Journal of Gynecologic Oncology最新文献

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.

Objective: To evaluate oncologic outcomes in women with recurrent platinum-sensitive ovarian cancer (OC) receiving antibiotics (ABX) during platinum-based chemotherapy.

Methods: A retrospective, single-institution cohort study was performed in women undergoing platinum chemotherapy for recurrent platinum-sensitive OC from 2009-2017. ABX for >48 hours, including anti-gram-positive antibiotics (G+ ABX), were recorded. The impact of ABX on time to second progression (PFS2), time to platinum resistance, and overall survival (OS) were assessed using univariate and multivariable Cox regression models.

Results: Of 261 women with recurrent platinum-sensitive OC, 80 (30.7%) received ABX during platinum chemotherapy, and 20 (7.7%) received G+ ABX. On univariate analysis for PFS2, there was no difference for ABX versus none (13.1 vs. 12.3 months: hazard ratio [HR]=1.23, 95% confidence interval [CI]=0.93-1.62, p=0.15), but this was decreased for G+ ABX versus none (10.2 vs. 12.3 months: HR=1.71; 95% CI=1.05-2.77; p=0.03). There was no difference in OS for ABX versus none (30.8 vs. 33.5 months: HR=1.01; 95% CI=0.73-1.39; p=0.97), but G+ ABX were associated with decreased OS compared to no ABX (26.4 vs. 33.4 months: HR=2.13; 95% CI=1.28-3.57; p=0.004) and other ABX (26.4 vs. 37.9 months: HR=2.43; 95% CI=1.34-4.41; p=0.003), respectively. On multivariable analysis, no ABX were associated with improved PFS2 (HR=0.54; 95% CI=0.33-0.88; p=0.014) and OS (HR=0.49; 95% CI=0.29-0.81; p=0.006) versus G+ ABX.

Conclusion: This retrospective study of women with recurrent platinum-sensitive OC treatment with G+ ABX during platinum chemotherapy was associated with decreased PFS2 and OS.

Platinum-based chemotherapies are widely used in the treatment of gynecologic malignancies and are standard treatment for initial treatment and recurrent diseases. Due to the widespread use of platinum-based regimens, the management of platinum hypersensitivity reactions (HSRs) is an important issue for physicians treating gynecologic malignancies. Patients receiving multiple lines of platinum therapy, with long intervals between platinum lines and history of allergic reaction, and status of germline BRCA mutation are at an increased risk of platinum HSRs. The development of desensitization protocols to allow patients with platinum hypersensitivity to receive further therapy is mandatory. Each institution should work with its' multidisciplinary team to select a protocol that best suits individual practice setting and patient population to maximize patients care.

Objective: This study aimed to evaluate the incidence of subsequent primary cancer (SPC) among cervical cancer survivors in Japan.

Methods: Data from the cancer registries of Osaka, Kanagawa, and Miyagi prefectures were combined. The cohort included individuals diagnosed with invasive and in situ cervical cancer between 1980 and 2010, with the SPC incidence evaluated until 2015. The incidence and standardized incidence ratio (SIR) for different SPC sites were calculated. In addition, the association between SPC and radiotherapy was examined via competitive regression analysis.

Results: A total of 49,824 cervical cancer survivors were followed for up to 35 years, during which 4,507 (9.0%) of these survivors experienced SPC. Aside from the initial cancer, SPC was the most common cause of death among cervical cancer survivors. The most frequent SPC sites were the colorectal, breast, lung, and stomach, consistent with the frequency in the general population. A significant increase in the SIRs for bladder, lung, and colorectal cancers was observed (2.52, 1.63, and 1.44, respectively). Individuals who underwent radiotherapy had a higher risk of developing bladder cancer than those who did not, with a subdistribution hazard ratio of 2.28. The SIR for lung cancer significantly increased, particularly for the smoking-associated types, indicating the influence of smoking habits among survivors. Increased risk of specific SPCs was seen in both invasive and in situ cancer survivors.

Conclusion: Cervical cancer survivors should be informed about the risks of SPCs and educated on the prevention methods. Our study provides valuable insights into specific actions SPC prevention.

Objective: To identify molecular subgroups in endometrioid endometrial cancer (EEC), evaluate their association with clinicohistopathological characteristics, and define low-intermediate risk groups by integrating these parameters.

Methods: This retrospective-cohort study included 1,040 patients who underwent surgery between January 2000 and June 2022. Among 900 EEC cases, 72 recurred. Patients with tumor recurrence (n=62) and those without (n=52) were matched. POLE exons 9-14 were examined using Sanger sequencing. p53 and mismatch repair (MMR) protein expression were assessed via immunohistochemistry.

Results: The molecular subgroups were POLE mutation (POLE-mut) 5%, mismatch repair-deficient (MMR-d) 43%, p53 mutation (p53-mut) 5%, and non-specific molecular profile (NSMP) 42%. 5% of cases displayed multiple molecular mutations. POLE-mut were more prevalent in high-grade tumors (p=0.026). MMR-d tumors exhibited higher rates of lymphovascular space invasion and myometrial invasion ≥50% (p=0.032, p=0.020). No recurrences occurred in POLE-mut tumors (p=0.002), while MMR-d was significantly associated with recurrence (p=0.002). Median disease-free survival (DFS) for MMR-d, p53-mut, and NSMP were 34, 49, and 107 months, respectively. Median overall survival (OS) for these groups was 128, 102, and 181 months. Multivariate Cox-regression analysis employing the Backward-Stepwise method identified stage as the strongest predictor of DFS, and grade and stage as predictors of OS.

Conclusion: POLE mutations were linked to the most favorable molecular prognostic factor. NSMP cases showed the longest DFS and OS, while p53-mut had the shortest OS. Except for POLE, molecular features alone were insufficient for establishing risk groups, highlighting the continued importance of histopathology in EEC management.

Objective: This study explored new insights into the selection criteria for maintenance therapy for platinum-sensitive recurrent ovarian cancer by comparing the efficacy of poly(ADP-ribose) polymerase inhibitors (PARPis) and bevacizumab in patients with a history of PARPi administration.

Methods: Between April 2014 and December 2024, 81 patients underwent maintenance therapy with either PARPi (52 patients) or bevacizumab (29 patients) at our institution. The primary endpoint was progression-free survival (PFS) after the end of the last chemotherapy treatment.

Results: The median PFS did not differ significantly between the PARPi and bevacizumab groups (9 vs. 12 months, p=0.942). Similarly, in the propensity score-matched cohort (15 pairs), no significant difference was observed between the PARPi and bevacizumab groups (p=0.444). In the PARPi group, a history of PARPi administration was associated with a significant difference in PFS in both univariate and multivariate analyses (PARPi-naïve vs. PARPi-experienced: 12 vs. 4 months, p=0.002; hazard ratio=3.24, 95% confidence interval=1.56-6.69). In the bevacizumab group, a history of PARPi administration was not associated with a significant difference in PFS. Among patients with a history of PARPi administration, the bevacizumab group had a significantly better PFS than the PARPi group (PARPi rechallenge vs. bevacizumab: 4 vs. 12 months, p=0.042), and the proportion of patients experiencing platinum-resistant recurrence during maintenance therapy was higher in the PARPi rechallenge group (58.8%) than in the bevacizumab group (20.0%) (p=0.049).

Conclusion: Maintenance therapy with bevacizumab may be more beneficial for patients with platinum-sensitive recurrent ovarian cancer who have a history of PARPi administration.

Objective: Although minimally invasive surgery (MIS) for cervical cancer is considered inferior to open surgery, many patients still prefer MIS, and their preferences regarding surgical options remain underexplored. Understanding how patients value surgical procedures is essential for informed, patient-centered decision-making.

Methods: A discrete choice experiment was conducted with 131 gynecologic cancer patients via face-to-face surveys from January 2023 to July 2023. The 6 attributes of MIS evaluated were hospital stay length, time to return to normal activities, serious surgical complications, cosmetic outcomes, 3-year overall survival (OS), and cost.

Results: Except for hospital stay length, the remaining 5 attributes-3-year OS (odds ratio [OR]=0.30; 95% confidence interval [CI]=0.22-0.43; p<0.001), out-of-pocket costs (OR=0.60; 95% CI=0.47-0.77; p<0.001), serious surgical complications (OR=0.67; 95% CI=0.57-0.79; p<0.001), cosmetic outcomes (OR=0.68; 95% CI=0.59-0.79; p<0.001), and time to return to normal activities (OR=0.71; 95% CI=0.61-0.82; p<0.001)-significantly influenced decision-making. The likelihood of choosing a procedure increased by 3.3-fold with a 5% improvement in OS, followed by a 1.4-fold increase with fewer serious complications, better cosmetic outcomes, or a faster return to normal activities. Patients under 50 valued survival, lower costs, cosmetic outcomes, and quicker recovery more than older women, who placed greater emphasis on minimizing serious complications.

Conclusion: Patients prioritized survival outcomes, while other non-oncologic MIS characteristics were also important. Incorporating patients' preferences and understanding age-related changes is essential for effective shared decision-making in clinical practice.

Objective: Recognition of homologous recombination deficiency (HRD) has revolutionized ovarian cancer (OC) treatment paradigm. Our study aimed to determine the prevalence of HRD in Taiwanese patients with high-grade serous ovarian cancer (HGSOC), high-grade endometrioid ovarian cancer (HGEOC), primary peritoneal cancer (PPC), and/or fallopian tube cancer (FTC).

Methods: The HALO-Taiwan, a cross-sectional, noninterventional study (NCT04991051) enrolled patients with stage III/IV HGSOC, HGEOC, PPC, or FTC having formalin-fixed paraffin-embedded tumor tissue blocks collected within the past 120 days of enrollment. The primary outcome was the prevalence of HRD. The secondary outcomes included prevalence of BRCA wild-type and loss of heterozygosity (LOH) positive status, tumor BRCA1/2 mutations, and other pathogenic mutations. The association of LOH status with demographic factors and pathogenic mutations was assessed using Cramer's V.

Results: Of 68 patients (median age [range]: 60.0 [39.0-81.0] years) enrolled, the majority (92.6%) had primary OC followed by PPC (2.9%) and FTC (4.4%). The overall prevalence of HRD was 52.9%; 14.7% had tumor BRCA mutations, and 38.2% had BRCA wild-type LOH-positive status. LOH status showed a strong, significant positive correlation with age and ECOG status (V=0.50, p=0.027, for both).

Conclusion: The HALO-Taiwan was the first observational study reporting HRD prevalence of 52.9% among patients with advanced OC in Taiwan. Our findings underscore the need to implement guideline-recommended testing for HRD as a part of the initial diagnostic work-up for all newly-diagnosed advanced high-grade OC patients to optimize treatment strategies.

Trial registration: ClinicalTrials.gov Identifier: NCT04991051.