Journal of Gynecologic Oncology最新文献

Objective: To evaluate upstaging, lymph node (LN) metastasis, and recurrence in patients with presumed stage I endometrial cancer using preoperative magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT).

Methods: Retrospective review of 422 patients with presumed clinical stage I endometrial cancer diagnosed via MRI and PET-CT (July 2014-June 2023). Surgical staging included pelvic lymph nodes (PLNs) and para-aortic lymph nodes (PALNs), classifying patients as low/intermediate- or high-risk groups.

Results: Post-operative upstaging rate was 14.5% (8.8% low/intermediate-risk vs. 22.8% high-risk, p<0.001). LN metastasis occurred in 5.5% of patients (2.0% low/intermediate-risk vs. 10.5% high-risk, p<0.001), with a dual imaging negative predictive value of 0.945. PLN metastasis was 4.5% (2.0% low/intermediate vs. 8.2% high-risk, p=0.003), and PALN metastasis was 2.6% (0.4% low/intermediate-risk vs. 5.8% high-risk, p=0.001). In low/intermediate-risk group: tumors ≤2cm had 1.1% LN metastasis rate, endometrium-limited 0.8%, and ≤2cm with endometrium-limited 0.9%. Deep myometrial invasion (odds ratio [OR]=4.4; 95% confidence intervals [CIs]=1.6-12.4) and tumor size >2 cm on MRI (OR=2.9; 95% CI=0.8-9.9) increased LN metastasis risk. Median 48.5-month follow-up showed an 8.1% overall recurrence rate (4.0% low/intermediate-risk vs. 14.0% high-risk, p<0.001), with 2.4% nodal recurrences (1.2% low/intermediate-risk vs. 4.1% high-risk).

Conclusion: High-risk patients had significant upstaging, LN metastasis, and recurrence rates. Even in low/intermediate-risk groups, some patients exhibited LN metastasis and nodal recurrence, underscoring the importance of comprehensive surgical staging, including PALN evaluation, for precise diagnosis and treatment.

Objective: To evaluate the efficacy of immune checkpoint inhibitors (ICIs) for fertility-sparing treatment in Lynch syndrome-associated endometrial cancer (LS-EC).

Methods: Four LS-EC cases received programmed cell death protein 1 (PD-1) inhibitors for fertility preservation at the Obstetrics and Gynecology Hospital of Fudan University from 2017 to 2023. The clinical data and long-term outcomes were retrospectively reviewed.

Results: Case 1, carrying germline MLH1 mutation, was diagnosed with Stage IIAm_MMRd (International Federation of Gynecology and Obstetrics 2023) endometrial cancer (EC) at 38 years old. She received PD-1 inhibitor treatment and achieved a pathological complete response (CR) at 42 weeks. Case 2, carrying MLH1 mutation, underwent colorectal cancer surgery at 22 years and was diagnosed with EC and synchronous ovarian cancer at 39 years. After 24-week PD-1 treatment, CR of EC and ovarian cancer was achieved. Case 3, carrying MSH2 mutation, was diagnosed with endometrial atypical hyperplasia (EAH) at 35 years. After receiving 7-month progestin, she had the progressed disease with Stage IA2m_MMRd EC and colon cancer was found soon after. She received PD-1 treatment for 18 weeks and achieved a CR of EC. She conceived naturally with full term delivery. Case 4, carrying MSH2 mutation, had a recurrence of Stage IBm_MMRd EC 15 months after CR from EAH treated with progestin at 40 years. She received PD-1 treatment for 18 weeks and achieved CR. No recurrence was found in all cases after 3-41 months of follow-up after CR.

Conclusion: ICIs might be an effective choice for LS-EC patients desiring fertility preservation.

Objective: To determine the accuracy of aspiration biopsy (AB), hysteroscopic biopsy (HB), and dilatation & curettage (D&C) in detecting uterine carcinosarcoma (UCS).

Methods: Pathology reports were retrieved from the Dutch Nationwide Pathology Databank PALGA for patients with a certain or suggested diagnosis of UCS in pre- and/or postoperative histology between 2001 and 2021. Patients without available pre- or postoperative pathology reports were excluded. The accuracy measures sensitivity, positive predictive value (PPV), accuracy, and concordance using Cohen's kappa were calculated for AB, D&C, and HB, using postoperative histology as the reference. This was analyzed for 2 scenarios: Analysis A compared samples with a certain or suggested diagnosis of UCS vs. no mention of UCS. Analysis B compared samples with a certain diagnosis of UCS vs those without UCS.

Results: The study included 1,481 patients, totaling 1,685 samples. Sensitivity was similar for AB and HB (52.4% and 50.5%, respectively, for analysis A; 45.1% and 42.2% for analysis B). D&C showed the highest sensitivity (70.8% and 64.9% for analysis A and B, respectively). AB had the highest PPV (85.3% and 90.9% for analysis A and B, respectively), HB had the lowest PPV (79.7% and 80.9%, respectively). Accuracy was highest for D&C (44.4%) compared to AB (32.8%) and HB (29.5%). All Cohen's kappa values were below 0.20, indicating poor correlation between preoperative and postoperative diagnoses.

Conclusion: The study reveals low accuracy measures across all conventional endometrial sampling techniques, highlighting the need for research to identify markers or tools to diagnose UCS.

Objective: Our study was aimed to construct a predictive model to advance ovarian cancer diagnosis by machine learning.

Methods: A retrospective analysis of patients with pelvic/adnexal/ovarian mass was performed. Potential features related to ovarian cancer were obtained as many as possible. The optimal machine learning algorithm was selected among six candidates through 5-fold cross validation. Top 20 features having the most powerful predictive significance were ranked by Shapley Additive Interpretation (Shap) method. Clinical validation was further performed to confirm whether our model could advance diagnosis of ovarian cancer.

Results: A total of 9,799 patients were collected. The inclusion criteria included age >18 years old, the first diagnosis being pelvic/adnexal/ovarian mass of undetermined significance, and pathological report indispensable. Four hundred and thirty-eight dimensional features were obtained after filtration. LightGBM showed the best performance with accuracy 88%. Among the top 20 features, 55% belonged to laboratory test report, 35% came from imaging examination report, and 10% were attributed to basic demographics and main symptom. Age, CA125, and risk of ovarian malignancy algorithm were the top three. Our predictive model performed stably in testing and clinical validation datasets, and was found to advance the diagnosis of ovarian cancer about 17 days before clinical pathological examination.

Conclusion: LightGBM was the optimal algorithm for our predictive model with accuracy of 88%. Laboratory test and imaging examination played essential roles in diagnosing ovarian cancer. Our model could advance the diagnosis of ovarian cancer before clinical pathological examination.

Objective: Surgery is the mainstay of treatment for low-grade endometrial stromal sarcoma (LG-ESS). While adjuvant hormone therapy is recommended for patients with advanced/recurrent disease, no consensus regarding its use among early-stage patients exists. We aimed to identify correlates of adjuvant hormone therapy use and associations of adjuvant hormone therapy and overall survival (OS) in stage I LG-ESS patients.

Methods: Retrospective cohort study of patients with stage I LG-ESS who underwent hysterectomy from 2004-2019 using data from the National Cancer Database. Categorical data were compared using χ² tests. Kaplan-Meier estimates and log-rank tests were used to compare OS according to adjuvant hormone use. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between adjuvant hormone use and OS were estimated using Cox proportional hazards regression.

Results: Of 2,386 patients included, 20.2% were treated with adjuvant hormonal therapy. Use of hormone therapy increased over time, with rates approximately doubling from 2004 to 2019 (12.6% to 24.6%). Age, tumor size, lymphovascular space invasion and adjuvant radiation were associated with adjuvant hormone therapy use. There was no association between adjuvant hormone therapy and OS (log-rank p=0.73; HR=1.05; 95% CI 0.76-1.46) for patients with LG-ESS.

Conclusion: Use of adjuvant hormone therapy for stage I LG-ESS has increased over time though is not associated with OS in this cohort of patients. Additional evaluation is needed to understand the impact of adjuvant hormone therapy on recurrence rates, progression rates, and quality of life to fully understand its value.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/- bevacizumab in rGCCC.

Methods: DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/- bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator's choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinum-based chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti-PD-1, anti-programmed death-ligand 1, or anti-programmed death-ligand 2 agent. The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Trial registration: ClinicalTrials.gov Identifier: NCT06023862.

Objective: To explore the application value of using 3-dimensional (3D) printing (3DP) technology to create individualized vaginal molds for brachytherapy (BT) in high-dose-rate 3D cervical cancer through reverse engineering of needle placement.

Methods: Prospectively, 11 patients with cervical cancer were treated with 3DP-intracavitary/interstitial (IC/IS) BT using 3DP to create individualized vaginal molds. All patients were performed BT after completion of external beam radiotherapy (EBRT). Each patient was treated with BT 5 times, the prescription dose was 600 cGy/F, which was performed once or twice a week, 2 of them were freehand IC/IS BT, and 3 were 3DP-IC/IS BT. The relevant planning parameters (bladder, rectum, sigmoid colon, and small intestine) and target conformity index (CI) for high-risk clinical target volume (HR-CTV) and organs at risk (OARs) were compared between the groups.

Results: There were significant advantages in the 3DP-IC/IS BT group compared with the freehand IC/IS BT group: HR-CTV D₉₀ (629.40±19.34 vs. 613.03±15.93 cGy, p=0.002), D₉₅ (580.74±18.31 vs. 567.44±23.94 cGy, p=0.032), bladder D_2cc (431.11±23.27 vs. 458.07±23.27 cGy, p<0.001), bladder D_1cc and bladder D_0.1cc. There was no statistically significant difference (p>0.05) between the 2 groups in rectal D_2cc (352.30±42.42 vs. 361.29±42.42 cGy, p=0.470), sigmoid colon D_2cc (236.73±78.95 vs. 246.50±58.17 cGy, p=0.621), CI (0.79±0.04 vs. 0.79±0.039 p=0.773), HR-CTV V₁₀₀, V₂₀₀, D₉₈, D₁₀₀ and other OARs parameters (p>0.05).

Conclusion: Compared with IC/IS BT, 3DP-IC/IS BT has apparent advantages with simple operation and high safety. In addition, individualized mold helps to improve the tumor target area's radiation dose while meeting the dose-limiting requirements for organs at risk and reduces the clinical proficiency requirements for operating physicians.

Objective: This cross-sectional study aimed to understand the actual situation of shared decision-making (SDM) and identify the challenges of implementing SDM among Japanese gynecologic cancer patients and healthcare professionals (HCPs).

Methods: Adult Japanese women undergoing chemotherapy for endometrial or ovarian/fallopian tube cancer and HCPs who prescribed/administered treatment were enrolled. Data were collected via a web-based questionnaire. Primary endpoints were the actual and desired status of SDM for patients by preferred role (active, collaborative, passive), and important aspects in drug selection for patients and HCPs. SDM treatment preferences were determined using the Control Preferences Scale.

Results: Respondents comprised 154 patients (77 for endometrial and 77 for ovarian/fallopian tube cancer), 153 physicians, 166 nurses, and 154 pharmacists. Among patients, 53.9% desired an active role in decision-making, and 55.8% participated; 25.3% desired a collaborative role, and 14.3% participated; and 20.8% desired a passive role, and 29.9% participated. Most patients with a collaborative role in decision-making (86.4%) were "very satisfied" or "somewhat satisfied" with their communication with physicians, compared with 60.4% and 73.9% of respondents with active and passive roles in decision-making, respectively. In daily practice, 23.5%, 47.6%, and 19.5% of physicians, nurses, and pharmacists, respectively, confirmed "awareness" of SDM. Regarding treatment expectations, patients ranked "complete elimination of cancer," and HCPs ranked "live longer" as the most important.

Conclusion: Most patients desire involvement in their treatment decisions. Additionally, treatment expectations differ between patients and HCPs. Increasing SDM awareness, implementing it systematically, and addressing patients' needs for collaborative roles in decision-making is essential.

Objective: This study aimed to evaluate the oncological safety of laparoscopic surgery for patients with benign tumors who underwent laparoscopic surgery at our facility and were subsequently diagnosed with borderline ovarian tumors or ovarian cancer.

Methods: We conducted a retrospective review of 45 patients initially diagnosed with benign ovarian tumors who underwent laparoscopic surgery at our institution from January 2009 to April 2024.

Results: Postoperative pathological examination identified 32 cases of borderline ovarian tumors and 13 cases of ovarian cancer. Laparoscopic cystectomy was performed in 14 (43.8%) borderline cases and 4 (30.8%) ovarian cancer cases. Out of 14 patients with borderline ovarian tumors who underwent cystectomy, 8 subsequently underwent staging laparotomy, whereas 6 underwent only ovarian tumor cystectomy. In contrast, none of the patients with ovarian cancer completed treatment with only ovarian tumor cystectomy. Recurrent disease was observed in 9.4% of borderline tumor cases, all of which were successfully managed with further surgery. In the ovarian cancer group, recurrence occurred in 31% of patients, with 3 resulting in tumor-related mortality.

Conclusion: Laparoscopic surgery for borderline ovarian tumors is suggested to be oncologically safe, with low recurrence rate and no adverse impact on survival. However, for ovarian cancer, particularly in cases with peritoneal dissemination, rapid disease progression remains a concern. While this study suggests that laparoscopic surgery may be a viable option for borderline ovarian tumors, further research is needed to validate these findings, particularly for ovarian cancer.

Objective: We evaluated the pharmacokinetics, tissue concentrations, and toxicities of belotecan during rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs.

Methods: We sprayed belotecan in 10% and 30% of doses for intravenous chemotherapy in six pigs (cohort 1, n=3, 0.50 mg/m²; cohort 2, n=3, 1.5 mg/m²). We evaluated the time-dependent plasma concentrations of belotecan before RIPAC to 120 hours for the pharmacokinetics, tissue concentrations in twelve peritoneal regions, and hepatic and renal functions before RIPAC to 120 hours in the 2 cohorts.

Results: Mean values of the peak plasma concentration (C_max), the time to C_max, the time taken for C_max to drop in half, and the area under the curve from time zero to the time of last quantifiable concentration were 905 and 3,700 ng/mL, 1.42 and 1.50 hours, 3.64 and 5.60 hours, and 2,260 and 17,900 pg·hr/mL in cohorts 1 and 2, respectively. Mean values of tissue concentrations were 1.5 to 15.3 times higher in cohort 1 than in cohort 2 despite the similar ratio of tissue to plasma concentration, and tissue concentrations in the two cohorts were higher in the parietal peritoneum than in the visceral peritoneum. However, hepatic and renal functions were not different before RIPAC to 120 hours in the two cohorts.

Conclusion: RIPAC using belotecan of 0.5 mg/m² and 1.5 mg/m² may be feasible with fewer hepatic and renal toxicities in pigs. Thus, belotecan of 1.5 mg/m² may be considered as the starting dose for RIPAC in a phase 1 trial.