Gynecologic Cancer Research Articles

713MO Nivolumab and ipilimumab combination treatment in advanced gynaecological clear cell cancers: Results from the phase II MoST-CIRCUIT trial

713MO Nivolumab and ipilimumab combination treatment in advanced gynaecological clear cell cancers: Results from the phase II MoST-CIRCUIT trial

82P Clinical and molecular characteristics of gynecologic cancer patients in FINPROVE: The national phase II drug repurposing trial in Finland

82P Clinical and molecular characteristics of gynecologic cancer patients in FINPROVE: The national phase II drug repurposing trial in Finland

METTL3 Regulates the Translation of Oncogene Myc through m6A Modification and Promotes the Occurrence and Development of Cervical Cancer.

Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms. Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of METTL3 and Myc was analyzed. Cell viability was detected after METTL3 knockdown in HeLa and SiHa cells, followed by cell counting Kit-8 (CCK-8) assays. The relative expression of METTL3 and Myc was detected via real-time quantitative PCR (qPCR) assays, and the protein expression was determined using Western blot. Meanwhile, cell invasion and migration capabilities were assessed utilizing transwell assays, and cell proliferation was detected using the EdU experiment. Furthermore, RNA methylation immunoprecipitation-qPCR detection was performed to determine the expression of Myc after N6-methyladenosine (m6A) modification. Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of METTL3, there was a significant reduction in the viability, proliferation, invasion, and migration abilities of HeLa and SiHa cells. Besides, the expression of METTL3 and Myc mRNAs and proteins was greatly reduced. The level of m6A Myc decreased significantly after METTL3 knockdown. METTL3 plays an important role in regulating cervical cancer cells. METTL3 promotes CC development through m6A modification to regulate the expression of the oncogene Myc.

Clinical trials involving rare gynaecological cancers

Clinical trials that investigate therapies for rare gynaecological cancers (RGC) are essential to provide evidence-based data towards new effective and safe treatments, however, they present unique challenges. The main objective of this narrative review is to summarize completed phase III clinical trials investigating therapies for RGC and to discuss the outcomes of these trials. PRISMA guidelines were used to report the steps of the review. We searched the WHO´s International Clinical Trials Registry Platform, clinicaltrials.gov and PubMed / Medline for publications reporting results from clinical trials on RGC including at least one medication. From 31 identified phase III clinical trials, 13 were still ongoing, four were terminated and just eight (25.8 %) had posted results and/or publications. The latter completed trials were mostly multi-center and located in at least two continents, participants were mainly adults, and the recruitment period varied from about 2.5 to 10.5 years. Allocation was randomized with parallel assignment in 7 out of 8 trials, while only one trial had double masking. The most common primary outcome measure was progression-free survival (PFS), followed by overall survival (OS). Patient-reported outcomes were secondary outcome measures in four completed trials, assessing quality of life by various questionnaires. Most of the trials did not meet their primary endpoints. By highlighting the scarcity of clinical trials on RGC, our findings further emphasize the need for designing, conducting and sustaining phase III clinical trials to investigate innovative therapies for these conditions and report meaningful outcome measures.

Efficacy of locoregional analgesic techniques after laparotomy for gynecologic cancer: a systematic review

ObjectiveTo determine which locoregional techniques are effective in managing post-operative pain in major open oncologic gynecologic surgery in terms of pain scores and opioid consumption when epidural analgesia is not...

720MO IBI354 (anti-HER2 antibody-drug conjugate [ADC]) in patients (pts) with advanced gynecological cancers (Gynecol C): Results from a phase I study

720MO IBI354 (anti-HER2 antibody-drug conjugate [ADC]) in patients (pts) with advanced gynecological cancers (Gynecol C): Results from a phase I study

18 Increasing Incidence of Brain Metastases and Intracranial Radiotherapy Among Gynecologic Cancer Patients

18 Increasing Incidence of Brain Metastases and Intracranial Radiotherapy Among Gynecologic Cancer Patients

Geographic and racial disparities in the quality of surgical care among patients with nonmetastatic uterine cancer

BackgroundWhile utilization of minimally invasive surgery and sentinel lymph node biopsy have increased considerably over time for surgical management of early-stage uterine cancer, practice varies significantly in the United States, with disparities among low-volume centers and patients of Black race. A significant number of counties in the US are without a gynecologic oncologist, and almost half of counties with the highest gynecologic cancer rates lack a local gynecologic oncologist. ObjectiveTo evaluate relationships of distance traveled and proximity to gynecologic oncologists with receipt of and racial disparities in the quality of surgical care in patients undergoing hysterectomy for nonmetastatic uterine cancer. Study designPatients who underwent hysterectomy for nonmetastatic uterine cancer in Kentucky, Maryland, Florida, and North Carolina were identified in 2012-2018 State Inpatient Database and State Ambulatory Surgery Services Database files. County-to-county distances were used for distances traveled and to nearest gynecologic oncologist. Factors associated with receipt of minimally invasive surgery and lymph node dissection were analyzed using multivariable logistic regression models including assessment for interactions of travel for surgery with patient race. ResultsAmong 21,837 cases, 45.5% lived in a county without a gynecologic oncologist; 55.5% overall traveled to another county for surgery, including 88% of those lacking a local gynecologic oncologist. Patients lacking local access to a gynecologic oncologist in their county who did not travel for surgery were more likely to receive open surgery and no lymph node dissection, and those in counties without access in any surrounding county were even more likely. Among patients in counties without a gynecologic oncologist, those who traveled for surgery had similar likelihood of minimally invasive surgery (71%) but greater likelihood of lymph node dissection (64.7% vs 57.2%) compared to non-travelers. Among counties without a gynecologic oncologist, longer distance traveled was associated with receipt of lymph node assessment. Compared to non-Black patients, Black patients were less likely to undergo minimally invasive surgery (57.0% vs 74.1%). In adjusted regression models controlling for a diagnosis of fibroids, Black race was an independent risk factor for receipt of open surgery. There was a significant interaction of Black race and travel for surgery, with Black patients who lived in counties without a gynecologic oncologist who did not travel facing incrementally lower likelihood of receiving minimally invasive surgery (OR=0.57 vs non-Black patients who traveled for surgery; OR=0.60 as interaction term; p<0.001 for both). Similar disparities in surgical quality by race were noted for Black patients who lived in counties with a gynecologic oncologist who traveled out of county for surgery. ConclusionsPatients, particularly those of Black race, who lack local access to gynecologic oncologist specialty care benefit from traveling to specialty centers to ensure access to high-quality surgery for nonmetastatic uterine cancer. Further work is needed to ensure equitable and universal access to high-quality care through patient travel or specialist outreach.

CN76 A study of sexual dysfunction in Moroccan female survivors of gynaecological cancer: A prospective study about 220 patients

CN76 A study of sexual dysfunction in Moroccan female survivors of gynaecological cancer: A prospective study about 220 patients

Exploring tumor microenvironment in molecular subtyping and prognostic signatures in ovarian cancer and identification of SH2D1A as a key regulator of ovarian cancer carcinogenesis

IntroductionA deadly gynecological cancer, ovarian cancer (OV), has a poor prognosis because of late-stage diagnosis and few targeted therapies. Addressing the tumor microenvironment (TME) in solid tumors has shown promise since it is crucial in promoting cancer progression. MethodsWe obtained bulk RNA-seq data from TCGA-OV, GSE26712, GSE102073, and ICGC cohorts, as well as scRNA-seq data from EMTAB8107, GSE118828, GSE130000, and GSE154600 cohorts using the TISCH2 database. The ConsensusClusterPlus package was used to cluster the OV tumor tissues hierarchically to determine two molecularly different groups (C1 and C2). A total of ten different types of machine learning techniques with 101 combinations were used for prognostic model construction. Using eight TME algorithms integrated into the IOBR R package, the bulk RNA-seq dataset was analyzed. For in vitro experiments, OVCAR3 and SKOV3, two OV cell lines, were used. The migratory potential of the ovarian cancer cells was assessed using Transwell assay, while proliferation was assessed using CCK8 assay. ResultsBased on TME-related gene set expression, two distinct molecular subgroups (C1 and C2) were identified through consensus clustering, with C1 showing higher TME activity. Further analysis indicated that C1 had increased cancer-associated fibroblasts (CAFs), M1 macrophages, and CD8+ T cells, suggesting a more activated and pro-inflammatory TME. Drug sensitivity analysis revealed that 5-Fluorouracil might be beneficial to C1 patients. Functional differences between C1 and C2 were identified, including cell adhesion, mononuclear cell differentiation, and leukocyte migration. A machine learning model was developed to create a TME-related prognostic signature, demonstrating strong prognostic capabilities across multiple datasets. High-risk patients showed a more immune-suppressive TME and higher tumor stemness. ScRNA-seq disclosed a highly activated TME-related signature in OV. Cancer cell lines had significantly higher SH2D1A mRNA expression than normal ovarian epithelial cells. We observed that SH2D1A knockdown in 2 ovarian cancer cell lines (OVCAR3 and SKOV3) reduced migration and proliferation through a series of in-vitro experiments. ConclusionTME-associated genes were efficient in ovarian cancer molecular subtyping. A TME-based prognosis model was constructed for vigorous prognostic stratification efficacy across multiple datasets. Moreover, we identified a pivotal role of SH2D1A in promoting proliferation and migration in ovarian cancer.

Screening log: Challenges in community patient recruitment for gynecologic oncology clinical trials

BackgroundClinical trial participation can improve overall survival and mitigate healthcare disparities for gynecologic cancer patients in low-volume community centers. This study aimed to assess the effectiveness of a centrally regulated but administratively decentralized electronic screening log system to identify eligible patients across a large catchment area for a National Cancer Institute (NCI)-designated cancer center's open clinical trials. MethodsElectronic screening log data collected between 2014 and 2021 from ten community partner sites in a single NCI-designated cancer center's catchment area were reviewed retrospectively. Clinical factors assessed included cancer site, primary versus recurrent disease status, and histology. Identification efficiency (the ratio of patients screened identified with an available trial) was calculated. Identification inefficiencies (failures to identify patients with a potentially relevant trial) were assessed, and etiologies were characterized. ResultsAcross ten community partner sites, 492 gynecologic cancer patients were screened for seven open clinical trials during the study period. This included 170 (34.5 %) ovarian cancer patients, 156 (31.7 %) endometrial cancer patients, and 119 (24.2 %) cervical cancer patients. Over 40 % had advanced stage disease, and 10.6 % had recurrent disease. Only three patients were identified as having a relevant open trial; none ultimately enrolled due to not meeting trial eligibility criteria. An additional 2–52 patients were retrospectively found to have a relevant trial available despite not being identified as such within the electronic screening log system. Up to 14.4 % of patients had one or more missing minimum data elements that hindered full evaluation of clinical trial availability. Re-screening patients when new trials open may identify 12-15 additional patients per recurrent disease trial. ConclusionsAn electronic screening log system can increase awareness of gynecologic oncology clinical trials at a NCI-designated cancer center's community partner sites. However, it is inadequate as a single intervention to increase clinical trial enrollment. Providing adequate support staff, documenting clinical factors consistently, re-screening patients at relevant intervals, and coordinating with central study personnel may increase its utility.

788P Pembrolizumab plus lenvatinib (PL) in recurrent clear cell gynecological cancer (CCGC): Phase II LARA trial (GCGS-OV4/ APGOT-OV3)

788P Pembrolizumab plus lenvatinib (PL) in recurrent clear cell gynecological cancer (CCGC): Phase II LARA trial (GCGS-OV4/ APGOT-OV3)

Unusual Scenario: Ipsilateral Pelvic Lymph Node Metastasis in High- Grade Serous Ovarian Carcinoma without Peritoneal Extension - A Case Report

Introduction:: Ovarian cancers are the third most common gynecological cancers worldwide with serous carcinomas being the most common subtype with 90% of them as high-grade carcinomas. Case Presentation:: In the present case report a 60 years postmenopausal, nulliparous woman presented with complaints of bleeding per vaginum for 1-2 months with a left-sided solid-cystic ovarian mass of size 4x5 cm and ipsilateral enlarged external iliac and obturator lymph nodes which were diagnosed on histopathological examination as high-grade serous ovarian carcinoma (HGSOCs) with ipsilateral pelvic lymph node metastasis in presence of intact ovarian capsule and no metastatic deposits over the uterus, contralateral ovary and fallopian tubes, omentum, or any other gross peritoneal deposits. There was coexisting non-atypical endometrial hyperplasia. The patient was managed successfully with staging laparotomy with modified radical hysterectomy, and bilateral pelvic lymphadenectomy followed by six cycles of adjuvant chemotherapy with Paclitaxel and Carboplatin injections. Conclusion:: Patients with HGSOCs can have varied presentations with unusual involvement of lymph nodes in the absence of peritoneal spread. Hence, the clinician must be aware of these unusual presentations for the successful management of such cases.

Upregulation of miRNA-450b-5p targets ACTB to affect drug resistance and prognosis of ovarian cancer via the PI3K/Akt signaling pathway.

Ovarian cancer (OC) is the most malignant gynecologic cancer, and chemoresistance is a major cause of treatment failure in patients with OC. The understanding of microRNA (miRNA) in cancer is limited, and the role of miRNA (miR)-450b-5p in cancer drug resistance is unknown. In this study, we aim to evaluate the role of miR-450b-5p in drug-resistant OC and its underlying mechanisms. MiR-450b-5p expression was assessed in drug-sensitive and resistant OC cells via quantitative real-time polymerase chain reaction. Cell viability was evaluated using the Cell Counting Kit-8 assay. Progression-free survival (PFS) and overall survival (OS) curves were generated using the Kaplan-Meier method and the log-rank test. Target genes of miR-450b-5p were identified from the Cancer MIRNome database. Co-expressed genes were obtained from The Cancer Genome Atlas and Cancer Genome cBioportal for pathway enrichment and functional clustering analysis. The miRNA-450b-5p expression was significantly increased in A2780 and SKOV3 OC-resistant cells and significantly increased by 17-fold in the A2780-CBP-Lv-miR-450b-5p cells compared to A2780-CBP and A2780-CBP-Lv-NC cells. The up-regulated expression of miR-450b-5p increased the cell viability and half maximal inhibitory concentration (IC50) of A2780 platinum-resistant cells and was associated with poor OS. We obtained 33 potential target genes of miR-450b-5p and beta-actin (ACTB) might be a potential target of miR-450b-5p. Low expression of ACTB predicted poor OS and PFS. We obtained 362 common genes co-expressed with ACTB, which involved 4 critical pathways. PI3K acted as an upstream pathway of the other three pathways, which ultimately responded to drug resistance regulation in OC. The genes enriched in four pathways were cross-analyzed and 13 overlapping genes were obtained. These 13 genes were also significantly and positively co-expressed with ACTB at both protein and mRNA levels. High expression of miRNA-450b-5p might affect drug resistance and prognosis in OC by targeting 13 co-expressed genes of ACTB directly through the PI3K/Akt signaling pathway. Thus, miR-450b-5p might provide a new therapeutic target for drug resistance in OC.

Improving clinical trial enrollment in minority racial and ethnic patients with gynecologic malignancy

PurposeRacial and ethnic minorities remain underrepresented in clinical trials . Underrepresentation of racial groups leads to the selection of therapeutic interventions that may not be representative of the population expected to use the medicine. This study evaluates the effectiveness of a set of implementation strategies to increase underrepresented patients in gynecologic cancer clinical trials. MethodsAn interrupted time series analysis evaluating implementation strategies (pre-screening and fast-track referral) was conducted from January 2021 to May 2022. Descriptive analysis of gynecologic oncology patient screening and accrual was compared before and after intervention implementation. ResultsDuring the study period (pre- and post-intervention), 26 patients were screened, and 9 patients enrolled in therapeutic gynecologic cancer clinical trials. Prior to the intervention, 7 patients were screened and 2 patients enrolled onto a clinical trial. Following the intervention, 19 patients were screened and 7 patients enrolled in a cancer clinical trial. Black patients comprised 13 of 19 (68.4%) of patients post-intervention compared to 1 of 7 (14.3 %) of patients screened pre-intervention (p < 0.05). All 7 patients enrolled post intervention were racial and ethnic minorities (non-Hispanic Black [4 of 7] and Hispanic White [3 of 7]) compared to no minority patients enrolled pre-intervention (p < 0.05). Screening increased 2.5-fold for all patients, and 5- fold for minority patients. Clinical trial enrollment increased 3.5-fold following intervention. ConclusionsA combination of pre-screening and fast-track referral intervention in a racial and ethnically diverse urban academic hospital was associated with a significant increase in minority screening and enrollment. Structured strategies to overcome barriers to underrepresented racial and ethnic patient accrual in academic hospitals are urgently warranted.

1870: Sexual sphere in gynaecologic cancer survivors: a Spanish survey (on behalf of GINECOR/SEOR)

1870: Sexual sphere in gynaecologic cancer survivors: a Spanish survey (on behalf of GINECOR/SEOR)

2644: Clinical experience of Adaptive Radiotherapy using MR-Linac or Tomotherapy for Gynecological Cancers

2644: Clinical experience of Adaptive Radiotherapy using MR-Linac or Tomotherapy for Gynecological Cancers

2576: Pelvic insufficiency fractures after EBRT for gynecological cancers: a single-institution experience

2576: Pelvic insufficiency fractures after EBRT for gynecological cancers: a single-institution experience

919: Randomised trial of nurse-led sexual rehabilitation after radiotherapy for gynaecological cancers

919: Randomised trial of nurse-led sexual rehabilitation after radiotherapy for gynaecological cancers

PET/MRI in Gynecologic Cancers: How Helpful is it?

PET/MRI in Gynecologic Cancers: How Helpful is it?