Journal of Gynecologic Oncology最新文献

Objective: Cervical cancer is the leading malignancy in terms of both incidence and mortality among cancers of the female reproductive system, and initial surgical treatment is still one of the main treatments. However, for many years, radical hysterectomy based on traditional anatomical principles has failed to substantially improve oncological outcomes for cervical cancer patients or reduce the incidence of perioperative complications. In recent years, radical surgery grounded in the membrane anatomy concept of embryonic development has demonstrated promising oncological outcomes in colorectal cancer surgery. Research in the field of cervical cancer, however, remains in its early stages, although it is steadily garnering increased attention. Consequently, this meta-analysis seeks to systematically assess the safety and efficacy of radical hysterectomy, rooted in embryonic developmental principles, for the treatment of early-stage cervical cancer.

Methods: This study systematically searched PubMed, Embase, Cochrane Library, Web of Science, Wanfang, and CNKI databases for relevant studies published from their inception to October 2024. Data on 5-year recurrence-free survival (RFS), overall survival (OS), and surgical complications were collected for further analysis.

Results: Eight studies involving 1,226 patients were included in the meta-analysis. The surgical complication rate was 35.2%. Two studies reported a 5-year RFS of 86% and an OS of 88%.

Conclusion: Radical hysterectomy based on embryo development-originated shows good safety and efficacy in treating early-stage cervical cancer.

Trial registration: PROSPERO Identifier: CRD42024602098.

Objective: To investigate the impact of age on the progression-free survival (PFS) and dose modification, discontinuation and adverse events of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in homologous recombination-deficient (HRD) ovarian cancer patients.

Methods: We analyzed 324 patients with advanced stage III-IV epithelial ovarian cancer who had either BRCA mutation or HRD between July 2019 and November 2022. The primary objective was to evaluate the efficacy of PARPis by comparing PFS between patients who received PARPis and those who did not, specifically within 2 age groups: patients aged <60 years and those aged ≥60 years. The secondary objective included evaluating the rates of dose modification, discontinuation, and occurrence of treatment-emergent adverse events in patients who used PARPis.

Results: Of the 324 patients, 139 patients (42.9%) were diagnosed at ≥60 years. The use of PARPis resulted in a significant improvement in PFS in both age groups (hazard ratio [HR]=0.37; p<0.01) for patients aged <60 years (HR=0.41; p<0.01) for those aged ≥60 years. The multivariable Cox proportional hazards analysis revealed no significant difference in the PFS benefit between the 2 age groups (HR=0.95; 95% confidence interval [CI]=0.65-1.37; p=0.76). Dose modifications were more frequent in the elderly cohort (63.9% vs. 46.5%; p=0.04).

Conclusion: PARPis significantly improved PFS in elderly ovarian cancer patients with BRCA mutations and HRD, with a toxicity profile similar to that of younger patients. Elderly patients benefited from frequent dose modifications without any negative impact on PFS outcomes.

Objective: Cervical cancer (CCa) significantly affects female fertility and quality of life. This study aimed to construct and validate a random survival forest (RSF) model to identify the factors that affect the overall survival (OS) in patients with CCa in China and compare its performance with that of the Cox proportional hazards model (Cox model).

Methods: Data on CCa patients were collected from Chongqing University Cancer Hospital. The performance and discrimination ability of the models were evaluated via the C-index, integrated Brier score (IBS), accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The Kaplan-Meier (K-M) survival curve was used to analyze the difference in OS between patients with high and low risk predicted by RSF model.

Results: A total of 3,982 patients were included in this study. Comparing to Cox model, the RSF model ranked important variables and identified radiotherapy (RT) as an important treatment measure. A comprehensive analysis of the evaluation indices confirmed that the RSF model outperformed the Cox model (IBS: 0.152 vs. 0.162, C-index: 0.863 vs. 0.764). The RSF model metrics for the validation cohort (VC) were as follows: 1-, 3-, and 5-year AUC (0.908, 0.884, and 0.869), sensitivity (0.746), specificity (0.825), and accuracy (0.808). The OS of low-risk patients predicted by RSF was greater than that of high-risk patients.

Conclusion: The RSF model demonstrated excellent discrimination, calibrated predictions, and stratified risk for CCa patients. Furthermore, it outperformed the Cox model in predicting risks, thus enabling the delivery of personalised treatment and follow-up strategies.

Objective: We aimed to 1) evaluate the efficacy of immune checkpoint inhibitors (ICIs) in cervical cancer patients according to the site of disease, 2) investigate the mechanism responsible for differential ICIs sensitivities with focuses on CD8⁺ T lymphocytes and programmed death-ligand 1 (PD-L1) expression.

Methods: We retrospectively reviewed clinical data from patients with recurrent or metastatic cervical cancer treated with pembrolizumab or cemiplimab between January 2019 and January 2024 (clinical cohort). Target diseases were classified according to the site of diseases: within previously irradiated field (in-field diseases), out-of-field diseases, and both. Immunohistochemical investigations were performed using paired tumor samples (i.e. initial cervical tumor and locally-recurrent tumor developed after definitive radiotherapy: Immunohistochemical cohort). Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test.

Results: Fifty patients treated with pembrolizumab-containing chemotherapies (n=39) or cemiplimab (n=11) were assessed. Of these, six patients (12.0%) had in-field diseases alone, twenty-eight patients (56.0%) had out-of-field diseases, and the remaining sixteen (32%) patients had both types of diseases. In-field diseases demonstrated a significantly lower response rate compared to out-of-field diseases (36.3% vs. 72.7%, p=0.004). Patients with in-field diseases demonstrated significantly shorter progression-free survival (p=0.003) and overall survival (p=0.003) than those with out-of-field diseases. In-field diseases were associated with decreased tumor-infiltrating CD8⁺ T lymphocytes and PD-L1 expression.

Conclusion: In-field cervical cancer recurrence was associated with decreased sensitivity to ICIs-containing chemotherapies when compared to out-of-field diseases. Decreased tumor-infiltrating CD8⁺ T lymphocytes and PD-L1 expression are possible reasons for this differential sensitivity to ICI-containing chemotherapies.

The incidence of endometrial cancer (EC) is unfortunately increasing. Often diagnosis is made at an early stage and surgery is the curative treatment. Nevertheless, adjuvant treatment is proposed to reduce the risk of relapse. This treatment is tailored based on the extent of the disease, such as the presence of distant metastasis, the extent of involvement of adjacent organs or lymph nodes. However, histological parameters such as myometrial invasion, substantial lymphovascular space invasion, invasion of the cervical stroma or tumor grade are also key to selecting adjuvant treatment. The Cancer Genome Atlas (TCGA) project has demonstrated the superiority of molecular classification over histological evaluation in EC to determine the prognosis. The International Federation of Gynecology and Obstetrics 2023 staging for EC is the first staging system that has incorporated molecular biomarkers on top of morpho-histological classification. Currently, all patients should have a molecular profile of their tumor and a lymph node assessment. The landmark treatment of stage I-III ECs is surgery followed by radiotherapy. The European guidelines updated in 2025 has divided EC in 4 risk categories with specific adjuvant treatment. For clinicians, it is seen as a complex landscape from surveillance to chemo-radiotherapy. Therefore, we propose here a practical pocket guideline for adjuvant treatment of early-stage EC patients based on a review of the different clinical trials in the adjuvant setting and on existing guidelines. This pocket guideline may also serve as a base for incorporation of new clinical trials under the RAINBO umbrella research program.

Objective: The role of systematic pelvic and para-aortic lymphadenectomy (PPAL) in completion staging surgery for early-stage (stage I-IIA) ovarian cancer (EOC) remains controversial. This study evaluates the impact of PPAL on the prognosis of EOC patients.

Methods: A retrospective cohort study was conducted using data from the Surveillance, Epidemiology, and End Results database. Patients with EOC (stage I-IIA) were included. Propensity score matching (PSM) was used at a 1:1 ratio based on age, marital status, race, tumor grade, histological type, FIGO stage, and postoperative adjuvant therapy. Post-matching overall survival (OS) and cancer-specific survival (CSS) were compared between the systematic PPAL group (pathological staging) and the non-lymphadenectomy group (clinical staging).

Results: After PSM, no significant differences were observed in OS (p=0.140) and CSS (p=0.066) between the two groups. Subgroup analysis showed that for tumor grade III patients, the pathological staging group had significantly higher OS (p=0.028) and CSS (p=0.010) than the clinical staging group. Multivariate Cox regression indicated that tumor grade III was an independent prognostic factor for OS (p=0.006) and CSS (p=0.020).

Conclusion: Systematic PPAL does not significantly improve survival in EOC patients. However, for tumor grade III patients, the pathological staging group demonstrates significantly better prognosis, offering a more personalized alternative to routine staging surgery, which requires further validation through prospective trials.

Objective: The emergence of drug resistance brings new challenges to the clinical management of ovarian cancer (OC) patients. This study aimed to explore the role and mechanism of ubiquitin-specific peptidase 7 (USP7) on the bevacizumab resistance of OC.

Methods: The mRNA levels of USP7 and protein tyrosine kinase 2 (PTK2) were measured using quantitative real-time polymerase chain reaction. Western blot analysis was used for detecting the protein levels of USP7, PTK2 and fused in sarcoma (FUS). Cell resistance, proliferation, apoptosis, invasion and angiogenesis were determined by cell counting kit 8 assay, colony formation assay, flow cytometry, transwell assay and tube formation assay. Glucose consumption, lactate production, and ATP/ADP ratio were used to evaluate glycolysis. The interactions between USP7 and PTK2/FUS were detected by co-immunoprecipitation assay. Mice xenograft model was also constructed to explore USP7 roles in vivo.

Results: USP7 was upregulated in OC tissues and bevacizumab-resistant cells. USP7 knockdown or its inhibitor P22077 inhibited the bevacizumab resistance of OC cells via suppressing cell growth, metastasis, angiogenesis and glycolysis. USP7 stabilized PTK2 protein expression via deubiquitinating. PTK2 overexpression reversed the effect of USP7 knockdown on the bevacizumab resistance of OC cells. Besides, FUS stabilized USP7 mRNA to regulate its protein level, and it could affect PTK2 expression by mediating USP7. USP7 knockdown enhanced the sensitivity of OC tumors to bevacizumab in vivo.

Conclusion: FUS-stabilized USP7 enhanced the bevacizumab resistance of OC by deubiquitinating PTK2, providing a new idea for overcoming bevacizumab resistance in OC.

Objective: Genomic instability has been identified in a subgroup of endometrial cancers (ECs) that are predominantly TP53 mutated (TP53mut). We report the features associated with loss-of-heterozygosity (LOH) in EC.

Methods: We conducted a retrospective analysis of EC patients from France and Singapore. All patients underwent comprehensive molecular profiling using the tumor based FoundationOne CDX panel. The degree of LOH was correlated with molecular and clinicopathologic findings. LOH-high, intermediate and low were defined as ≥14%, 4%-14%, and <4%, respectively.

Results: One hundred twelve patients were identified, including 66% Asian and 34% Caucasian. Fifty nine percent had International Federation of Gynecology and Obstetrics III/IV diseases, 34% low-grade endometrioid, 19% high-grade endometrioid, and 15% serous. The 63% and 50% of tumors expressed estrogen receptor (ER) and progesterone receptor (PR). One percent had a POLE mutation, 18% were microsatellite instability (MSI)-, 40% TP53mut and 41% non-specific molecular profiles. The 17% of patients were classified LOH-high, 37% LOH-intermediate and 46% LOH-low. LOH-high was significantly associated with serous and carcinosarcomas, ER/PR negative tumors, TP53 mutations, BRCA1 mutations and TERC amplification whereas LOH-low with low-grade endometrioid, MSI, ARID1A, PIK3CA, CTNNB1, and PTEN mutations. The median overall survival was 42.2, 55.2, and 100.8 months in the LOH-high, intermediate, and low respectively (p=0.034). Among TP53mut EC, LOH-low patients had significantly poorer outcomes (p<0.001).

Conclusion: In this large multiethnic cohort, 17% of EC exhibited high LOH and correlated with hormone-receptor-negative tumors and poorer survival rates. LOH may serve as a tool for identifying EC cases with high genomic instability that could potentially benefit from PARP inhibitors.

Objective: Rare studies focused on patients with incidental diagnosis of endometrial cancer (EC) after hysterectomy. We intended to construct a prediction model of lymph node metastasis (LNM) based on Fully-Connected Network (FC Network) for these patients.

Methods: A total of 3,920 cases of EC that met the criteria from Obstetrics & Gynecology Hospital of Fudan University between January 2016 and February 2023 and 1995 cases from Fudan University Shanghai Cancer Center between January 2013 and October 2020 were retrospectively included for the construction of a predicting model which was based on FC Network. At the same time, 572 cases were prospectively collected for external validation.

Results: The sensitivity of the model was 0.946. Lympho-vascular space invasion, myometrial invasion, tumor grade, microcystic elongated and fragmented invasion, progesterone receptor, and cancer antigen 125 were used to construct a simplified nomogram. The area under the curve of the nomogram was 0.890 and 0.885 in validation and prospective cohorts, respectively.

Conclusion: The model we proposed has good sensitivity and can be used to predict the risk of LNM in patients with incidentally found EC. The simplified nomogram can be used as a substitute in certain situations. Based on another study, the threshold of 5% and 25% can be used for risk stratification.

Background: Although recent clinical trials proved survival benefit from the addition of immune checkpoint inhibitors to standard chemotherapy, treatment of mismatch repair-proficient (pMMR) advanced or recurrent endometrial cancer (arEC) is challenging. As poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effects of immune checkpoint inhibitors when combined, improvement of survival is expected by dual maintenance in this population. The PENELOPE trial will investigate the efficacy and safety of dual maintenance with nesuparib, an orally active PARP1/2 and tankyrase 1/2 inhibitor, and pembrolizumab after paclitaxel/carboplatin plus pembrolizumab (TCP) treatment in patients with pMMR arEC.

Methods: In this multicenter, randomized, open-label, non-comparative phase II trial, patients with pMMR arEC, naïve to first-line chemotherapy, will be enrolled. Six patients will be enrolled in stage 1 (safety run-in) and treated with TCP for 6 cycles followed by dual maintenance with nesuparib and pembrolizumab. The study will proceed to stage 2 (dose expansion) if less than 33% of patients in stage 1 experience a dose-limiting toxicity. Otherwise, additional patients will be enrolled in stage 1 at a lower dose level. In stage 2, 80 patients will be randomized (1:1) to: arm A) TCP followed by maintenance with pembrolizumab; arm B) TCP followed by dual maintenance with nesuparib and pembrolizumab. Patients are planned to receive maintenance treatment up to 14 cycles every 6 weeks. Primary endpoint is investigator-assessed progression-free survival (Response Evaluation Criteria in Solid Tumors 1.1) of each arm vs. historical control, which is the placebo arm for pMMR patients in the NRG-GY018 study, and key secondary endpoints are overall survival, overall response rate, disease control rate, duration of response, and safety. Enrollment began in Q4 2024.

Trial registration: ClinicalTrials.gov Identifier: NCT06502743.