Journal of Gynecologic Oncology最新文献

Objective: Recent advancements highlight promising outcomes with immune checkpoint inhibitors (ICIs) when combined with concurrent chemoradiotherapy (CCRT) or chemotherapy in the treatment of locally advanced cervical cancer (LACC). This systematic review and meta-analysis aimed to assess the efficacy and safety of ICIs combined with CCRT/chemotherapy in patients with LACC.

Methods: We searched PubMed, Embase, Cochrane and ClinicalTrials.gov for randomized controlled trials (RCTs) and non-RCTs assessing the efficacy and safety of ICIs plus CCRT/chemotherapy in patients with LACC. All analyses were performed in R software (v.4.4.0).

Results: Our systematic review and meta-analysis included 3 RCTs and 4 observational studies, corresponding to 1,250 patients. The 1-year progression-free survival (PFS) was 78% (95% confidence interval [CI]=75-80, I²=0%), while the 1-year overall survival (OS) reached 93% (95% CI=89-95, I²= 50%). The objective response rates were 88% (95% CI=74-95, I²=74%). We performed a comparative analysis of PFS and OS using data from the 2 RCTs. The results indicated that the ICI plus CCRT group had a significantly lower risk of disease progression or death compared to the CCRT group alone (PFS: hazard ratio [HR]=0.76, 95% CI=0.64-0.91, I²=4%; OS: HR=0.76, 95% CI=0.58-0.98, I²=0%), representing an approximate 25% reduction in risk. The analysis of grade ≥3 adverse events revealed the low incidences, with none exceeding 15%.

Conclusion: Our findings suggest that ICIs are effective and safe to use with CCRT/chemotherapy in LACC patients. Further RCTs are needed to confirm these findings.

Trial registration: International Prospective Register of Systematic Reviews Identifier: CRD42024576145.

Objective: Adult-type granulosa cell tumors of the ovary (aGCTs) show ambiguous morphology and may be misdiagnosed as other tumors. Recently, heterozygous FOXL2 C402G mutations and TERT promoter C228T mutation have been reported as diagnostic and prognostic biomarkers of aGCTs. The objective of this study was to identify the characteristics of true aGCT cohort using these biomarkers in 72 aGCT samples.

Methods: FOXL2 and TERT promoter mutational statuses of 64 primary and matched 8 recurrent aGCT samples were assessed. Non-aGCTs were excluded by the combination of FOXL2 mutational analysis and the pathological review. The characteristics and prognosis of molecularly/pathologically confirmed aGCTs (MP-aGCTs) were analyzed.

Results: Of 18 FOXL2 wild-type (WT) tumors, 3 were excluded as they were of other histotype. None of 20 samples with the FOXL2 C402G mutation include other histotype. Clinical stage and age were prognostic factors for recurrence. Of the 61 MP-aGCTs, 46 harbored FOXL2 C402G mutation (44 heterozygous, 2 homozygous/hemizygous) and 15 had WT FOXL2. The presence of the FOXL2 mutation was associated with a worse prognosis. The mutational status of the TERT promoter in MP-aGCTs was 10 heterozygous and 51 WT. The TERT promoter mutation was highly identified in older patients and in larger tumors but had no prognostic impact.

Conclusion: This is the first study to clearly demonstrate its practical application of FOXL2 in the diagnosis of aGCTs. Application of the molecular analysis to a large aGCT cohort is crucial for understanding true characteristics and establishing novel treatment strategy of this disease.

Objective: We aimed to compare the oncological outcomes of patients with bilateral sentinel lymph nodes (SLNs) detection and removed with those who underwent pelvic lymphadenectomy (PLA) in addition to bilateral SLNs removal.

Methods: This multicenter, retrospective study included cases of endometrioid type, grade I-II endometrial cancer, in which bilateral SLNs were detected and removed. Patients who had only bilateral SLNs detected and removed (group I) and patients who had bilateral SLNs detected and removed and subsequent additional bilateral PLA (group II) were included in the evaluation.

Results: In group I (n=216), SLN metastasis rate was 5.5% and in group II (n=251), it was 10.3%. The low-volume disease detection rate was 4.6% in group I and 4.8% in group II. In group II, in patients with SLN macrometastasis had also 28.6% non-SLN macrometastasis. No false-negative results occurred in group II. Recurrence was detected 1.8% in group I and 5% in group II; however, there was no significant difference (p=0.083). Disease-free survival and overall survival, were almost same between the groups (hazard ratio [HR]=2.11; 95% confidence interval [CI]=0.681-6.588; p=0.187) and (HR=1.531; 95% CI=0.392-5.975; p=0.537), respectively.

Conclusion: SLN mapping, ultrastaging, and immunohistochemical staining can identify low-volume metastases that may not be identified with classic lymphadenectomy and hematoxylin & eosin staining. It has been observed that adding PLA beyond SLN mapping did not provide an additional positive contribution to survival. For endometriod type grade I-II patients, detection of bilateral SLNs in both hemipelvis only, if detectable, is an adequate approach.

Objective: To assess the necessity of restaging surgery for patients with suspected International Federation of Gynecology and Obstetrics (FIGO) stage I-II epithelial ovarian cancer (EOC) following incomplete surgical staging.

Methods: This multicenter retrospective study evaluated patients with early-stage EOC referred for restaging. These patients were diagnosed with suspected FIGO stage I-II EOC between January 2007 and November 2022 after incomplete surgical staging, and no residual region was confirmed by radiological evaluation. Progression-free survival (PFS) and overall survival (OS) were examined.

Results: Among the 173 patients included in the study, 56 were assigned to the no restaging surgery group, and 117 to the restaging surgery group. After restaging, 23 were upstaged to other main stage. However, PFS and OS were not significantly different between the groups, also, dividing the groups into 4 groups who underwent chemotherapy and those who did not also did not show significant differences. In multivariate analysis, histologic grade independently influenced PFS outcomes.

Conclusion: While restaging surgery resulted in upstaging in some patients, it was not associated with significant differences in PFS or OS in this retrospective analysis. However, the omission of any additional treatment warrants careful consideration and further discussion. Nevertheless, the observation that patients who did not undergo restaging surgery but received adjuvant chemotherapy did not show significantly different prognoses highlights the need for further research to establish appropriate treatment strategies tailored to diverse patient contexts.

Objective: Our aim was to assess the potential correlation between resection-free margin and local recurrence in the treatment of squamous cell vulvar carcinoma (SCC).

Methods: Seventy-five patients with primary SCC of the vulva and adequately follow-up that were operated in our university hospital between January 2008 to December 2018, were retrospectively evaluated with focus on resection-free margin and its impact on local recurrence. Several prognostic factors were analysed for possible correlation.

Results: Median patient age and follow-up was 62.8 years and 57.4 months, respectively. Among all patients, 27 (36%) local recurrences were documented, for a median local recurrence-free survival (LRFS) of 68.1 months for patients resected R0 and 65.6 months for those initially R1 resected (p=0.750). There was also no statistically significant difference (p=0.750) when evaluating the LRFS relative to the absence or not of inguinal lymph node involvement, although there was a numerical difference of approximately 17 months (73.9 vs. 57.3 months). For initially R0 resected patients, no significant influence of the resection-free margin in millimeters on LRFS was noted for a median of 58.4 versus 57.3 months for patients with a free margin of 0.1-3 mm and those with a free margin of >3 mm, respectively (p=0.800). Eleven patients received adjuvant chemoradiotherapy, all for nodal inguinal involvement. Among them, 5 patients developed recurrence, while the other 6 remained free of disease.

Conclusion: The extend of resection-free margin does not appear to adversely affect LRFS suggesting that smaller margins could be applied to minimize morbidity without compromising local control.

Objective: Intraoperative frozen section examination is crucial for confirming the oncological safety of radical abdominal trachelectomy (RAT) for early-stage cervical cancer. This study evaluated the diagnostic accuracy of frozen section during RAT at our institution.

Methods: We retrospectively identified patients with International Federation of Gynecology and Obstetrics 2008 stage IA1-IB1 (tumor size ≤2 cm) cervical cancer treated between 2002 and 2021. In performing RAT, frozen section analysis was routinely performed on uterine surgical margins and grossly enlarged lymph nodes, and was confirmed to be negative. Medical records were reviewed to compare the frozen section diagnoses with the final pathology.

Results: Among the 326 patients initially planned to undergo RAT, 298 (91.4%) underwent RAT, while 28 (8.6%) were converted to radical hysterectomy. The histological types were squamous cell carcinoma in 251 (77.0%) patients and adenocarcinoma in 67 (20.6%). Of 361 frozen section for surgical margins, 4 false negatives were identified. Discrepancies were due to freezing artifacts, staining quality on frozen sections, and slight differences in cross-sections between frozen and paraffin-embedded sections. Among 446 intraoperative lymph-node biopsies, one false-negative was recorded. Sensitivities of frozen section examination were 93.5% (58/62) for surgical margins and 94.1% (16/17) for lymph nodes. Lymph-node metastases were identified in systematic lymphadenectomy specimens of 21/326 (6.4%) patients planned to undergo RAT, with 10/21 (47.6%) detected intraoperatively. Lymph-node metastases were found in 7/112 (6.3%) patients without lymph-node biopsy.

Conclusion: Frozen section examination during RAT provides satisfactory diagnostic performance, although biopsy of grossly enlarged lymph nodes is an unreliable method.

Objective: Radical hysterectomy with pelvic lymph node dissection is the treatment of choice for cervical cancer. All gynecologic oncologists should master this technique. The surgical procedure requires a wide dissection of the female pelvis. Performing radical hysterectomy without a thorough knowledge of the anatomy of the female pelvis can lead to serious complications. For novice surgeons to safely perform radical hysterectomy, mastering the 3-dimensional anatomy of the pelvis and aligning the dissection lines of radical hysterectomy to the female pelvic anatomy is crucial. Educational materials that demonstrate the anatomical relationship between dissection lines in radical hysterectomy and the surrounding pelvic structures are lacking. We aimed to create educational material to overcome these problems.

Methods: Laparoscopic nerve sparing, non-nerve sparing, and super-radical hysterectomies, exposing pivotal pelvic anatomical structures, were performed on a Thiel-embalmed cadaver.

Results: Nerve sparing, non-nerve sparing, and super-radical hysterectomies were laparoscopically performed in the right hemi-pelvis of the cadaver. We exposed the external and internal iliac vessels; obturator, sciatic, femoral, hypogastric, and pelvic splanchnic nerves and the pelvic nerve plexus; internal obturator, piriform, and coccygeal muscles; sacrospinous ligament; and ischial spine. Thus, we demonstrated where the dissection lines of the various radical hysterectomies are in a female pelvis.

Conclusion: Using a Thiel-embalmed cadaver, we demonstrated the relationship between the dissection lines of various radical hysterectomies and pivotal sidewall anatomical structures in a female pelvis. The anatomical detail shown in the video captured during this procedure may assist surgeons to safely perform various radical hysterectomies.

Objective: To develop and externally validate a machine learning-based preoperative model integrating molecular typing and clinical features to predict lymph node metastasis (LNM) in patients with early-stage endometrial carcinoma (EC).

Methods: This retrospective study included 465 patients with clinically early-stage EC treated at Qilu Hospital of Shandong University. Tumors were classified into molecular subtypes using The Cancer Genome Atlas-based methods. Least Absolute Shrinkage and Selection Operator regression identified five preoperative predictors: molecular typing (CN-H vs. non-CN-H), histological subtype, depth of myometrial invasion, neutrophil-to-lymphocyte ratio, and CA125 levels. Multiple machine learning algorithms were evaluated, and logistic regression (LR) was selected based on optimal discrimination and clinical applicability. Model performance was assessed using area under the curve (AUC), calibration plots, and decision curve analysis (DCA). A web-based nomogram was developed for clinical use.

Results: The LR model demonstrated excellent discrimination, with AUCs of 0.843 in the training cohort and 0.809 in the testing cohort. The CN-H subtype was significantly associated with increased LNM risk. The model enabled effective risk stratification and calibration curves and DCA confirmed the model's accuracy and clinical utility.

Conclusion: By integrating molecular and preoperative clinical features, this model offers accurate LNM risk stratification for early-stage EC. It supports clinical decision-making and has been implemented as a user-friendly online tool. Further prospective multicenter validation is warranted.

Objective: More efficient immune targets are needed for the treatment of cervical cancer. This study aimed to identify potential targets for immunotherapy and prediction in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) by conducting bioinformatics analysis and verifying the results with clinical tissue samples.

Methods: A retrospective analysis of RNA sequencing data from 304 patients sourced from The Cancer Genome Atlas (TCGA) and another 300 patients from the Gene Expression Omnibus (GEO) was performed to investigate the correlation between suppressor of TCR signaling 2 (Sts-2) expression and clinical parameters in cervical cancer. To authenticate our findings, we utilized a combination of immunohistochemistry, quantitative polymerase chain reaction, and western blotting techniques in a separate cohort consisting of 6 cervical cancer tissue samples.

Results: The Sts-2 gene was discovered to be substantially co-expressed with a multitude of immune checkpoint molecules, including programmed cell death protein 1 (r=0.8, p<0.001), TIGIT (r=0.87, p<0.001), LAG3 (r=0.71, p<0.001), and CTLA4 (r=0.74, p<0.001), in CESC patients. Both the TCGA and GEO datasets have independently validated that Sts-2 expression levels significantly correlate with overall survival rates, thus demonstrating its prognostic importance. A single-gene Gene Set Enrichment Analysis indicated that Sts-2 was highly enriched in T cell-related immune pathways. Moreover, using the Tumor Immune Dysfunction and Exclusion algorithm, it was suggested that high Sts-2 expression might predict a more favorable response to immunotherapy.

Conclusion: The heightened expression of Sts-2 serves as a dual indicator of elevated T cell content and a favorable prognosis in cervical cancer.