Journal of Gynecologic Oncology最新文献

Objective: To investigate whether neuroendocrine carcinoma of the cervix (NECC) with coexisting non-neuroendocrine tumor components (mixed subtype) is associated with a worse prognosis compared to the pure subtype.

Methods: A total of 121 patients diagnosed with NECC at 4 participating hospitals in the Republic of Korea between August 1997 and November 2023 were included. All diagnoses were confirmed through surgical specimens obtained via conization or hysterectomy. Clinical and pathological variables were collected through medical record review. The association between tumor heterogeneity (pure vs. mixed subtype) and progression-free survival (PFS) was analyzed using a Cox proportional hazards model.

Results: The majority of patients was diagnosed at stage I (62%), had small cell histology (63%), and presented with the pure subtype (66%). Most patients (n=106) underwent surgery with or without adjuvant therapy as initial treatment. In univariate analysis, there was no significant difference in PFS between the pure and mixed subtypes (p=0.952). However, after adjusting for covariates, the mixed subtype was significantly associated with worse PFS compared to the pure subtype (adjusted hazard ratio=3.16; 95% confidence interval=1.58-6.35; p=0.001).

Conclusion: NECC with non-neuroendocrine components is associated with significantly worse prognosis than the pure subtype.

Objective: Protoporphyrin IX, a metabolite of 5-aminolevulinic acid (5-ALA), emits red fluorescence. Photodynamic diagnosis (PDD) using 5-ALA has been successfully applied in fluorescence-guided surgery for various malignancies. This pilot study directly compared the diagnostic performance of conventional white light (WL) inspection and 5-ALA-based PDD for detecting intraperitoneal dissemination in advanced ovarian cancer (OC).

Methods: This prospective single-center study included patients with advanced OC undergoing staging laparoscopy. Each patient received oral 5-ALA (20 mg/kg) 4 hours preoperatively. Tumor and non-tumor locations were identified under WL and fluorescent light (FL). Biopsy specimens were collected from tumor locations visible under both WL and FL, only under WL, and only under FL and from non-tumor locations visible under both WL and FL. Pathological examination confirmed malignancy, and results were correlated with imaging findings.

Results: Seven patients were enrolled between January and March 2019 and 71 biopsies were performed. The diagnoses included four cases of high-grade serous carcinoma, one clear cell carcinoma, one grade 3 endometrioid carcinoma, and one pseudomyxoma peritonei. The sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy under WL were 87.8%, 59.0%, 82.7%, and 68.4%, respectively, compared with 96.0%, 90.5%, 96.0%, and 90.5% under FL. Additional metastatic lesions were identified in three patients subjected to 5-ALA imaging. No severe 5-ALA-related adverse events were observed.

Conclusion: 5-ALA-based PDD demonstrated higher diagnostic accuracy than WL for detecting intraperitoneal dissemination of advanced OC. Its ability to enhance tumor detection may improve surgical precision and outcomes.

Background: Gastric-type endocervical adenocarcinoma (G-EAC) is a distinctive form of adenocarcinoma that is not associated with human papillomavirus. This neoplasm exhibits a low incidence, low screening and biopsy positivity, low preoperative diagnosis, and a high susceptibility to underdiagnosis and misdiagnosis. It is associated with a poor prognosis for patients. Currently, there is an absence of a standardized postoperative adjuvant treatment plan for G-EAC, which constitutes an urgent clinical problem that demands resolution. However, there is still no prospective analysis on the adjuvant treatment of cervicogastric adenocarcinoma. This study is the first randomized phase III trial, which aims to recommend better adjuvant treatment options for G-EAC patients at high risk of recurrence in China, in order to better optimize and personalize patient care and improve progression-free survival (PFS) and overall survival (OS).

Methods: This trial is a prospective, multicenter study led by the Department of Radiotherapy, Women's Hospital of Zhejiang University. Recruitment will begin in March 2025, and it is expected that 238 patients with postoperative G-EAC with high risk of recurrence will be recruited from 16 clinical centers in China. Patients will be randomly assigned to the experimental group or the control group in a 1:1 ratio. The experimental group will receive paclitaxel combined with platinum-based concurrent chemoradiotherapy (CCRT) and short-term adjuvant chemotherapy, and the control group will receive the current standard treatment regimen, i.e., platinum-based CCRT, without adjuvant chemotherapy. The primary endpoint of the study is the 2-year PFS rate, and the secondary endpoints are disease treatment failure pattern, OS rate, acute/chronic toxicity incidence, and quality of life assessment.

Trial registration: ClinicalTrials.gov Identifier: NCT06870565.

Objective: This study aimed to assess prognosis related to poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy (MT) in newly diagnosed patients with advanced-stage epithelial ovarian cancer (adsOC, primary setting). Additionally, it evaluated the effect on recurrent patients after the front- or second-line PARPi MT (recurrence setting).

Methods: This multicenter retrospective study analyzed adsOC patients undergoing standard of care therapy (cytoreductive surgery and chemotherapy), regardless whether PARPi MT was followed or not from December 2011 to May 2023. The prognostic factors affecting survival outcomes (progression-free survival [PFS] and overall survival [OS]) in primary and recurrence settings were analyzed.

Results: A total of 218 patients were analyzed, including 25% with BRCAm, 13% with homologous recombination deficiency (HRD), and 62% with homologous recombination proficiency (HRP). The median follow-up was 35.5 months. In primary setting, International Federation of Gynecology and Obstetrics IIIC/IV, Eastern Cooperative Oncology Group (ECOG) >1, neoadjuvant chemotherapy, non-high-grade serous carcinoma (HGSOC) or non-endometrioid, HRP and absence of PARPi MT were associated with worse outcome. In recurrence setting, ECOG >1, platinum-resistance, non-HGSOC or non-endometrioid, non-BRCAm and previous PARPi MT were associated with poor prognosis. Rechallenge of PARPi in recurrent patients did not show statistically different outcome compared to those without PARPi.

Conclusion: Besides, the best survival occurring in adsOC patients with BRCAm, HRD patients treated with PARPi MT also experienced significantly prolonged PFS and OS. However, prior frontline PARPi MT was associated with poorer OS if the recurrence occurred. Treatment for recurrence status with PARPi MT did not show survival benefits.

Objective: This study aims to update the latest epidemiology of ovarian cancer.

Methods: Incidence and mortality data of ovarian cancer were extracted from 2 databases, the GLOBOCAN 2022 and the Global Burden of Disease 2021, to analyze age-standardized rates across 185 countries. The Age-Mortality-Population method and average annual per cent change (AAPC) were employed to calculate the lifetime risk of incidence (LRI) and lifetime risk of mortality (LRM), and to evaluate temporal trends (2000-2021) for ovarian cancer, respectively. Incidence cases and deaths of ovarian cancer were projected to 2050.

Results: The number of incidence cases and deaths of ovarian cancer is projected to rise from 300,000 and 200,000 in 2022 to 477,000 and 337,000 by 2050. Low sociodemographic index (SDI) countries are projected to experience increases of 153% in incidence and 165.2% in mortality, while high SDI countries are expected to see modest increases of 21.8% and 36.4%. The overall trend of LRI and LRM decreased from 2000 to 2021. However, LRI in high SDI countries declined from 1.6% to 1.2%, LRM from 1.1% to 0.85%; LRI in low SDI countries increased from 0.46% to 0.63%, LRM from 0.37% to 0.49%. AAPCs for LRI and LRM both increased by >1% in low and low-middle SDI countries, but declined by >1% in high SDI countries.

Conclusion: The incidence and mortality rates for ovarian cancer are expected to rise, but this burden is distributed unevenly across regions and SDI levels. The stark divergence underscores an urgent need for coordinated efforts to ensure equitable cancer care globally.

Objective: Vaginal stenosis (VS) is a common adverse effect of pelvic radiotherapy. Current guidelines recommend vaginal dilation to maintain tissue elasticity and prevent VS. Previously, patients were instructed to self-dilate using own fingers. The current study assessed the effectiveness of using a 3-dimensional (3D) printed vaginal dilator (VD) for mitigating vaginal narrowing and shortening in cervical cancer patients within 1 year after radiotherapy.

Methods: VDs were developed and validated by radiation therapists using a 3D printer. We enrolled 67 female patients diagnosed with cervical cancer at Chulabhorn Hospital to test the dilators. As a baseline, vaginal diameter and length were measured using the dilator before intracavitary radiotherapy. The patients were instructed on the use of VDs and provided with information guides and logbooks. Physical examinations were conducted at intervals of 1, 3, 6, 9, and 12 months post-radiotherapy.

Results: The patients' average age was 51.75 years (standard deviation=13.23). 57% of all patients were diagnosed with stage III squamous cell carcinoma, and 66% underwent concurrent chemoradiation therapy. With the use of dilators, patients exhibited shortened and narrowed vaginal canals at 9 months and 1 month after receiving radiotherapy treatment. Most patients went on to develop VS. However, in most cases patients exhibited grade 1 VS according to the Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic classification, with only 15.79% of patients exhibiting grade 2 VS.

Conclusion: The use of a VD could potentially lessen the severity of VS induced by radiotherapy/brachytherapy.

Trial registration: Thai Clinical Trial Registry Identifier: TCTR20250309001.

Objective: Epithelial ovarian cancer (EOC) has the highest mortality among gynecologic malignancies, with frequent recurrences despite initial responsiveness to platinum. Poly(ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, have improved progression-free survival in BRCA-mutated and homologous recombination-deficient EOC. However, emerging evidence suggests that prior exposure to PARP inhibitors may reduce the efficacy of subsequent platinum-based chemotherapy, raising concerns about treatment sequencing. To evaluate whether prior olaparib use affects the sensitivity to subsequent platinum-based chemotherapy in patients with recurrent platinum-sensitive ovarian cancer, and to explore potential predictive biomarkers such as the neutrophil-to-lymphocyte ratio (NLR).

Methods: We retrospectively analyzed 46 patients with recurrent ovarian cancer treated between 2008 and 2024. Patients were divided into an olaparib group (n=22) and a control group (n=24) without prior PARP inhibitor use. The primary endpoint was the difference between progression-free survival interval after second- and first-line therapy (PFS2 and PFS1). Secondary endpoints included time to first subsequent therapy (TFST)-time to second subsequent therapy (TSST) and correlations of NLR and CA125 with PFS2-PFS1.

Results: The olaparib group had a significantly shorter PFS2-PFS1 (mean 6.40 vs. 11.17 months, p=0.023). TFST-TSST was shorter in the olaparib group (7.73 vs. 11.46 months) but not statistically significant (p=0.156). NLR was inversely correlated with PFS2-PFS1, and was strongest at 4 months (r=-0.515) and 5 months (r=-0.624) post-treatment in the olaparib and control groups, respectively. CA125 showed no significant correlation.

Conclusion: Olaparib exposure may impair later chemotherapy efficacy. Careful treatment sequencing and biomarker development are warranted to optimize outcomes.

Objective: We compared the outcomes of adjuvant chemotherapy (CT) alone vs. adjuvant CT combined with radiation therapy (CRT) in patients with stage III endometrial cancer. All patients received 6 cycles of CT before radiation therapy (RT) were initiated. We also explored specific patient subgroups that might benefit from the addition of RT.

Methods: Between 2007 and 2019, we analyzed 118 patients after propensity score matching, with 59 patients in each group (CT alone vs. CRT). The primary endpoint was pelvic recurrence; the secondary endpoints were progression-free survival (PFS). We conducted exploratory subgroup analyses stratifying patients by stage, histological grade, lymphovascular space invasion (LVSI), and cervical involvement to assess whether these factors influenced outcomes between the 2 treatments.

Results: Patients receiving CRT had significantly lower 5-year pelvic recurrence rates than those receiving CT alone (1.8% vs. 17.9%; hazard ratio [HR]=0.09 [0.01-0.71]; p=0.004). There was no significant difference in 5-year PFS between the 2 groups overall (67.6% vs. 72.3%; HR=0.75 [0.39-1.46]; p=0.393). However, in high-risk _{subclass III} patients (stage IIIC, grade 3 endometrioid or non-endometrioid carcinoma, LVSI, and cervical involvement), CRT significantly improved 5-year PFS (62.5% vs. 90.9%; p=0.049) and 5-year pelvic recurrence rates (0% vs. 54.6%; p=0.008). No differences in distant recurrence or overall survival were identified.

Conclusion: Compared with CT alone, CRT improved pelvic control overall and significantly improved pelvic control and PFS in high-risk _{subclass III} patients. Therefore, RT may be considered for these subclasses to optimize treatment outcomes.

Objective: To compare the predictive performance of the International Federation of Gynecology and Obstetrics (FIGO) 2009 and FIGO 2023 staging systems for endometrial cancer (EC) and to assess whether FIGO 2023 system better predicts patient prognosis.

Methods: A retrospective analysis of 640 EC patients was conducted, with staging according to the 2009 and 2023 FIGO systems. Kaplan-Meier survival analysis, hazard ratios (HRs), Harrell's concordance index (C-index), and Akaike's Information Criterion (AIC) were used to assess model performance.

Results: A change to a higher substage occurred in 148 patients (23.1%), whereas 12 patients (1.9%) were down-staged, based on the FIGO 2009 staging system. Among early-stage patients, 9 and 62 were reclassified from early-stage (I and II) to IAm_POLEmut and IICm_p53abn, respectively, according to the molecular subtypes POLEmut and p53abn, and showed distinctly different prognoses (5-year overall survival [OS]: 100% vs. 75.3%). The 5-year OS and disease-free survival (DFS) rates were better for stage IA3 than for stage IIIA1 (OS: 91.7% vs. 71.6%, DFS: 91.7% vs. 71.3%). Among patients with advanced EC, those with the p53abn molecular subtype had the worst prognoses (5-year OS: 41.6%). Compared to FIGO 2009, FIGO 2023 showed significantly higher HRs for OS and DFS (p<0.001), higher C-index values (0.751 vs. 0.711, 0.750 vs. 0.709), and lower AIC values (1,316.919 vs. 1,338.928, 1,315.444 vs. 1,337.864).

Conclusion: The FIGO 2023 system provided a better model fit and higher predictive accuracy than the FIGO 2009 system. Molecular subtyping was crucial for prognoses of patients with advanced EC (stage III/IV).

Objective: To investigate the clinicopathological and prognostic significance of homologous recombination deficiency (HRD) in high-grade serous ovarian carcinoma (HGSC) and evaluate the impact of neoadjuvant chemotherapy (NACT) on HRD detection.

Methods: HRD status was assessed in 126 surgically resected HGSC samples (30 post-NACT, 96 primary surgery) using the AmoyDx^® HRD Complete Panel. HRD positivity was defined as a pathogenic/likely pathogenic BRCA1/2 mutation and/or genomic scar score (GSS) ≥45. Correlations with clinicopathological variables, histological subtypes (classic vs. solid, endometrial-like, and transitional [SET] patterns), and survival were analyzed.

Results: HRD positivity was detected in 76 (60.3%) cases, with BRCA1/2 mutations in 26.2%. HRD-positive tumors showed larger size (p=0.034) and more SET patterns (p=0.001). Notably, among BRCA1/2 wild-type patients, the NACT group showed significantly lower HRD positivity (22.2% vs. 56.1%; p=0.003) and decreased median GSS (19.5 vs. 55.2; p<0.001) than the primary surgery group. Multivariate analysis identified HRD positivity (hazard ratio [HR]=0.488; p=0.023) and first-line maintenance therapy (HR=0.435; p=0.008) predicted better progression-free survival (PFS), while lymph node metastasis predicted worse PFS (HR=2.674; p=0.001). R0 resection improved both PFS (HR=0.410; p=0.006) and overall survival (HR=0.074; p=0.013).

Conclusion: HRD status is a prognostic biomarker in HGSC. Its correlation with SET patterns supports histology as an initial screening tool. Importantly, NACT is correlated with reduced detectable HRD positivity and lower GSS, underscoring the need for HRD testing before chemotherapy to ensure accurate assessment and guide treatment.