically favored chemotherapy over Olaparib with a hazard ratio of 1.33. In both analyses, the confidence interval crossed one. Overall, in the post hoc subgroup analysis presented, patients with two prior lines of chemotherapy had a numerically favorable overall survival and progression-free survival with Olaparib over chemotherapy. And these results were supported by the ORR. In patients with three or more prior lines of chemotherapy, PFS and ORR numerically favored Olaparib over chemotherapy. However, overall survival numerically favored chemotherapy over Olaparib. In patients with four or more prior lines of chemotherapy, OS, PFS, and ORR numerically favored chemotherapy over Olaparib. The greatest numerical benefit for chemotherapy was observed in patients with four or more prior lines of chemotherapy. Disease progression was the most common cause of death in both subgroups with no new safety signals identified. And there were no imbalances in either MDS or AML between the two arms. BRCA reversion mutations are a mechanism of resistance to both platinum-based chemotherapy as well as PARP inhibitor therapy. As previously presented at SGO 2022, BRCA reversions were detected in baseline at 3.5% of patients in Solo 3, most of whom had received four or more prior lines of therapy. These reversions are likely to have occurred on prior platinum-based therapy. No responses to Olaparib were seen for patients with BRCA reversions. At disease progression, we detected BRCA reversions in 22% of patients in the Olaparib group and 3% of patients in the chemotherapy arm. And most of these reversions were acquired on Olaparib therapy, meaning they occurred at prognosis, at progression. To conclude, in this descriptive post hoc subgroup analysis of Solo 3, a numerically favorable overall survival was observed with Olaparib over chemotherapy. In patients with two prior lines of chemotherapy, but a potential detrimental effect was observed in patients with three or more prior lines of chemotherapy. A numerically favorable PFS was observed with Olaparib over chemotherapy regardless of whether patients had received two prior lines or three or more prior lines of chemotherapy. Although in patients with four or more prior lines of chemotherapy, PFS favored chemotherapy over Olaparib. Adverse events were consistent with known safety profiles of Olaparib and with previous Solo 3 analyses. No new safety analyses or signals were noted. BRCA reversions are a mechanism of resistance to PARP inhibitors and platinum-based chemotherapy. And further work will explore whether BRCA reversions acquired in patients receiving Olaparib may impact outcomes of subsequent therapy. Finally, I'd like to thank the women who participated in the trial, their families, my co-authors, and your attention this morning. Thank you. Congratulations on your study, Dr. Leith. Now we will hear from Dr. Robert Coleman and his recent work. Thank you, Dr. Alavade and Dr. Copeland. On behalf of Dr. Letterman, it's my pleasure to present the overall survival rates from Ariel 3, a randomized phase 3 trial, double-blind, comparing RECAPRIB to placebo in patients with response to platinum-based chemotherapy for recurrent ovarian cancer. These are my disclosures. As many of you are aware, RECAPRIB is an orally administered PARP inhibitor, which is approved in the U.S. and Europe as maintenance therapy for patients who achieved a partial or complete response to platinum-based chemotherapy. The approval was based on significant improvement in progression-free survival in each of three planned nested analytical cohorts, namely patients with BRCA-mutated tumors, patients with tumors that demonstrated homologous recombination deficiency, and finally, an intent-to-treat population. Subsequent reports also provided information on important clinical outcomes, including time-to-second progression, chemotherapy-free interval, time-to-first subsequent therapy, and time-to-second subsequent therapy, each reporting improvement with RECAPRIB relative placebo. Sorry. Thank you. You think I got used to this by now. In this presentation, I will share the final overall survival results of the updated post-progression survival outcomes and an updated safety assessment from Ariel 3. As a brief reminder, patients eligible to participate in Ariel 3 had recurrent platinum-sensitive high-grade serous endometrioid epithelial ovarian cancer who had responded to platinum-based therapy and had not received a prior PARP inhibitor. There were randomized two-to-one RECAPRIB or placebo, and there was an important stratification variable made, variables made for homologous recombination repair gene status by next-gen sequencing, quality of the response to platinum-based chemotherapy, and the platinum-free interval following the penultimate platinum-based therapy. Treatment with RECAPRIB or placebo was continued until disease progression, death, or withdrawal from study treatment. As previously reported, the primary endpoint was progression-free survival in the three nested analytical cohorts. The overall survival analysis was pre-specified to occur at 70% data maturity. The statistical analytical plan for Ariel 3 was constructed to hypothesis test the treatment arms in these three nested cohorts. Passing the alpha, if successful, rejection of the null hypothesis occurred at each step. In the primary analysis, PFS was found to be significantly improved in each cohort. In the stepwise algorithm, the next assessment was the FOSI-18 disease-related symptom physical subscale in the BRCA-mutated tumor cohort. Since this analysis was not statistically significantly different, the analytical plan stopped. As can be seen, the overall survival was to be assessed analytically if the PRO factors were significantly improved with RECAPRIB. The median duration of follow-up for this analysis was 6.4 years with a data lock at April 4, 2022. At that time, all patients randomized to placebo had discontinued study treatment. Over 95% of these for progression. In the RECAPRIB arm, 96% of patients had discontinued therapy with approximately 73% of these being for progression. This slide provides the details of the post-progression therapy in the nested analytical cohorts. Overall 70% of patients randomized to RECAPRIB and 89% of patients randomized to placebo received at least one additional line of therapy with the median number of lines of therapy being three in each group except for the BRCA-mutated tumor cohort where the median number of subsequent lines was two at data lock. As expected, the proportion of patients randomized to placebo had a higher use of subsequent PARP inhibitor administration. However, the proportion varied substantially in the nested analytical cohorts being highest in the BRCA-mutated tumor cohort at 72%. In patients who received subsequent treatment, 21% of RECAPRIB-treated patients and 46% of placebo-treated patients had received a PARP inhibitor. Providing more detail on the non-nested individual cohorts in the placebo group, namely the BRCA wild-type LOH high and the LOH low populations, a clear trend to decreased subsequent PARP inhibitor use was seen in these cohorts. While the time to start a PARP inhibitor was longest in the LOH low cohort, the duration of therapy was shortest in this cohort. The mature final overall survival results are presented here for the three nested pre-specified analytical cohorts. The Kaplan-Meier curves are presented with their 95% confidence intervals to provide more detail as to the performance of both RECAPRIB and placebo throughout the duration of their treatment exposure. In the BRCA-mutated tumor cohort, the hazard ratio was 0.083, with a 95% confidence interval of 0.58 to 1.19. In the HRD test-positive cohort, the hazard ratio was 1.005, with a 95% confidence interval of 0.77 to 1.32, and in the intent-to-treat population, the hazard ratio was 0.995, with a confidence interval of 0.81 to 1.22. Of note, crossover to PARP inhibitor therapy was common and occurred more than twice as often in the placebo arm. To provide further clarity by genotype, I present the non-nested cohorts of patients without BRCA-mutated tumors categorized by their tumor LOH status as high, low, and unknown. Again, the CAM curves are presented here with their corresponding 95% confidence interval was clearly show overlap throughout the duration of exposure. The hazard ratio for the LOH high group was 1.28, for the LOH low group of 1.15, and in the LOH unknown group, just 49 patients, was 0.67, all with confidence intervals spanning 1.0. The proportion of subsequent PARP use in each of these cohorts varied widely, but was consistently two times higher in the placebo arm relative to the recaptive arm. So given the heterogeneity and uncontrolled use of therapy in the multiple lines of subsequent therapy, we updated the analysis of PFS2. This measures the time from randomization to the time of progression in the next line of therapy. In each of the nested cohorts, you can see that there is a persistent advantage to the recaptive treatment, and similar findings were seen for the non-nested cohorts. In the updated analysis for safety, we did not identify any new signals. As previously reported and consistent with the primary analysis, grade 3 or higher treatment emergent adverse events, treatment interruption, dose reduction, and treatment discontinuations were all higher on the recaptive arm. The incidence of ALT-AST elevations, the overall and grade 3-4 adverse events for this side effect was nearly identical to the initial report, highlighting that this side effect occurs early in treatment and is reversible. Deaths due to toxicity were similar and consistent, including the occurrence of MDS-AML at 3.8% in the recaptive arm and 3.2% in the placebo arm. So in conclusion, these data provide robust support for the use of recaptive maintenance therapy for recurrent platinum-sensitive ovarian cancer. The PFS benefit was maintained through the subsequent line of therapy. We did not observe a benefit to overall survival, although these data were confounded by imbalance and potential selection bias of subsequent treatments, including PARP inhibitors, both of which were not controlled for after treatment. Fortunately, the safety and tolerability profile remains consistent with prior reports, now enhanced with longer follow-up. And further investigation on the impact of post-progression treatment on lines of therapy such as platinum is warranted and underway. This study required the skill and expertise of an army of investigators around the world, as well as committed sponsor Clovis Oncology, to whom we are so grateful. We also owe an incredible debt of gratitude to the patients and their families who entrusted us with their lives to address these critically important hypotheses. I'd like to thank you for your attention. Thank you, Dr. Coleman. Dr. Konstantinopoulos, please begin your distillation. Thank you very much for the opportunity to do the distillation of these two very important studies. These are my disclosures. So analysis, which was hypothesis-generating in SOLO3, suggests that there may be a favorable OS for olaparib versus chemotherapy in patients with two prior lines, but a potential detrimental effect in patients with at least three prior lines of chemotherapy. Can we explain these observations? So olaparib may indeed have conferred cross-resistance to subsequent platinum therapy, because the most common mechanism of PARP inhibitor resistance, which are secondary BRCA, HRR alterations, and replication for protection, also cause and induce platinum resistance. At the same time, drugs in the chemotherapy arm have different potential for cross-resistant to platinum. Topotecan and liposomal doxorubicin, which induce double-strand breaks, which are at least partly repaired by homologous recombination, can cause resistance by secondary BRCA mutations that restore HRR, and that resistance is possible, and that also can cause platinum resistance. However, Pataxil and gemcitabine are drugs with a completely different mechanism of action, and the restoration of HRR is not a mechanism of resistance to these agents, and are less likely to cause cross-resistance to platinum. So is it possible that cross-resistance between nolaparib and platinum was more pronounced in patients with more prior lines of therapy? The answer is yes. Several models of resistance have shown that emergence of resistance is a function of two factors, tumor mass and intrinsic tumor genomic instability. And both of these factors, tumor mass and tumor heterogeneity and genomic instability, are higher in more heavily pretreated patients. Furthermore, resistant clones with secondary BRCA mutations are more likely to be already present in patients with multiple prior lines of chemotherapy. These resistant clones may then be selected by olaparib therapy. Six patients in the olaparib arm had baseline BRCA reversion mutations, and five of six of them had at least four prior lines of therapy. Again, it's important to underscore that many of these BRCA reversion detection assays are not sensitive enough, and many of those BRCA reversion subclonal or low-level events may be missed. So if you have clones with BRCA reversion mutations that are highlighted in red, these can be selected by olaparib, thereby causing resistance to subsequent platinum therapy. At the same time, conversely, using drugs like Taxol or gemcitabine, these drugs may actually reduce or eradicate even some of these clones with BRCA reversion mutations, leading to sensitivity to subsequent platinum therapy. In Ariel 4, Paclitaxel decreased BRCA reversion mutations in three of four patients with pre- and post-plasma samples, as reported by Dr. Oza in ESMO 2022, thereby leading credence to the model below. It is therefore important to assess the BRCA reversion mutations at baseline, and after treatment with topotecan, Doxil, Paclitaxel, and gemcitabine in SOLO3, to formally evaluate the effect of each one of these drugs. So more prior lines of therapy, to summarize, olaparib is more likely to induce cross-resistance to platinum, while use of non-cross-resistant drugs, such as Taxol or gemcitabine, are less likely to induce cross-resistance to platinum. And more prior lines of therapy, olaparib is more likely to select pre-existing BRCA reversion platinum-resistant clones, while use of non-cross-resistant drugs, such as Taxol or gemcitabine, may decrease these pre-existing BRCA reversion platinum resistant clones, and may increase sensitivity to subsequent platinum chemotherapy. The fact that Taxol may decrease pre-existing BRCA reversion clones may explain the Ariel 4 findings in platinum-resistant cohort, where there was a 75% PARP inhibitor crossover, whereby rucaparib-weaklitaxel was worse than weaklitaxel followed by rucaparib. So sequence may matter. Conversely, Doxil, which is more cross-resistant with platinum and PARP than Taxol, may be less likely than Taxol to decrease pre-existing BRCA reversion clones, which may explain why in the olaparib versus single Doxil trial, that's the old study 12, in G-BRCA-mutated patients, there was no suggestion for an adverse OS effect seen. So how should we treat platinum-sensitive PARP inhibitor-naive BRCA-mutated ovarian cancer? As we know, AZ, Clovis, and GSK voluntarily withdrew the treatment indications for olaparib-rucaparib-eniraparib monotherapy in recurrent ovarian cancer. Where personally, even before these withdrawals, I treated these patients with a platinum doublet followed by PARP inhibitor maintenance, and I will continue to do that so. This strategy is supported by MITO8, the OS survival data from SOLO2, and the current regulatory approvals. But it also makes biologic sense. Because if we think about this, if we give initially platinum, especially combined with a non-cross-resistant drug, then we may eradicate some of these BRCA-reversion clones, and therefore have better response to subsequent maintenance PARP inhibitor therapy than treating this disease with PARP inhibitor alone. If platinum allergy, it's reasonable to consider olaparib alone in patients with two prior lines of therapy. And the study reported by Dr. Leith gives credence to that. So switching gears now to ARIEL3. I put here all phase 3 second-line maintenance study. So strikingly similar PFS results. I have put here in this slide the overall survival data for ARIEL3-NOVA-SOLO2. That's only for reference, not for comparison. And I have included also the PARP inhibitor crossover percentage in the placebo arm. So starting in the BRCA-mutated population, we see that there was a more favorable hazard ratio for SOLO2 because the PARP inhibitor crossover there was only 38 percent, much lower than what it was in ARIEL3 and NOVA. But it's also important to highlight by looking at ARIEL3 and SOLO2, there was in ARIEL3 a very big jump in the hazard ratio from PFS to PFS2, suggesting that this was likely an effect of PARP inhibitor crossover, which was higher in ARIEL3, and also the effect of reduced response to subsequent platinum-based chemotherapy. This is the hazard ratio for BRCA-WAL type HRD-positive population, and the hazard ratio for the HRP population. I want to emphasize that in the BRCA-WAL type, in ARIEL3, HRD versus HRP does not appear to have any predictive functional role for subsequent therapy, especially in the setting of recurrent platinum-sensitive disease, because the median duration of first subsequent PARP inhibitor therapy was exactly the same between the two, 9.2 versus nine months. So it's therefore the difference between the two hazard ratio of 1.28 versus 1.15 may just be reflective of less crossover in the HRP. So why was there an adverse OS hazard ratio for PARP inhibitor in BRCA-WAL type HRD tumors in ARIEL3 and NOVA? We need to wait for mature OS and evaluate missing data. We need to assess the effect of crossover. However, if the adverse OS hazard ratio is indeed observed only in the PARP inhibitor crossover population, why would patients in the placebo arm who crossed over did better than patients who got PARP inhibitor right away? In other words, why platinum followed by PARP fared worse in terms of overall survival than platinum followed by placebo followed by platinum followed by PARP? At the same time in PILO1, the first line, the OS hazard ratio for Olaparib and BRCA-WAL type HRD was 0.71. So it's very possible that the type of platinum doublet used before PARP inhibitor maintenance is important. So if we think about this and look back, two thirds of patients in ARIEL3 and NOVA were randomized after second line platinum therapy. In other words, most likely after they had received garbodoxil. We know that globally most patients get garbodoxil as second line platinum therapy. So patients in the PARP inhibitor arm got garbodoxil followed by PARP, but patients in the placebo arm got garbodoxil followed by placebo followed by CARBOGEM or CARBOTAXEL followed by PARP. So there is an imbalance and it's possible that use of CARBOTAXEL or CARBOGEM before PARP because we're using a CARBO with a non-cross-resistant agent like TAXEL or JEG may be better than using CARBODOXIL prior to PARP in terms of both induction of resistance or selection versus reduction of pre-existing BRCA reversion clones. In PALO1, patients got olaparib after CARBOTAXEL and with Avastin as a reminder. So key points here. PARP inhibitor crossover in the placebo arm of ARIEL3 was high. OS analysis is eventually asking an early versus later PARP inhibitor question which the study was not designed and not powered to address. The effect of crossover and overall survival needs to be analyzed. The effect of subsequent therapies on OS need to be assessed. The effect of types and sequencing of subsequent therapies which may have different effects on induction of resistance or selection versus reduction of pre-existing resistant disease need to be assessed. Especially drugs, type of drugs used immediately prior to PARP inhibitor therapy. Response to subsequent therapies, for example, lower response to subsequent platinum as observed in SOLO2 needs to be assessed. An analysis of BRCA or HRR reversion mutations and other mechanism of PARP inhibitor resistance at baseline and after its therapy has immense clinical translational implications. I want to finish by adding a few thoughts on the key problem of cross resistance between PARP inhibitor and platinum. Can we delay or prevent cross resistance to platinum in patients receiving PARP inhibitor therapy? I have two thoughts on that. The first thought has to do with the fact that a lot of these BRCA reversion mutations are actually mediated by micro homology mediated and joining, which is one of the DNA repair pathways that gets in effect when homologous recombination is not functional. So if we use both theta inhibitors, which may delay or which block the micro homology mediated and joining, we may be able to delay or even prevent development of resistance by decreasing the incidence of BRCA reversion. So there's a strong argument for incorporation of PARP inhibitor or theta combinations early in the treatment and we need to look at novel endpoints such as incidence of secondary BRCA HRR mutations or response to subsequent platinum therapy in all of our studies. Finally, is there an optimal duration of PARP inhibitor maintenance therapy that is specific for each patient? So after we complete platinum-based chemotherapy, we're giving PARP inhibitor and we're able to decrease tumor volume and by the same token, possibly resistance, but there is eventually a point where the effect of PARP inhibitor on the tumor volume is very, very insignificant and the only thing we're doing is inducing resistance. So can we define that sweet spot, that optimal duration of PARP inhibitor maintenance for each patient? Could it be circulating tumor DNA? Could it be BRCA HRR reversion mutations or other biomarkers? I think we have a lot of patients on this PARP inhibitor maintenance studies and we need exploratory correlation of duration of PARP inhibitor maintenance with PFS and OS and exploratory evaluation of concomitant blood samples looking at CT DNA, BRCA reversion mutations and other possible biomarkers with PFS and OS. With these thoughts, I would like to thank you very much for your kind attention and my thoughts and prayers to the people of Florida. time for questions because we're about 25 minutes behind. I'm so impressed by the science in this session. Next up is an interesting abstract from Dr. Su Jin Park. Today I would like to talk about the selection criteria for omitting interval deburking surgery after Newsman chemotherapy for advanced high-grade serous ovarian cancer. I have nothing to disclose. Recent clinical trials have shown comparable survival outcomes of Newsman chemotherapy followed by interval deburking surgery compared to primary deburking surgery. Therefore Newsman chemotherapy can be applied to patients with advanced unrespectable ovarian cancer patients without impairing their survival. Despite the survival benefit of PARP inhibitors in the first-line treatment of advanced ovarian cancer, optimally deburking surgery with no residual disease is the most important part of first-line treatment to improve survival. Recently, several clinical factors including CA125 has been studied to predict the response of Newsman chemotherapy. However, most of the evidence is still weak to be incorporated into the clinical setting. CA125 kinetics represented by CA125 elimination constant K, Kalym's score has been evaluated based on clinical trials at secondary endpoints. Kalym's score has been shown to predict progression-free survival and overall survival in advanced ovarian cancer. Also, platinum sensitivity is shown to be associated with Kalym's score. This study aims to explore the selection criteria to omit interval deburking surgery for advanced ovarian cancer patients undergoing Newsman chemotherapy using Kalym's score. This study is a single institution retrospective cohort design. We collected data from patients diagnosed with ovarian cancer from 2000 to 2021 at Seoul National University Hospital. Among 3,356 patients, we selected stage 3, 4 ovarian cancer patients with high-grade serocytology who underwent Newsman chemotherapy. Also, we excluded patients who received PARP inhibitors or anti-angiogenic agents to evaluate chemosensitivity. Finally, 61 patients who underwent chemotherapy without surgery and 194 patients who underwent Newsman chemotherapy followed by interval deburking surgery were included in the final analysis. First, we analyzed the Kalym's score after 1, 2, and 3 cycles of Newsman chemotherapy. Three scores could predict 12-month recurrence with statistical significance after chemotherapy only treatment. So, we selected a cutoff value of 0.95 Kalym's score after a single cycle of Newsman chemotherapy. When we look at the table for baseline characteristics, all patients had stage 3c and 4 disease. According to the Kalym's score after a single cycle of chemotherapy, 41% and 33.5% of patients showed high Kalym's scores with no statistical difference. Pathologic complete response was shown in 22 patients after interval deburking surgery. Among the high- and low-Kalym patients, 70% and 65.5% of patients underwent optimal deburking surgery without statistical difference. But more patients were treated with chemotherapy alone in high-Kalym group. Around 95% of patients in both groups showed complete or partial response after first-line treatment. High- and low-Kalym groups were treated with a median number of 6 cycles of chemotherapy without statistical difference. In survival outcome, the chemotherapy-only group showed poor portion-free survival and overall survival in the low-Kalym group. However, in the high-Kalym group, we found no survival difference in patients regardless of the interval deburking surgery. When we compared survival for patients who underwent optimal, suboptimal surgery and chemotherapy only, the chemotherapy-only group showed poor overall survival in the low-Kalym group. However, the chemotherapy-only group showed no difference in survival compared to optimally deburred patients in the high-Kalym group. In multivariate analysis, chemotherapy-only treatment was associated with poor portion-free survival and overall survival in the low-Kalym group. However, chemotherapy-only treatment did not impair portion-free survival and overall survival. Six or more cycles of chemotherapy was associated with better survival in the low-Kalym group. This result is consistent with previous publications, which have shown that the role of maximal cytoreductive surgery affects survival differently according to the Kalym score. Indeed, the extent of maximal cytoreductive surgery largely impacts the low-Kalym group with less impact in the high-Kalym group. Even though R0 and R0 resection is an important prognostic factor regardless of the Kalym score, the corresponding concept of surgical extent cannot be applied to patients treated without surgery. So we incorporated radiology response as an alternative for evaluating treatment response regardless of the interval deburring surgery. When we incorporated radiology response, instead of surgical outcome, radiology complete response or partial response was associated with better survival in both groups. The chemotherapy-only treatment still impaired overall survival in the low-Kalym group while not affecting survival in the high-Kalym group. To summarize, radiology complete response or partial response is strongly associated with improved survival in low- and high-Kalym group. In the low-Kalym group, over six cycles of chemotherapy are associated with better survival due to low chemosensitivity. In the high-Kalym group, due to high chemosensitivity, over six cycles of chemotherapy is not associated with better survival. In conclusion, radiology response or partial response after texin- and platinum-based chemotherapy is important for improving the survival of advanced high-grade serous ovarian cancer. In those with low-Kalym, radiology complete response or partial response by interval deburring surgery or over six cycles of chemotherapy is crucial for improving survival due to lower chemosensitivity. In those with high-Kalym, chemotherapy only without interval deburring surgery can be considered with comparable prognosis to Newsburn's chemotherapy followed by interval deburring surgery due to higher response to chemotherapy due to higher chemosensitivity. Thank you for your attention, and I deeply appreciate my colleagues shown in this slide. Thank you. Thank you, Dr. Park, for your excellent presentation. Now we will hear Dr. Dennis Chee's distillation. Dennis. Thank you, Larry and Alex. Thank you to the program committee for allowing me to do this distillation. And welcome to New York. So I was asked to distill this excellent article or study called the SCORE study. These are my disclosures. Sorry that I didn't use the right form. I have a little difficulty following directions sometimes. So regarding CE125, it's been utilized, published, and studied in numerous settings, including screening and surveillance, like the PLCO study and the various Kentucky studies. It helps us to distinguish benign from malignant adnexal masses, sometimes not with great accuracy. At Memorial, we use it to assess receptability for advanced stage disease to determine neoadjuvant versus primary debulking strategies. Obviously with the Ruston criteria and other criteria, it helps us analyze whether there's a response to chemotherapy. I'll be honest, before I was assigned this study to review, I didn't have any idea what KELM was, but basically it stands for the constant K. They moved it up to the beginning. And it's the CE125 elimination rate with a constant of K. And it's thought to predict tumor chemosensitivity, be prognostic, and even predict cytoreductive outcome. This is where I found it to be the first description of the KELM model by Yu et al. using CLPSO trial data, basically following longitudinal CE125s and thought to be a marker for chemosensitivity and progression-free survival. Its analysis of the rate of CE125 declined during systemic treatment. So when I was originally assigned this article, I thought that this was going to tell us who to avoid surgery on because it was going to lead to a futile laparotomy, that these were such platinum-resistant, platinum-refractory, chemo-resistant patients that you shouldn't even bother operating. But it's actually the flip of that. It's actually who are doing so well with chemotherapy that you can avoid that dreaded interval cytoreductive procedure. It takes into account CE125 tumor production, or K-PROD, tumor growth beta, treatment kinetics. So when I went to undergrad, I was a mathematics major, and after one year, after looking at mathematical models like I show you on the right, I became an English major because I just could not understand this kind of computation. I presume there's some sort of app where you can come up with the number. But basically, the bottom line is, the higher the KLM, the faster the C125 elimination, decreasing, and so presumably, the higher chemotherapy sensitivity and or efficacy. So in the SCORE study, this is the patient flow. It was using that KLM model and retrospectively reviewing 279 patients who underwent neoadjuvant chemotherapy with or without interval debulking. And as you can see, 194 patients underwent interval debulking. 61 did not. Retrospectively putting the KLM data onto these patients, 65 patients had a high KLM. As you saw, there were 0.95. 25 of those patients underwent interval debulking surgery. And in the no IDS group, 25 had a high KLM. So grouping those 90 patients together and looking at the survival data after their intervention of interval or no interval debulking surgery, you see that if you had a complete gross resection or minimal residual disease, the PFS was 20.3 months, the overall survival, 55 months. Only two patients had suboptimal cytoreduction with PFS of 11.7 or 20.3 months. And if you didn't do any surgery at all, 25 patients with a high KLM, the pre-FS was 13.8 and 46.7. On the side here, I have the PFS and OS of just grouping those who had a complete gross resection, optimal, suboptimal cytoreduction. So all 65 patients who underwent some sort of interval debulking surgery, and you see the PFS is 18.2 versus 13.8 and 55.5 versus 46.7. In both groups, not thought to be statistically significant. So that leads to the conclusions. And I'll get to the one about the no IDS in a second. So in conclusions, the authors state that complete interval debulking surgery with radiologic CRPR after platinum-based chemotherapy is important for improving survival of advanced high-grade serious ovarian cancer patients. I agree. Complete interval debulking surgery is crucial for improving survival in advanced high-grade serious carcinoid patients with lower KLM, presumably not as chemosensitive during neoadjuvant chemotherapy. Definitely agree. The last conclusion is chemotherapy alone without interval debulking surgery is expected to show comparable prognosis with neoadjuvant chemotherapy and interval debulking surgery in high KLM patients during neoadjuvant chemotherapy. So I have two questions, and I do congratulate Dr. Park and my Korean brothers and colleagues on an excellent study, but I do have these two questions and a little bit of skepticism. Since you are applying the KLM score to patients retrospectively, what were the reasons that you did not operate on those 25 patients with a high KLM score, number one? And number two, the major part of my skepticism is that given in this study, 70% of the patients who had a high KLM, theoretically, they have the best prognosis. They're doing very well, they're responding well to the chemotherapy, and an interval cytoreduction led to a complete gross resection in most of them, and the PFS was 20.3 months compared to 13.8 months for no IDS. So that's a difference of six to seven months, as good as Avastin. Would you really wanna recommend no IDS to these patients who would have a much higher expected PFS with an interval debulking surgery? Maybe not even do a laparoscopy like the LANCE trial is proposing? I'm a little bit worried that this would be a little bit difficult to sell to patients and might lead to some not expected, not so good results. Thank you all very much. Thank you. Thank you, Dr. Che. Again, we are not going to be able to take questions from the audience. Next is our late-breaking abstract by Dr. Yong J. Lee, who will share the presentation on effectiveness of HIPEC following interval cytoreductive surgery in patients with advanced-stage ovarian cancer. It is a great honor for me to be here and present my results in the IGCS. Today, I am going to talk about the Multi-Center Prospective Core Study of Comparative Effectiveness of HIPEC following interval cytoreductive surgery in patients with advanced-stage ovarian cancer. I have nothing to disclose. And in advanced-stage ovarian cancer, maximal surgical cytoreduction followed by platinum-based chemotherapy has been the standard of care. However, even after complete remission, approximately 60 to 80% of patients with advanced-stage disease experience relapse. HIPEC represents a new treatment option in ovarian cancer with survival benefit in the neoadjuvant setting. Recently, two randomized trials have demonstrated survival benefits of HIPEC in advanced-stage ovarian cancer. In the OV-HIPEC study, comparing survival outcomes between surgery without HIPEC and surgery with HIPEC, surgery with the HIPEC group had improved survival outcomes. In the Korean HIPEC study, this study failed to show benefit of HIPEC in primary treatment, including primary reworking surgery or neoadjuvant chemotherapy. But in subgroup analysis and neoadjuvant chemotherapy group, surgery with the HIPEC group had the survival benefit in terms of DFS and OS. However, there are unanswered questions from OV-HIPEC. There are many patients who underwent neoadjuvant chemotherapy at stage four. The benefit of the HIPEC in patients with stage four are still unknown. Recently, maintenance therapy was adopted in first-line treatment. The impact of maintenance therapy after HIPEC were also unknown. Lastly, we need more evidence for the pattern of recurrence after HIPEC, which may affect the survival outcomes. Despite the survival benefits of HIPEC in randomized trials, there are still limited use of HIPEC with ICS in real world. First reason is the barriers of adopting HIPEC to the institution, such as potential hazard to the clinicians or long surgery time and expensive HIPEC instruments. Second, there are no data for HIPEC with ICS in the era of maintenance therapy. In these reasons, the incorporation of HIPEC into clinical practice varies significantly among institutions and clinicians in South Korea. Therefore, we conducted the comparative effectiveness study. This study was conducted in stage three and four epithelial ovarian cancer patients. Neoadjuvant chemotherapy was conducted to patients with high tumor burden on diagnostic laparoscopy or pretreatment radiology images. ICS with HIPEC or ICS without HIPEC was decided at the clinician discretion. The primary endpoint was PFS, and secondary endpoint was OS and safety. In this study, seven institutions have participated in South Korea of KGOG members, and 205 patients were registered, and nine patients were excluded because of these ineligibilities. Finally, 87 patients were assigned to the ICS without HIPEC group, and 109 patients were assigned to the ICS with HIPEC group. In statistical consideration, we calculate the sample size based on the OB-HIPEC study, and we plan the sufficient follow-up for the observation of 102 events of disease progression or death. In the patient's characteristics, age and histology type and the stage, or the grade, show no significant differences between two groups. Also, the BRCA mutation status or the maintenance therapy, and the total cycles of chemotherapy show also no difference between the two groups. In the surgical characteristics, the proportion of the HIPEC using cesplatin was about 69%, and about 57% of patients underwent HIPEC with open technique. There was no difference in residual disease between two groups. Estimated blood loss was higher in the HIPEC group, and mean operation time and mean duration of hospitalization. The medium and time interval between the surgery and the start of the adjuvant chemotherapy was longer in HIPEC group. In the comparison of recurrence patterns, we classified the recurrence pattern into four categories, extraperitoneal recurrence, or the visceral, or the lymph node, or the peritoneum. Peritoneal recurrence were less common in ICS with HIPEC group, and more common in lymph node compared to the ICS without HIPEC group. In the summarized table, the recurrence rate of the peritoneum was significantly lower in ICS with HIPEC group, and the ICS with HIPEC group had a higher rate of lymph node recurrence. In the progression-free survival, HIPEC with ICS group had improved the survival outcome, and hazard ratio was 0.61. In the exploratory subgroup analysis, ICS with the HIPEC group was associated with improved PFS across most of the subgroups. OS shows remarkable difference between two groups. The median OS was not reached in the ICS with HIPEC group, and 53 months in the ICS without HIPEC group, it has a ratio of 0.31. There was no significant difference in post-operative complications between two groups. Grade two complications were most common in two groups, and the three cases of grade three and four complications were observed. Two cases of post-operative hemorrhage, and one case of a hydronephrosis. These complications were not directly related to the HIPEC. In conclusion, this is the first prospective and multi-center comparative effective study of the HIPEC, and we demonstrate that ICS with HIPEC improved survival outcomes in patients with stage three and four epithelial ovarian cancer without any serious advanced events. Therefore, increasing ICS with HIPEC using clinical practice may be an important strategy to improve survival outcomes in advanced stage ovarian cancer. Randomized control trial is needed in the era of maintenance therapy. Special thanks to the investigators of seven institutions and members of the KGOG. Thank you for your attention. Thank you, Dr. Lee, for your impressive study. Unfortunately, we're gonna cut Dr. Leslie Randall's distillation. It will be available online. Apologize for that. We'll get you back, Leslie. Okay. Okay, very, we, hopefully, Dr. Randall's distillation will be online, and you're welcome to look it up. It's going to be interesting. The last abstract presented in this plenary session will come from Dr. Amy Jamieson, followed by a distillation by Dr. Shannon Weston. Dr. Jamieson. Okay, thank you. So I'd like to thank the organizing committee for the opportunity to present this abstract promise to a one-step DNA-based endometrial cancer molecular classifier. I have nothing to disclose. So following the discovery of the four molecular subtypes of endometrial cancer by the Cancer Genome Atlas in 2013, two research groups working independently, so a group from Vancouver and the Portet Group, used surrogate markers to develop and validate a clinically relevant endometrial cancer classification tool that was able to recapitulate the TCGA survival curves. This tool uses a combination of focused sequencing of poly and mismatched repair and p53 immunohistochemistry to assign endometrial cancer to one of four molecular subtypes. And PROMIS was developed following Institute of Medicine guidelines for developing an omics-based test with discovery, confirmation, and validation cohorts. So to assign a PROMIS subtype, all components must be available. So you must have poly mutation status as well as mismatched repair and p53 immunohistochemistry. Often components are performed at different stages of care and at different centers, resulting in delays in management plans. And finally, reimbursement can be challenging as these different steps of IHC and NGS come from different resource allocations. So a common example for us is that mismatched repair IHC is performed on the biopsy at the community center of origin. And then p53 immunohistochemistry is requested after referral to our tertiary cancer center. And then NGS for poly is not performed until the final hysterectomy specimen at our surgical hospital, which is now a third different site. So by the time you get the results back from all three of these components, the patient may have already been referred for adjuvant therapy with a missed opportunity to act on this molecular information. And why is this important? Well, molecular classification was endorsed by the WHO in 2020. And recently, we've seen societal guidelines change to incorporate molecular classification into restratification and treatment algorithms. So a way to overcome some of these challenges with the PROMIS tool, we felt there was a substantial appeal in moving towards a one-step, one-cost DNA-based molecular testing model. This would simplify the financial reimbursement as well as avoiding the current challenges of the results coming in at different times from different centers and often having to wait on one component before the PROMIS molecular subtype can be assigned. So we worked with a local company to develop PROMIS-2. For PROMIS-2, DNA is extracted from FFPE tumor and next-generation sequencing is performed for poly and TP53 mutations, replacing P53 immunohistochemistry. And mismatched repair IHC is replaced by a micro-satellite instability assay. So previous studies have compared MMR IHC versus MSI assays and TP53 mutations on sequencing versus P53 immunohistochemistry specifically in endometrial cancer with discordance rates ranging from approximately 5% to 9%. And there certainly are pros and cons of both ways of testing. So there are some explanations for why we see this discordance. So an example for why you can get abnormal P53 protein expression on immunohistochemistry with no detectable TP53 mutation on sequencing is related to difficulties in detecting large deletions or insertions using current NGS methods. Another example of why you can have a mismatched repair deficient case that's detected on mismatched repair IHC that can potentially be missed on MSI testing is specifically related to MSH6 mutations that tend to result in weaker or no MSI in the tumors. So the aim of our study was to assess concordance metrics as well as the prognostic ability of a one-step DNA-based molecular classifier compared to the original PROMIS. DNA was extracted from endometrial cancers that had previously undergone molecular classification using PROMIS, and PROMIS-2 was assigned using a next-generation sequencing assay to assess for mutations in POLE, mutations in TP53, as well as in other endometrial cancers. And we found that PROMIS-2 was the most effective in TP53 as well as the presence of microsatellite instability. So in terms of results, PROMIS-2 was assessed in 91 endometrial cancers. Two cases initially failed sequencing coverage thresholds. However, on resequencing, both of these cases passed. So in the end, 87 out of 91 cases were concordant with a Kappa statistic of 0.93, representing excellent agreement and an overall accuracy of 0.96. Five out of six cases where PROMIS-2 was performed on matched biopsy and hysterectomy specimens were concordant, and I will go over these discordant cases shortly. Perhaps even more important than the concordance of PROMIS and PROMIS-2 subtype assignment is that the prognostic value of PROMIS-2 was maintained. You can see from these Kappa myopods with the original PROMIS on top and PROMIS-2 below that there was recapitulation of the TCGA survival curves. So just looking at these four discordant cases in more detail, the first case was polymutated in the original PROMIS and NSMP on PROMIS-2, and on review of this polymutation, it had very low variant allele frequency, which was confirmed on repeat sequencing, so it was likely an artifact, therefore not a discordant case, and it was incorrectly classed as polymutant on the original PROMIS. The second case was p53 abnormal on the original PROMIS and NSMP on PROMIS-2, and as I've already said on a previous slide, we know you can have abnormal p53 protein expression on immunohistochemistry with no detectable t53 mutation on sequencing due to the difficulties in detecting large deletions or insertions using NGS. The third discordant case was NSMP on the original PROMIS and MSI on PROMIS-2, and we know that with mismatched repair IHC, we can get low levels of MSH6 expression, which is significantly weaker than internal control cells, and this is an expression pattern known to be associated with MSH2 loss and can be incorrectly interpreted as MMR intact, and that was the case in this discordant case. And finally, the fourth discordant case was the case that was discordant on biopsy and hysterectomy. There was a t53 mutation found on the biopsy, and it was classed as NSMP on the hysterectomy specimen for both PROMIS-2 and the original PROMIS, and this is likely explained by tumor heterogeneity. So, in conclusion, we demonstrate a high concordance of a one-step DNA-based endometrial cancer molecular classifier when compared to the original multi-step PROMIS classifier. Importantly, the prognostic value was maintained with recapitulation of the TCGA survival curves. This presents an option for centers where routine MMR and p53 IHE is not currently being performed. This can be performed in preoperative biopsies to get this important prognostic information earlier and avoid delays in management. Further validation is needed before implementation into clinical practice, and we are currently assessing PROMIS-2 in a much larger cohort of endometrial cancers. Obviously, the cost-effectiveness of a one-step DNA-based test is very important, and this is also currently being assessed. And it's important to note that all components of PROMIS-2 can be performed by other commercial or institution-based assays, and I would like to thank the team involved with this project. Thank you. Thank you. Dr. Weston, please begin your presentation. I would love to. I think my slides are getting pulled up. So, thank you, everybody, and I'm so excited to be here to discuss this really important work, and I think the authors are to be congratulated in our ability, moving forward with how we classify endometrial cancer. So, these are my disclosures. So, as discussed, the TCGA really moved us forward, going from histologic and pathologic classification into a more molecularly-based classification strategy, and I think the PROMIS algorithm has made a very pragmatic way for us to assess and bin these patients and their tumors and appropriately understand both prognosis and perhaps treatment, right? So, what we know is when we utilize the PROMIS algorithm, starting with poly-sequencing, followed by immunohistochemistry for mismatched repair proteins and then assessment of P53, either by sequencing or through IHC, that we see consistent prognostic information to what we see when we do the full TCGA assessment. And as such, it's been incorporated into the NCCN guidelines with the suggestion that molecular analyses should be performed on all patients with endometrial cancer, although you'll know that little sub-bar that the decision to utilize this testing depends on availability of resources and the multidisciplinary team of each center. There's also not a really great description of what we should do from a treatment standpoint in the NCCN guidelines. Now, the ESCO, ESTRO, and ESP guidelines do get a little bit more prescriptive. And importantly, they bin patients into risk groups based on either if they've had molecular testing or not. And I think one of the most important pieces of this, or one of the critical pieces, is that movement of poly mutant population into that lower-risk group. Getting at this idea, do they need adjuvant therapy based on their excellent prognosis? Now where do we stand? Well, we definitely can feel comfortable that these molecular classifiers are prognostic. We've seen that in assessment of PORTEC1 and 2. We've seen it in assessment of PORTEC3, where binning the patients into the TCGA or the PROMIS classifiers is very consistent prognostically. We're still trying to figure out if there is prediction, or should we be utilizing these classifiers for treatment? Now there was a suggestion in the assessment of PORTEC3 that certain groups, again, poly, may not need any adjuvant therapy. They do the same no matter what they're treated with. And conversely, groups like the P53 group do poorly and benefit more from chemotherapy. We're very excited about a number of ongoing prospective trials that will really help us identify the use of these classifiers and understand how we can bin patients to treatment. We've got PORTEC4A in our so-called lower-risk group, and we've got the RAINBOW umbrella trial, which is in a more high-risk group, where they're utilizing these molecular classifiers to actually guide therapy. So these prospective trials are going to help us understand how to use this in our clinical practice. But to date, the uptake of molecular testing has been very inconsistent. And as Dr. Jamison said, some of that is because the care of these women is often fragmented. They see their outpatient, they get their endometrial biopsy, then they move to their hysterectomy, and the testing is occurring at each of these pieces. And so the PROMISE-2 really addresses that issue. The other issue, though, is just availability of this testing across different centers, and importantly, the cost. And I'm very excited and eager to see the assessment of cost-effectiveness, because specifically in the States, next-gen sequencing is very expensive, and so the utilization of this strategy is hard without truly knowing how is it going to guide our therapy. So our unmet need really is equity across countries and practices. So Dr. Jamison presented this one-step DNA-based endometrial classifier, which moves from that next-gen POLE sequencing, mismatch repair assessment, and then P53 into one-step DNA extraction, assessment of next-gen sequencing for POLE and P53, and a microsatellite instability assay, all for one cost. And as you saw, they were successful, and I was excited to see the updated data that all of the endometrial cancers were able to be successfully sequenced with this one-step strategy, and there was very clear concordance between doing the full PROMISE algorithm as opposed to the PROMISE-2. They also had some really interesting opportunities with the matched biopsy and hysterectomy specimens indicating that potentially all of this testing could be done with that endometrial biopsy, and as we learn more about how to use these molecular classifiers in treatment, we could get all that information prior to hysterectomy, which is very exciting. Importantly, they were able to show that that PROMISE-2 did demonstrate similar prognostic information as what they saw with a full PROMISE algorithm, so again, getting that consistent validation. And the bottom line is, we see concordance, right? We see concordance between PROMISE and PROMISE-2. We see that that prognostic value is maintained. We have addressed this multi-step issue by getting everything in one step, but we still need validated data, and it still requires next-gen testing. And so I think our existing questions are looking at this validation in a larger cohort and really, again, understanding the predictive value. As I mentioned, there are a number of prospective trials that are trying to understand what we can use this molecular classification for. The TAPIR trial is a great example. Can we de-escalate care based on the results of next-gen sequencing? Because I think this is essential to be able to get the payers, frankly, to pay for next-gen sequencing in the absence of, you know, protein testing. We still have an issue with availability, so as we get more of these data, the hope is that this will become more broadly available and, of course, the cost. And I just wanted to call everyone's attention to a really important paper that was just published by Battella and colleagues that attempted to move away from the next-gen sequencing or at least reduce the next-gen sequencing to provide a more cost-effective strategy. So what they did was actually start with mismatch repair. And based on if the patient was early stage, if the patient had an aberration in P53, they moved into a different risk classification. They found that they were able to reduce the number of tests, which was really exciting, 67% reduction in poly mutation sequencing. So again, a potential way to keep utilizing this molecular classification strategy but reduce the cost. And then finally, I think that, you know, we do see issues with multiple classifiers. In about 3% of patients, they're going to have multiple tests positive, either poly and mismatch repair, poly and P53, and really understanding where to bin those patients and how to best treat them. So I'm really impressed with these data, and I'm so excited. I wish we had a little time to go through some of these questions, but I'll thank you all for your attention. Well, this has been an amazing opening session. This now concludes this portion of the session. I will now ask Dr. Coleman to come back up to introduce the guest lecturer. Thank you. Thanks so much, Alex and Larry, and for your fantastic time management. I'm just kidding. No comment. I think we're still getting over the clunkiness of getting back in person, but I do want to congratulate all the speakers from this morning's session, myself excluded, for their excellent presentations. So we now have a special presentation on the impact of the war on gynecologic cancer care from the experience of the Polish-Ukrainian cooperation. Only a few days after the Russian invasion began in Ukraine, the Polish Society of Gynecologic Oncology began coordinating treatment of Ukrainian patients with gynecologic cancers. The full-scale military conflict in a developed country is a unique experience and is an exceptional challenge for healthcare systems, both in the invaded country and in the neighboring countries. The cooperative initiative organized by the Polish and Ukrainian oncogynecologists is based on a network of interpersonal contacts, which included Dr. Marcin Stanislav Babinski from Lublin, Poland, and Dr. Olga Hapniana from Kiev, Ukraine. Unfortunately, Dr. Hapniana could not travel here today, and she very kindly provided a video, which we will make available online. However, we do have Dr. Marcin Babinski here, who will come up and tell us about his experience with the cooperation from Poland and present the results of the pan-European survey studied aimed to measure the scale of patients' translocation and identify their needs. I'd like to welcome Dr. Babinski. Oh, there he is. Thank you. I really appreciate you taking the time to come up and tell us about this unique situation. Thank you. Thank you. So here, just advance from here. Okay. Good morning. Thank you, Dr. Koleman, for a warm introduction. My name is Marcin Babinski. I work as a gynecologist in Poland, as Dr. Koleman said. These are my disclosures. I came here from the middle-sized city in Poland, Lublin. Lublin is the city located almost 4,500 miles away from here, but it's located only 55 miles away from the border of country in war, Ukraine. Russian aggression in Ukraine was a deep shock for all the Polish people. Since the war, 6 million Ukrainians crossed the Polish border. Some of them came back. Some of them went to other countries. But about 1.3 million people stayed and deeply changed our society. In the hottest moment, right after the war started, the population of my home city rised almost twice. 80% of refugees are women and children. Among them, about 1,000 women may suffer from gynecological cancer. It includes about 700 cases of endometrial cancer, 200 of ovarian cancer, and about 140 of cervical cancer. These numbers are only calculations to illustrate the scale of challenge we faced. The exact numbers will remain unknown due to lack of statistics, especially at the beginning of war. We quickly realized that everyone in Poland should do what he can do best. So we decided to start acting in field of gynecological oncology. From initiative of these two wonderful women, Magdalena Studnicka, who is coordinator of Polish Gynecology Group, and Renata Buda, who is director of Polish Society of Gynecological Oncology, we established an initiative to provide support for Ukrainian patients. We invited Polish patients, governed in patient's organization, Blue Butterfly Association and Coalition for Life, to help us in logistics. To be honest, it was really moving moment when we were talking with our patients and they invited Ukrainians to their own houses to help them, saying, I know how it feels to have a cancer and I want to go through all this together with these other people. We raised collaboration with Ukrainian doctors, looking for contacts from friends of our friends, and it started. Patients started to come. Importantly, the treatment expenses were from the beginning covered by National Health Fund, so it was not limitation for our actions. In this picture, you can see me and Luba, one of our first patients. Just after her operation, this picture was taken March 9th this year. The exact number of centers treating Ukrainian patients remain unknown. No such statistics were published so far. Patients were treated across the country in almost all of gynecology centers. On this map, only centers cooperating with Polish society in this initiative are marked. I just want to express my very great grateful for all the doctors involved. And what happened then? Ukrainian forces stopped advances of Russians and liberated some areas. The situation somehow stabilized. Ukraine received a lot of military, financial, and material support, including medical supplies. Unfortunately, according to the recent United Nations report, the needs of Ukraine in field of medical support are only satisfied in less than 50%. So further initiatives are still very important. Today, it's 216th day of war. What we have learned during this time? We learned that taking care of patients at war is much more than health care. It's taking care about their families, housing, transportation, psychological needs. Medical support of health care for refugees is crucial. In Poland, it was not a problem, since the beginning refugees received equal insurance to Polish citizens. But I know it was an important issue in other countries. Additionally, it's worth to be mentioned that medical societies are very important part of such support. Societies are based on networking. Usually, we use it to cooperate in field of science, medicine, but such networks might be very efficient when will be used in field of humanitarian help. As I mentioned before, patients' organization really helped. These people simply understand what does it mean to suffer from cancer. Interestingly, the flow of Ukrainian patients coming to Poland rapidly grow after the war started and then it fall when Ukraine received the support. It's much more convenient to every patient to be treated in their own country. So the most important lesson, in my opinion, is the crucial role of humanitarian help for these brave people fighting for their country. But this initiative also experienced a few challenges. The biggest problem we faced, surprisingly, was not the capacity of the hospitals, but accommodation, especially after and doing treatment that sometimes was long-lasting. Million people came to Poland, so problems with housing, especially in bigger cities when the most of oncologic centers are located, appeared. Additionally, the transportation was a barrier. Sometimes patients just arrived on our border in the middle of the night and someone had to pick them up. During the war, it was almost impossible to schedule something like transportation from any city in Ukraine to the border. So sometimes it was simply a doctor on his private car, the doctor from hospital nearby the border, who we asked for help. There were also more problems, such a language barrier. Soon we realized that informed forms for surgery or chemo have to be translated. So in this field, we really received a huge help from Ukrainian doctors working in Poland. Finally, such situation is also a psychological challenge, especially for oncological patients. So finding Ukrainian-speaking psychotherapists was also a task for us. At this moment, I would like to pay your attention on a person we were supposed you will be able to hear today, Olga Khoptyana from Kyiv. To be honest, I've never met her offline. We only communicate via internet. She was the person that was mostly involved in initiative of patient's translocation. During the battle of Kyiv, when the city was almost encircled by Russian troops, I called her and I offered her to evacuate to Poland. She refused then. She stayed with her patients and keep working even under bombing. Then, this young woman in my eyes became one of the most brave person I've ever known. So at this moment, thank you, Olga. I hope you are hearing me now. Thank you so much. But there is also many, many more people who deserves to be mentioned today. I had to choose. I'm sorry to most of you. I would like to say thank you to Professor Luis Chiva and Professor Pedro Ramirez due to their support, we prepared a short article in International Journal of Gynecological Cancer describing the situation and our initiative. It was also a field to inform Ukrainian doctors that we can help their patients then. It was really important contribution, so thanks for that. But this is not the end. There are next steps in supporting Ukrainian gynecological patients. I'm standing here also to express my gratitude to America and other countries for enormous help you offer to Ukraine. Without you, the resistance there wouldn't be possible. They are now fighting not only for Ukraine. They are fighting also for Poland and entire Western world and its way of life. So our duty is to support them and maintain the support for gynecologic patients remaining out of Ukraine. There are also long-term goals we need to achieve in this initiative. One day the war will be over. I hope it will be very soon and Ukraine will remain free country. But challenges for us will not end up there. The country is partially destroyed and will need a lot of work to be restored. Ukrainian doctors will need us in field of material support and education to serve their patient better and better. These are challenges that will come soon. To better define the needs and measure the scale of gynecology patients evacuated to other countries, the European network of young gynecologists established Pan-European Survey. If some of you treated Ukrainian patients, please feel it. It will really help us. The link you will see on my next slides. Thank you so much. Thank you. Thank you so much. Why don't you have a seat there? Welcome. Wow. We were so pleased to be able to get his story and Professor Olha's story here. Unfortunately, she couldn't make it, as I mentioned before, but I do encourage you to go online and view that video. I also would encourage anybody here who wants to know more about this to reach out to Dr. Bobinski to learn more about how he was able to accomplish this. Again, collaboration, interpersonal communication, interpersonal goals, common mission. Phenomenal. I'm just so glad that you could come here to tell the story. So for this, you know, it's my distinct honor to present the IGCS Global Humanitarian Award to the Polish Society of Gynecologic Oncology and to Dr. Olha Hapniana. Dr. Marcin Bobinski, it's only fitting for me to present you this award for the Polish Society of Gynecologic Oncology. We applaud you for your cooperative effort. Anna's not here? Okay. So we were also going to honor Dr. Hapniana because she was unable to come. We had President of the Ukrainian Association of Gynecologic Oncologists, Dr. Valentin Svitsky, and I really apologize for messing up these names, but Dr. Svitsky, who was going to... Is he here? Is he here? He's not here. He's in... Okay. So we'll have you take care of that award as well on behalf... Oh, is he here? Oh, excellent. Dr. Valentin, he is part of the Ukrainian Association for Gynecologic Oncologists. Please. It's so nice to see you. Thank you. Thanks a lot for every people of goodwill who help Ukraine, especially our Polish friends, our American friends, and all, all civilization countries who help a lot with humanitarian and other, and other help. Wow, I'm so excited we were able to do that. Okay, we're going to do a few more awards before the break, but I wanted to take this time to introduce Dr. Jonathan Barak, who is here now to receive the IGCS Lifetime Achievement Award. For more than four decades in service to our profession, including his time on the IGCS Council as a member and as the president of the society, he has, he has significantly improved gynecologic care and treatment of outcomes around the world. With his achievements in surgical innovation, extensive research in immunology and immunotherapy, and his work to encourage effective and compassionate medical communication, he is an esteemed leader within gynecologic cancer care community. Dr. Barak, I welcome you to the stage as you are and congratulate you. Thank you very much. Wonderful. I have a few comments. First of all, let me just say my heart goes out to the courageous people of Ukraine. That's, it was very moving to hear that presentation. Thank you for this very special award. It's an extraordinary honor and humbling to receive a Lifetime Achievement Award. Of course, it's my fervent hope that my lifetime will continue long enough that I can contribute more to global women's health and advances in gynecologic cancer care. I'm grateful to my mentors and colleagues who supported me during my 47 years as a physician. When I was a medical student at Johns Hopkins, J. Donald Woodruff served as my advisor and encouraged me to enter this profession, this noble profession. And my department chair at Harvard, Kenneth J. Ryan, was my role model. For their wisdom, guidance, and mentorship, special acknowledgment to Dean Sherman Mellencoff and Dean Phil Pizzo, the emeritus deans respectively at UCLA and Stanford Schools of Medicine. My esteemed colleague, Neville Hacker, and I began a lifelong collaboration at UCLA, and I cherish our friendship. My greatest strength comes from my family, my spouse of 52 years, Deborah, who is here with me today. Thank you, Deborah, love you. Made my career possible through her support and patience. She kept me going during all the challenges of an academic medical profession. I could not have achieved any degree of success without her love and guidance. My children and grandchildren also provide great wisdom and lots of good humor. It was a great privilege to have served as president of the IGCS over a decade ago, and I look forward to many more years of association with you. Working together, we will continue to have a profound impact throughout the world on the diagnosis and treatment of women's cancer. Thank you for this wonderful award, which I share with you. And congratulations to each one of you for your dedication to the care and welfare of your patients and their loved ones. Thank you. Thank you so much, Dr. Barak. The next award will be for the IGCS Excellence in Teaching Award, and this year we present this award to Dr. David Attala. His commitment to teaching and spreading knowledge is evident throughout his career. He is a respected educator, a leader in gynecologic cancer care in Lebanon, throughout the Middle East and worldwide. He's a founder of the Middle East and Mediterranean Association of Gynecologic Oncologists, the MIMAGO, and realizing the power of global collaboration and embracing education throughout the region, he brought MIMAGO into the IGCS Strategic Alliance Partnership and the IGCS Project ECHO program, a monthly educational tumor board where trainees learn from international volunteer experts. Please go to the IGCS website to read more about his impressive accomplishments and dedication to teaching. Dr. Attala, I invite you to accept this award. Thank you very much. Thank you very much. I'm really humbled. And I dedicate this award to my fellows and especially to my colleagues in the Middle East who are trying to do their best to improve, sometimes in difficult situations, to improve quality of care for gynecologic cancers. Congratulations. We'll be doing a few more awards before the keynote speech, but I also wanted to take a moment to pay special tribute to someone who is very special to many of us, someone who has had a huge impact on patient advocacy and health equity awareness. Mary Dicey Jackson-Scroggins, many of you know, passed away on August 1st. She was IGCS's first Director of Global Outreach and Engagement and the founder of our advocacy network, the International Gynecologic Cancer Advocacy Network. We have had a great day of celebration yesterday honoring her legacy at the Advocacy Summit. Out in the hall, you can find a memory book with articles and photos and notes inside. Please feel free to stop by and add a message inside or contribute to the joint art project. We will send the book to her family with gratitude so they can see just how much Dicey meant to this community. For Dicey and for all affected by gynecologic cancers, we will carry on and we'll continue the work that she has been so passionate about. Please join me in congratulating her. Okay, so IGCS is now thrilled to announce the very generous donation from the Women's Global Cancer Initiative. Women's Global Health Initiative has pledged a multi-year grant of $10,000 to the IGCS to use in our global curriculum and mentorship program. This vital contribution will help train and educate a fellow each year in gynecologic oncology and enable them to effectively treat women in their community, saving hundreds of lives. Dr. Anne-Marie Bideau is the co-founder of this organization. And I see you've already snuck up on stage. So please come and honor this, accept this award. Thank you. Thank you so much. On behalf of the Women's Global Cancer Initiative, I want to announce that we are so thrilled to be in collaboration with IGCS for the wonderful work they're doing in training fellows in low and mid-income countries. And I encourage all of you out there to pitch in and help because this is such a vital service to so many countries. Thank you. You like that plug? The shameless plug, we love it. We'll take it every day. Okay, so later this afternoon, Dr. Pedro Ramirez will honor the, or provide the editor-in-chief report and present awards to the, to the, his awards in his session. So we are really hoping that you all will come back in the afternoon to come celebrate with us. So thank you for all joining us this morning. It's now time to take a short break. So debate your, your colleague will resume in this hall next and downstairs we will have the surgical film session and the endometrial focus plenary. Please enjoy the rest of the meeting. I'll see you soon.

SOLO3 trial

post-hoc analysis

overall survival

recurrent ovarian cancer

rucaparib

PARP inhibitor

prior lines of chemotherapy

survival benefit

chemotherapy

small sample size

placebo arm

PARP inhibitor therapy

cross-resistance

platinum therapy

BRCA reversion mutations