Journal of Gynecologic Oncology最新文献

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.

Objective: In vulvar squamous cell carcinoma (VSCC), the presence or absence of groin lymph node metastases (LNM) is relevant for choice of treatment and outcome. Risk stratification at time of primary diagnosis could impact choice of treatment, especially since VSCC often affects elderly patients with increased surgical risks. This study evaluates the prognostic value of histopathological features and immunohistochemical (IHC) markers (p16, p53, L1CAM, and PD-L1) for predicting groin LNM in primary biopsy specimens.

Methods: A retrospective cohort study was conducted, including patients with macroinvasive VSCC (depth of invasion >1mm) undergoing primary surgery between 2005 and 2015. Pathological revision of both the primary biopsy and definitive resection was performed. IHC staining with p16, p53, L1CAM, and PD-L1 was applied to all biopsies. The primary outcome was the risk of groin LNM at primary diagnosis.

Results: A total of 118 patients were included, of whom 34.7% (n=41) had groin LNM. In resected specimens, groin LNM correlated significantly with depth of invasion ≥4mm (p=0.002), poor differentiation (p=0.002), invasive or spray-patterned growth (p=0.024), and lymphovascular space invasion (LVSI) (p<0.001). In biopsy samples, poor differentiation (p=0.039) and invasive/spray-patterned growth (p=0.044) were associated with higher groin LNM risk. IHC markers did not demonstrate significant predictive value.

Conclusion: These findings suggest that poor differentiation and invasive/spray-patterned growth in biopsies are indicative of increased groin LNM risk, whereas well-differentiated tumors and pushing growth patterns may confer a more favourable prognosis. Further research is warranted to optimize surgical decision-making regarding groin node management. IHC markers evaluated herein showed no significant prognostic utility.

Objective: Immune checkpoint inhibitors (ICIs) have shown promising results in treating gynecologic malignancies. However, they may induce a unique response pattern known as pseudoprogression (PP), which can be misclassified as true progression, leading to premature discontinuation of effective therapy. To address this challenge, immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) were developed. This study aimed to assess the utility of iRECIST and to characterize cases that may benefit from its application.

Methods: We retrospectively reviewed 64 patients with gynecologic cancers treated with ICIs at our institution. Tumor responses were evaluated using both RECIST version 1.1 and iRECIST. Cases initially showing tumor enlargement but continuing the same regimen were further analyzed if subsequent imaging demonstrated tumor shrinkage.

Results: The cohort's ages ranged from 38 to 83 years (median=62). The cohort included 34 patients with endometrial cancer and 25 with cervical cancer. ICIs used included pembrolizumab (n=59) and cemiplimab (n=5). Among the 64 cases, 3 exhibited tumor changes consistent with PP. In one case, progressive disease was initially observed, but later imaging revealed tumor regression, ultimately achieving complete response. These cases highlight the utility of iRECIST in distinguishing PP from true progression. However, no consistent histologic type or tumor location was associated with PP. Notably, cases showing tumor enlargement after the first CT scan did not subsequently show shrinkage.

Conclusion: Although PP incidence remains low, these findings suggest that continuing treatment beyond initial progression may be beneficial in select cases. However, since this study is retrospective, further validation is necessary.

Objective: Early-stage uterine leiomyosarcoma (uLMS) remains a clinical challenge due to high recurrence and mortality rates. As most early-stage cases are diagnosed at stage IB, this study aims to investigate the prognostic factors and optimal management for stage IB uLMS.

Methods: A retrospective review was conducted of medical records for patients who underwent surgical intervention and were diagnosed with stage IB uLMS at the Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center from January 1, 2006, to August 31, 2023.

Results: After a median follow-up time of 70.1 months (range: 2.3-234.1), we observed a median disease-free survival (DFS) of 18 months and overall survival (OS) of 67.9 months, respectively. Median DFS was 14.7 months in the observation group and 18.4 months in the adjuvant chemotherapy group. Median OS was 75.4 months in the observation group and 66.6 months in the adjuvant chemotherapy group. Five-year DFS rates were 14.1% and 15.7%, and OS rates were 66.5% and 54.1% for the observation and chemotherapy groups, respectively. Poor DFS was associated with age >48 years, postmenopausal status, tumor size >12 cm, elevated Ki-67 levels, and lymphadenectomy, but these factors did not correlate with OS outcomes. No significant DFS or OS differences were found between chemotherapy and observation groups or across chemotherapy regimens. Ovarian preservation did not affect prognosis.

Conclusion: Age >48 years, postmenopausal status, larger tumor size, higher Ki-67, and lymphadenectomy predicted poor DFS but not OS in stage IB uLMS. Ovarian preservation is safe. Adjuvant chemotherapy with different regimens showed no significant survival benefits.

Objective: To evaluate the clinical characteristics, treatment outcomes, and the impact of delayed debulking surgery in recurrent adult-type granulosa cell tumors (AGCTs).

Methods: This retrospective cohort study analyzed patients diagnosed with recurrent AGCT between January 2003 and December 2023 at Peking Union Medical College Hospital. Kaplan-Meier analysis, along with univariate and multivariate Cox proportional hazards models, were utilized to identify factors associated with progression-free survival following the first, second, and third recurrences, as well as overall survival (OS).

Results: The study included 92 patients with recurrent AGCT, with approximately 90% of tumors initially staged as stage I. The median follow-up time was 136.0 months (range, 30.0-402.0 months). Extra-pelvic and multifocal lesions were common in recurrent cases. Most patients underwent tumor cytoreductive surgery (CRS) at each recurrence. A time interval from recurrence to CRS of ≥6 months had no adverse impact on OS (multivariate hazard ratio [HR]=1.53; 95% confidence interval [CI]=0.33-7.05; p=0.582), but significantly prolonged the interval between relapses after the first (median interval not reached in the ≥6-month group vs. 40.0 months in the <6-month group; log-rank p=0.023) and second recurrence (median interval, 65.0 vs. 25.0 months; log-rank p<0.001). Gross residual disease after CRS was associated with poorer OS (multivariate HR=7.44; 95% CI=1.95-28.46; p=0.003).

Conclusion: Delaying CRS by ≥6 months can prolong the time to the next recurrence without compromising OS, while gross residual disease remains an independent risk factor for poor survival.

Objective: Combining cisplatin and gemcitabine (CG) in the concurrent and adjuvant treatment phase of advanced cervical cancer has improved oncological outcome at the cost of excess toxicity. We aimed to investigate the feasibility and safety of this treatment intensification in the era of modern radiotherapy.

Methods: A retrospective review was performed on patients treated with definitive chemoradiation including CG for advanced cervical cancer. Treatment consisted of chemoradiotherapy (weekly cisplatin 40 mg/m² and gemcitabine 125 mg/m² with volumetric-modulated arc therapy) followed by image-guided adaptive brachytherapy and 2 cycles of adjuvant CG.

Results: Fifty-five patients were included with a median follow-up of 48 months (range, 7-130). Patients with FIGO stage IIIC1 accounted for 49.1% of cases, with an additional 23.6% being stage IIIC2. The median number of concurrent gemcitabine and cisplatin administrations was 4 (range, 1-6), and 5 (range, 2-8), respectively. Forty-four patients (80%) received adjuvant chemotherapy. Hematological severe short-term toxicity (grade ≥3) occurred in 22 patients (43.1%). There was no deviation from planned radiotherapy-schedule. No treatment-related death occurred. Five patients experienced late grade ≥3 adverse events. Local, locoregional and distant control rates at 5 years were 82.0%, 70.5% and 69.3%, respectively. Five-year progression-free survival was 50.9% and overall survival was 70.9%.

Conclusion: Concurrent chemoradiation with CG followed by image-guided adaptive brachytherapy and adjuvant CG is feasible and associated with a lower toxicity profile than previously reported. Further research is needed to refine patient selection for different treatment intensification strategies in advanced cervical cancer.

Objective: To investigate the associations of homologous recombination repair (HRR) gene mutations with clinical prognosis in epithelial ovarian cancer (EOC) patients with various histological subtypes.

Methods: The EOC patients treated at our institute from January 2014 to March 2021 were included. Gene mutations were detected using 24 target HRR genes. The associations between HRR gene mutations and clinical outcomes were analyzed.

Results: A total of 318 patients were evaluated, 37 patients had BRCA, and 21 patients had other HRR gene mutations. EOC patients with HRR gene mutations were associated with platinum sensitivity than wild type (82.8% vs. 68.7%, p=0.033), and it remained significant in patients with advanced stage (79.5% vs. 57.6%, p=0.007), serous carcinoma (89.4% vs. 66.2%, p=0.002) or optimal debulking surgery (97.1% vs. 79.1%, p=0.013). In serous carcinoma, advanced stage (hazard ratio [HR]=2.11; p=0.031), HRR mutation (HR=0.62; p=0.021) and 1st line poly(ADP-ribose) polymerase inhibitor (PARPi, HR=0.28; p<0.001) were significant for cancer recurrence. Suboptimal debulking surgery (HR=1.58; p=0.044) and HRR gene mutation (HR=0.33; p=0.001) were important for cancer-related death. In non-serous carcinoma, mucinous carcinoma (HR=3.91; p=0.023), advanced stage (HR=3.10; p<0.001) and suboptimal debulking surgery (HR=2.63; p=0.001) were significant for cancer recurrence. Mucinous carcinoma (HR=9.17; p=0.001), advanced stage (HR=4.26; p<0.001), and suboptimal debulking surgery (HR=3.80; p<0.001) were important for cancer-related death.

Conclusion: HRR gene mutations were associated with platinum sensitivity, PARPi response and favorable survival in serous EOC patients. In non-serous EOC, HRR gene mutations did not show the same trend, which warrants further investigation.

Objective: Recurrence patterns and survival outcomes in advanced epithelial ovarian cancer (EOC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remain poorly understood. This post hoc analysis aimed to evaluate patterns of initial recurrence in patients with advanced EOC.

Methods: This analysis of the KOV-HIPEC1 trial included 142 patients with recurrent EOC divided into HIPEC and non-HIPEC groups. Baseline characteristics, recurrence patterns, and post-recurrence survival (PRS) were analyzed.

Results: Among 142 patients with recurrent disease, recurrence patterns were comparable between the HIPEC and non-HIPEC groups, including rates of peritoneal seeding (80.0% vs. 70.1%, p=0.178), lymphatic involvement (47.7% vs. 49.4%, p=0.844), and parenchymal metastases (10.8% vs. 15.6%). In the BRCA-mutated subgroup, peritoneal seeding was significantly more common in the HIPEC group than in the non-HIPEC group (81.8% vs. 33.3%, p=0.036). PRS did not differ significantly between the HIPEC and control groups (p=0.571). Gastrointestinal events at recurrence were less frequent in the HIPEC group, including intestinal obstruction (1.9% vs. 9.3%), ostomy formation (0% vs. 3.1%), intestinal surgery (0% vs. 5.6%) and nasogastric tube placement (1.9% vs. 7.4%).

Conclusion: No significant differences in recurrence pattern or survival outcome were observed between CRS with HIPEC and CRS alone. However, distinct recurrence patterns observed in BRCA-mutated patients suggest potential biological differences that may influence treatment outcomes. A trend toward reduced gastrointestinal morbidity in the HIPEC group, potentially reflecting a more subtle, less invasive recurrence pattern. Further research is warranted to elucidate these observations.