Ehn P, Ioannou C, Malmsten C
… +4 more, Holmberg E, Rådestad AF, Dahm-Kähler P, Stålberg K
Int J Gynecol Cancer
· 2026 May · PMID 42302708
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OBJECTIVE: The use of ovary-sparing surgery and menopausal hormone therapy after endometrial cancer is controversial, requiring a balance between a presumed increased risk of recurrence and the well-known adverse effects...OBJECTIVE: The use of ovary-sparing surgery and menopausal hormone therapy after endometrial cancer is controversial, requiring a balance between a presumed increased risk of recurrence and the well-known adverse effects of premature menopause. Studies on this topic, specifically in pre-menopausal women, are scarce and heterogeneous. This nationwide, population-based, retrospectively conducted cohort study aimed to describe the use of ovary-sparing surgery and post-treatment menopausal hormone therapy in pre-menopausal women with endometrial cancer and to analyze related factors. METHODS: The study population comprised women aged ≤50 years diagnosed with endometrial cancer and registered in Sweden between 2010 and 2021. Data from validated Swedish registers were supplemented with manual review of medical records. Factors associated with ovary-sparing surgery were presented separately. Menopausal hormone therapy prescription was defined as at least 1 dispensing within 5 years of diagnosis. Cumulative incidence of menopausal hormone therapy prescription over 5 years was presented by sub-group. Multivariable regression was used for assessing potential factors affecting prescription patterns and included all endometrial cancer cases. RESULTS: The study included 731 women, of whom 42 (5.7%) underwent ovary-sparing surgery. Cumulative incidence of menopausal hormone therapy prescription was 45% for women aged 18 to 39 years, 27% for those aged 40 to 44 years, and 15% for those aged 45 to 50 years (p <.001). Among women aged <40 years with low-grade endometrioid adenocarcinoma, stage I to II, 38.1% received neither ovary-sparing surgery nor menopausal hormone therapy. Multivariable regression analyses showed that younger age, body mass index <30 kg/m, International Federation of Gynecology and Obstetrics stage I to II, and later year of diagnosis were independently associated with increased prescription of menopausal hormone therapy. CONCLUSIONS: This study demonstrates that the use of ovary-sparing surgery and menopausal hormone therapy remains low, even in young women with low-risk endometrial cancer. Menopausal hormone therapy appears to be under-utilized, which may be attributable to inconclusive evidence regarding its impact on recurrence risk, whereas the long-term adverse consequences of premature menopause are well known.
Al-Rubaish S, Awad A, Mehros W
… +2 more, Mutahar E, Elfadali MA
Int J Gynecol Cancer
· 2026 Apr · PMID 42284982
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OBJECTIVE: Venous thromboembolism is a common complication after gynecologic cancer surgery. While enoxaparin is the standard for prevention, oral apixaban may improve adherence. This review compares apixaban and enoxapa...OBJECTIVE: Venous thromboembolism is a common complication after gynecologic cancer surgery. While enoxaparin is the standard for prevention, oral apixaban may improve adherence. This review compares apixaban and enoxaparin for post-operative venous thromboembolism prevention. METHODS: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines, 6 databases were searched through August 2025 for studies comparing apixaban and enoxaparin for venous thromboembolism prevention after gynecologic cancer surgery. Eligible studies included randomized controlled trials and cohort studies. The systematic review and meta-analysis was registered in International Prospective Register of Systematic Reviews (CRD42024490564). The databases searched were PubMed, Embase, Web of Science, ClinicalTrials.gov, Scopus, and Cochrane Library. Outcomes included venous thromboembolism incidence at 30 and 90 days, and major and minor bleeding. Adherence and cost-effectiveness data, initially listed as secondary outcomes, could not be formally combined because of inconsistent reporting across studies, and are thus presented as a narrative summary only. RESULTS: Pooled odds ratios with 95% confidence intervals were calculated using random-effects models (DerSimonian-Laird estimator). Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool for randomized controlled trials and the ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) tool for observational studies. Certainty of evidence was evaluated using the GRADE approach. Four studies with 1108 patients found no significant difference between apixaban and enoxaparin in 30- and 90-day rates of venous thromboembolism. Bleeding rates were similar; minor bleeding favored apixaban, but the difference was not statistically significant. Bias concerns were noted in the randomized controlled trials and cohort studies. Adherence to apixaban was >80% in 2 studies. Overall, the certainty of evidence was low to moderate owing to risk of bias and imprecision. CONCLUSIONS: Apixaban and enoxaparin demonstrated similar outcomes for venous thromboembolism and bleeding after gynecologic oncology surgery; however, the evidence is limited by risk of bias and imprecision. Apixaban may be convenient for some patients, but current data do not support it as a first-line therapy. Larger, high-quality trials are needed. Until then, treatment should be individualized. The oral route offers practical advantages for select patients.
Olaitan A, Pashayan N, Butler J
… +15 more, Cibula D, Costas L, Davidson EJ, Falconer H, Fotopoulou C, Akapo PK, MacDonald N, Moss E, Mueller M, Rosenthal AN, Sundström K, Hillemanns P, Manchanda R, Sleigh S, Widschwendter M
Int J Gynecol Cancer
· 2026 May · PMID 42284981
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Abnormal uterine bleeding is the most common symptom of endometrial cancer, but due to the low prevalence of underlying malignancy (3%), clinicians must distinguish those who can be quickly reassured from those who requi...Abnormal uterine bleeding is the most common symptom of endometrial cancer, but due to the low prevalence of underlying malignancy (3%), clinicians must distinguish those who can be quickly reassured from those who require urgent diagnosis and cancer treatment. The current diagnostic pathway is limited by the low specificity of transvaginal ultrasound, which leads to large numbers of invasive follow-up tests (hysteroscopy and biopsy). Transvaginal ultrasound may also miss almost a quarter of serous cancers, which have the poorest prognoses, and overall performance of this test, particularly specificity, is much lower in Black women. Many approaches have been explored to develop simple, objective, molecular triage tests, of which quantitative polymerase chain reaction-based DNA methylation tests in cervicovaginal samples have made significant progress. These data call on clinicians, researchers, and policymakers to invest in innovative diagnostic solutions and to reshape the diagnostic landscape for a cancer whose incidence and mortality continue to rise.
Lof P, Koole SN, Stiekema A
… +18 more, Jansen M, Fons G, Amant F, van Gent MDJM, Mom CH, Rosier-van Dunné FMF, van Baal WM, Verhoeve HR, Hermsen BBJ, Verbruggen MB, Hemelaar M, van de Swaluw JMG, Knipscheer HC, Huirne JAF, Westenberg SM, Retèl VP, van den Broek D, Lok CAR
Int J Gynecol Cancer
· 2026 Apr · PMID 42275792
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OBJECTIVE: Human epididymis protein 4 has been shown to be an effective biomarker for detecting early-stage ovarian cancer. However, its cost-effectiveness has not been systematically investigated. Therefore, this study...OBJECTIVE: Human epididymis protein 4 has been shown to be an effective biomarker for detecting early-stage ovarian cancer. However, its cost-effectiveness has not been systematically investigated. Therefore, this study aims to compare the cost-effectiveness of different referral policies in patients with an ovarian mass, based on current practices and the potential use of human epididymis protein 4. METHODS: A decision-tree health-state transition model was constructed to model costs and outcomes of 4 different referral strategies: human epididymis protein 4 and Risk of Malignancy Index combined, Risk of Malignancy Index alone, referral of all patients, and no referral at all. Costs (€) and outcomes were included with a time horizon of 1 year. RESULTS: Risk of Malignancy Index + human epididymis protein 4 resulted in the lowest mean costs per patient (€8905, standard deviation -1340), compared to Risk of Malignancy Index (€9,261, standard deviation -1394), referral of all (€10,117, standard deviation -1684), and no referral at all (€9357, standard deviation -1536). The mean quality-adjusted first life year was almost similar among all strategies (ranging from 0.785 to 0.789). Risk of Malignancy Index + human epididymis protein 4 was the most cost-effective in all sensitivity and scenario analyses. CONCLUSIONS: Risk of Malignancy Index + human epididymis protein 4 is a cost-effective strategy in the referral decision-making process of a general hospital for patients with an ovarian mass, compared to Risk of Malignancy Index alone or no strategy.
Gill SJ, Cornel K, Aversa I
… +5 more, Swift B, Covens AL, Vicus D, Kupets R, Gien LT
Int J Gynecol Cancer
· 2026 May · PMID 42275791
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OBJECTIVE: To evaluate the feasibility of sentinel lymph node biopsy in vulvar tumors ≥4 cm and compare groin recurrence rates to tumors <4 cm. METHODS: This retrospective single-center cohort study included patients wit...OBJECTIVE: To evaluate the feasibility of sentinel lymph node biopsy in vulvar tumors ≥4 cm and compare groin recurrence rates to tumors <4 cm. METHODS: This retrospective single-center cohort study included patients with invasive vulvar squamous cell carcinoma between 2008 and 2024. All patients underwent primary surgical excision with planned sentinel lymph node biopsy. Sentinel lymph node procedures in tumors ≥4 cm were performed at the surgeon's discretion. Patients were stratified by tumor size (<4 cm vs ≥4 cm). Analysis included descriptive statistics, Kaplan-Meier curves for groin recurrence-free survival, and multivariate analysis using a Cox proportional hazards model. RESULTS: Among 298 patients (490 groins), 233 had tumors <4 cm and 65 had tumors ≥4 cm. A sentinel lymph node was identified in 93.9% of tumors ≥4 cm. Larger tumors were associated with older age (p = .04), deeper depth of invasion (p < .0001), higher grade (p < .0001), and lymphovascular space invasion (p = .0002). Tumors ≥4 cm had significantly more positive sentinel lymph nodes (p = .04), extracapsular extension (p = .01), and groin node dissections (p = .048). Among 339 groins with negative sentinel lymph node (275 in tumors <4 cm and 64 in tumors ≥4 cm), isolated groin recurrences occurred in 15.6% of larger tumors and 5.1% of smaller tumors (p = .0002). The 3-year groin recurrence-free survival was higher for tumors <4cm (92.5% vs 73.3%, p=.0097). Multivariate analysis revealed that tumor size ≥4 cm was associated with an increased risk of groin recurrence (hazard ratio 1.17, 95% confidence interval 1.05 to 1.29, p = .003). CONCLUSIONS: Sentinel lymph node identification in tumors ≥4 cm was feasible but associated with worse groin recurrence-free survival despite negative sentinel lymph nodes. For patients with tumors ≥4 cm, cautious patient selection is important to balance morbidity and prognostic information.
Shore A, Abreu do Valle H, Kaur P
… +4 more, Kwon JS, Law MR, McAlpine JN, Hanley GE
Int J Gynecol Cancer
· 2026 May · PMID 42275703
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OBJECTIVE: There are widespread changes occurring in contraceptive use, with people moving away from oral contraceptive pills and toward intrauterine devices. Considerable data support the risk reduction for ovarian canc...OBJECTIVE: There are widespread changes occurring in contraceptive use, with people moving away from oral contraceptive pills and toward intrauterine devices. Considerable data support the risk reduction for ovarian cancer with oral contraceptive use, but there is little evidence on how levonorgestrel intrauterine device use affects ovarian cancer risk. This paper examines ovarian cancer risk in levonorgestrel intrauterine device users in British Columbia, Canada, between 2002 and 2021. METHODS: This research used population-based data from British Columbia to analyze the risk of ovarian cancer in levonorgestrel intrauterine device users, compared with never users, while controlling for previous oral contraceptive use and age. RESULTS: The final cohort included 788,736 individuals, of whom 52,888 were exposed to the levonorgestrel intrauterine device. Exposed individuals were younger on average and were more likely to have used oral contraceptives. During follow-up, ovarian cancer was diagnosed in 17 exposed individuals and 1184 unexposed individuals. After adjustment for age and oral contraceptive use, levonorgestrel intrauterine device exposure was associated with a reduced risk of ovarian cancer (adjusted hazard ratio 0.57, 95% confidence interval 0.35 to 0.93). In an age-matched 1:1 cohort (n = 105,776), the association was similar but less precise (adjusted hazard ratio 0.61, 95% confidence interval 0.24 to 1.12). In a subgroup restricted to individuals older than 60 years by the end of follow-up (n = 211,866), based on 8 exposed and 720 unexposed ovarian cancer cases, levonorgestrel intrauterine device exposure was not associated with reduced ovarian cancer risk (adjusted hazard ratio 1.59, 95% confidence interval 0.79 to 3.21). CONCLUSIONS: While the findings from the main cohort suggest that use of the levonorgestrel intrauterine device reduced the risk of ovarian cancer, this effect appeared to be confounded by age. These results should be interpreted with caution, as many levonorgestrel intrauterine device users are young and have not reached an age at which they are at a significant risk of ovarian cancer.
Viveros-Carreño D, Agustí N, Mora-Soto N
… +9 more, Beshar I, Angeles MA, Rodríguez J, Krause KJ, Iniesta MD, Wilke RN, Melamed A, Rauh-Hain JA, Pareja R
Int J Gynecol Cancer
· 2026 May · PMID 42263579
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OBJECTIVE: The objective of this systematic review and meta-analysis was to estimate the incidence of lymph node metastasis among patients with clinically early-stage (International Federation of Gynecology and Obstetric...OBJECTIVE: The objective of this systematic review and meta-analysis was to estimate the incidence of lymph node metastasis among patients with clinically early-stage (International Federation of Gynecology and Obstetrics 2014 stage I-IIA) low-grade serous ovarian carcinoma undergoing primary surgical treatment. METHODS: Registered in International Prospective Register of Systematic Reviews (CRD420251165472), this systematic review was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We searched Ovid MEDLINE, Embase, and Web of Science from inception through September 2025. Eligible studies included patients with pathologically confirmed low-grade serous ovarian carcinoma who were clinically presumed to have International Federation of Gynecology and Obstetrics 2014 stage I to IIA disease at surgery and underwent primary surgical management with pelvic and/or para-aortic lymph node dissection. We conducted a meta-analysis of single proportions to estimate the pooled rate of lymph node metastasis. Study-specific proportions (events/total) were pooled using an inverse-variance random-effects model with Freeman-Tukey double-arcsine transformation and back-transformed to proportions with 95% confidence intervals. Subgroup analyses excluded registry-based studies, studies at high risk of bias, and stage II disease. RESULTS: Among 129 screened records, 8 studies met the inclusion criteria after full-text review. Overall, 77 patients had lymph node metastasis, corresponding to a pooled incidence of lymph node metastasis of 9.6% (95% confidence interval 4.4% to 16.0%; I 58.8%). In the 3 studies reporting stage migration attributable only to nodal disease, 16 of 153 patients were upstaged, yielding a pooled upstaging proportion of 10.0% (95% confidence interval 5.6% to 15.5%; I 30.6%). Subgroup analyses showed no statistically significant differences associated with these factors. None of the included studies provided perioperative complication rates for lymphadenectomy. CONCLUSIONS: Approximately 1 in 10 patients with clinically early-stage low-grade serous ovarian carcinoma harbors occult nodal metastasis. These findings support discussing lymph node assessment as a source of staging information during preoperative counseling and individualized surgical planning. The prognostic and therapeutic value of identifying isolated nodal disease and the morbidity trade-offs in this setting remain unclear.
Zhao W, Yao Q, Qiu H
… +7 more, Xue Y, Shao Z, Zhang H, Yin X, Yang X, Song K, Liu P
Int J Gynecol Cancer
· 2026 May · PMID 42259217
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OBJECTIVE: Single-agent chemotherapy is the standard treatment for patients with low-risk gestational trophoblastic neoplasia. However, approximately 25% to 30% of these patients exhibit chemoresistance and require subse...OBJECTIVE: Single-agent chemotherapy is the standard treatment for patients with low-risk gestational trophoblastic neoplasia. However, approximately 25% to 30% of these patients exhibit chemoresistance and require subsequent multi-agent chemotherapy. This study sought to develop a risk stratification to identify patients at high risk of chemoresistance to single-agent chemotherapy. METHODS: The study cohort comprised 350 patients with low-risk gestational trophoblastic neoplasia from 3 tertiary centers from 2013 to 2022. All patients underwent standard chemotherapy and were randomly assigned in a ratio of 7:3. Logistic regression was performed to identify risk factors for chemoresistance. The final model was presented as a nomogram, and its performance was evaluated in terms of discrimination, calibration, and clinical utility. RESULTS: Pre-treatment serum human chorionic gonadotropin above 10,000 mIU/mL (odds ratio 11.70, 95% confidence interval 4.37 to 35.09), antecedent pregnancy of a non-hydatidiform mole (odds ratio 4.94, 95% confidence interval 2.07 to 12.16), and lung metastasis (odds ratio 3.07, 95% confidence interval 1.52 to 6.50) were independently associated with chemoresistance. A prediction model incorporating these factors demonstrated strong discriminative power, with an area under the receiver operating characteristic curve of 0.793 in the training cohort and 0.811 in the validation cohort. Furthermore, calibration curves and decision curve analysis indicated good calibration and clinical utility. Ultimately, we established a risk stratification approach that can identify 3 populations as the high-risk sub-groups for single-agent chemoresistance. CONCLUSION: Based on the multi-center data, we developed a predictive model and a risk stratification approach to estimate the probability of single-agent chemoresistance in patients with low-risk gestational trophoblastic neoplasia. This model may provide additional insight for individualized risk assessment, although its direct clinical utility requires further validation.
Eyada MF, Michael V, Patel S
… +8 more, How JA, Wilke RN, Jazaeri AA, Fleming ND, Soliman PT, Sood AK, Westin SN, Sims TT
Int J Gynecol Cancer
· 2026 May · PMID 42259216
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OBJECTIVE: Bevacizumab combined with oral cyclophosphamide has demonstrated activity in recurrent ovarian cancer, but data in heavily pre-treated high-grade disease are limited. We evaluated the safety and efficacy of th...OBJECTIVE: Bevacizumab combined with oral cyclophosphamide has demonstrated activity in recurrent ovarian cancer, but data in heavily pre-treated high-grade disease are limited. We evaluated the safety and efficacy of this combination regimen in this setting. METHODS: We conducted a retrospective review of patients with recurrent high-grade epithelial ovarian cancer treated with oral cyclophosphamide (50 mg daily) and bevacizumab (15 mg/kg every 3 weeks) at a single institution. Objective response rate was defined as complete or partial response. Progression-free survival was estimated using the Kaplan-Meier method, and adverse events were graded per Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Among 100 patients (median age 58 years; range; 38-80), 94% had high-grade serous histology and 96% had stage IIIC to IV disease. Fourteen (14%) were platinum-sensitive and 86 (86%) platinum-resistant, with a median of 3 prior treatment lines (range; 1-9). Patients received a median of 5 cycles (range; 2-34). The objective response rate was 40% (95% confidence interval 31 to 51), including 4% complete and 36% partial responses; 20% achieved stable disease. Response did not differ by prior bevacizumab exposure (36% vs 43%, p = .59) or platinum sensitivity status. Median progression-free survival was 4.6 months (95% confidence interval 3.4 to 5.9). Twenty-four (24%) patients experienced adverse events. The most common grade 3 or 4 toxicities included hypertension (3%), thrombocytopenia (3%), and hemorrhagic cystitis (1%). CONCLUSIONS: Bevacizumab combined with oral cyclophosphamide demonstrated meaningful activity and manageable toxicity in heavily pre-treated high-grade ovarian cancer, supporting its use as a feasible treatment option.
Int J Gynecol Cancer
· 2026 May · PMID 42250478
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OBJECTIVES: To evaluate the effectiveness and safety of prophylactic low-dose methotrexate in preventing progression to gestational trophoblastic neoplasia in women with high-risk hydatidiform mole. METHODS: A prospectiv...OBJECTIVES: To evaluate the effectiveness and safety of prophylactic low-dose methotrexate in preventing progression to gestational trophoblastic neoplasia in women with high-risk hydatidiform mole. METHODS: A prospective comparative study was conducted from March 2021 to February 2023 at hospitals affiliated with the University of Medicine-1, Yangon, Myanmar. Women with high-risk hydatidiform mole were enrolled using pre-defined clinical criteria. After evacuation, treatment allocation was determined by patient preference: 51 received intra-muscular methotrexate (0.4 mg/kg/day for 5 days), and 51 were managed expectantly. All patients underwent serial serum β-human chorionic gonadotropin monitoring for six months. Multi-variable logistic regression was performed to adjust for potential confounders. RESULTS: A total of 102 women were included. Baseline characteristics were comparable between groups; mean age was 31.1 ± 10.3 years in the prophylactic group and 35.5 ± 10.1 years in the control group, and complete hydatidiform mole accounted for 60.8% and 64.7% of cases, respectively. Progression to gestational trophoblastic neoplasia occurred in 11/51 patients (21.6%) in the prophylactic group compared with 31/51 patients (60.8%) in the control group (p <.001). Prophylactic methotrexate was independently associated with reduced gestational trophoblastic neoplasia progression (adjusted odds ratio 0.16, 95% confidence interval 0.06 to 0.42, p <.001). Treatment-related adverse events occurred in 31/51 patients (60.8%), most commonly elevated liver enzymes (39.3%), fatigue (41.2%), and mucositis (37.3%), predominantly Common Terminology Criteria for Adverse Events grade 1 to 2. One patient developed grade 3 pancytopenia and recovered fully with supportive care. No grade 4 events or treatment-related deaths occurred. CONCLUSION: Prophylactic low-dose methotrexate was associated with a reduced risk of gestational trophoblastic neoplasia in women with high-risk hydatidiform mole. Given the non-randomized, preference-based design, these findings should be interpreted with caution. Selective use in carefully chosen high-risk patients may be beneficial, particularly in settings where reliable follow-up is limited.
Coleman RL, Ray-Coquard I, Herzog TJ
… +8 more, Gonzales-Martin A, Slomovitz B, Harter P, Campbell-Simms K, Colombo N, Copeland LJ, Gynecological Group Foundation, Inc, and, European Network of Gynaecological Oncological Trial Groups
Int J Gynecol Cancer
· 2026 May · PMID 42250473
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BACKGROUND: The GOG Foundation and the European Network of Gynaecological Oncological Trial Groups have collaborated on industry-partnered gynecologic oncology trials since the formation of their joint Liaison Committee...BACKGROUND: The GOG Foundation and the European Network of Gynaecological Oncological Trial Groups have collaborated on industry-partnered gynecologic oncology trials since the formation of their joint Liaison Committee in 2016. Their 2019 joint publication established shared requirements for trial sponsorship, conduct, and authorship. Since then, the scope and global complexity of co-branded trials have grown substantially, with an increasing number of third-party cooperative groups and consortia participating alongside GOG Foundation and European Network of Gynaecological Oncological Trial groups, and with as an expanded volume of secondary and ancillary publications arising from major trials. PURPOSE: To address these evolving needs, the GOG Foundation/European Network of Gynaecological Oncological Trial groups Liaison Committee has developed updated publication and authorship guidelines (Version 2.0), replacing and substantially expanding the authorship provisions of the 2019 framework. SUMMARY: Key updates include the formalization of the Third-Party Group designation for non-GOG Foundation/non-European Network of Gynaecological Oncological Trial groups cooperative participants; detailed accrual-based authorship calculation and positioning rules for primary and secondary publications; guidance on ancillary and translational research authorship; conference presentation rotation; and explicit governance provisions for enrollment-related exceptions and deviations from these guidelines. CONCLUSIONS: These updated guidelines provide a transparent and equitable framework for publication and authorship in GOG Foundation-European Network of Gynaecological Oncological Trial groups industry-partnered trials, reinforcing scientific integrity, encouraging broad participation, and supporting the responsible dissemination of results in gynecologic oncology.
Int J Gynecol Cancer
· 2026 May · PMID 42248788
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OBJECTIVE: This study aimed to characterize national trends in hyperthermic intra-peritoneal chemotherapy utilization and associated survival outcomes among patients with stage III high-grade serous ovarian cancer underg...OBJECTIVE: This study aimed to characterize national trends in hyperthermic intra-peritoneal chemotherapy utilization and associated survival outcomes among patients with stage III high-grade serous ovarian cancer undergoing interval cytoreductive surgery following the OVHIPEC-1 trial. METHODS: A retrospective cohort study using the National Cancer Database. Women diagnosed with stage III high-grade serous ovarian cancer who underwent interval cytoreductive surgery, with or without hyperthermic intra-peritoneal chemotherapy, between 2004 and 2022 were included. hyperthermic intra-peritoneal chemotherapy utilization trends were assessed relative to the 2018 OVHIPEC-1 publication. Survival was analyzed with Kaplan-Meier and Cox proportional-hazards models adjusted for age, stage, and comorbidity. Sensitivity analysis was performed for propensity-matched cohort, and for a cohort restricted to patients treated at centers performing hyperthermic intra-peritoneal chemotherapy. RESULTS: Among 15,946 women included, 335 (2.1%) received hyperthermic intra-peritoneal chemotherapy. Hyperthermic intra-peritoneal chemotherapy utilization was 1.4% before 2018 and 3.2% thereafter, with a 61% relative increase from 2018 to 2022, and an average annual percent change increase of 12.6% (p < .001). The median overall survival for hyperthermic intra-peritoneal chemotherapy cases was 66 months (95% confidence interval 56.7 to 75.2) versus 42 months (95% confidence interval 41.2 to 42.7), log rank p < .001. Cox regression adjusted for age, race, residual disease, and Charlson-Deyo comorbidity score-hyperthermic intra-peritoneal chemotherapy was associated with reduced risk of death; hazard ratio 0.71 (95% confidence interval 0.59 to 0.84). Following propensity matching for patients age, race, insurance type, median income, residual disease, and comorbidity score-hyperthermic intra-peritoneal chemotherapy was associated with a significantly longer median overall survival; 66 months (95% confidence interval 56.7 to 75.2) versus 45 months (95% confidence interval 39.9 to 50.1), log rank p = .013. When the analysis was restricted to patients treated at centers performing hyperthermic intra-peritoneal chemotherapy, it was associated with a significantly longer median overall survival; 66 months (95% confidence interval 56.7 to 75.2) versus 44 months (95% confidence interval 42.5 to 45.4), log rank p < .001. Hyperthermic intra-peritoneal chemotherapy was associated with a longer hospital stay and higher rates of 30-day readmission and mortality. CONCLUSIONS: Hyperthermic intra-peritoneal chemotherapy adoption, although limited nationally, has increased modestly since OVHIPEC-1, with probable survival benefits for selected patients. Translating pivotal trial evidence into widespread clinical practice continues to face implementation barriers.
Flethe C, Netkova-Heintzen M, Postl M
… +10 more, Tascón Padrón L, Tauber C, Sieghartsleitner E, Pruss M, Kohlen M, Aigner A, Grech C, Pietzner K, Stroisch F, Sehouli J
Int J Gynecol Cancer
· 2026 May · PMID 42248787
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OBJECTIVE: This study aimed to assess the association of CA125 levels at pre-defined clinical time points with survival outcomes and to evaluate its role in recurrence detection in low-grade serous ovarian cancer. METHOD...OBJECTIVE: This study aimed to assess the association of CA125 levels at pre-defined clinical time points with survival outcomes and to evaluate its role in recurrence detection in low-grade serous ovarian cancer. METHODS: In this retrospective multi-center cohort study, patients with low-grade serous ovarian cancer of all International Federation of Gynecology and Obstetrics stages treated between 2007 and 2023 at 9 tertiary centers in Germany and Austria were included. Clinical data and serial CA125 measurements were extracted from medical records at pre-defined time points: diagnosis, after debulking surgery, during adjuvant therapy, follow-up, and recurrence. Associations with progression-free survival and overall survival were analyzed using Kaplan-Meier estimates and Cox regression. Sensitivity of CA125 for recurrence detection was assessed. RESULTS: A total of 368 patients were included; 84.2% had International Federation of Gynecology and Obstetrics stage IIB to IV disease. Median baseline CA125 was 113 U/mL, declining to 16 U/mL after primary treatment and remaining below 35 U/mL during follow-up. A 10-fold increase in baseline CA125 was associated with worse overall survival (hazard ratio 2.24, 95% confidence interval 1.37 to 3.67), remaining significant after adjustment for International Federation of Gynecology and Obstetrics stage, residual disease, age, and ascites (hazard ratio 1.90; 95% confidence interval 1.13 to 3.19). Elevated post-operative CA125 was associated with shorter progression-free survival. Persistently elevated CA125 after 6 cycles of adjuvant chemotherapy was associated with a higher hazard of progression or death (hazard ratio 5.54; 95% confidence interval 2.21 to 13.9). At recurrence, CA125 detected most relapses; however, 15.7% occurred despite normal marker levels, corresponding to a sensitivity of 84% (95% CI 74.0 to 90.4). CONCLUSIONS: CA125 in low-grade serous ovarian cancer correlates with disease stage, reflects treatment response, and shows prognostic relevance for progression-free survival at pre-defined clinical time points. It may support recurrence detection but should not be used as a stand-alone marker.
Rubagumya F, Shankar V, Kwizera V
… +18 more, Ndoli DA, Umubyeyi C, Manirakiza A, Mizero AF, Mutabazi E, Ngaji F, Maniragaba T, K Rutikanga K, Muvunyi J, Mugenzi P, Kamanzi JD, Rangira L, Nkurunziza E, Barihamwe C, Zaki B, Chamberlin M, Mutesa L, Kabiriti R
Int J Gynecol Cancer
· 2026 May · PMID 42247771
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OBJECTIVE: This study aimed to describe overall survival outcomes by treatment modality among women with International Federation of Gynecology and Obstetrics stage I to IVA cervical cancer treated with external beam rad...OBJECTIVE: This study aimed to describe overall survival outcomes by treatment modality among women with International Federation of Gynecology and Obstetrics stage I to IVA cervical cancer treated with external beam radiotherapy using a boost technique in Rwanda, where brachytherapy is unavailable. METHODS: We conducted a retrospective cohort study of women with International Federation of Gynecology and Obstetrics stage I to IVA cervical cancer treated at the Rwanda Cancer Centre/Rwanda Military Teaching Hospital between July 2018 and April 2023. All patients were planned for pelvic external beam radiotherapy with a simultaneous integrated boost (45 Gy to the whole pelvis with a boost to 70 Gy to the primary tumor and involved nodes in 30 fractions) delivered using intensity-modulated radiotherapy. Overall survival was defined as the time from the date of pathologic diagnosis to death or last contact, and was censored at 3 years. Overall survival was estimated using Kaplan-Meier methods and compared using log-rank tests. Multi-variable Cox regression with multiple imputation for missing covariates was used to assess associations between treatment modality and overall survival. RESULTS: Of 591 women seen, 577 met the eligibility criteria. Most (42.7%) presented with stage III disease. Treatment allocation was as follows: no treatment (12.7%), radiotherapy alone (3.9%), concurrent chemoradiotherapy (67.5%), and induction chemotherapy followed by concurrent chemoradiotherapy (15.9%). Two-year overall survival was 13.9% for no treatment, 44.1% for radiotherapy alone, 62.2% for concurrent chemoradiotherapy, and 76.4% for induction chemotherapy plus concurrent chemoradiotherapy. In adjusted models, all active treatment modalities were associated with lower hazards of death compared with no treatment. CONCLUSIONS: In this cohort in which brachytherapy was unavailable, survival among women with cervical cancer was strongly determined by treatment modality. Timely delivery of concurrent chemoradiotherapy, with or without induction chemotherapy, achieved 2-year overall survival comparable to regional reports, whereas absence of treatment was associated with dismal outcomes. These findings reinforce the urgent need to invest in brachytherapy capacity in Rwanda and similar resource-constrained settings.
Rotenberg O, Leone FPG, Groszmann Y
… +6 more, Winkeler M, Rotenberg N, Wu H, Alcazar JL, Dar P, Van den Bosch T
Int J Gynecol Cancer
· 2026 May · PMID 42247730
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OBJECTIVE: This study aimed to compare the diagnostic performance of 3-mm, 4-mm, and 5-mm trans-vaginal ultrasound endometrial thickness thresholds for detecting endometrial neoplasia and to determine the optimal clinica...OBJECTIVE: This study aimed to compare the diagnostic performance of 3-mm, 4-mm, and 5-mm trans-vaginal ultrasound endometrial thickness thresholds for detecting endometrial neoplasia and to determine the optimal clinical cutoff. METHODS: In this prospective cohort study, 1170 women aged ≥50 years referred for endometrial evaluation between February 2014 and October 2020 were included, with follow-up through January 2021. All participants underwent trans-vaginal ultrasound performed by certified sonographers across 4 ultrasound units within a large academic medical center with an ethnically diverse patient population. Diagnostic accuracy measures (including sensitivity, specificity, positive predictive value, and negative predictive value) were calculated for each endometrial thickness threshold. The McNemar test was used to compare diagnostic performance across cutoffs. The main outcome was the detection of endometrial cancer or hyperplasia. RESULTS: Among the 1170 eligible women, 82 (7.0%) had endometrial cancer and 42 (3.6%) had hyperplasia. Analyses were limited to 975 cases with a clearly visualized endometrial stripe. Sensitivity for endometrial neoplasia detection was 100%, 97.8%, and 90.2% for the 3-, 4-, and 5-mm thresholds, respectively, while specificity was 9.5%, 16.1%, and 24.4%. Sensitivity and negative predictive value did not differ significantly between the 3- and 4-mm thresholds (p =.16 and p =.40); however, both metrics were significantly higher for the 3- and 4-mm thresholds compared with the 5-mm threshold (p =.005 and p =.01). The 4-mm cutoff demonstrated significantly higher specificity and positive predictive value compared with the 3-mm cutoff (p <.001). CONCLUSIONS: Both the 3-mm and 4-mm endometrial thickness thresholds provided excellent sensitivity for excluding endometrial neoplasia. The 4-mm cutoff achieved greater specificity, minimizing unnecessary invasive procedures, and may represent the optimal threshold for clinical application.