Journal of Gynecologic Oncology最新文献

Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer.

Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing.

Results: Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11-0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016).

Conclusion: High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.

Objective: The study aimed to establish humanized patient-derived xenograft (PDX) mouse models of ovarian clear cell carcinoma (OCCC) and evaluate their therapeutic responses.

Methods: PDX models and their humanized counterparts (CD34+ humanized PDX models) derived from the same tumor source were developed, and the therapeutic responses were compared between the models.

Results: Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor significantly reduced tumor size in traditional OCCC PDX models (p=0.021). Although differences in tumor growth between traditional PDX models and humanized PDX models were observed, they were not statistically significant (p=0.438). However, treatment effects of PI3K inhibitor differed significantly between conventional and humanized mice (p=0.006). In the Humanized PDX cohort, both programmed cell death protein-1 antibody monotherapy and PI3K inhibitor treatment slowed tumor growth relative to controls, with a synergistic effect noted during the latter part of the study, though these effects were not statistically significant.

Conclusion: This pioneering study successfully develop a humanized PDX model for OCCC, highlighting differential responses to treatments compared to conventional PDX models.

Objective: A retrospective, multi-center propensity score-matched (PMS) analysis was conducted to investigate the efficacy and safety of the treatment strategy that combines bevacizumab and chemotherapy for patients with relapsed epithelial ovarian cancer (EOC) who previously received poly ADP-ribose polymerase inhibitors (PARPis).

Methods: A total of 250 ovarian cancer (OC) patients relapsed after PARPi received chemotherapy with or without bevacizumab at 4 medical centers were enrolled in the study. For both treatments, Kaplan-Meier analysis and Cox regression were used to compare PFS.

Results: In the multivariable analysis of 250 patients, the incorporation of bevacizumab into chemotherapy demonstrated a significant enhancement in PFS (hazard ratio [HR]=0.49; 95% confidence interval [CI]=0.34-0.72; p<0.001). Fifty-five patients were enrolled in Group A (bevacizumab combined with chemotherapy) and 55 were enrolled in Group B (chemotherapy alone regime) after PSM analysis. A statistically significant difference in PFS was observed between the 2 regimens (HR=0.62; 95% CI=0.40-0.97; p=0.036), suggesting that the bevacizumab combined with chemotherapy regimen confers superior clinical benefits. The median PFS was 11 months in Group A and 9 months in Group B. A significant variation was noted in PFS between patients without RCRS (HR=0.50; 95% CI=0.30-0.82) and the platinum-resistant subgroup (HR=0.31; 95% CI=0.14-0.68). Adverse effects of Grade 3-4 were more prevalent in Group A than in Group B. Additionally, instances of severe hypertension and bowel perforation were reported solely within Group A.

Conclusion: In patients diagnosed with EOC relapsed after PARPi, the regime of chemotherapy combined with bevacizumab is associated with better PFS.

Objective: This study aimed to assess the diagnostic performance of the Risk of Ovarian Malignancy Algorithm (ROMA), Copenhagen Index (CPH-I), and Ovarian Adnexal Reporting and Data System (O-RADS) for the preoperative prediction of ovarian cancer (OC).

Methods: A prospective cohort study was conducted on 462 patients diagnosed with ovarian tumors admitted to the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital, and Hue Central Hospital from May 2020 to December 2022. ROMA and CPH-I were calculated using cancer antigen 125 (CA125), human epididymal protein 4 (HE4) levels, and patient characteristics (age and menopausal status). O-RADS criteria were applied to describe ovarian tumor characteristics from ultrasound findings. Compared with histopathological results, the predictive values of ROMA, CPH-I, and O-RADS alone or in combination with CA125/HE4 for OC were calculated.

Results: Among 462 patients, 381 had benign tumors, 11 had borderline tumors, and 50 had OC. At optimal cut-off points, ROMA's and CPH-I's areas under the curves (AUCs) were 0.880 (95% confidence interval [CI]=0.846-0.909) and 0.890 (95% CI=0.857-0.918), respectively, and ROMA and CPH-I sensitivities/specificities (Se/Sp) were 68.85%/95.01% and 77.05%/91.08%, respectively. O-RADS ≥3 yielded an AUCs of 0.949 (95% CI=0.924-0.968), with Se/Sp of 88.52%/88.98% (p<0.001). Combining O-RADS with CA125 demonstrated the highest predictive value, with AUCs of 0.969 (95% CI=0.949-0.983) and Se/Sp of 98.36%/86.09% (p<0.001).

Conclusion: The ROMA, CPH-I, O-RADS, O-RADS + CA125, and O-RADS + HE4 models demonstrated good predictive values for OC; the combination of O-RADS and CA125 yielded the highest values.

Objective: This study aims to explore the role of SH2D3A in cervical cancer, as well as its potential interaction with human papillomavirus (HPV) E7 and microRNA (miRNA).

Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to compare the expressions of SH2D3A in tissues. To assess the effects of SH2D3A on cervical cancer cell phenotypes, SH2D3A was knocked down in SiHa and HeLa cells, followed by cell proliferation (Cell Counting Kit-8 assay), apoptosis (flow cytometry), and invasion (Transwell assay) analyses. A transplantation tumor model was established to compare the tumorigenic ability of cervical cancer cells before and after SH2D3A silencing. Bioinformatics analysis predicted and dual-luciferase reporter assays verified the sponge adsorption effect of SH2D3A on miRNA. Western blot and qRT-PCR analyses were conducted to examine the impact on target genes following the downregulation of HPV E7 and SH2D3A.

Results: SH2D3A expression was significantly elevated in cervical cancer tissues. SH2D3A silencing inhibited cell proliferation and invasion, induced apoptosis, and reduced tumorigenesis in nude mice. Bioinformatics tools identified a binding relationship between SH2D3A and miR-143-3p, confirmed by the luciferase reporter assays. Western blot analysis revealed that SH2D3A knockdown led to decreased levels of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) proteins. Additionally, qRT-PCR showed that SH2D3A mRNA levels decreased after HPV E7 silencing, whereas miR-143-3p levels significantly increased.

Conclusion: HPV E7 influences SH2D3A expression through miR-143-3p, thereby regulating the JAK1/STAT3 pathway. This mechanism promotes the occurrence and development of cervical cancer.

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries, and endometrial intraepithelial neoplasia (EIN) is the defined precancerous lesion. Obesity is considered a risk factor for both EC and EIN. On the other hand, mortality is often attributed to obesity-related conditions in patients with early-stage EC. Bariatric surgery has been shown to improve oncological outcomes and obesity-related morbidity and mortality in patients with EC. Therefore, combination surgery addressing both uterine disease and obesity is a very recent point of interest. Here, we present a video article to demonstrate the crucial surgical steps for a simultaneous robotic-assisted total laparoscopic hysterectomy and sleeve gastrectomy in a patient with super obesity and EIN. A patient in her 40s with a body mass index of 62.4 kg/m² and a diagnosis of EIN was scheduled for combo surgery. The operation started with sleeve gastrectomy in the reverse Trendelenburg position. The da Vinci Xi Surgical System™ (Intuitive Surgical Inc., Sunnyvale, CA, USA) with left-side docking was used for surgery. After the mobilization of the stomach, gastric resection was performed using a stapler. Following sleeve gastrectomy, the patient was positioned in the Trendelenburg position, and the robotic system was positioned for hysterectomy. Hysterectomy and salpingectomy were performed. The excised stomach and hysterectomy material were removed through the vagina. A frozen examination revealed EC below 2 cm with superficial invasion, and bilateral oophorectomy was performed. The whole surgery took approximately 4 hours. No postoperative complications occurred, and the patient was discharged on the 3rd day.

Objective: The pathogenesis of endometrial cancer (EC) and hyperplasia is complex and poorly understood. Autophagy has emerged as a crucial aspect of this process.

Methods: This study examines the role of autophagy in the pathogenesis of EC and hyperplasia by investigating the expression of the autophagy-related 4B cysteine peptidase (ATG4B) gene, protein, and miR-665-3p levels in patients compared to a control group. This cross-sectional case control study analyzed 90 endometrial tissues, including 30 tumors, 30 normal controls, and 30 hyperplasia, using quantitative reverse transcription polymerase chain reaction and Western blot to assess ATG4B gene and protein levels.

Results: Higher ATG4B gene expression levels were found in the endometrial tissue of EC patients than in hyperplasia patients and controls. Furthermore, protein levels of ATG4B were also higher in EC and hyperplasia patients than in controls. ATG4B gene expression and protein levels were positively correlated in EC patients. However, in EC patients, miR-655-3p showed a significant negative correlation with the ATG4B gene and protein levels.

Conclusion: ATG4B gene and protein expression is elevated in EC tissue, suggesting their role as a tumor promoter. Evaluating their levels could serve as markers for monitoring EC progression and prognosis.

Objective: To evaluate the cost-effectiveness of tisotumab vedotin to treat recurrent or metastatic cervical cancer in second- or third-line from the U.S. payer perspective.

Methods: A Markov model with three-state was employed to simulate recurrent or metastatic cervical cancer patients who were administered either tisotumab vedotin or investigator's choice of chemotherapy based on the phase III, open-labeled innovaTV 301 randomized clinical trial. The data on cost and health preferences were collected from the literature.

Results: Tisotumab vedotin generated an additional 0.25 quality-adjusted life-years (QALYs) compared to chemotherapy, but at an additional cost of $206,779. This results in incremental cost-effectiveness ratios of $839,107.88 per QALY. The results of the univariate sensitivity analysis indicated that cost of tisotumab vedotin, utility of progressive disease and progression-free survival had the greatest impacts on the outcomes. Probability sensitivity analysis showed that tisotumab vedotin had a 0% chance of being considered cost-effective.

Conclusion: Tisotumab vedotin was unlikely cost-effective compared to chemotherapy for recurrent or metastatic cervical cancer patients at a willingness-to-pay threshold of $150,000/QALY from the perspective of a U.S. payer. Lowering the prices of tisotumab vedotin could potentially enhance its cost-effectiveness.