Good afternoon everyone, we're going to go ahead and get started so if you could please take your seats. Welcome to plenary two, oral abstract presentations. Before we begin the oral presentation, we'd like to recognize the Mentorship and Training Program graduates and Pedro Ramirez, Dr. Pedro Ramirez, who will give away the IJGC Editorial Awards. So Pedro, why don't you please come to the stage here. Dr. Pedro Ramirez is the Editor-in-Chief for the International Journal of Gynecologic Cancer and he will present the awards for the journal. Pedro? Alright. Good afternoon everyone, thank you Rob for the introduction and certainly this is an opportunity for us to recognize the great value of the work that has been submitted to the journal and to also recognize the effort from many of our reviewers who are recognized for their outstanding work in terms of the quality of their reviews, in terms of the timeliness of their reviews. So we're really always very proud of this segment and the session of the meeting. So the first award is awarded as the Editor's Choice Award and this year's award is going to go to Kathleen Schmaler from MD Anderson for the Prospective Trial on Conservative Surgery for Low-Risk Early-Stage Cervical Cancer. Outstanding. These next three awards are for the most downloaded articles. So this year's most downloaded article was Uterine Serious Carcinoma, Key Advances in Novel Treatment Approaches. Stuart Ferris from Johns Hopkins. Stuart. Thank you very much. I get to meet you in person. The second most downloaded article award, and I think that certainly we changed our whole schedule, actually, not because of the timing of this morning's session, but we just wanted to make sure that Cristina Fotopoulou is here to receive her award. So she receives the second most downloaded article for the European Society of Gynecologic Oncology Guidelines for the Perioperative Management of Advanced Ovarian Cancer Patients Undergoing Debulking Surgery. Congratulations. Thank you. I'm coming with my car. It's nice to see you. All right, outstanding. And the third most downloaded article, it was actually a clinical trial. This is the ATARI trial ATR inhibitor in combination with olaparib and gynecologic cancers with ARID1A, loss or no loss, ANGOT, GYN1, NCR, Susanna Managy from the Royal Marsden in the UK. And the next series of awards, these go out to the top 10 reviewers for our journal this year. And again, this is a recognition for the timeliness of the reviews, the quality of the reviews, the extent of the reviews. So these are individuals who we want to recognize. They're not going to come up here. Certainly they're welcome to come up at the end to receive their awards. But first goes to David Viveros, Shari Damast, Giovanni Aletti, Emma Allison, Nico Bizzari, Eric Estrada, Ainoa Madariaga, Kike Enrique Chacon, Katie Kernan, and Phillip Harder. Thank you so, so much to all of you. And congratulations. Awesome. Thank you so much, Pedro. So now we have the mentorship and training graduates gather the stage here. This brings me to a very, please say, okay, good, you guys are on. Okay, good. So this brings me to a very special recognition of those involved in our global curriculum and mentorship program. A program training gynecologic cancer specialists in low-resource countries. In 2017, the IGCS launched the global curriculum for gynecologic oncology training to address gaps in global women's cancer care. The global curriculum is a comprehensive two-year education and training program designed for regions around the world that do not currently have formal training in gynecologic oncology. The vision is to develop expertise locally to meet the specific needs on the ground. As of today, the IGCS global curriculum program has graduated 27 fellows from all over the globe. And we are fortunate to have 10 fellows here with us here in New York. This program was the vision of Dr. Michael Quinn, who was former president of the society and was brought to life under the leadership of Kathleen Schmieler and Dr. Joe Ng, Linus Chuang, and Thomas Randall. And of course, our CEO, Mary Aiken. So in doing so, we'd like to recognize the exam committee. This is a huge thanks goes out to Al Covins, who's the chair of the exam committee, and all the examiners, including those who can't be with us today, and for your help for giving these exams and all the hours, both day and night. This program would not be possible without the dedicated faculty that volunteer their time and expertise to equip IGCS fellows all over the world. If you are an international mentor or a local supervisor for an IGCS mentorship and training site, please stand so we can recognize and thank you for your contribution. That is great, you guys. Fantastic. Thank you so much. I also want to acknowledge that all of the faculty that join the ECHOs on the regular basis to share their knowledge and teach fellows and help women all over the world. It's just a great and amazing program. I hope you have an opportunity to observe those. Without further ado, I would like to recognize the graduated fellows to come up on stage. We have Dr. Bethel Derjigoulat, Dr. Birgashwabiza, and Dr. Dawit Wirku from Ethiopia, Dr. Benjamin Elie and Dr. Anissa Mburo, graduates from Kenya, Dr. Eric Estrada from Guatemala, Dr. Pius Moulamira from Uganda, and Dr. Mukatumui Kalima Munalua from Zambia. And our most recent graduates of the last week, Dr. Ngoc Phan from Vietnam and Dr. Saida Bo from the Bahamas. Please join me in congratulating these fine individuals. All right. So amazing to see this group. Oh, great work, you guys. Thank you. Absolutely. Congratulations. I love it. It's such an important aligned mission of ours to do. Thank you. It's good to see you. Thank you. Okay. So now I will turn this over to our chairs, Dr. Ramesh Iskander and Dr. Jessica McAlpine to start the oral abstract presentations. Thank you. Hey, everyone, Ramesh Iskander. It is my pleasure to be joined by my co-chair, Dr. Jessica McAlpine. And this session consists of four oral abstract presentations and that will be followed by distillations by renowned and exceptional speakers. We hope we have time to invite you to come to the microphone and ask questions. We know we have a great session and we are going to go ahead and get started. The first abstract presented today is a randomized trial of pelvic radiation with and without concurrent cisplatin in patients with a pelvic-only recurrence of endometrial cancer by Dr. Ann Klopp. And that will be followed by a distillation by Dr. Carol Agajanian. Thank you very much. My pleasure to present the results of this trial on behalf of the large group of individuals that have worked for many years on this study. So first, my disclosures. First of all, I think it's important to note that local recurrences are quite common in early stage endometrial cancer. In fact, looking at some of the largest randomized trials in early stage endometrial cancer, the majority of the recurrences initially involved the vaginal apex. And here you see on the right side an MRI with a typical tumor arising at the apex of the vagina extending in to the vagina. There have been many retrospective studies, a few of them highlighted here, that have demonstrated that radiation therapy can be a curative modality for the treatment of isolated recurrences of endometrial cancer on the order of 50 to 70 percent of patients surviving at five years after treatment of their recurrent disease. The question that needed to be answered was, does the addition of concurrent chemotherapy improve that rate further? So this study that was conceived many years ago asked a question which is still very relevant today, which is for women with recurrent endometrial cancer confined to the vagina and the pelvis, what is the potential impact of adding concurrent chemotherapy? So in the standard arm, the treatment was whole pelvic radiation, 45 gray and 25 fractions to the whole pelvis. If brachytherapy was possible, they could receive brachytherapy with either intracavitary or interstitial, meaning needles placed directly into the tumor. And if brachytherapy was not feasible, then they could receive an external beam boost. The other arm was identical to the control arm with the addition of weekly cisplatin. So cisplatin was delivered at 40 milligrams per meter squared in the chemoradiation arm. IMRT was allowed and sites had to undergo a credentialing process in order to deliver IMRT and the note was made that if the tumor involved the distal vagina, the inguinal nodes were treated as well with radiation. This is the characteristics of the patients that were enrolled on this study. You can see in general in the radiation and the chemoradiation arm, they were very similar. Some notable observations, so the mean age was about 65. The vast majority of individuals were of white race. The grade was predominantly grade one. So about 50 to 60% of the patients had a grade one endometrioid endometrial cancer. The grade two endometrial cancers comprised about 20% and grade three endometrial cancers plus high risk histologies was a relatively small proportion of the patients that were enrolled on this study. So about 10%. And the majority of recurrences were in the vagina. The other possibility was in the pelvic lymph nodes, but the vast majority were in the vaginal apex plus minus involved lymph nodes. The toxicity was very much what you would expect. So when you look overall, the highest grade toxicity was higher in the patients who also received chemotherapy. If you break that down by types of toxicity, the GI toxicity was quite equivalent, not impacted by the chemotherapy. As contrasted as you would expect, bone marrow toxicity accounted for the higher rates of toxicity in the patients that received chemotherapy. So this is the accrual of the study, which happened between 2008 and 2021. The red line is the projected accrual and the blue line is the observed accrual. So it accrued slowly. Possible reasons for that included the fact that many patients may have been recommended or treated with concurrent chemotherapy off-protocol based on a bias, thinking that that may be a benefit. Additionally, the RT approach evolved over the course of the study. So HDR interstitial became much more common, so the protocol was amended to allow that approach in the course of the years of the study. This is the outcome. So this is progression-free survival, the primary endpoint of the study. The blue line is the patients treated with radiation therapy alone, and the maroon, the patients who received chemotherapy as well. There was no statistically significant difference, but you can observe that the absolute rates were higher in the radiation-only cohort. This is overall survival, no differences. This is the clinical factors and their relationship with outcome, the primary outcome being progression-free survival. You can see there's wide confidence intervals, performance status being the only one statistically associated with adverse outcomes. So conclusions from the study. Number one, that the addition of concurrent chemotherapy does not improve outcomes for patients treated with definitive radiation for recurrent endometrial cancer. I think it's important to note that primarily the patients that were enrolled had low-grade tumors and vaginal apex recurrences, so I would argue that the results of the trial are applicable to those individuals. It's notable that this is the first prospective trial demonstrating the durable long-term survival with treatment with radiation for recurrent endometrial cancer. And I think the trial is an excellent demonstration of the value of a randomized trial and less common presentations. So thank you to the patients accrued to Energy Oncology and to the team of physicians that designed and persisted to get this trial to the finish line. Thanks very much. Good afternoon, everyone. I want to thank the program committee and the session chairs for this invitation to distill the abstract. And welcome, everyone, to my hometown of New York City. It's so nice to have you all here. Congratulations to Dr. Klopp and colleagues for completing this study, which has important impact for us all in our daily work in our clinics, GOG-238, a randomized trial of pelvic radiation with and without concurrent cisplatin in patients with pelvic-only recurrence of endometrial cancer. These are my disclosures. The statistical design of GOG-238 is with a primary endpoint of progression-free survival. The trial was originally designed to, at maturity, the study was planned to accumulate 94 PFS events to have a power of 0.8 to detect a hazard ratio of 0.645 using a one-sided alpha. There was a preplanned interim futility analysis when approximately 60 progression or death events reported. And if the observed rate of recurrence or death in the pelvic radiation with concurrent cisplatin arm is greater than that of the pelvic radiation-only arm or a hazard ratio greater than 1, accrual was to be terminated. The interim futility analysis was triggered in December 2021 with 57 PFS events. At the time of triggering the interim analysis, which we are presenting today, the accrual was completed. And not only that, but the last patient had completed treatment over a year before the interim analysis was performed. And the median follow-up due to the extended period of accrual Dr. Klopp described was five years. These results were reviewed at a DMC meeting in February 2022. And the decision of the DMC was to release the data from this study. And this press release was then issued after the interim analysis informing people that the hazard ratio was 1.4, favoring pelvic radiation-only as the treatment for this disease. In addition to wanting to get this information out, it also became very clear that that 94 events would never be reached. The updated Kaplan-Meier curve estimates here, these were updated as August 2022 following that interim analysis with now 59 events, which were really the additional events were only the result of a data sweep. You see that hazard ratio of 1.5 with wide confidence intervals but with clearly separated lines and the curves become flat. We know now that when we're designing these trials, we cannot be waiting for a median PFS because we would never report this trial. That we need to be careful when designing these trials not only to use PFS as an endpoint but to put a timeline on reporting because I think these are really going to be our final results. A point is achieved where the patient's cured or not. When you look at who entered this trial, 81.5% had endometrioid grade 1 or 2 cancers. And we know from the TCGA that those cancers would most likely fall into either the copy number low or MSI groups. These cancers are not represented in the copy number high group. While molecular data is not available to perform a promise like molecular classification for the patients who entered this trial, again, we know with endometrioid grade 1 and 2 that we would have patients being in the MSI high group and copy number low group, which would be about, for endometrioid cancers at large, about 40 and 60% of patients prospectively. So what other trial do we have that looked at radiation alone versus concurrent chemo radiation in endometrial cancer? The PORTEC-3 looked at patients in the primary setting, not recurrence like this trial, but similar treatment naive group, and showed an advantage to the chemo RT that was in the overall group present but modest. When the molecular classification was performed, the strong prognostic value of molecular endometrial cancer classification that was shown in the TCGA was confirmed, but we also, the study also showed a potential predictive capacity of molecular endometrial cancer classification for the benefit of chemotherapy. And I put a box over the two groups that were the predominant patients in this trial, and you can see for the MSI high patients, the addition of chemotherapy did not add benefit, and in the copy number low group, the results reflect more those of the overall study. So perhaps the, you know, the trial is really underpowered to look for a modest benefit in a particular subtype of patients. So radiation therapy remains the standard of care for pelvic-only vaginal cuff recurrences. This trial had low-grade endometrial cancers, grade one and two, highly represented. This could have been due to bias, that people didn't want to randomize patients to not receive chemo who had high-grade tumors, or it could be the biology of the disease, that this is what is seen in this clinical situation of pelvic-only recurrence, with perhaps higher-grade lesions being more likely to have widespread recurrences. Further studies are needed, 32% of the patients who participated and received radiation therapy still had recurrence, and molecular subtypes and better statistical designs are going to be important to inform future trial design. Thank you. Thanks very much to Dr. Klopp and to Dr. Agajanian for excellent trial review and distillation. So next up, we'll hear post-hoc analysis of objective response rate by mismatch repair protein dimer loss, or mutation status, in patients with mismatch repair deficient endometrial cancers treated with Dostar-Lamab. Dr. Tinker, thank you. Distillation will be, sorry, by Dr. Nam to follow. Thank you. Thank you. Good evening. Thank you, all of you, for lasting to the end of the day and being here for this presentation. So it's my honor to present our analysis on behalf of my co-authors, and as you just heard the title, I won't repeat it, but we are looking at mismatch repair protein dimer loss and mutation status, and how that might impact response to Dostar-Lamab as part of the GARNET study. This is my disclosure slide and the disclosure of my colleagues. And we've already heard, and we all know very well, that endometrial cancer is the most common gynecologic cancer, and the incidence of this disease is rising globally. And we also know that approximately 30% of endometrial cancers have been shown to be mismatch repair deficient or have the MSI-high phenotype. And this particular molecular subgroup has been demonstrated to have a high response rate to anti-PD-1 therapy. Mismatch repair deficiency is caused by loss of expression of mismatch repair proteins, MLH1, PMS2, MSH2, and MSH6. And these function as heterodimers, MLH1 and PMS2 are a heterodimer pair, and MSH2 and MSH6, and these mediate DNA repair. The loss of expression can be caused by two main mechanisms, either a genetic mutation which may be inherited and associated with Lynch syndrome, so a germline mutation, or a somatic mutation in one of the MLH genes. And the other mechanism is through epigenetic methylation of the MLH1 promoter. So genes, genetic mutation or epigenetic silencing of one gene leads to a loss of the expression of the heterodimer, typically. So that's the most common mismatch repair staining pattern, and this results in defective mismatch repair and genomic instability, although other patterns of MLA, excuse me, mismatch repair deficiencies have been described. And MLH1 promoter hypermethylation is a very common mechanism by which mismatch repair deficiency arises and is present or accounts for approximately 75 to 80 percent of cases. The remainder, the majority of the remainder are due to somatic or germline mutations. And one question that's somewhat unanswered and is the subject of our review is, what is the relationship between the mechanism of mismatch repair deficiency and the outcome on immunotherapy? So here we report our post hoc analysis examining the objective response rate in patients with deficient MMR advanced or recurrent endometrial cancer who were treated with Dostarlimab, and we examined the outcomes based on MMR heterodimer loss pattern or the mutation status of the MLH1 gene. And as you all know, the GARNET study was a multicenter open-label single-arm phase 1 study, and cohort 1A enrolled endometrial patients with deficient MMR advanced or recurrent endometrial cancer. Mismatch repair protein status was determined either by local or central immunohistochemical staining, and a proportion of cases also had their mismatch repair gene mutation status determined by centralized testing using the Foundation 1 sequencing panel. So just to remind you the demographics and baseline characteristics of this study, the majority of patients on this trial had endometrioid endometrial cancer, and all patients had had prior systemic therapy for their advanced disease. Substantial proportion, roughly 30-35%, also had two or more lines of therapy for their recurrent metastatic disease. So looking at our data, we had a cohort of 143 patients, and amongst those, 94, or 66%, had the MLH1-PMS2 dimer loss. Eleven percent had MSH2-MSH6 dimer loss, and there is a category of other which accounts for approximately 23% of cases. This pattern is similar to what we would expect in terms of protein loss patterns in the mismatch repair deficient endometrial cancer population, and you can see here what's important to note is the objective response rate by dimer loss seems to be essentially equivalent, and the median or the duration of response, the median duration of response is not reached in any of the molecular groups. Likewise, when we looked at objective response and duration of response in those who had MLH1 loss, what we saw was amongst the cohort of 143 patients, 101 had available mutation data, and of those, 78 had MLH1 loss by IHC. When sequencing for mutations, 71 of the 78 did not have a mutation in either of the dimers, so not the MLH1 gene or the PMS2 gene, so 91% did not have a mutation, and 9% did in one of those two genes. What you see again is the objective response rate is similar in these molecular groups, and once again, the duration of response is not being reached for those who responded to therapy. We infer that the patients who have MLH1 loss by immunohistochemistry and who do not harbor a genetic mutation, the mechanism of MLH1 loss would be due to promoter methylation. So in conclusion, consistent with the literature, the most common pattern of mismatch repair protein loss was the MLH1-PMS2 heterodimer, and tumors that have lost MLH1 and do not have a mutation identified in either MLH1 or PMS2 are likely to have MLH1 promoter methylation, but we did not conduct direct testing of this, which would have been the more accurate method for identifying these cases. There is really no notable difference in observed objective response rates by pattern of mismatch repair protein loss or mismatch repair gene mutation status, and this is the largest dataset available to date to examine these relationships between MMR deficiency and response to therapy. We do view these data as hypothesis generating, given that the Garnett study was not powered to study the effect of mismatch repair protein pattern or mutation status on response to dostarlimab. Therefore, this data suggests that the route to mismatch repair deficiency does not influence response to dostarlimab treatment. I'd like to acknowledge and thank all the patients and their families, as well as all the members of the clinical trials across the world who participated in this study, and thank you very much for your time and interest. Good afternoon, everyone. My name is Injin Nam. I'm very happy to do the distillation of this important research. I have nothing to disclose. As Dr. Tinker presented, the endometrial cancer is reported to have the highest prevalence of DMML among other cancers at 25% to 30%. However, less than 5% of all endometrial cancers are hereditary. Therefore, the majority of patients with abnormal DMML testing results will not have underlying Lynch syndrome-related mutation. The most commonly mutated genes in Lynch syndrome are MLH1 and MSH2. However, when we look at the ISGC data, the abnormal expression rate of MLH1 protein was higher. This is thought to be because of the MLH1 promoter hypermethylation, methylation. The DMML protein expression is usually evaluated by IHC and the advantages are that it can be evaluated even when the tumor percentage is very low and that is very simple, does not require normal match data, and short turnaround time. However, it has relatively high false positivity and is very subjective and the issue of intratumoral heterogeneity issue could be a problem. Most importantly, according to the result of GARNET study presented at ASIMO 2020, the MMR proficient group also showed a meaningful disease control rate and duration of response. The study group concluded the telomere demonstrated that durable anti-tumor activity in both the MMR and P-MMR advanced to recurrent endometrial cancer. If so, is the MMR expression a good biomarker for the telomere efficacy? If there are multiple causes of the MMR, shouldn't we looking at the outcome, not the process? As a clinician, I have been curious about why endometrial cancer uses the MMR instead of PD-L1 expression as a biomarker, unlike other carcinomas. PD-L1 was used in the initial study to determine the efficacy of PD-L1 inhibitors in endometrial cancer, but only the MMR was used as a biomarker afterwards. I think the reason is the very high rate of PD-L1 expression in primary and metastatic endometrial cancer, so it is difficult to use PD-L1 as a biomarker to see the efficacy. In MSI testing, we see accumulation of errors in DNA by the MMR with PCR or NGS method, so we can see the results, not process. Because we see the results, not the root of the MMR, MSI test results may be more compressive than the MMR, and the MMR results are not necessarily MSI high. For example, endometrial cancers with MSH6 mutation often display low or absent MSI. TMB could be used as the biomarker. TMB is defined as a number of mutations per coding region within the tumor genome. Not all TMB, high tumors, have the MMR. Could TMB, the biomarker for those telemep in endometrial cancer? So here is my conclusions and questions. The root two MMR deficiency does not influence response to those telemep. I agree with that. However, those telemep demonstrated durable anti-tumor activity in both the MMR and PMMR, advanced and recurrent endometrial cancer. So do we need further study to see mutation or hypermethylation of TMMR in a larger dataset? Loss of MLH1 protein showed a better response rate regardless of the root. Then what could be used as a new biomarker predicting those telemep response? MSI by NGS or PCR or TMB? I heard that biomarkers also tested in GARNET study, but they did not present it, the results. So maybe we should find new one. Thank you for listening. Thank you. Thank you, Dr. Tinker, Dr. Nam. I would like to welcome Dr. Michael Fromovitz who's gonna discuss therapeutic strategies for neuroendocrine disease. Thank you. Thank you, Ramez and Jessica. It's a pleasure to be here and thank you for sticking around. I'd like to thank my partners from MD Anderson who've turned out in droves to see me speak this afternoon. Pedro, thank you for being here. So I'm gonna talk about our abstract topotic N-taxol and bevacizumab for recurrent high-grade neuroendocrine cervix cancer. These are my disclosures. So if you look at the NCCN guidelines, essentially there are no options listed for recurrent high-grade neuroendocrine cervical cancer in patients who've recurred less than six months from completing cisplatinamidotoposide. And this is the most recent NCCN guidelines. So you can imagine back in 2013, 2014 when we were trying to figure out what to give these patients, we really had no idea. We landed upon a three-drug regimen, paclitaxel, topotecan, and bevacizumab. And we chose that regimen for a couple of reasons. First, topotecan and taxotere are commonly used as single agents in small cell lung cancer, and they've been shown to have good activity. Second, small cell cervix cancer has high expression of VEGF receptors, so over 95% will express the VEGF receptor. So adding bevacizumab made sense. And this was right around the publication of GOG240. And so most people remember GOG240, the main arms being cisplatinam, taxol, and bevacizumab. But if you remember, it was a four-arm study that had a non-platinum arm of topotecan, taxol, and bevacizumab. And so we knew that the patients who had recurrent neuroendocrine cervix cancer would at least be similar to those who had recurrent cervix cancer in GOG240, most of them having received prior chemoradiation. And so we knew it would be tolerable in that group. And because bevacizumab had been recently approved after GOG240, we knew that all three drugs would be insured, insurers would pay for all three drugs. And so we had no problem getting insurance to cover all three drugs. So that was how we landed on this. So the objective of this study is to compare outcomes in women with recurrent high-grade neuroendocrine carcinoma of the cervix who received topotecan, paclitaxel, and bevacizumab to those who received non-topotecan, paclitaxel, bevacizumab regimens. So we did this through a retrospective review of our tumor registry called NECTR. NECTR stands for the Neuroendocrine Cervical Tumor Registry. These are women who had recurrent high-grade neuroendocrine cervical cancer. The NECTR Registry is an international registry that is maintained at MD Anderson. We have two people who manage the registry and essentially collect medical records quarterly from women around the world in either English or Spanish-speaking countries. So both the registry, the registry has a long-term IRB, and this specific study was individually IRB approved. So these are the two groups, the TPB group, topopaclitaxel, bev, and the non-TPP group. You can see we had 62 in the TPP group and 56 in the non-group, and they were balanced between, demographics were balanced between both groups. You can see, I just want to point out the young age of this group at 39. For those who did not receive topotaxel, bev, there were a variety of regimens used. You can see over about half the patients got some sort of platinum doublet. For the women who received topotecan, paclitaxel, and bevacizumab, 18% had a complete response, 39% had a partial response, and 15% had stable disease as their best response. And so the clinical benefit ratio of complete, partial, and stable disease was 74%. Looking at progression-free survival, you can see there was a progression-free survival advantage of receiving the three-drug regimen over those who didn't of 8.7 versus 3.7 months with a hazard ratio for progression. Sorry, there's a typo there, of 0.27. When you look at how long patients were on treatment, you can see that the topotaxel-bev group was superior at six months and 12 months. And although it wasn't statistically significant at 24 months, 7% of patients remained on treatment. Overall survival was 16.8 months in the topotaxel-bev group versus 14 months in the non-group with a hazard ratio of 0.87. Neither met statistical significance. So in conclusion, the combination of topotaxel-bev improves progression-free survival compared to those patients who receive regimens other than topotaxel-bev. More patients remain on treatment at six and 12 months with topotaxel-bev than on non-topotaxel-bev. And if you remember, 7% remained on treatment for over two years versus zero in the other group, although it wasn't statistically significant. So we've made this our standard regimen for recurrent high-grade neuroendocrine cervical cancer, and we recommend topotaxel-bev as treatment in these patients. I'd like to thank our MD Anderson Rare Tumor Team, in particular Gloria Salvo and Naomi Gonzalez, who really manage the Nectar database, and the rest of our team who focus on rare tumors. Thank you, and again, thank you for the invitation. Thank you. Thanks. Thanks so much, Dr. Primovitz, all the challenges of studying rare tumors. So we're now gonna move to next-generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes among patients with uterine sarcoma. It'll be presented by Dr. Nasutis, followed by a distillation by Dr. Covins. Thanks. Good evening. Thank you for the opportunity to present our research today. I have no conflicts of interest to report. So we know uterine sarcomas are a rare group of tumors with high rates of relapse and overall poor prognosis. To date, the unique profile has yet to be capitalized with targeted therapy agents, and novel agents exploiting defects in homologous recombination DNA damage response, such as PARP inhibitors, have been already successfully introduced in other malignancies. The HRDDR pathway is involved in the repair of double-strand breaks and prevents genomic instability. So our objective was to investigate the incidence of HRDDR genomic alterations among patients with uterine sarcomas. We accessed the ACR Project Zeni genomic database that collects the identified NCS molecular data from 18 institutions and identified patients with uterine lyme sarcoma, adenosarcoma, and undifferentiated uterine sarcoma, as well as endometrial stromal sarcoma. We examined the incidence of pathogenic alterations in 27 genes that are involved in HRDDR, and these included ATN, ARID1A, ATRX, as well as BRCA-RAD51. So we identified 483 patients that contributed 495 samples. The majority of the samples were drawn from adenometastasis, and most patients, 65%, had lyme sarcoma, followed by adenosarcoma with 12%. Overall, in our study population, 29% of the patients harbored a pathogenic alteration in a gene involved in HRDDR. Apart from ATRX, which is already described, that was 19%, another 10% of patients had pathogenic alterations in a plethora of other genes, and the most common of them were BRCA2, RAD51B, ARID1A, and ATM. When we looked at the incidence of HRDDR alteration based on histology, lyme sarcoma had the higher instances with 35.8%, followed by adenosarcoma with 29%, and undifferentiated sarcoma, 29%. Apart from HRDDR alterations for patients with lyme sarcoma, other common genomic alterations were P53 mutations, RB1 gene mutations, as well as P10 gene mutations. For patients with adenosarcoma, other common genomic alterations were P53 gene alterations, as well as one in four patients had a P3K-AKT pathway mutation. So in conclusion, one in three patients with uterine sarcoma, especially those with lyme sarcoma and adenosarcoma, harbor a pathogenic alteration in HRDDR genes. So these results provide further rationale for the design of molecularly-driven investigations and clinical trials that explore agents targeting the HRDDR pathway, and moving beyond PARP inhibitors, investigating ATR, WE1, and TEC1 inhibitors, especially in combinations. I would like to acknowledge the American Association for Cancer Research and the Project Zeni, as well as the contributing institutions for the support, and thank you for your attention. Thank you. Thank you. So I'd like to congratulate the two previous authors for their presentations and their work in this rare field. I'd like to thank the program committee and the audience here who has the time to spend with us late into this day. I have few disclosures. So to start with Dr. Frumovitz's paper in neuroendocrine tumors, the optimal therapy for this disease continues to remain elusive. Most patients are treated with surgery, radiation, and or chemotherapy, usually consisting of platinum with a toposite. And this is really taken from the more common lung variant. Typical classifications include small cell, large cell, and undifferentiated. And this diverse histological subtypes can make reliability in diagnosis, particularly if one is considering some type of clinical or prospective trial, very difficult. Interestingly, the majority or a high proportion are HPV positive, particularly type 18. And for the most part, to date, publications tend to be case reports and retrospective. I applaud the authors on their long-standing continued commitment to identify better treatments for this rare disease, as these patients are hard to find, and for the most part, they've explored this through the use of a tumor registry. The rationale for the use of these drugs listed on the previous slide, while not exactly the most compelling, seem rational, good reason to use. I've taken this table from an MD Anderson publication by Salvo in 2019, where you can identify that they really represent only about 1% of all cervical cancers, with a high proportion presenting with advanced disease and poor survival, median survival of 40 months and a five-year overall survival of 35%. So we're looking at this, you know, could there be bias in the registry in terms of what patients received? Absolutely, and it's highly likely. If you review the regimens that they used, I would classify it as everything but the kitchen sink. The results in this table demonstrate a prolongation of PFS with the use of, as it's called, the Texas cocktail that I got from the Salvo article. However, overall survival was no different. And as you can see, if you look at this Kaplan-Meier curve, you can't get your thumb between the blue and the red. So clearly in this disease, there is room for and need for improvement. It's best to define this as hypothesis generating. Normally, one would be encouraged to identify similar findings from another database. However, good luck. So now what? How do we make significant, impactful advances in ultra-rare tumors? I have two following questions for Dr. Frumovitz. What do you believe to be the optimal first-line therapy, and how do we evaluate it? Secondly, how do we move forward and determine better therapies in such a rare disease? The second study by Dr. Nasudias, next-generation sequencing reveals a high prevalence of pathogenic mutations and homologous recombination DNA damage repair genes among patients with uterine sarcomas. There has not been meaningful changes in the management and outcomes of uterine sarcomas in many years. For those patients that recur, the vast majority are incurable. Whoops, I hit the wrong, sorry, let's go back a slide, can I go back a slide, yes. Dr. Nasudias and colleagues evaluated the prevalence of alterations in homologous HR DNA repair genes among patients with leiomyosarcomas, adenosarcomas, endometrial stromal sarcomas using a database. The specific genes investigated are listed on this slide. It should be noted, this is not the first time this has been evaluated in uterine sarcomas. The MSKCC group, led by Dr. Marti Hensley, reported a similar investigation in 2020. And finally, they even administered PARP inhibitors to those patients with identified genetic mutations. Again, this data is hypothesis generating. So what do we do with this information? Most cancer models that have demonstrated genetic abnormalities in HR-DDR pathways have identified these to be not only prognostic, but actionable with targeted agents. It would therefore seem logical to investigate these in a prospective manner with preselected patients based upon the above. While funding agencies might disagree with the lack of suitable alternatives, I would favor going direct to human trials to investigate in small cohorts. Again, the rarity of these diseases are going to preclude any large randomized studies. Question I have for Dr. Nasutias is, how do we move forward with investigation of testing these potential therapeutic agents in these diseases? Thank you. Thank you, Dr. Covins. And really, I appreciate the punctuality of all the speakers. We actually, despite the awards in the beginning and the excellent presentations, have a minute or two for questions. So I don't know if there are any questions from audience members. I know it's been a long day. And it's okay if there aren't. No? I don't see anybody. All right. Well, if that's the case, this officially ends Day 1 of the IGCS meeting in 2022. Thank you for joining us, both in person and for those of you who are still logged on virtually. Tomorrow morning begins at 7 a.m. and it will be packed with educational materials. As a reminder, there will also be pictures on the patio sponsored by Immunogen. Perfect. Okay. Is he? Okay. Perfect. I think Dr. Coleman, is Dr. Coleman going to come back in? No. I don't know. They gave me one that's crossed out. Yeah. Pics on the patio sponsored by Immunogen. And that's going to be from 6.30 p.m. to 8 p.m. on the Javits Terrace on the fourth floor. And we hope to see you there. Have a great evening. Please enjoy the rest of your night. Rest up. And we'll see you tomorrow.

gynecologic oncology

abstracts

Mentorship and Training Program

IJGC Editorial Awards

oral abstract presentations

conservative surgery

novel treatment approaches

ATARI trial

top 10 reviewers