Surgical randomized controlled trials (RCTs) have fundamentally reshaped gynecologic oncology, yet surgical interventions remain far less likely than medical therapies to be supported by prospective evidence. This disparity arises not from a deficit of scientific ambition or a scarcity of clinically meaningful surgical questions but rather from the methodological constraints intrinsic to surgical research: operative variability across institutions and surgeons, operator-dependent outcome heterogeneity, and the difficulty of standardizing complex intraoperative decision-making. This article, the first in a three-part series on surgical trials in gynecologic oncology, addresses the pre-trial phase, the period when a clinical question evolves into a rigorously justified, ethical, and feasible phase III trial. We examine five components of the trial planning process. First, we discuss equipoise, which refers to the genuine uncertainty among experts that must exist before a trial can be ethically justified, and this uncertainty gives shape and purpose to the trial design that follows. Second, we explore research questions which should precisely delineate the target population, clearly define the surgical intervention and comparator, and include a pre-specified primary endpoint that directly addresses the knowledge gap. Third, we distinguish between pilot and feasibility studies and argue that rigorous feasibility testing, including recruitment capacity, protocol adherence, regulatory infrastructure, randomization logistics, and surgeon credentialing, is foundational rather than optional. Third, we address the role of patient and stakeholder engagement, including the assessment of patient equipoise, the integration of patient-reported outcomes into endpoint selection, and the use of patient preference trial designs when strong a priori preferences exist. Fifth, we review the ethical and regulatory obligations unique to surgical trials, including the dual consent requirements for procedure and trial participation, and strategies for optimizing informed consent comprehension. These pre-trial decisions determine not only whether a surgical RCT can be launched, but whether it can be completed and ultimately transform care for patients with gynecologic malignancies.
INTRODUCTION:p53 status is prognostic in endometrial cancer (EC). Missense TP53 mutations typically produce an aberrant p53 overexpression phenotype by immunohistochemistry (IHC), and truncating mutations generally result in a p53 null phenotype. Given the role of p53 in modulation of the innate immune response through the type I interferon pathway (IFN-I), we hypothesized that IFN-I pathway expression and engagement would differ by p53 IHC status. METHODS:Multiplex IHC assessed a convenience sample of 50 specimens (p53wild-type = 25; p53mut overexpressed = 15; p53mut null = 10) for IFN-I pathway components. Quantitative digital analysis and TCGA validation through single sample gene set enrichment analysis (GSEA) was performed. Clinicopathologic data was abstracted for correlative analysis. RESULTS:Expression of several IFN-I pathway components (ADAR1, STING, MDA5, RIG-I) differed significantly by p53 status. Expression of all components was directionally consistent: p53mut overexpressed samples demonstrated the highest expression levels, and null samples demonstrated the lowest. Pathway substrate availability was assessed with K1 (an antibody for double-stranded RNA) was significantly increased in p53mut overexpressed samples. Pairwise Pearson correlation coefficients revealed signaling alterations by p53 status: DHX9 emerged as a central hub with increased network density in p53mut overexpressed tumors. GSEA confirmed findings, with significant divergence noted in IFN-I gene expression by missense versus truncated samples. Univariate analysis revealed high PKR IHC expression was associated with reduced odds of recurrence (OR 0.13, 95% CI: 0.03-0.68, p = 0.02). CONCLUSION:p53mut overexpressed EC reveals patterns of IFN-I expression that reflect a chronic inflammatory state, whereas p53mut null tumors demonstrate an immunosuppressed state. These hypothesis-generating findings warrant further study in an expanded clinical cohort.
Background Molecular profiling has transformed endometrial carcinoma management, yet its value in predicting response to fertility-sparing conservative treatment remains undefined. Objective To provide pooled estimates of oncologic outcomes of fertility-sparing treatment in women with early-stage endometrioid endometrial carcinoma (EEC), stratified by molecular groups. Data sources and selection criteria Six electronic databases (MEDLINE, Google Scholar, Scopus, Web of Science, ClinicalTrials.gov, Cochrane Library) were searched from inception to December 2025. Peer-reviewed studies providing extractable data on oncologic outcomes of fertility-sparing treatment by molecular group in EEC women were included; literature reviews and case reports were excluded. Main outcomes Rates of complete response (CR), stable disease (SD), progressive disease (PD), and recurrence were pooled within each molecular group using a random-effects model with Freeman-Tukey transformation; heterogeneity was assessed with the I2 index, and risk of bias with MINORS. Results Nine studies were included and the pooled population comprised 295 conservatively treated EEC women (POLE-mt n = 23; MMRd n = 46; p53-abn n = 14; NSMP n = 212). Pooled CR was 95% in POLE-mt, 82% in NSMP, 62% in MMRd, and 41% in p53-abn groups. Pooled PD was 2%, 3%, 14%, and 38%, respectively. Pooled recurrence was 27% (POLE-mt), 26% (NSMP), 41% (MMRd), and 41% (p53-abn). Conclusion In EEC women undergoing fertility-sparing management, molecular profiling might predict treatment response, with POLE-mt showing the best outcomes, p53-abn the worst, and MMRd and NSMP intermediate. If confirmed in larger cohorts, molecular profiling could be integrated into the pre-treatment workup to guide counselling.PROSPERO Registration Number: CRD420261322951.
Endometrial cancers classified as having no specific molecular profile (NSMP) represent the most prevalent molecular subtype of the disease. In this review, we summarize the immunogenomic landscape and phenotypic features of NSMP endometrial cancer and discuss current and emerging therapeutic strategies, including endocrine therapies, targeted agents, immunotherapies, and antibody-drug conjugates. We further highlight the need for future clinical trials to incorporate molecular stratification and prioritize the development of predictive biomarkers and rational combination approaches to improve outcomes for patients with NSMP endometrial cancer.
Surgical trials have been among the most important drivers of practice change in gynecologic oncology, generating evidence across ovarian, endometrial, cervical, and vulvar cancer. These studies have demonstrated that the surgical approach, extent of resection, treatment sequence, and integration with systemic therapies profoundly affect survival, perioperative morbidity, and long-term quality of life, yet the credibility, interpretability, and clinical impact of surgical trials depend not only on their design but also on the way they are conducted. Unlike pharmacologic trials, surgical trials are uniquely vulnerable to bias arising from variability in surgeon expertise, intraoperative decision-making, institutional infrastructure, and adherence to protocol-defined techniques. Failure to adequately standardize or consistently implement treatment protocols may obscure the true effects of an intervention, compromise the internal validity of the study, and diminish the external validity and generalizability of the findings. Conversely, rigorous and well-executed trials enable researchers to make definitive, practice-changing conclusions. This review provides a comprehensive framework for the conduct of multicenter, surgical trials, focusing on key domains including eligibility determination, the timing and implementation of randomization, surgical credentialing, the standardization of surgical procedures, quality assurance, outcome selection, the integration of patient-reported outcomes, patient accrual and informed consent, and equitable trial participation. By outlining principles that balance methodological rigor with pragmatic relevance, this review highlights how optimized trial conduct is essential to generating reliable evidence, accelerating surgical innovation, and improving oncologic and patient-centered outcomes for women with gynecologic cancers.
OBJECTIVE:To develop and validate a predictive tool to estimate the risk of ovarian cancer in a screening setting. METHODS:Machine learning was leveraged to create a predictive model for ovarian cancer diagnosis within one year of screening. Data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were used in model creation. Participants in this trial were comprised of females aged 55-74 years who underwent annual screening and prospective follow up for development of ovarian cancer. Stratified 15-fold cross validation was performed followed by external validation on a retrospective cohort. RESULTS:A random forest model was created using data from 150,907 screening events with a mean age of 62.5 ± 5.6 years. Ovarian cancer was diagnosed in 112 participants within one year of screening. The primary model was strongly predictive of ovarian cancer diagnosis, noting AUC of 0.930 (95% CI 0.886-0.974), sensitivity of 77.7% (66.4-88.9%), specificity of 98.0% (97.9-98.2%), positive predictive value of 2.9% (2.4-3.4%), negative predictive value of 99.9% (99.98-99.99%), and a positive likelihood ratio of 38.9. This model retained strong predictive value in external validation with AUC 0.910, sensitivity of 91.9%, and specificity of 72.6%, positive predictive value 29.6%, and negative predictive value of 98.6%. CONCLUSIONS:This model utilizes artificial intelligence to predict the risk of development of ovarian cancer within one year of screening demonstrating high levels of discrimination, sensitivity, and specificity. Machine learning techniques should be considered in the development of a multimodal approach to the early detection and prevention of ovarian cancer.
OBJECTIVE:To compare early- vs. late-phase gynecologic oncology trials with respect to rates of trial completion and enrollment of racial and ethnic minority groups (REMGs). METHODS:Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified and compared between early- and late- phase trials. Reporting and publication rates were compared. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. RESULTS:Of 223,690 trials identified, 2146 (0.9%) were focused on gynecologic oncology. Most gynecologic oncology trials investigated ovarian cancer (n = 1092, 50.8%), followed by cervical cancer (n = 350, 16.3%), and uterine cancer (n = 334, 15.6%). Only 22.1% (n = 474) of trials either reported results or led to publication. Early-phase trials were more likely to be published than late-phase trials (18.4% vs. 8.6%, p < 0.001). Among US-based trials which published (n = 252), 199 were early-phase (79.0%; phase I, phase I/II, or phase II), and 45 late-phase (17.9%; phase II/III, III or phase IV). 33.7% of early-phase trials (n = 67) reported race/ethnicity data compared to 64.4% of late-phase trials (n = 29, p < 0.0001). Of those trials which reported race/ethnicity, more patients identified as White (85.7%) in late-phase trials as compared to early-phase trials (72.0%, p < 0.001). CONCLUSION:In clinical trials in gynecologic oncology, early-phase trials were more likely to reach publication than late-phase trials. While late-phase trials were more likely to report race/ethnicity data compared to early-phase trials, early-phase trials were more likely to enroll REMGs. Further research must be conducted to determine reasons for the overall low publication rates of gynecologic oncology trials and relative under-enrollment of REMGs in late-phase trials, in order to work towards reducing these inequities in the future.
OBJECTIVE:Endometrial, ovarian, and cervical cancers predominantly affect middle-aged and older women, but temporal trends may differ in younger women due to distinct risk factors and clinical characteristics. We therefore assessed temporal trends in incidence, prevalence, mortality, and survival across these cancers in younger women. METHODS:Using population-based NORDCAN registry data, we identified women aged 0-49 years diagnosed with endometrial, ovarian, or cervical cancer in the Nordic countries between 1980 and 2023. Incidence, prevalence, mortality, and five-year relative survival (RS) were age-standardized, with the latter estimated using the Pohar-Perme method. RESULTS:Endometrial cancer incidence rates increased from 1.4 to 1.9 cases per 100,000 person-years (PY) between 1998 and 2000 and 2021-2023 (36% increase). Over the full study period, incidence rates declined for both ovarian cancer (4.2 to 2.1 cases per 100,000 PY; 50% decrease) and cervical cancer (6.5 to 5.5 cases per 100,000 PY; 15% decrease). Mortality rates decreased for women with ovarian cancer (1.9 to 0.6 per 100,000 PY; 75% decrease) and cervical cancer (1.5 to 0.5 per 100 00 PY; 67% decrease), while remaining steady at ≤ 0.2 per 100,000 PY for endometrial cancer. RS estimates remained high for endometrial cancer (90-95%). Cervical cancer five-year RS improved from 77-83% in 1979-1983 to 89-93% in 2019-2023, while ovarian cancer increased from 48 to 64% to 68-81%. CONCLUSIONS:Gynecological cancers show distinct temporal trends among young women in the Nordic countries. These findings underscore the importance of age-specific prevention strategies, including obesity prevention, monitoring contraceptive trends, and continued implementation of HPV-based screening and vaccination.
OBJECTIVE:To identify targetable pathways that can overcome resistance to trastuzumab deruxtecan (T-DXd) in endometrial cancer. METHODS:We used four endometrial cancer cell lines with different genetic backgrounds (KLE, HEC-1B, Ishikawa, and AN3 CA). Patient-derived endometrial organoids were established from surgically resected tumors and maintained in basement membrane extract with optimized media. Drug interactions were evaluated using Bliss synergy modeling. Organoid growth and treatment response were quantified by imaging-based size measurements. Protein signaling changes were analyzed by immunoblotting and comprehensive phosphoproteomic profiling. Cell cycle effects were assessed by flow cytometry. In vivo efficacy was evaluated using HEC-1B xenograft models treated with T-DXd and trametinib alone or in combination. Immunohistochemistry was performed on tumor and organoid samples to assess pathway activation and proliferation markers. Statistical analyses were conducted using GraphPad Prism 9, R and Python packages. RESULTS:T-DXd treatment increases ERK1/2 activation and reduces HER2 expression across various endometrial cancer cell lines. The addition of trametinib, a MEK1/2 inhibitor, to T-DXd, restores HER2 expression and markedly reduces the growth of both endometrial cancer cell lines (in vitro and in vivo), and organoids. Phosphoproteomic assays showed that T-DXd increases phosphorylation of proteins involved in DNA damage and the cell cycle, including ATR. We also found that ERK1/2 plays a key role in activating ATR and causing cell cycle arrest in the G2/M phase. CONCLUSION:T-DXd activates ERK1/2 and ATR, which contributes to resistance, and combining T-DXd with a MEK1/2 inhibitor enhances treatment response.
OBJECTIVE:To provide evidence-based guidance on the role of metabolic and bariatric surgery (MBS) and other weight loss interventions in the management of obesity among women with endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC). METHODS:This clinical practice statement, developed collaboratively by the Society of Gynecologic Oncology (SGO) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), synthesizes current literature on obesity, EC outcomes, and weight loss interventions, including lifestyle modification, anti-obesity medications, endoscopic bariatric therapies, and MBS. RESULTS:Obesity is a major modifiable risk factor for EC and is associated with worse oncologic and overall outcomes, with cardiovascular disease representing the leading cause of mortality in this population. Lifestyle and pharmacologic interventions can achieve modest weight loss but are often limited by sustainability. In contrast, MBS produces substantial and durable weight loss, improves obesity-related comorbidities, and is associated with reduced risk of hormone-related cancers, including EC. Emerging evidence supports the feasibility of incorporating MBS at various time points in cancer care, including as a bridge to definitive surgery or as an adjunct to conservative management, with early weight loss contributing to improved surgical candidacy and metabolic health. CONCLUSIONS:MBS represents the most effective and durable treatment for obesity in women with EIN and EC and may reduce cancer risk and improve overall health outcomes. Early multidisciplinary evaluation and integration of obesity treatment into oncologic care are essential to optimize patient outcomes.
INTRODUCTION:The prospective SENTIX study (NCT02494063) demonstrated non-inferiority in PFS of sentinel lymph node biopsy (SLNB) without pelvic lymphadenectomy (PLND) compared with the reference rate. We report the final analysis of quality of life (QoL), lower limb lymphoedema (LLL), and postoperative complications. METHODS:Patients with early-stage cervical cancer (tumours ≤4 cm) underwent SLNB. Patients with bilateral SLN detection and negative frozen sections (SLN group; n = 594) did not undergo further lymphadenectomy. Patients with unilateral or unsuccessful SLN detection underwent unilateral or bilateral PLND (PLND group; n = 134), enabling comparison of morbidity, lymphoedema and quality-of-life outcomes. EORTC QLQ-C30 was completed at baseline, 6, 12, and 24 months. LLL was assessed subjectively as patient-reported lymphoedema (S-LLL) and objectively (O-LLL) using circumferential measurements of both limbs. RESULTS:Global Health Status and functional scales were preserved in the SLN group, whereas the PLND group showed small declines in several functional domains that did not reach the threshold for clinical relevance. Fatigue and pain were transient after surgery, resolving by 6-12 months. Severe O-LLL was rare (≤2% of patients in both groups). S-LLL occurred less frequently in the SLN group (7% vs. 16%), and cases of LLL were more often graded as mild after SLNB. Symptomatic lymphoceles were rare, with no difference between groups. Early postoperative complications occurred in 12.5% vs. 21.5% of patients in the SLN and PLND groups (P = 0.01), with most being grade I-II. CONCLUSION:SLNB was associated with preserved QoL, less frequent and milder lymphoedema, and fewer early postoperative complications than PLND.
OBJECTIVE:Human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugates have emerged as a promising therapy, making accurate HER2 assessment important. We assessed HER2 expression in recurrent cervical cancer, examined clinicopathological factors associated with HER2 positivity at recurrence, and analyzed HER2 discordance between matched primary and recurrent tumors. METHODS:We retrospectively identified patients with recurrent cervical cancer treated at a single center between 2013 and 2024. HER2 immunohistochemistry was performed on recurrent and matched primary tumors and scored according to the 2017 ASCO/CAP guideline for gastroesophageal adenocarcinoma. Tumors scoring 2+ or 3+ were classified as HER2-positive. Factors associated with HER2 positivity were analyzed by logistic regression. RESULTS:Among 118 patients, the HER2-positive rate in recurrent tumors was 15.3% (18/118). HER2 positivity was higher in endocervical adenocarcinoma than in squamous cell carcinoma (30.6% vs 8.6%, P = 0.009). Adenocarcinoma (adjusted odds ratio [OR] 4.80; 95% confidence interval [CI], 1.60-15.66) and recurrence outside the prior radiotherapy field (adjusted OR 7.92; 95% CI, 1.68-77.86) were independently associated with HER2 positivity. Among the 72 matched pairs, HER2 discordance was observed in 7 (9.7%), including HER2 gain in 4 of 61 (6.6%) and HER2 loss in 3 of 11 (27.3%). Adenocarcinoma was the only factor associated with discordance (OR 10.33; 95% CI, 1.99-104.04). CONCLUSIONS:In recurrent cervical cancer, HER2 positivity was associated with endocervical adenocarcinoma and recurrence outside the prior radiotherapy field. Reassessing HER2 by re-biopsy at relapse may inform treatment selection in a subset of patients.
BACKGROUND:Risk-reducing hysterectomy (RRH) is the most effective endometrial cancer preventive strategy. Understanding health-related quality-of-life using health-related utility-scores (HRUS) is essential for counselling, shared decision-making, and informing health-economic evaluations of endometrial cancer prevention. This study aimed to determine HRUS for premenopausal RRH, with and without bilateral salpingo-oophorectomy (BSO). METHODS:Preventing Endometrial-Cancers: Comparing Risk-Reducing Strategies (PRESCORES) (ISRCTN17432105) part-2 is a UK-based randomised vignette study. Following a robust development process, vignettes described four postoperative health-states for a 40-year-old otherwise-healthy woman: "RRH at 1-month", "RRH at 1-year", "RRH-BSO at 1-month", "RRH-BSO at 1-year". These were valued using EQ-5D by participants recruited from the UK general-population and HRUS calculated. Utilities were subsequently adjusted by age-and sex-matched general-population reference values. Association of variables was explored with ordinary-least-squares regression with non-parametric bootstrapping. FINDINGS:Overall, 1001 women were included and randomised to 1-of-4 groups. The mean-age(±SD) was 53.6 (±11.4) years. Mean(±SD) HRUS were 0.942 (±0.072) for "RRH at 1-year", 0.841 (±0.137) for "RRH-BSO at 1-year", 0.670 (±0.149) for "RRH at 1-month", and 0.733 (±0.190) for "RRH-BSO at 1-month", with significant difference between each group (p < 0.001). Adjusting for age-sex-matched population reference utilities, HRUS were 1.000(95% CI:1.00-1.00), 0.994(95% CI:0.97-1.00), 0.866(95% CI:0.84-0.90) and 0.791(95% CI:0.77-0.81), respectively. Participant factors associated with vignette valuations included age, obesity, heavy menstrual-bleeding, higher income and mixed/other ethnicity. CONCLUSION:This randomised study provides HRUS following premenopausal RRH with and without BSO at two postoperative time-points, with adjustment against the age-and sex-matched general reference-population. These values are of relevance for informing counselling of women at increased endometrial cancer-risk regarding RRH and for health-economic evaluations.
OBJECTIVE:Clinical trials are essential for advancing treatment, yet inefficiencies across the trial lifecycle may hinder progress. We evaluated trial-level characteristics associated with non-completion among gynecologic cancer clinical trials. METHODS:We conducted an analysis of interventional cervical, ovarian, and uterine cancer trials registered on ClinicalTrials.gov. Trials with at least one U.S. site initiated between 2008 and 2021 and classified as completed or not completed were included (n = 1033). Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with non-completion. Reasons for premature trial termination were categorized into predefined groups. RESULTS:The majority of trials included ovarian cancer (68.3%), followed by uterine (25.8%), and cervical (24.7%) cancers. Overall, 30.3% of trials did not complete. In multivariable analyses, intervention type, year of initiation, and U.S. region were significantly associated with non-completion. Compared with drug/biologic trials, those evaluating multiple (OR 0.62, 95% CI 0.42-0.93) or other interventions (OR 0.49, 95% CI 0.25-0.98) had lower odds of non-completion. Trials initiated between 2018 and 2021 had substantially higher odds of non-completion compared with trials initiated 2008-2012 (OR 2.30, 95% CI 1.58-3.36). There was also heterogeneity of non-completion across region; however, no region was significantly different from the reference category of Northeast. Insufficient patient accrual was the most common reason for non-completion (28.8%). CONCLUSIONS:Thirty percent of gynecologic cancer trials fail to complete, with temporal trends playing a role. Findings highlight the need for improved trial design and feasibility planning to enhance efficiency in gynecologic oncology.
OBJECTIVE:Antibody-drug conjugates (ADCs) are expanding treatment options in endometrial carcinoma, but the distribution of actionable surface targets across histologic, molecular, and genomic subgroups remains incompletely defined. METHODS:This single-institution retrospective tissue microarray (TMA) study included 312 endometrial carcinomas: 158 endometrioid and 154 serous tumors. Trophoblast cell-surface antigen 2 (TROP2) was quantified by histochemical score (H-score); human epidermal growth factor receptor 2 (HER2) was assessed using endometrial carcinoma-specific and gastric/DESTINY-PanTumor02 criteria; and folate receptor alpha (FRα) positivity was defined as ≥75% viable tumor cells with ≥2+ membranous staining. Molecular class was assigned using a hierarchical DNA polymerase epsilon (POLE)-mutant, microsatellite instability/mismatch repair-deficient (MSI/MMRd), p53-abnormal, and no specific molecular profile (NSMP) classifier. Tumor mutational burden (TMB) and recurrent genomic alterations were analyzed in relation to biomarker expression. RESULTS:TROP2 was broadly expressed, with median H-scores of 280 in endometrioid and 200 in serous carcinomas. HER2 gastric-score 2+/3+ expression and FRα positivity were enriched in serous versus endometrioid carcinoma (22.5% vs 8.9% and 20.1% vs 4.4%), restricted to FIGO grade 3 tumors, and concentrated in p53-abnormal disease. FRα positivity was absent in POLE-mutant and MSI/MMRd tumors. HER2 2+/3+ expression correlated with erb-b2 receptor tyrosine kinase 2 (ERBB2) alterations, whereas FRα-positive tumors were enriched for TP53 alterations and showed lower frequencies of ARID1A and PTEN alterations. Triple-negative TROP2/HER2/FRα tumors were uncommon (6/308, 1.9%). CONCLUSIONS:TROP2 is broadly expressed in endometrial carcinoma, whereas HER2 and FRα define a more restricted high-grade, serous/serous-like, p53-abnormal compartment, supporting biomarker-informed ADC development.
OBJECTIVE:To evaluate feasibility, adherence, and participant experience of home-based cognitive training for gynecologic cancer survivors with cancer-related cognitive impairment (CRCI). METHODS:This was an open-label pilot randomized mixed-methods trial at a tertiary academic cancer center. Eligible participants were gynecologic cancer survivors with screen-positive cognitive concerns after chemotherapy. Participants were randomized 2:1 to 10 weeks of home-based BrainHQ cognitive training or usual care. Feasibility was completion of baseline and week 10 assessments. Adherence was completion of at least 1200 adjusted BrainHQ minutes, corresponding to 80% of the prescribed dose. Post-intervention mixed-methods interviews were analyzed using inductive thematic text analysis. RESULTS:Among 155 patients screened for subjective CRCI, 88 (57%) screened positive, 64 consented, and 60 were randomized to BrainHQ (n = 40) or usual care (n = 20). Overall, 59 of 60 randomized participants (98%) completed baseline and week 10 assessments, exceeding the prespecified 65% feasibility threshold (p < 0.001). Among participants randomized to BrainHQ, median use was 1442 min (IQR 747-1831), and 22 of 40 (55%) met the prespecified adherence threshold. Ten BrainHQ participants completed interviews. Qualitative themes showed that participants were motivated by cognitive concerns, perceived cognitive and functional value, used routine and accountability to support engagement, and were often interested in continued cognitive training. Barriers included time burden, competing health or life demands, and platform frustration. CONCLUSIONS:Trial procedures were feasible, and adherence to the full prescribed BrainHQ dose was variable. Qualitative findings support refinement of intervention dose, adherence support, and participant-facing materials before a larger efficacy trial. CLINICALTRIALS:GOV: NCT06662435.
BACKGROUND:Metastatic cancer patients receiving systemic chemotherapy face increased risks for venous thromboembolism (VTE). Benefit has been shown for prophylactic anticoagulants in risk-stratified populations. Ovarian cancer (OC) is commonly advanced at diagnosis and treated with chemotherapy. Despite high VTE rates among OC patients, predictors of risk in this population are not well studied, and information on the benefit of oral anticoagulants is lacking. OBJECTIVE:A quality improvement (QI) intervention to improve appropriate anticoagulation in risk-selected OC patients receiving first-line chemotherapy was implemented, prospectively assessing VTE risk reduction. METHODS:Patients receiving first-line chemotherapy for OC at Sheba Medical Center 2020-2025 were included. A QI program (launched 07/2023) included staff education, EMR-incorporated Khorana scoring, integrated apixaban prescriptions and targeted chemo-suite questionnaires. Data was extracted from the EMR using MDClone® software with Natural Language Processing to identify VTE events in imaging reports. Descriptive statistics were used to compare patients treated before and after program implementation. Predictors of VTE were evaluated with logistic regression. RESULTS:Patient characteristics were comparable before and after program implementation. VTE rates were high at 16.9% before, and 12.5% following roll-out. No increase in bleeding events or blood products consumption was appreciated. Program implementation was found to be a significant protective factor on multivariable analysis, adjusting for other risk factors (aOR = 0.39 (0.17-0.81), p = 0.015). CONCLUSION:The implementation of an oral anticoagulation QI program successfully decreased VTE events during first-line chemotherapy for OC with no appreciable increase in risk. Future work will focus on improved risk stratification and selection for thromboprophylaxis.
OBJECTIVES:To identify patient, provider, and system-level factors associated with delayed diagnosis of vulvar squamous cell cancer (SCC). METHODS:An IRB-approved retrospective single-institution cohort study was conducted in patients with vulvar SCC diagnosed from 2009 to 2020. Patients were compared by time from symptom onset to biopsy using a prespecified threshold of <6 months versus ≥6 months. Demographic, tumor, provider, and healthcare utilization variables were collected. Progression-free survival (PFS) and overall survival (OS) were examined. RESULTS:Among 157 eligible patients, 39 (24.8%) experienced a diagnostic delay of ≥6 months. Delayed diagnosis was not associated with age, race, smoking status, dermatologic conditions, tumor size, stage, insurance, or income. Patients with delayed diagnosis underwent more clinic visits, examinations, empiric therapies, and encounters before biopsy (all p ≤ 0.003). Initial provider specialty differed significantly between groups: patients diagnosed within 6 months were more likely to first present to a gynecologic provider, whereas those initially evaluated by non-gynecologic providers had longer median time to diagnosis (1.9 vs 4.7 months, p < 0.0001) and were more likely to experience delay ≥6 months (34.7% vs 16.5%, p = 0.0098). On multivariable analysis, higher BMI (aOR 1.05 per kg/m2, 95% CI 1.01-1.10) and initial evaluation by a non-gynecologic provider (aOR 2.24, 95% CI 1.03-5.01) independently predicted delay ≥6 months. CONCLUSIONS:Delayed diagnosis of vulvar SCC was associated primarily with provider and healthcare system-related factors rather than patient or tumor characteristics. Earlier biopsy, timely gynecologic referral, and improved patient and provider education may help facilitate more prompt diagnosis and therapeutic intervention.
