Ovarian cancer (OC) is one of the most aggressive and lethal cancers of the female reproductive system, with the highest mortality rate among the four major gynecological malignancies. Circulating tumor DNA (ctDNA), as an emerging biomarker, has shown great potential in early screening, minimal residual disease (MRD) monitoring, disease recurrence prediction, and personalized treatment of OC This article reviews the application of ctDNA in OC, exploring its role in early diagnosis, MRD monitoring, recurrence prediction, and personalized therapy. The review also summarizes the current technical challenges and future research directions. Compared to traditional tumor markers, ctDNA offers higher sensitivity and specificity, particularly in detecting early tumors and predicting treatment responses. Although ctDNA holds enormous potential for clinical applications, challenges remain in early-stage detection sensitivity and standardization of detection methods. Future research should focus on optimizing ctDNA detection techniques and integrating it with other biomarkers to promote its broader clinical use.

OBJECTIVE:To characterize epidemiology, treatment efficacy, and prognosis in cervical cancer patients aged <25 years using SEER data and institutional validation, and propose personalized strategies. METHODS:We analyzed 73,869 SEER database patients (2000-2021), including 544 aged <25 years. Epidemiological trends, histology, and staging were assessed. Survival models compared 3-/5-year survival rates: surgical (n = 25) vs. non-surgical (n = 9) treatment for stage IB3; surgical (n = 18) vs. non-surgical (n = 4) for stage IIA2; and adjuvant chemotherapy (n = 51) vs. non-chemotherapy (n = 6) for stages IIIA-IIIB. Findings were validated against institutional data (n = 12; 2009-present). RESULTS:Among SEER Database, the proportion of young patients significantly declined from 1.36% (2004) to 0.39% (2021), with poorly differentiated carcinoma predominating (51.65%). Squamous cell carcinoma accounted for the majority (59.56%), rare histological subtypes accounted for (12.68%) including small cell neuroendocrine carcinoma and clear cell carcinoma, with notable prognostic implications. Most young patients presented with early-stage disease (77.94%, n = 298/424). For stage IB3, surgery yielded higher 3-year (84% vs 55.56%) and 5-year survival (80% vs 44.44%) than non-surgical management. Stage IIA2 comparisons showed conflicting trends (potentially due to small samples). In stages IIIA-IIIB, adjuvant chemotherapy was associated with trends toward improved survival, and cumulative risk analysis suggested a potential reduction in long-term mortality risk in the chemotherapy group versus non-chemotherapy. Institutional data mirrored SEER treatment patterns. Histologic subtype emerged as a critical prognostic determinant; Both institutional deaths occurred in patients with rare histologies (stage IVB small cell neuroendocrine carcinoma; stage IIB clear cell carcinoma), suggesting histology may represent an important prognostic factor, potentially interacting with stage. CONCLUSION:Most young cervical cancer patients present with early-stage, poorly differentiated disease. Surgery may be beneficial for early-stage (≤IIB) disease in selected patients localized disease, while concurrent chemoradiotherapy (CCRT) plus brachytherapy remains the standard for advanced stages (IIIA-IIIB); the role of Adjuvant chemotherapy did not demonstrate a significant survival benefit and should be interpreted with caution. Tumor histology may outweigh stage as a prognostic determinant in this population. These findings are exploratory and require validation in prospective studies.

Endometrial cancer is increasingly diagnosed in patients who have not yet completed childbearing. For carefully selected patients with grade 1 endometrioid endometrial carcinoma confined to the endometrium, fertility-sparing treatment (FST) can preserve reproductive potential but requires rigorous histologic surveillance. In eligible patients, oral progestins and/or the levonorgestrel-releasing intrauterine system (LNG-IUS) remain the mainstay of fertility-sparing treatment, with hysteroscopic lesion resection incorporated in selected cases. Obesity, polycystic ovary syndrome, abnormalities in glucose metabolism, molecular subtype, and primary or acquired progestin resistance collectively contribute to heterogeneity in treatment response and the risk of recurrence. This narrative review critically integrates current guidelines, randomized controlled trials, prospective studies, retrospective cohorts, and early exploratory evidence to evaluate the biological rationale, clinical positioning, efficacy, safety, and maturity of evidence for progestin-based therapy, metabolic interventions, combined endocrine approaches, molecularly guided strategies, and exploratory immunotherapeutic approaches. We further propose an integrated clinical pathway encompassing candidate selection, molecular assessment, response evaluation, transition to pregnancy, retreatment after recurrence, and timely conversion to definitive surgery. Importantly, this review distinguishes guideline-supported approaches from adjunctive, investigational, and exploratory strategies. Major evidence gaps include inconsistent definitions of treatment response, limited prospective molecularly stratified data, uncertain reproductive safety of emerging systemic therapies, and insufficient long-term data on pregnancy outcomes and offspring.

5627 Background: SSGJ-707 is a fully human immunoglobulin G4 bispecific antibody targeting programmed death 1 (PD-1) and vascular endothelial growth factor (VEGF). SSGJ-707 has demonstrated promising efficacy and manageable safety alone and in combination with chemo in phase 2 studies in solid tumors. We report results from the phase 2 SSGJ-707-ST-II-02 study (NCT06522828) of 1L SSGJ-707 + chemo in advanced/recurrent EC. Methods: Pts with newly diagnosed stage lIl/IV or recurrent EC with low potential for cure by radiation therapy (tx) or surgery and systemic tx-naive were enrolled. Pts received SSGJ-707 5 mg/kg or 10 mg/kg Q3W + chemo (carboplatin AUC 5 + paclitaxel 175 mg/m 2 ) Q3W for 6 cycles, followed by SSGJ-707 maintenance tx until loss of clinical benefit or intolerable toxicity for up to 2 years. Primary endpoints were safety and ORR (RECIST 1.1). Secondary endpoints include duration of response (DOR), PFS, OS, PK, and biomarkers. Results: At data cutoff (Nov 28, 2025), 32 pts with EC (26 mismatch repair proficient [pMMR], 6 MMR deficient [dMMR]) received 5 mg/kg (n=16) or 10 mg/kg (n=16) SSGJ-707 + chemo. Median SSGJ-707 tx duration was 5.6 mo (range, 0.2-13.6); 8 pts (25.0%) discontinued tx. In the evaluable population, confirmed ORR was 85.7% (12/14 pts) for the 5 mg/kg dose and 80.0% (12/15) for the 10 mg/kg dose. Results for pMMR and dMMR groups are in the Table. Median PFS, OS, and DOR were not reached for either dose. Any-grade tx-related adverse events (TRAEs) were reported in 30/32 pts (93.8%) and grade ≥3 TRAEs in 22/32 pts (68.8%). The most common TRAEs (≥40%) included neutrophil count decreased (59.4%), white blood cell count decreased (59.4%), anemia (56.3%), and platelet count decreased (56.3%). No TRAEs led to death. TRAEs led to discontinuation of SSGJ-707 in 2 pts (6.3%). Immune-related AEs occurred in 6 pts (18.8%): hypothyroidism (n=4), hyperthyroidism (n=3), and rash (n=2). VEGF-related AEs occurred in 13 pts (40.6%): blood pressure elevation (n=6), proteinuria (n=6), hemorrhage (urinary occult blood positive; n=2), perforation and fistula (n=2), and venous thrombosis (n=1). Conclusions: SSGJ-707 + chemo demonstrated promising efficacy with a manageable safety profile in pts with tx-naive advanced/recurrent EC, supporting further investigation of SSGJ-707 in these pts. Clinical trial information: NCT06522828 . 5 mg/kg Q3W (n=14) 10 mg/kg Q3W (n=15) pMMR (n=12) dMMR (n=2) pMMR (n=11) dMMR (n=4) Confirmed ORR, n (%) [95% CI] 10 (83.3) [51.6, 97.9] 2 (100)[15.8, 100.0] 9 (81.8)[48.2, 97.7] 3 (75.0)[19.4, 99.4] Complete response 0 0 1 (9.1) 0 Partial response 10 (83.3) 2 (100) 8 (72.7) 3 (75.0) Stable disease 2 (16.7) 0 2 (18.2) 1 (25.0) Progressive disease 0 0 0 0 CR/PR pending – – 1 a 1 Unconfirmed ORR, n (%) [95% CI] 10 (83.3) [51.6, 97.9] 2 (100)[15.8, 100.0] 10 (90.9)[58.7, 99.8] 4 (100)[39.8, 100.0] a One additional pt in the 10 mg/kg group confirmed in Dec.

5573 Background: Ovarian cancer (OC) remains the leading cause of mortality among gynecological malignancies, primarily due to delayed diagnosis. Current diagnostic modalities, including imaging and serum biomarkers, exhibit suboptimal specificity, leading to unnecessary surgical interventions for benign adnexal masses. This study explores the clinical utility of cell-free DNA (cfDNA) fragmentomics, a high-dimensional genomic feature reflecting chromatin accessibility, in distinguishing malignant from benign ovarian tumors. Methods: This multi-center study enrolled 595 participants across three cohorts: a training set (n=236) and an internal validation set (n=172) from Yunnan Cancer Hospital, and an independent external validation set (n=136) from Beijing Obstetrics and Gynecology Hospital. Additionally, a prediction cohort included borderline ovarian tumors (BOT, n=51). Using whole-genome sequencing (WGS), we characterized cfDNA via four fragmentomic dimensions: copy number variations (CNVs), fragment size profiles (FSPs), nucleosome footprints (NFs), and genomic element perturbations (ARTEMIS). An ensemble model was trained to classify malignant ovarian cancer versus benign disease, and a generalized linear model was constructed by integrating fragmentomic scores with CA125 and HE4 levels to further improve the performance. Results: The cfDNA-only model demonstrated robust performance with Area Under the Curve (AUC) values of 0.937, 0.930, and 0.932 in the training, internal, and external cohorts, respectively. At 90% sensitivity in training (internal: 88.4%; external: 89.2%), specificities remained stable at 77.12%, 77.91%, and 78.87%. The model exhibited exceptional sensitivity for High-Grade Serous Ovarian Cancer (HGSOC) (>90%) with sensitivity increased with stages; early-stage (I–II) sensitivities were maintained ≥77%. Integrating the cfDNA fragmentomic score with CA125 and HE4 significantly enhanced AUCs to 0.961 (training), 0.964 (internal) and 0.964 (external). While maintaining high sensitivity (~90%), the combined model substantially increased specificity to 90.1% (training). Among 37 surgically treated stage I–III patients, higher pre-operative predictive scores were significantly associated with shorter disease-free survival (DFS) (p < 0.05), independent of age, stage, and histology. In BOT patients, 39.2% were classified as higher malignant-risk, consistent with an intermediate phenotype. Conclusions: The integration of cfDNA fragmentomics with traditional biomarkers provides a highly sensitive and specific non-invasive tool for the differential diagnosis of ovarian masses. This multi-modal approach significantly outperforms current clinical standards, offering a promising strategy for early detection and clinical risk stratification in ovarian cancer management.

Human papillomavirus (HPV) infection does not drive all cervical adenocarcinomas. HPV-independent cervical adenocarcinomas exhibit distinct histologic subtypes, metastatic patterns, and prognoses. This study aimed to compare the incidence of ovarian metastasis between HPV-related and HPV-independent cervical adenocarcinomas.​​ We conducted a retrospective analysis of cervical adenocarcinoma patients treated at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from 2012 to 2022. Ovarian metastasis rates were compared between HPV-related and HPV-independent cohorts.​ Among 444 cervical adenocarcinoma patients, 10.58

e17612 Background: FRUSICA-1(NCT03903705) is an open label, single-arm, pivotal phase II study, demonstrated the promising efficacy and favorable safety of fruquintinib (F) + sintilimab (S) in previously treated advanced EMC patients (pts) with pMMR status, with objective response rate (ORR): 35.6%; median progression-free survival (mPFS): 9.5mo; median overall survival (mOS): 21.3mo (Wu X, et al; 2024 ASCO). PPES and hypothyroidism are two common adverse events in the combination therapy of angio-genesis tyrosine kinase inhibitors and PD-1 antibody. Researches have indicated patients with PPES may experience better treatment outcomes in various cancer types. Immune related adverse events (irAE) were also deemed as predictor of response in gynecologic cancers. Therefore, we launched a subgroup analysis of the treatment outcome in patients who developed PPES or hypothyroidism in FRUSICA-1. Methods: EMC pts with centrally confirmed pMMR status who progressed after ≤ 2 platinum-based systemic therapy were treated with F (5mg QD orally, 2w on/1w off) + S (200mg IV, Q3W), in a 3-week cycle until disease progression or unaccepted toxicity. Patients who developed PPES or hypothyroidism were extracted and the efficacy analysis was then conducted accordingly. Results: As of 15th May 2024, 98 eligible pts were enrolled and evaluated with a median follow-up of 22.0 mo (95%CI: 20.5, 23.7). In the full analysis set (FAS), 38 (38.8%) pts experienced PPES, 45 (45.9%) experienced hypothyroidism. Assessed by independent review committee (IRC), Patients who developed PPES showed numerically higher efficacy with an ORR 47.4% (95% CI: 31.0, 64.2), DCR 92.1% (95% CI: 78.6, 98.3), mPFS and mOS not reached (NR), 15-mo PFS rate 60.7% (95% CI: 39.3, 76.6), 24-mo OS rate 59.3% (95% CI: 40.5, 73.9). Patients who had irAE hypothyroidism, also showed a higher efficacy, with an ORR 44.4% (95% CI: 29.6, 60.0), DCR 93.3% (95% CI: 81.7, 98.6), mPFS 16.6 mo (95% CI: 6.9, 27.4), mOS 24.0 mo (95% CI: 17.7, NR), the maturity of PFS and OS were 53.3% (24/45) and 46.7% (21/45). Conclusions: In FRUSICA-1 study, PPES and irAE hypothyroidism may be associated with higher ORR, longer PFS and OS in advanced EMC patients. PPES and irAE hypothyroidism could potentially be predictive of clinical outcomes for pts with treatment with fruquintinib plus Sintilimab. Clinical trial information: NCT03903705 .

Platelets are implicated in ovarian cancer development and progression, and exploration of platelet proteomics may assist in ovarian cancer diagnosis. This study aimed to investigate the platelet proteomics via mass spectrometry in ovarian cancer patients, and construct disease risk models for ovarian cancer by machine learning. Thirteen ovarian cancer patients and eighteen control subjects were enrolled. Blood samples were obtained followed by platelets isolation, then proposed to mass spectrometry. Differentiated expressed proteins (DEPs), enrichment, and weighted gene co-expression network analysis (WGCNA) were completed. Disease risk models were established by 6 machine learning models. A total of 609 downregulated DEPs and 39 upregulated DEPs were observed in ovarian cancer patients compared with control subjects. The DEPs were mainly enriched in Golgi vesicle functions, immune regulation, carcinogenesis, infections, and platelet functions. WGCNA classified all proteins into 8 modules, among which blue module was most important that highly correlated with disease risk and stage of ovarian cancer, consisting of 135 proteins. By cross analysis between DEPs and blue module proteins, 113 proteins were identified and used for disease risk model construction. Among 6 machine learning models, random forest model revealed the highest area under the curve (AUC) of 0.923 for identifying ovarian cancer risk, followed by naïve bayes model (AUC = 0.901), then kernelpls model (AUC = 0.857), bayesglm model (AUC = 0.855), nnet model (AUC = 0.813), and Lasso model (AUC = 0.731). This study uncovers the landscape of platelet proteomics of ovarian cancer, and establishes an effective ovarian cancer risk model (random forest) by machine learning.

BackgroundYolk sac tumor (YST) is the third most common highly malignant germ cell tumor, predominantly arising from the ovary and testis. The standard treatment for ovarian YST is surgery combined with BEP (bleomycin, etoposide, and cisplatin) chemotherapy in which bleomycin has a cumulative lifetime dose and pulmonary toxicity. Advancements in treatment have yielded favorable prognoses for YST patients. Here, we present the clinical, imaging, pathological features, and individualized treatment of a case of primary cervical YST which is extremely rare in previous reports.Case reportA 46-year-old female patient with primary cervical YST received neoadjuvant chemotherapy(1 cycle of paclitaxel+carboplatin, 2 cycles of BEP), radical surgery and 4 cycle of adjuvant BEP chemotherapy. The patient achieved complete remission after initial treatment but developed disease recurrence shortly thereafter, with confirmed BEP resistance. Salvage treatment with TC (albumin-bound paclitaxel and carboplatin) combined with bevacizumab was then administered, leading to a durable complete response; the patient subsequently received bevacizumab as maintenance therapy.ConclusionsYST of the cervix is extremely rare. This article reviews the clinical characteristics, treatment, and survival of advanced cervical YST. In addition, the complete response of this patient provides a new option for patients with recurrent and metastatic cervical YST, and TC regimen combined with VEGF inhibitors is expected to serve as a salvage treatment.

This report presents the primary analysis of the endometrial cancer (EMC) cohort of FRUSICA-1 (ClinicalTrials.gov identifier, NCT03903705), a multicenter, single-arm, phase Ib/II study evaluating fruquintinib plus sintilimab. The cohort included Chinese patients with inoperable or advanced mismatch-repair proficient (pMMR) EMC who had progressed on or could not tolerate up to two prior platinum-based therapies, and comprised exploratory and pivotal phases. Patients received fruquintinib (5 mg orally once daily on a 2 weeks on/1 week off schedule) plus sintilimab (200 mg intravenously once every 3 weeks). The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC). Secondary endpoints included ORR as assessed by the investigator, disease control rate, time to response, duration of response, progression-free survival (PFS) and tumor shrinkage as assessed by both the IRC and investigator, overall survival, and safety. By May 15, 2024, 98 patients with pMMR EMC were enrolled and treated. IRC-assessed ORR was 32.7

ObjectiveTo evaluate the mechanism of Kielin/chordin-like protein (KCP) in the resistance of cervical cancer cells to paclitaxel.MethodA cervical squamous carcinoma cell line (SiHa) with KCP knockout was constructed and treated with paclitaxel. Key cell functions were assessed by colony formation assay, measurement of cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and FACS-based detection of apoptosis. The downstream mechanism of KCP-mediated resistance to paclitaxel was then examined using human gene chip detection and IPA bioinformatics analysis, and qPCR analysis was used to validate its downstream genes.Results①Functional studies of SiHa cells showed that KCP knockout (sgRNA) inhibited colony formation and proliferation of SiHa cells in the presence of paclitaxel (p<0.05). ②Using a whole human genome microarray, a total of 491 differentially expressed genes were identified in KCP knockout versus the NC SiHa cells. IPA-based bioinformatics analysis of upstream regulators showed that SPI1 was strongly activated and that SPI1 inhibited CCND1 and activated PML and CEBPA, which is consistent with results from gene chip analysis showing CCND1, PML, and CEBPA expression after KCP knockout. ③A total of 30 differentially expressed genes associated with tumor cell proliferation were identified by gene microarray and IPA analyses. The changes in the aforementioned genes after KCP knockout were verified by qPCR, and SERPINB3 and CEBPA expression were significantly lower and higher, respectively, compared to in the control group.ConclusionKCP increased resistance of cervical cancer to paclitaxel by enhancing cell proliferation and colony formation. We observed that KCP could act positively on the downstream gene SERPINB3 and negatively on the downstream gene CEBPA to affect the resistance of cervical carcinoma cells to paclitaxel.

5611 Background: FRUSICA-1 (NCT03903705) was an open-label, single-arm, pivotal phase 2 study to evaluate the efficacy and safety of fruquintinib (F, a highly selective VEGFR inhibitor) plus sintilimab (S, an anti-PD-1 monoclonal antibody) in previously treated advanced EMC patients (pts) with pMMR (proficient mismatch repair) status. The primary results of FRUSICA-1 have demonstrated encouraging efficacy (objective response rate [ORR]: 35.6%; median progression-free survival [PFS]: 9.5 mo; median overall survival [OS]: 21.3 mo) in the overall population (Wu X, et al; 2024 ASCO). In this updated exploratory analysis (data cutoff: May 15, 2024), we evaluated the association between prior NACT/ACT and clinical outcomes in this study. Methods: Pts who had histologically confirmed advanced EMC with pMMR status confirmed by central lab and had progression on 1 standard systemic therapy were eligible. They received F (5 mg QD, 2 weeks on/1 week off, orally) plus S (200 mg, IV, Q3W) in 21-day cycles until disease progression or unacceptable toxicity. The efficacy subgroup analysis was performed by prior NACT/ACT (Yes vs No). Results: As of May 15, 2024, a total of 98 EMC pts with pMMR status were enrolled and received the treatment with the median follow-up of 22.0 mo (95%CI: 20.5, 23.7). Based on pts with or without prior NACT/ACT (Yes vs No = 47 pts vs 51 pts), the baseline demographics and disease characteristics were well balanced. Independent Review Committee (IRC)-assessed ORR (34.0% vs 31.4%) and disease control rate (DCR, 85.1% vs 82.4%) were comparable, respectively. Median duration of response (DoR) in pts with NACT/ACT was 11.1 mo while not reached for pts without NACT/ACT. Median PFS were 7.1 mo (95%CI: 4.7, 13.8) vs 9.5 mo (95%CI: 5.5, not estimable), respectively with two 95%CIs highly overlapped. The 6-mo PFS rates were also comparable at 56.8% vs 59.7%. Median OS pending maturity, the 18-mo OS rates were nearly identical (58.7% vs 59.1%). Conclusions: In this updated exploratory analysis of pts with advanced EMC enrolled in FRUSICA-1 study treated with F plus S, encouraging outcomes were achieved in the overall population, including patients who had received prior NACT/ACT and those who had not, with durable and clinically meaningful responses. Clinical trial information: NCT03903705 .

Objective:Lymph node metastasis (LNM) critically determines recurrence and survival in cervical cancer (CC), yet current imaging-based methods lack accuracy. Retroperitoneal lymph node dissection leads to many adverse events. This study aimed to develop a clinically actionable molecular signature to predict LNM, enabling personalized surgical planning and improved patient outcomes. Methods:Transcriptome profiles and clinical data from 193 CC patients, encompassing information on LNM from The Cancer Genome Atlas (TCGA) and an external cohort (GSE26511), were analyzed. The differential expression of mRNAs and lncRNAs was identified using DESeq2. Subsequently, dual machine learning strategies-LASSO regression and the Boruta algorithm-were applied to select robust biomarkers. Finally, the seven-mRNA-lncRNA gene cluster was verified in tumor tissues of CC patients with and without LNM using qRT-PCR. Results:The seven-mRNA-lncRNA gene cluster included four mRNAs (ART3, HRG, MAPT, and SYTL5) and three lncRNAs (AC011239.1, AC125616.1, and RUVBL1.AS1). The expression patterns of the seven DEGs align with their levels in CC tissues. The signature demonstrated high predictive accuracy (AUC: 0.855 in training and 0.807 in testing cohorts). External validation using the GSE26511 dataset confirmed its clinical applicability (AUC: 0.611). Patients with high LNM scores exhibited poorer survival outcomes than those with low LNM scores (p = 0.0034). Conclusion:We constructed a reliable prediction model of LNM in CC patients with a seven-mRNA-lncRNA gene cluster. This model guides lymphadenectomy decisions, reduces overtreatment, and enhances patient survival. Our work bridges molecular insights with clinical practice and provides a foundation for further research into the management of CC.

Concurrent chemoradiation is the preferred treatment recommendation for stage IIIC1 cervical cancer. Radical surgery is the alternative treatment for this population without parametrial invasion. Approximately 85

Background: Tumor recurrence significantly impacts the quality of life and fertility of patients with serous borderline ovarian tumors (SBOT) and early-stage low-grade serous ovarian carcinoma (LGSOC). This study aims to characterize recurrence patterns, identify independent risk factors for recurrence, and develop a nomogram to predict recurrence-free survival (RFS). Methods: We conducted a retrospective case-control study to investigate recurrence in patients undergoing fertility-sparing surgery (FSS) and radical surgery (RS). Logistic regression and Cox regression were used to identify risk factors. Kaplan–Meier analysis was applied to evaluate RFS. A nomogram was developed based on identified variables to predict RFS. Results: Tumor capsule disruption and micropapillary were associated with higher recurrence risk in the FSS group. Non-invasive implants were associated with higher recurrence risk in the RS group. The nomogram prediction model was developed based on identified risk factors. The area under the curve (AUC) for RFS predictions was 0.74 (95% CI: 0.62–0.85) at 3 years and 0.78 (95% CI: 0.67–0.89) at 5 years for the FSS group and 0.87 (95% CI: 0.76–0.98) at 3 years and 0.81 (95% CI: 0.65–0.97) at 5 years for the RS group. Conclusions: We identified the risk factors for recurrence of SBOT and early-stage LGSOC following FSS and RS procedures and developed a predictive model for forecasting RFS. This model provides valuable guidance for patients and clinicians in predicting recurrence risk for patients.

The female reproductive system (FRS) exhibits unique immunological characteristics, balancing defense against pathogens with tolerance to sperm and semi-allogeneic embryos. Key players include decidual natural killer (dNK) cells, immune checkpoint molecules (ICMs) and a complex immune microenvironment (IME). Dysregulation of these elements contributes to diseases like recurrent spontaneous abortion (RSA), endometriosis, primary ovarian insufficiency (POI), and infertility. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapy, shows significant promise in treating gynecological malignancies (e.g., cervical, endometrial, ovarian cancers), especially in advanced/recurrent settings or with specific biomarkers like mismatch repair deficiency. However, challenges persist, including limited efficacy in microsatellite stable tumors, resistance mechanisms and significant immune-related adverse events (irAEs). Critically, emerging evidence indicates potential detrimental effects of immunotherapy (especially ICIs) on female reproductive function, including diminished ovarian reserve, impaired oocyte maturation, hormonal disruption, and possible infertility, mediated by inflammatory responses, gonadotoxicity, and disruption of immune tolerance. Management of female-specific toxicities requires personalized strategies, fertility assessment, and consideration of preservation techniques. Future directions emphasize the development of predictive biomarkers, optimization of combination therapies, and implementation of truly individualized treatment regimens that account for the unique FRS IME, sex hormone influences, and the imperative to preserve fertility. Addressing the reproductive toxicity of novel immunotherapies remains a critical unmet research need.

Objective:This study aimed to evaluate the epidemiological trends in the incidence, age distribution, and pathological types of malignant female reproductive system tumors over the past 60 years at the Beijing Obstetrics and Gynecology Hospital. Methods:The types of diseases and basic clinical information of 18,921 patients with malignant female reproductive system tumors admitted to our hospital between January 1960 and December 2019 were collected. Results:A total of 18,921 patients were diagnosed and treated in the last 60 years. Since the establishment of the Department of Gynecological Oncology at our hospital in 1970, the number of patients with gynecological tumors has doubled, and the number of tumor types has also increased, with the highest incidence of cervical cancer, followed by endometrial cancer, ovarian cancer, and trophoblastic tumors. The three most common tumor types were most prevalent among women aged over 36 years. The average age of patients was 49.43 ± 11.65 years for those with cervical cancer, 53.95 ± 9.45 years for endometrial cancer, and 43.04 ± 13.79 years for ovarian cancer. Over the last 20 years, the age of patients with cervical cancer has been decreasing, and the age of patients with endometrial or ovarian cancers has slowly increased. Squamous cell carcinoma (85.61%-100%) was the most prevalent cervical cancer subtype; while, adenocarcinoma (88%-100%) was the most common endometrial cancer subtype and epithelial carcinoma was the most common ovarian cancer subtype. Conclusion:The establishment of a gynecological oncology subspecialty correlated with improved diagnostic capabilities and a marked increase in the number of cases. The observed epidemiological shifts underscore the need for targeted screening programs, as well as preventive and control policies. Furthermore, the proportion, classification, and age distribution characteristics of malignant tumors in the female reproductive system changed over time. These findings provide a foundation for refining national cancer prevention policies.

5596 Background: Serous carcinoma represents approximately 10% of all EMC, has the highest recurrence rate and is responsible for a disproportionate 40% of mortality in EMC. Additionally, the overall 5-year survival rate is only 33% for stage III-IV serous carcinoma. Fruquintinib (F, a highly selective VEGFR inhibitor) plus sintilimab (S, an anti-PD-1 monoclonal antibody) was evaluated in an open-label, single-arm phase 2 pivotal study (FRUSICA-1, NCT03903705), and demonstrated encouraging efficacy and favorable safety profile in treated advanced EMC pts with pMMR (proficient mismatch repair) status (Wu X, et al; 2024 ASCO). Here, we report the ad hoc updated analysis results of the serous carcinoma subgroup (data cutoff: May 15, 2024). Methods: Eligible pts had histologically confirmed, previously treated advanced EMC with pMMR status confirmed by central lab. They received F (5 mg QD, 2 weeks on/1 week off, orally) plus S (200 mg, IV, Q3W) in 21-day cycles until disease progression or unacceptable toxicity. Ad hoc analyses were conducted to evaluate the primary endpoint (ORR) and secondary endpoints (DCR, DoR, TTR, PFS, OS, and safety) of F+S in pts with endometrial serous carcinoma. Results: As of data cutoff date (May 15, 2024), 98 EMC pts with pMMR status were enrolled and received the combination treatment (ITT population), among them, 27 pts had serous carcinoma. In these 27 pts, median age was 63.1 years, 22 (81.5%) pts were in stage Ⅳ disease, 7 (25.9%) pts had received prior bevacizumab therapy, and 5 (18.5%) pts had received prior pelvic radiotherapy. IRC-assessed ORR was 37.0% (95%CI: 19.4%, 57.6%), DCR was 88.9% (95%CI: 70.8%, 97.7%). Median DoR and TTR was 17.9 (95%CI: 3.3, not estimable [NE]) months, and 2.4 (95%CI: 1.2, 4.0) months, respectively. With the median PFS and OS follow-up of 8.3 and 21.7 months, the median PFS and OS was 8.8 (95%CI: 6.9, 19.2) months and 19.0 (95%CI: 11.4, NE) months, respectively. These efficacy findings were similar with those observed in ITT population. Grade ≥3 treatment related adverse events (TRAE) occurred in 63.0% pts, and the most common ≥Grade 3 TRAEs included palmar-plantar erythrodysesthesia syndrome (22.2%) and hypertension (11.1%). Conclusions: F+S was tolerable and showed clinically meaningful efficacy in endometrial serous carcinoma, characterized by durable responses that were comparable across the ITT population. Clinical trial information: NCT03903705 .

BackgroundMenopause, a natural transition, affects women’s health risks, including gynecologic cancers. Early menopause, linked to lower estrogen, may increase cancer susceptibility. This study analyzed NHANES data from 1999 to 2020 for 8,219 postmenopausal women to explore the relationship between menopausal age and gynecologic cancers. We used regression models and RCS models to assess the risk.MethodsThis study utilized data from the NHANES spanning 1999 to 2020, focusing on 8,219 postmenopausal women selected through stratified sampling. Variables including socioeconomic factors, health behaviors, nutritional status, and medical history were assessed in relation to participants’ menopausal age and gynecologic cancer prevalence. We analyzed the relationship between menopausal age and gynecologic cancers (cervical, ovarian, and uterine) using multiple regression models. Additionally, we employed RCS models to evaluate nonlinear relationships between menopausal age and gynecologic cancer risk.ResultsOur findings indicate a significant inverse association between menopausal age and the risk of gynecologic cancers. After controlling for confounding factors such as age, race, BMI, and lifestyle variables, a later age at menopause was associated with a reduced risk of cervical, ovarian, and uterine cancers. The RCS model revealed a non-linear, low-L-shaped relationship, particularly highlighting increased cancer risks at younger menopausal ages. Subgroup analyses demonstrated consistent results across demographic and lifestyle factors, confirming the robustness of the observed associations.ConclusionThis study reveals the link between menopausal age and gynecologic cancer prevalence. Early menopause is a significant risk factor for cervical, ovarian, and uterine cancers. Our findings support tailored cancer screening based on menopausal age, potentially improving preventive care for postmenopausal women.

ObjectiveME1 catalyzes the conversion of malic acid into acetic acid, thereby linking glucose metabolism to the citric acid cycle. In recent years, the role of ME1 in various tumors has only been superficially explored. Therefore, our objective is to analyze the potential functions of ME1 in pan-cancer, with a particular focus on its role in ovarian cancer.MethodsWe analyzed the ME1 expression levels in both normal and tumor tissues across various cancer types. CBIOPORTAL was utilized to assess the mutation frequency and specific sites of ME1. Additionally, we examined the correlation between ME1 expression and several factors, including methylation status, tumor mutation burden (TMB), microsatellite instability (MSI), immune regulator genes, immune checkpoints, tumor microenvironment scores, functional enrichment, single-cell analysis, and drug sensitivity. The Estimate Algorithm assessed the correlation between ME1 expression and the tumor immunochemical microenvironment. Small interfering RNA and chronic viruses were utilized to downregulate and upregulate ME1 expression in two ovarian cancer cell lines, respectively, to conduct experiments on cell proliferation and migration.ResultsOur results revealed that ME1 exhibited disorders across various tumors, with the predominant form of genetic mutation identified being a missense mutation. Among the various tumors analyzed, ME1 demonstrated a significant correlation with methylation levels, TMB, MSI, immune checkpoints, immunomodulatory regulatory genes, tumor microenvironment scores, and immune infiltration. Functional enrichment analysis and single-cell analysis indicated that ME1 expression was associated with metabolic regulation, macrophage immune responses, antioxidant defense mechanisms, and the potential tumor microenvironment. The elevated levels of ME1 may be associated with a more favorable response to specific immunotherapy, suggesting that ME1 has potential applications in guiding immunotherapeutic strategies. In vitro research results demonstrated that in ovarian cancer cell lines, the knockdown of ME1 inhibited the proliferation and migration of tumor cells. Conversely, the overexpression of ME1 appeared to promote tumor cell proliferation and migration.ConclusionsME1, a metabolic-related factor, has the potential to serve as a biomarker for tumor progression and immune infiltration, particularly in ovarian cancer. It may signify a metabolic reprogramming that supplies energy for tumor progression and immunotherapy, offering valuable insights for the development of personalized therapies.