Journal of Gynecologic Oncology最新文献

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: 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: 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: 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.

Objective: To investigate perceptual and practical differences regarding radiotherapy (RT) for recurrent ovarian cancer (ROC) among gynecologic oncologists (GOs) and radiation oncologists (ROs) in Korea.

Methods: An anonymous cross-sectional survey was conducted from June 5 to September 5, 2024, targeting experienced members of the Korean Gynecologic Oncology Group and Korean Radiation Oncology Group. A structured questionnaire with approximately 25 main items covered 4 domains: demographics, perceptions/attitudes, practice patterns, and clinical case scenarios.

Results: This study included 116 oncologists (80 GOs and 36 ROs; 47.1% and 45.6% response rate, respectively). Demographic characteristics (age, clinical experience, and patient volume) differed between groups (p<0.05). Although 68.8% of GOs and 91.7% of ROs considered RT effective, their primary goals differed: GOs prioritized local control (78.8%) and palliation (15.0%), whereas ROs emphasized local control (66.7%) and consolidation (22.2%) (p=0.016). Platinum-sensitive ROC, specific ROC subtypes, localized abdominal recurrence, and the definitions of oligometastasis (p<0.05) varied between GOs and ROs. Among GOs, 68% had partial knowledge of stereotactic ablative radiotherapy (SABR), citing low side effects (65%) as an advantage and limited indications (81%) as a disadvantage. Among ROs, SABR doses and fractionation protocols were relatively consistent for lung, liver, and spine lesions, whereas approaches varied significantly for abdominal lesions (p=0.029).

Conclusion: Although most oncologists recognize RT as effective for ROC, substantial differences in perception and clinical practice exist between GOs and ROs, highlighting the need for enhanced multidisciplinary collaboration and stronger clinical evidence to establish standardized treatment strategies for ROC.

Objective: The treatment effects of lymphadenectomy in early-stage ovarian clear cell carcinoma (OCCC) reported in previous studies may have been overestimated owing to confounding factors. This study aimed to investigate the treatment effect of pelvic and para-aortic lymphadenectomy (PeNPAN) in early-stage OCCC, with careful adjustment for potential confounders.

Methods: This retrospective multi-center cohort study involved women with preoperatively suspected stage I OCCC. We included patients who underwent surgery for OCCC between 2005 and 2019 at 11 affiliated institutions. The exposure (PeNPAN) group comprised patients who underwent PeNPAN. The primary outcome was disease-free survival (DFS). Additionally, hazard ratios (HRs) of lymphadenectomy for DFS were estimated using unadjusted and propensity score-weighted Cox regression models and biased models applied in previous studies. To identify strong confounders, we further examined factors associated with recurrence that differed between the groups.

Results: We analyzed 304 women who underwent surgery for preoperatively suspected stage I OCCC. The unadjusted HR for DFS was 0.63 (95% confidence interval [CI]=0.36-1.09; p=0.10), and the propensity-score adjusted HR was 0.82 (95% CI=0.42-1.58; p=0.55). The biased model showed a statistically significant HR of 0.59 (95% CI=0.36-1.00; p=0.048). Adhesions in the Douglas' pouch and cardiovascular disease were associated with recurrence and were more prevalent in the control group, suggesting potential confounders.

Conclusion: After adjusting for potential confounders, the observed treatment effects of lymphadenectomy in the biased models were no longer statistically significant. Future investigations should carefully account for possible confounders, including intraoperative adhesions and comorbidities.

Background: The current standard for treating locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy (CCRT). Overexpression of the epidermal growth factor receptor (EGFR) has been linked to reduced responsiveness to CCRT and poorer outcomes. Therefore, targeting EGFR represents a promising therapeutic approach in cervical cancer. The purpose of this study is to evaluate the efficacy and safety of nimotuzumab concurrent with and following CCRT vs. CCRT alone in patients with locally advanced cervical squamous carcinoma. Adding nimotuzumab to CCRT will enhance progression-free survival (PFS) in patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages IB3 to IVA cervical squamous carcinoma, compared to CCRT alone.

Methods: The NOTABLE-306 trial comprises a phase Ib dose-escalation stage (3+3 design) to determine the optimal nimotuzumab dose, followed by a phase III randomized, multicenter, double-blind, placebo-controlled stage. Patients will be randomized 1:1 to receive weekly nimotuzumab or placebo for 8 cycles, followed by biweekly maintenance for 24 weeks. All participants will undergo external beam radiotherapy (EBRT, 45-50 Gy in 25 fractions) with cisplatin (40 mg/m², weekly) for 5 weeks, followed by image-guided brachytherapy. Eligible patients are treatment-naïve females aged 18-80 with histologically confirmed cervical squamous carcinoma (FIGO 2018 stages IB3-IVA) and no prior definitive treatments. The primary endpoints include dose-limiting toxicity in phase Ib and PFS in phase III, which were assessed by an independent review using Response Evaluation Criteria in Solid Tumors v1.1 criteria. Stage I includes up to 26 patients to determine dosing. Stage II will enroll approximately 460 patients randomized 1:1 to receive either nimotuzumab or placebo with and following CCRT. Patient enrollment was started in April 2024 with an estimated completion date of April 2030.

Trial registration: ClinicalTrials.gov Identifier: NCT06333821.