Gynecologic Malignancies Research Articles

Risk factors for major complications following pelvic exenteration: A NSQIP study

ObjectivesDue to the rarity of pelvic exenteration surgery, it is challenging to predict which patients are at an increased risk for postoperative complications. We aimed to study the predictors for postoperative complications among women undergoing pelvic exenteration for gynecologic malignancy. MethodWe used the National Surgical Quality Improvement Program registry to evaluate postoperative course and complications of those patients undergoing pelvic exenteration in the period 2012–2022. The primary objective of the analysis was to estimate the major postoperative complications following pelvic exenteration. ResultsOverall, 794 pelvic exenterations were included. Of those, 56.5 % were anterior exenteration, 43.5 % were posterior exenteration, and 13.9 % were a combined exenteration. The rate of minor complications was 72.5 % (n = 576), and the rate of major complications was 31.5 % (n = 250). The most common minor complications were blood transfusion (n = 538, 67.8 %), followed by superficial surgical site infections (SSI) and urinary tract infections (9.8 % and 9.4 %, respectively). Among the major complications, the most common was organ/space SSI (11.2 %), followed by sepsis (9.2 %), reoperation (8.6 %), and wound dehiscence (5.2 %). Death within 30 days occurred in 1.5 % of patients. In multivariable regression analysis, the following factors were independently associated with major complications: higher BMI [adjusted odds ratio (aOR) 1.03 95 % confidence interval (CI) (1.01–1.05)], diabetes [aOR 1.82 95 % CI (1.13–3.22)], low serum albumin [aOR 0.73 95 % CI (0.54–0.98)], and high serum creatinine [aOR 1.70 95 % CI (1.05–2.77)]. ConclusionsMajor postoperative complications occur in approximately one third of pelvic exenterations for gynecologic malignancies. Our study highlights independent factors associated with major postoperative complications, of which some are potentially modifiable.

New Insights into the Assessment of Peri-Operative Risk in Women Undergoing Surgery for Gynecological Neoplasms: A Call for a New Tool

Existing tools for predicting postoperative complications in women undergoing surgery for gynecological neoplasms are evaluated in this narrative review. Although surgery is a very efficient therapy for gynecological tumors, it is not devoid of the possibility of negative postoperative outcomes. Widely used tools at present, such as the Surgical Apgar Score and the Modified Frailty Index, fail to consider the complex characteristics of gynecological malignancies and their related risk factors. A thorough search of the PubMed database was conducted for our review, specifically targeting studies that investigate several aspects impacting postoperative outcomes, including nutritional status, obesity, albumin levels, sodium levels, fluid management, and psychological well-being. Research has shown that both malnutrition and obesity have a substantial impact on postoperative mortality and morbidity. Diminished sodium and albumin levels together with compromised psychological well-being can serve as reliable indicators of negative consequences. The role of appropriate fluid management in enhancing patient recovery was also investigated. The evidence indicates that although current mechanisms are useful, they have limitations in terms of their range and do not thoroughly address these recently identified risk factors. Therefore, there is a need for a new, more comprehensive tool that combines these developing elements to more accurately forecast postoperative problems and enhance patient results in gynecological oncology. This paper highlights the need to create such a tool to improve clinical practice and the treatment of patients.

Investigating PPT2’s role in ovarian cancer prognosis and immunotherapy outcomes

Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients.

TERT promoter mutations and survival outcomes in adult-type granulosa cell tumors

ObjectivesT0 evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase (TERT) promoter mutations.MethodsThis is a retrospective cohort study using the MD Anderson Rare Gynecologic...

A nanoscale natural drug delivery system for targeted drug delivery against ovarian cancer: action mechanism, application enlightenment and future potential.

Ovarian cancer (OC) is one of the deadliest gynecological malignancies in the world and is the leading cause of cancer-related death in women. The complexity and difficult-to-treat nature of OC pose a huge challenge to the treatment of the disease, Therefore, it is critical to find green and sustainable drug treatment options. Natural drugs have wide sources, many targets, and high safety, and are currently recognized as ideal drugs for tumor treatment, has previously been found to have a good effect on controlling tumor progression and reducing the burden of metastasis. However, its clinical transformation is often hindered by structural stability, bioavailability, and bioactivity. Emerging technologies for the treatment of OC, such as photodynamic therapy, immunotherapy, targeted therapy, gene therapy, molecular therapy, and nanotherapy, are developing rapidly, particularly, nanotechnology can play a bridging role between different therapies, synergistically drive the complementary role of differentiated treatment schemes, and has a wide range of clinical application prospects. In this review, nanoscale natural drug delivery systems (NNDDS) for targeted drug delivery against OC were extensively explored. We reviewed the mechanism of action of natural drugs against OC, reviewed the morphological composition and delivery potential of drug nanocarriers based on the application of nanotechnology in the treatment of OC, and discussed the limitations of current NNDDS research. After elucidating these problems, it will provide a theoretical basis for future exploration of novel NNDDS for anti-OC therapy.

Updates in palliative care of gynecologic oncology patients

Purpose of review This review assesses the impact of early integration of palliative care and the disparities that exist among patients with gynecologic malignancies. It also highlights the recent advances in symptom management, goals of care communication, and end of life care. Recent findings Although palliative care has been utilized earlier, there are still barriers to its integration both nationally and worldwide, manifesting as predominantly late hospice referrals and aggressive care at the end of life. However, there are increasing efforts to promote earlier integration and discussion around goals of care through multidisciplinary approaches. Apart from symptom burdens, patients with gynecologic malignancies experience financial toxicity that impact various aspects of their lives, leading to potentially harmful choices to mitigate costs. A growing area of interest in palliative care is the realm of psychedelic-assisted therapy, which has shown benefits in treating advanced cancer patients with depression. Summary While significant strides have been made in incorporating palliative care earlier, continued research in palliative care is needed to address symptomatic and psychosocial suffering worldwide.

Aging affects regrowth of stealthperitoneal dissemination of advanced ovarian cancer: a multicenter retrospective cohort study

Ovarian cancer (OvCa) is one of the most lethal gynecological malignancies, and most patients are diagnosed at advanced stage with peritoneal dissemination. Although age at diagnosis is considered an independent prognostic factor, its impact on peritoneal recurrence after combined cytoreductive surgery and chemotherapy is not clear. The objective of this study was to investigate the impact of aging on peritoneal recurrence from stealth dissemination and gain insight of the pathophysiology of OvCa in elderly patients. A total of 243 patients with pT2b-pT3 epithelial ovarian who achieved complete surgery, no-residual tumor at first surgery, were selected to be analyzed the risk of peritoneal seeding and recurrence. We found that age over 65 years was independently associated with an increased risk of peritoneum-specific (PS) recurrence (. Furthermore, pT3 stages and positive ascites cytology also worsen the PS-relapse-free survival. Collectively, our findings suggest that age, especially over 65 years, predicts reduced peritoneum-specific tumor recurrence in patients with advanced ovarian cancer after complete cytoreduction surgery, particularly those with pT3 tumors and positive ascites cytology.

Preparation of dual drug-loaded polymer nanoconjugate to enhance treatment efficacy for ovarian cancer cells

Ovarian cancer is the deadliest gynecological malignancy, representing 2.5 % of all female cancers and accounting for 5 % of female cancer-related fatalities. Despite numerous strategies in its treatment, the disease shows a high recurrence rate and a low survival rate. Consequently, there is a growing focus on targeted therapies in ovarian cancer treatment. It is well-known that VEGFR and LPA pathways undergo alterations in ovarian cancer and stimulate survival, adhesion, migration, invasion, tumor growth and angiogenesis. Cabozantinib (CBZ) is a multi-receptor tyrosine kinase inhibitor that effectively targets MET, VEGFR-1, 2, 3, FLT3, c-KIT, and RET. Ki16425 is a selective inhibitor of LPA receptors 1, 2, and 3. Therefore, targeting LPA receptors and combining with VEGFR inhibitor is a strategic approach for ovarian cancer treatment. In this study, it was aimed to prepare polymer-drug nanoconjugate for both VEGFR and LPAR inhibition. For this, O-(2-Carboxyethyl) polyethylene glycol (PEG5000) which advantages are known in cancer studies, was chosen as the carrier system, and a nanoconjugate containing Ki16425 and CBZ (Ki-PEG-CBZ) was synthesized and its potential was evaluated. Initially, CBZ and Ki16425 were conjugated to the PEG5000 through pH-sensitive hydrazone and ester bonds. After nanoconjugate characterization, in vitro release and its ovarian cancer treatment potential were evaluated on A2780, OVCAR3 and SKOV3 ovarian cancer cell lines. A nanoconjugate was obtained with a particle size of 169 ± 15.23 nm, a zeta potential of −13.5 ± 1.21 mV, and a release profile lasting 48 h, containing CBZ and Ki16425 with drug loading efficiencies of 73.71 ± 0.53 % and 77.72 ± 2.51 %, respectively. In vitro studies have demonstrated that Ki-PEG-CBZ is highly effective against ovarian cancer. We suggest that the developed polymer-drug nanoconjugate is an effective and safe nanoconjugate for the treatment of ovarian cancer.

Targeting KRAS in gynecological malignancies.

Cervical, endometrial, and ovarian cancers stand prominently as the leading gynecological malignancies of the female reproductive system. The conventional therapeutic modalities for gynecological malignancies have predominantly encompassed surgery, chemotherapy, and radiotherapy. However, efficacy of these approaches remains limited in cases of relapse or drug resistance. KRAS is one of the most frequently mutated oncogenes in human cancers. The KRAS gene encodes a small guanosine triphosphatase protein that acts as a molecular switch for crucial intracellular signaling pathways. KRAS mutations are deeply involved in the occurrence and development of gynecological malignancies. The present review aims to expound upon the role of oncogenic KRAS as a biomarker, elucidating various therapeutic approaches under investigation targeting the KRAS pathway in gynecological tumors.

Early non-compliance to ERAS in gynecological open surgery for malignancies, and post-operative complications: a multicenter, prospective, observational, cohort study

BackgroundOpen surgical procedures for gynecological malignancies have a potential risk of post-operative complications and hence prolonged hospitalization, despite adherence to an Enhanced Recovery After Surgery (ERAS) protocol.Primary ObjectiveTo investigate the...

8314 Masculinizing Hormone Therapy and Gynecological Neoplasm: a Single Institution Cohort

Abstract Disclosure: S. Korpaisarn: None. T. Ngaothepphurktharam: None. Y. Tingthanatikul: None. Background: Gynecological neoplasm/malignancy is one of the concerned areas among transgender men on masculinizing hormone therapy (MHT). Long-term MHT and gynecological neoplasm/malignancy remain unclear. Methods: A retrospective cohort chart review was done on all transgender men (TM) who underwent hysterectomy with or without oophorectomy between January 2014 and October 2022. Intraoperative findings and pathological results of genital organs, including the cervix, endometrium, myometrium, and fallopian tubes, were extracted. The pathological results were classified as benign, precancerous, and malignant. Descriptive statistical analysis was used to demonstrate the prevalence of gynecological neoplasm and malignancy. Results: A total of 30 TM underwent hysterectomy with oophorectomy. Twenty-eight (93%) had bilateral oophorectomy, and 7% had unilateral oophorectomy due to gynecological conditions. The mean age when TM underwent surgery was 32.1 ± 5.1 years, and the mean age of gender-affirming hormone initiation was 28.7± 5.1 years. The median duration of MHT before gynecological surgery was 32 months (IQR 22-59). Most TM (73%) used testosterone enanthate, 17% testosterone undecanoate, and 2 transgender men did not start MHT before genital surgery. All TM who used GHT became amenorrheic before surgery. The median preoperative testosterone level was 561.5 ng/dL (IQR 776-1189). Intraoperative findings revealed that most TM (86.7%) had unremarkable uterus size, and 13% showed enlarged uterus size. In the latter, all were from myoma uteri. Most intraoperative findings of ovaries showed 93% unremarkable. One TM had intraoperative polycystic ovarian morphology, and one showed a unilateral ovarian cyst. Cervical pathological reports showed unremarkable results in 67%. Five TM (17%) had chronic cervical inflammation. There was 1 TM (3%) who showed low-grade squamous intraepithelial lesion (LSIL) with squamous metaplasia. Regarding endometrial pathology, the mean endometrial thickness was 0.13 ± 0.08 cm. Most endometrial reports (66%) were in a proliferative phase, 27% were in an atrophic or inactive endometrium, and 7% were in the secretory phase. Regarding pathological reports of ovaries, 80% had cystic ovaries. None of the TM showed precancerous or malignant conditions of endometrium, ovaries, and fallopian tubes. PAP smear was available in 27 TM; all were negative for intraepithelial lesions or malignancy. Conclusion: Among a cohort of TM who received MHT for 32 months, there is no evidence of precancerous or malignant pathology of the endometrium, ovaries, and fallopian tubes. Most of them had thin endometrium with cystic ovaries. One TM showed LSIL with squamous metaplasia of the cervix. Healthcare providers should follow local gynecological cancer screening guidelines developed for cisgender women in their clinical practice. Presentation: 6/2/2024

Safety and efficacy of thermo-expandable metallic stent in ureteral stricture following gynecological malignancy surgery and radiotherapy: a single center experience with 33 cases.

The effectiveness of metallic stents in treating ureteral strictures following surgery and radiotherapy for gynecological tumors is currently uncertain. We aimed to investigate the efficacy and safety of thermo-expandable metallic stent (Memokath) in the treatment of ureteral stricture after radiotherapy for gynecological tumors. In this descriptive cross-sectional study, 27 patients with ureteral stricture were treated with Memokath stent after gynecological tumor radiotherapy with or without chemotherapy that was admitted to our hospital from August 2021 to August 2023. Clinical data on efficacy, safety, and complications during stent insertion and indwelling were analyzed. The successful insertion of thirty-three stents in twenty-seven patients studied. The stenosis length was 10.14 ± 6.76cm, and the hospitalization was 4.43 ± 1.83 days. One patient has died from the primary disease carrying a patency stent. The Kaplan-Meier graph showed that the cumilative patency rate of patients with thermo-expandable metallic stent were 92.4% (SD = 5.2%) in eight months, 77.4% (9.1%) in 12 months and 67.7% (SD = 12%) in 29 months, while the cumilative survival rate was 87.5% (SD = 11.5%) in 29 months. The stent patency was 81.48% and later complications of stent indwelling were 5/27, including refractory urinary tract infection (UTI) in three cases, stent migration, and stent intolerance respectively. The creatinine levels, hydronephrosis degree, and glomerular filtration rate improved after the operation, and the first two indicators were statistically significant. Memokath stent is a safe and effective treatment for ureteral stricture after surgery and radiotherapy with or without chemotherapy for gynecological tumors.

Deep Learning Models for Early Detection of Ovarian Cancer: A Systematic Review of Ultrasound-Based Diagnostic Tools

Ovarian Cancer (OC) remains one of the most lethal gynecological malignancies, with a global 5-year survival rate of only 45%. This project aimed to assess the potential of deep learning-based diagnostic tools in improving early detection of ovarian cancer, particularly through ultrasound imaging. The primary research problem lies in the challenge of accurately diagnosing OC at an early stage, as traditional imaging techniques often rely on subjective interpretations, leading to inconsistent results. To address this issue, a systematic review was conducted following PRISMA guidelines, evaluating studies published between January 2018 and May 2023 in the Scopus and PubMed databases. These studies employed deep learning or artificial intelligence models for the diagnosis, prognosis, or identification of OC from ultrasound images. Of the 101 studies screened, 9 met the inclusion criteria. The included studies reported diagnostic accuracies of deep learning models ranging from 75% to 100%, with sensitivities between 85% and 99%. The conclusions indicate that deep learning models significantly enhance the diagnostic accuracy of ovarian cancer, offering a promising non-invasive tool for early detection. This research underscores the importance of integrating AI technologies into clinical practice to improve survival outcomes for OC patients.

Losartan rewires the tumor-immune microenvironment and suppresses IGF-1 to overcome resistance to chemo-immunotherapy in ovarian cancer.

Ovarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. This lack of effectiveness is partly due to the abnormal ovarian tumor microenvironment (TME), displaying a desmoplastic, highly fibrotic extracellular matrix. High extracellular matrix deposition leads to a buildup of compressive forces that cause tumor blood vessel collapse, reduced vessel perfusion, poor delivery of drugs, and compromised trafficking of cytotoxic T-cells to these tumors. Using two syngeneic OvCa models, we tested the effect of losartan, a widely prescribed anti-hypertensive drug, on reprogramming the TME and chemosensitizing the cancer cells. Losartan treatment (i) reprograms the TME leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and (ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. The safety and low cost ( < $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.

Oncolytic activity of a coxsackievirus B3 strain in patient-derived cervical squamous cell carcinoma organoids and synergistic effect with paclitaxel

BackgroundCervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids.MethodsThe oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro.ResultsCVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication.ConclusionsCVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

RNF144A as a potential risk gene for endometrial carcinoma: Insights from Mendelian randomization, bulk RNA sequencing, single-cell RNA, and experimental analysis.

Endometrial carcinoma (EC) is a prevalent gynecological malignancy that poses a significant threat to women's health worldwide. However, its pathogenesis and underlying mechanisms remains unclear. In this study, expression quantitative trait loci data, Mendelian randomization analysis, and differential expression analysis were performed to identify potential targets. A prognostic risk signature was subsequently constructed for EC patients based on the expression of these genes. Four bioinformatics algorithms, including generalized linear model, extreme gradient boosting, support vector machine, and random forest, were used to identify hub genes in EC. The expression of ring finger protein 144A (RNF144A) was validated using quantitative real-time polymerase chain reaction. Cellular proliferation and migration ability were evaluated using CCK-8 and Transwell assays, respectively. The genes RNF144A, ketohexokinase, and Rab interacting lysosomal protein like 2 were identified as potential targets for EC. Their differential expression was observed in EC patients, and Mendelian randomization analysis revealed a negative correlation between these genes and the development of EC. Mechanistic analyses suggested a strong association between these genes and the tumor immune microenvironment. The constructed risk signature was significantly associated with the prognosis, age, cancer stage, and grade of EC patients. Furthermore, based on interacted model algorithms, RNF144A was identified as a hub gene in EC. It was found to be significantly downregulated in EC samples, and its expression was positively correlated with the stage and grade of EC patients. In vitro experiments showed that overexpression of RNF144A significantly promoted cell growth and migration in EC cells. In conclusion, this study provides insights into the molecular mechanisms underlying EC progression and identifies preliminary candidate biomarkers for the development of EC treatment strategies.

Impact of estradiol in inducing endometrial cancer using RL95-2

BackgroundEndometrial cancer is the most common gynecological malignancy that originates from the inner lining of the uterus and predominantly affects postmenopausal women. Prolonged exposure to estrogen, family history of endometrial cancer, obesity, and hormonal imbalance are some of the risk factors associated with endometrial cancer. In our study, we investigated the effect of estradiol, a potent form of estrogen at various concentrations on endometrial cell line RL95–2. MethodsEndometrial cell RL95–2 were cultured in DMEM medium with optimal conditions required to maintain the cells. MTT assay and colony formation assay were further performed after treating the cells with different concentrations of estradiol (1, 10, and 100 nM) and TAM (100 nM). Moreover, the effect of genes regulated by estradiol was also examined using microarray and validated using real-time polymerase chain reaction (qRT-PCR). ResultsTime-dependent MTT assay shows a significant change in the ability of the cells to survive relative to concentrations. Colony formation was found to be directly proportional to the concentration of the estradiol (p < 0.05). Among genes, MMP14 (p = 0.03), SPARCL1 (p = 0.005), and CLU (p = 0.06) showed a significant up-regulation in their expression after estradiol treatment while NRN1 (p < 0.001) showed significant downregulation in expression pattern compared to control. However, the TAM treatment was found to be significantly effective after 72 h (p < 0.001) compared to control and 100 nM E2 (p = 0.0206). ConclusionOur study suggests that estradiol significantly contributes to regulating the viability, colony formation, and expression of genes associated with endometrial cancer.

Race- associated molecular differences in uterine serous carcinoma.

Endometrial cancer (EMCA) is the most common gynecologic malignancy, and new diagnoses are increasing in the United States. Black patients are more likely to present with advanced stage, be diagnosed with high-risk uterine serous carcinoma (USC) and die of their cancer. Patients with endometrial adenocarcinoma who received tumor FoundationOne CDx testing at our institution between January 2017 and August 2022 were identified. Genomic alterations, demographic and clinical characteristics were collected. Descriptive statistics and Fisher's exact test were used to analyze data. A total of 289 patients (29.4% Black and 52.6% White) with advanced or recurrent endometrial adenocarcinoma underwent FoundationOne CDx testing. USC comprised 26.3% (76 of 289) of tested tumors. Of USC tumors, 33 of 76 (44%) were of Black race. USC occurred more frequently in Black patients (33 of 85 [38.8%] Black patients compared to 30 of 152 [19.7%] White patients, p<0.05). Among USC, CCNE1 amplification occurred more frequently in Black patients than in White patients (12 of 33 [36.36%] vs 2 of 30 [6.67%], p<0.05) while PI3K/AKT/mTOR pathway mutations occurred less frequently (16 of 33 [48.5%] vs 26 of 33 [86.7%], p=0.17). Among patients with CCNE1 amplification 73.3% (11 of 15) progressed on or within 12 months of first-line platinum-based therapy. CCNE1 amplification had significantly shorter median overall survival (97.3 months vs 44.3; HR (95%CI): 7.1 (10.03, 59.4) p< 0.05). Black patients constituted 44% of patients with USC in our study and had an increased frequency of CCNE1 amplification. Patients whose tumors harbored CCNE1 amplification had shorter overall survival. Identifying actionable mutations in this high unmet need population is crucial to improving outcomes among Black patients with uterine malignancy. Development of new targeted-therapies will need to keep these alterations at the forefront as trials are being designed.

Comparative Molecular Docking of Apigenin and Luteolin versus Conventional Ligands for TP-53, pRb, APOBEC3H, and HPV-16 E6: Potential Clinical Applications in Preventing Gynecological Malignancies.

This study presents a comparative analysis of molecular docking data, focusing on the binding interactions of the natural compounds apigenin and luteolin with the proteins TP-53, pRb, and APOBEC, in comparison to conventional pharmacological ligands. Advanced bioinformatics techniques were employed to evaluate and contrast binding energies, showing that apigenin and luteolin demonstrate significantly higher affinities for TP-53, pRb, and APOBEC, with binding energies of -6.9 kcal/mol and -6.6 kcal/mol, respectively. These values suggest strong potential for therapeutic intervention against HPV-16. Conventional ligands, by comparison, exhibited lower affinities, with energies ranging from -4.5 to -5.5 kcal/mol. Additionally, protein-protein docking simulations were performed to assess the interaction between HPV-16 E6 oncoprotein and tumor suppressors TP-53 and pRb, which revealed high binding energies around -976.7 kcal/mol, indicative of their complex interaction. A conversion formula was applied to translate these protein-protein interaction energies to a comparable scale for non-protein interactions, further underscoring the superior binding potential of apigenin and luteolin. These findings highlight the therapeutic promise of these natural compounds in preventing HPV-16-induced oncogenesis, warranting further experimental validation for clinical applications.

Relationship between self-reported challenges with social determinants of health and delayed time-to-treatment initiation for gynecologic malignancies.

90 Background: Delays in time to treatment initiation (TTI) for gynecologic malignancies have been associated with worse survival. Worsened outcomes and presentation with more advanced disease are more common for gynecologic cancer patients who come from socioeconomically disadvantaged populations and whose healthcare is negatively impacted by their social determinants of health (SDoH). There is a need to characterize the particular social determinants of health that are associated with delays in treatment initiation in patients with gynecologic malignancy, particularly in underserved urban populations. Methods: Retrospective cohort study at an urban community-based academic center. Participants were 257 patients with primary gynecologic malignancy either of the cervix, ovary, uterus, vulva/vagina or NOS diagnosed between January 2017 and August 2022, identified through the Montefiore Medical Center Cancer Registry. The primary exposure was TTI, defined as the duration between histopathological diagnosis and initial treatment. Univariate and multivariate logistic regression analyses were conducted to examine the association between delays in TTI and SDoH. Multivariate Cox proportional hazard regression was used to obtain hazard ratios and 95% confidence intervals associated with TTI. Results: Among 257 patients with gynecologic malignancy (median [IQR] age 63 [56-72] years), 205 patients were treated within 45 days of diagnosis, and 52 were treated at or after 45 days. Predictors of delayed TTI (defined as ≥45 days) included positive SDoH screening in univariate logistic regression (OR = 3.12, 95% CI 1.39-6.98, p = 0.0061) and in multivariate logistic regression (OR = 3.06, 95% CI 2.62-3.57, p&lt;0.001) as well as increased age in multivariate logistic regression (OR = 1.02, 95% CI 1.02-1.03, p&lt;0.001). Multivariate logistic regression showed that protective factors for delayed TTI were Non-Hispanic Black race/ethnicity (OR = 0.87, 95% CI 0.77-0.99, p = 0.0351), non-Hispanic white race/ethnicity (OR = 0.37, 95% CI 0.30-0.46, p&lt;0.001), inpatient stay within 30 days of diagnosis (OR = 0.74, 95% CI 0.62-0.88, p=0.001) and AJCC clinically late stage (OR = 0.57, 95% CI 0.50-0.66, p&lt;0.001). Conclusions: In patients with gynecologic malignancies, greater SDoH burden increases risk for delays in treatment ≥ 45 days from diagnosis. Non-Hispanic race/ethnicity, inpatient stay within 30 days of diagnosis and clinically late-stage diagnoses are protective factors for expedited treatment initiation. Identification of predictive and protective factors for treatment delay will help identify at-risk patients and facilitate earlier intervention in hospitals with underserved populations.