Oncology Research and Treatment

Identification of Biomarkers for Cervical Cancer Radiotherapy Sensitivity and Survival Prognosis

Introduction: Radiotherapy resistance leads to treatment failure and disease progression in patients with cervical cancer. This study aims to elucidate the molecular underpinnings of radiotherapy response in cervical cancer by identifying radiotherapy sensitivity genes (RSGs). Methods: We utilized two GEO expression profiling datasets (GSE3578 and GSE6213) comprising cervical cancer biopsy samples taken before and during radiotherapy to identify differentially expressed genes (DEGs) using the RankProd meta-analysis approach. Subsequent analysis was conducted using data from the TCGA-CESE project to further determine the RSGs and investigate their associations with survival prognosis, immune cell infiltration, and drug sensitivities. The differential expressions of the candidate RSGs were validated in an independent set of cervical cancer patients by qPCRs. Results: A total of 518 DEGs were identified, with 305 genes upregulated and 213 genes down-regulated during radiotherapy. Six key RSGs were identified as significantly associated with radiotherapy response. Cox regression analysis revealed that upregulations of IL1RAP and GPR15 were associated with an increased risk of poor survival prognosis. Functional enrichment analysis highlighted the involvement of these genes in critical biological processes such as cytokine signaling and immune regulation. Correlation analyses demonstrated significant associations between RSG expressions and M2 macrophage and γδT cell abundances in tumor microenvironment, as well as drug sensitivities. The expression of IL1RAP was significantly higher in the complete response group, supporting the bioinformatic finding. Conclusion: Our findings on RSGs could potentially serve as potential biomarkers for predicting radiotherapy response and as therapeutic targets to enhance the efficacy of radiotherapy.

Clinicopathological Features and Survival Trends of Non-Epithelial Ovarian Cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database

Introduction: Owing to their low incidence, no reliable statistics about prognostication derived from large sample sizes have been reported of malignant ovarian germ cell tumors (MOGCTs) and sex cord-stromal tumors (SCSTs). The present study aimed to investigate the clinicopathological prognostic factors and the survival trends of MOGCTs and SCSTs. Materials and Methods: Patients with MOGCTs and SCSTs were recorded in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2000 and 2019. Clinical, demographic, and treatment characteristics were compared between groups of MOGCTs and SCSTs. Cox risk regression analysis and Kaplan-Meier survival curves were used to compare overall survival (OS) and cancer-specific survival (CSS) and to assess the prognostic factors. Results: Information about 2,506 patients with MOGCTs and 1,556 patients with SCSTs was extracted from the SEER database, respectively. Aged <40 years and single were more common in patients with MOGCTs than in those with SCSTs. The vast majority of patients with MOGCTs and SCSTs underwent surgery (98.1% vs. 94.5%; p < 0.001), and women with MOGCTs were more likely to receive chemotherapy than women with SCSTs (56.1% vs. 32.2%; p < 0.001). For both patients before and after propensity-score matching, the 5-year OS rates of patients with SCSTs were lower than those of patients with MOGCTs (p < 0.05). In multivariate Cox regression analysis, both age and surgery were independent predictors of OS in patients with MOGCTs and SCSTs. FIGO staging was an independent predictor of CSS in MOGCT patients. Tumor size and chemotherapy were also independent predictors of CSS in patients with SCSTs. Conclusion: Compared to patients with SCSTs, those with MOGCTs tended to be younger and had a higher OS and CSS. Adjuvant chemotherapy after surgery did not prolong OS and CSS in patients with SCSTs.

Impact of Epidural Anesthesia on the Outcome of Elderly Patients with Endometrial Cancer: Results of a Propensity Score-Matched Analysis

Introduction: Epidural anesthesia is a standard procedure to mitigate pain during surgery for endometrial cancer (EC). Little data exist about the influence of epidural anesthesia on the oncological outcome in elderly patients with EC. This retrospective study aimed to investigate potential correlations between epidural anesthesia and cancer recurrence in patients with EC. Methods: We screened the medical records of patients ≥60 years treated surgically for EC at the University Medical Center Mainz between January 2008 and December 2019. All women underwent general anesthesia (GA) alone or combined with epidural anesthesia (EGA). Cox regression, the Kaplan-Meier method and propensity score matching were used to analyze the prognostic influence of the anesthesiologic regime on survival. Results: A total of 152 women with EC were included. Twenty-nine patients (19.1%) formed the EGA cohort. The median time of follow-up (FU) was 31 months (interquartile range [IQR]: 8–67.5). The EGA cohort showed more in-hospital complications (27.6 vs. 8.9%; p = 0.006), especially thromboembolic events (3 vs. 0 events; p = 0.006), as well as a longer hospital stay (11 [IQR: 8–13] vs. 7 [IQR: 4–9] days; p < 0.001). Twenty-six patients (17.1%) developed a recurrence in the follow-up at a median of 13 months [IQR: 7.75–29.5]. Thirty-two patients died during FU (21.1%). The EGA cohort showed higher FIGO stages and a higher histological grading than the GA cohort. In the Kaplan-Meier analysis, EGA showed a significantly reduced 5-year recurrence-free survival (RFS) (36.5% vs. 72.6%, p < 0.001) and overall survival (OS) (58.6% vs. 79.9%, p = 0.008). However, in multivariate Cox regression analysis including FIGO stages and histological grading, EGA did not influence RFS (HR: 2.02; 95%-CI: [0.99–4.12], p = 0.054), and OS (HR: 1.03; 95%-CI: [0.40–2.66], p = 0.951). This was backed up by the propensity score- matched analysis for survival (RFS: p = 0.604, OS: p = 0.86). Conclusion: Considering risk factors, epidural anesthesia in combination with GA did not differ in recurrence-free and overall survival compared to GA. Prospective randomized trials are warranted in order to further evaluate this topic.

Decision-Making in Gynaecological Oncology Multidisciplinary Team Meetings: A Cross-Sectional, Observational Study of Ovarian Cancer Cases

<b><i>Introduction:</i></b> Multidisciplinary team (MDT) meetings are widely used across the UK to provide expert decisions and improve cancer outcomes. However, little is known about the underlying mechanisms of MDT decision-making. We investigated how decisions are made regarding the management of advanced ovarian cancer in gynaecological oncology MDT meetings. <b><i>Methods:</i></b> A cross-sectional observational study was performed, focussing on 41/ 223 MDT case discussions across six hospitals. The validated MDT-MODe tool was adapted to increase relevance to gynaecological oncology. Case information and contributions from seven disciplines were rated on a five-point Likert scale. Spearman’s correlation investigated relationships between factors and an exploratory factor analysis examined the underlying structure of MDT discussion. <b><i>Results:</i></b> Forty-one MDT decisions were made for patients with FIGO Stage III/IV ovarian cancer. MDT case discussions were structured by four factors: “Clinical Presentation,” “Patient Factors,” “Chair’s Direction” and “Input from Other Specialties.” Nurses were often quiet but facilitated discussion of patient factors. Junior doctors were not involved in MDT decision-making. <b><i>Conclusions:</i></b> The decision-making process in MDT meetings is driven by four underlying factors, the most significant of which represents patient history, tumour markers, images and radiologist input. Patient factors were underrepresented, and nurses should be empowered to overcome this.

Preoperative Conization May Have a Positive Impact on Survival in Early-Stage Cervical Cancer: A Propensity-Matched Study

<b><i>Introduction:</i></b> A recent prospective randomized study demonstrated that minimally invasive surgery (MIS) was inferior to open surgery in disease survival in early-stage cervical cancer. Our aim was to investigate whether there were survival benefits of preoperative conization prior to MIS for early-stage cervical cancer. <b><i>Methods:</i></b> We retrospectively analyzed patients who eventually underwent definitive MIS with stage IA2 to IB1 (no >2 cm) squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. Preoperatively, the patients were separated into 2 groups: one managed with conization and the other undergoing biopsy without conization. Propensity scoring weight and matching were used to reduce the influence of possible allocation biases. The Cox regression model was used for univariate and multivariate analyses of disease recurrence and survival. <b><i>Results:</i></b> 227 patients were contained in this study (99 patients in the conization group and 128 patients in the nonconization group). The 5-year DFS of the conization group was statistically better than that of the nonconization group (98.4% vs. 91.8%, <i>p</i> = 0.011). By univariate analysis, conization (HR = 0.11, 95% CI = 0.01–0.87, <i>p</i> = 0.03) and histologic cell type (<i>p</i> = 0.01) were considered as risk factors for recurrence. Multivariate analysis further confirmed conization (HR = 0.04, 95% CI = 0.01–0.51, <i>p</i> = 0.01) and histologic cell type (<i>p</i> < 0.01) correlated with DFS. After propensity score matching (1:1), 84 patients were included in the conization and nonconization groups, respectively, with 5-year DFS still higher in the conization group (98.3% vs. 92.9%, <i>p</i> = 0.037). The results after univariate and multivariate analyses were consistent with those prior to propensity score matching. <b><i>Conclusion:</i></b> Preoperative conization in conjunction with MIS seemed to be a safe and feasible approach, with results that may have implications for the reduction of recurrence. Histologic cell type also impacted survival. Therefore, more future prospective studies are warranted.

Comparison of Radical Surgery and Radiotherapy for the Treatment of Early-Stage Cervical Carcinoma: A Meta-Analysis

<b><i>Objective:</i></b> To compare the efficacy and safety of radical surgery with radiotherapy in patients with early-stage cervical carcinoma. <b><i>Methods:</i></b> PubMed, Web of Science, and Embase were systematically reviewed, and studies comparing radical surgery with radiotherapy were included. The main efficacy outcomes included overall survival (OS), and disease-free survival (DFS). Safety endpoints were adverse events. Hazard ratios (HR) or risk ratios (RR) with 95% CI were used to pool the estimates. <b><i>Results:</i></b> A total of 6 studies were included in this meta-analysis. Radical surgery was associated with comparable survival effects in OS (HR = 0.73; 95% CI 0.46–1.17; <i>p</i> = 0.196) and DFS (HR = 0.84; 95% CI 0.64–1.10; <i>p</i> = 0.207) as compared with radiotherapy. Moreover, positive lymphangiography (HR = 3.67; 95% CI 2.86–4.70; <i>p</i> < 0.001), adeno-carcinomatous histotype (HR = 2.53; 95% CI 1.80–3.56; <i>p</i> < 0.001), adenosquamous histotype (HR = 1.55; 95% CI 1.27–1.89; <i>p</i> < 0.001), tumor size ≥4 cm (HR = 1.60; 95% CI 1.14–2.23; <i>p</i> < 0.001), stage IB2 (HR = 1.71; 95% CI 1.43–2.04; <i>p</i> < 0.001), and stage IIA (HR = 1.85; 95% CI 1.54–2.22; <i>p</i> < 0.001) were all independent predictors of decreased survival. Patients treated with radical surgery had a rate of adverse events similar to that of those treated with radiotherapy (RR = 1.23; 95% CI 0.61–2.48; <i>p</i> = 0.557). <b><i>Conclusion:</i></b> The present study suggested that radical surgery and radiotherapy offered similarly effective treatment in terms of OS and DFS in early-stage cervical carcinoma. Moreover, the complication rate between the 2 treatments was not significantly different. Considering the potential limitations of this study, more large-scale well-designed randomized controlled trials are needed to verify our findings.

Patterns of Treatment Failure after Concurrent Chemoradiotherapy or Adjuvant Radiotherapy in Patients with Locally Advanced Cervical Cancer

<b><i>Objective:</i></b> To identify patterns of therapy failure after radiotherapy in Chinese patients with locally advanced cervical cancer (LACC). <b><i>Methods:</i></b> A retrospective study was conducted at a Chinese hospital from June 2012 to July 2018. All analyses were done using SPSS 26. <b><i>Results:</i></b> 105 patients with treatment failure were included. After a median follow-up of 27 months (range 10–82), the 3-year survival rate after therapy failure was 19.4%. In multivariate analysis, squamous cell carcinoma antigen (SCC-Ag) <4 ng/mL (<i>p</i> < 0.001) and disease-free interval >12 months (<i>p</i> = 0.013) showed significant survival benefits. We identified 3 types of failure: distant lymph node metastasis (<i>n</i> = 50), hematogenous metastasis (<i>n</i> = 53) and pelvic failure (<i>n</i> = 48). Most metastatic para-aortic lymph nodes (PALN) were inferior to the level of left renal hilum (84.8%, <i>n</i> = 28). A total of 80% of patients with supraclavicular lymph nodes (SCLN) metastasis ignored imaging on supraclavicular region. For solitary SCLN or lung metastasis, the prognosis was better than that combined with other sites failure, respectively (<i>p</i> = 0.005; <i>p</i> = 0.001). Many patients with central sites recurrence received insufficient doses of intracavitary brachytherapy (IBT) for low tolerance to pain. <b><i>Conclusion:</i></b> The distribution of metastatic PALN is asymmetrical and optimizing clinical target volume to minimize toxicity of para-aortic radiation is necessary. The effect of ultrasonography as preliminary screening and follow-up means on SCLN metastasis can be expected. Pain management and psychological interventions are essential for patients receiving IBT.

Prognosis and Therapy of Ovarian Cancer, Part 3: Follow-Up Care, Recurrence, and Screening, the Full Round Circle

Background: Ovarian cancer (OC) accounts for the most cancer deaths in women worldwide, despite it being the 8th most common one. Almost two-thirds or OC cases present in advanced stages (III/IV) and will require maintenance therapy lasting for up to 36 months in some patients. Despite the introduction of innovative treatments, OC recurs in about 80% of cases in advanced stage disease. Management of recurrent OC is based on multiple factors and includes either surgery, in suitable candidates, followed by chemotherapy or systemic treatment alone. Due to its heavy physical, psychological and economic burden, reducing mortality of OC through prevention and early diagnosis is of utmost importance. Summary: Prolonged maintenance treatment period in advanced OC led to a more complex follow-up care, which will start during active treatment and hence include management of therapy side effects. Intensifying follow-up through routine measurements of serum CA-125 and the consequent early induction of treatment in asymptomatic relapsed patients failed to improve overall survival compared to symptom oriented follow-up. In recurrent OC patients with a long treatment-free interval, good performance status, low ascitic fluid volume and completely operable tumor in the first diagnosis were found to benefit form a secondary cytoreductive surgery. Several drug classes were heavily tested in recurrent OC, antibody-drug conjugates (ADCs) have been showing some promising results in platinum-resistant recurrent OC. Studies investigating Immunotherapy on the other hand have been much less encouraging. Despite achieving a stage shift toward early stage detection in some trials, large, well-designed studies have so far failed to develop an effective OC screening program that reduces mortality. Key Messages: Managing long-term treatment side effects has become an indispensable part of follow-up care in OC. Symptom oriented follow-up with tumor marker measurement and imaging reserved for symptomatic patients is the standard of care. Allocating the right therapy plan in patients with recurrent OC, to secondary cytoreductive surgery versus systemic treatment will significantly impact progression-free (PFS) and OS. To date, there is no effective screening program for prevention and early detection of OC.

Prognosis and Therapy of Ovarian Cancer: Part 2 – the Shifting Landscape of Medical Treatment in Ovarian Cancer

Background: Ovarian cancer (OC) remains the most common cause of death among all gynecological cancer. For early-stage disease (FIGO stages I and II), staging surgery followed by chemotherapy (CT) with carboplatin ± paclitaxel often results in high rates of progression-free and overall survival. However, this is not the case for advanced-stage disease (stages III and IV), where recurrence rates are significantly higher. Consequently, additional therapeutic strategies, such as maintenance treatment, are essential to improve outcomes in these patients. Summary: Several randomized controlled trials have proven the benefit of bevacizumab, an anti-vascular endothelial growth factor antibody (anti-VEGF) as first-line maintenance treatment. Molecular testing led to the introduction of poly (ADP-ribose) polymerase inhibitors (PARPis), with outstanding results in BRCA-mutated (BRCAmt) and homologous recombination-deficient without BRCAmt (HRd) tumors, but not as ideal in HR-proficient (HRp) tumors, which make up the majority of the OC tumors; therefore, further research in this category of tumors is urgently warranted. Immunotherapy, both with CT and as maintenance, failed to improve survival in advanced OC. Key Messages: Combining multiple drug classes (immune checkpoint inhibitors, anti-VEGF, and PARPi) was able to improve survival; results in HRp tumors are however still pending. Phase 2 and 3 trials are underway to investigate more innovative treatment of OC.

Prognosis and Therapy of Ovarian Cancer, Part 1: Patient Selection and Surgical Management in Advanced Ovarian Cancer – What Tools Do We Have to Make the Right Decision?

Background: Ovarian cancer is the gynecological cancer with the worst overall survival worldwide. Around 70% of patients are diagnosed in an advanced stage. Since low residual tumor after surgery has been repeatedly observed to deeply affect survival, achieving complete resection of tumor with no macroscopic residual disease through primary debulking surgery (PDS) has become the standard of care in advanced ovarian cancer. Summary: The concept of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) was introduced in order to improve resectability in patients who otherwise, due to advanced age, poor performance status, or extensive tumor burden, cannot be optimally operated. Patient-related factors like age, performance status, comorbidities, and nutritional status can all affect the survival and are all key factors in the selection process. Accurately assessing tumor extension and therefore allocating a patient to the NACT/IDS strategy is of great importance and can be achieved either through imaging (CT scan, ultrasound, MRI, PET scan) or laparoscopy using different validated laparoscopic scoring systems. Key Messages: There is sizable randomized evidence to support the NACT/IDS as an acceptable strategy in patients with advanced ovarian cancer, in whom a PDS is not possible or would have a suboptimal outcome. Patient- and tumor-related factors play a key role in allocating the right management plan to the right patient.

Clinicopathological Features, Prognostic Factors, Survival Trends, and Treatment of Malignant Ovarian Germ Cell Tumors: A SEER Database Analysis

<b><i>Objective:</i></b> The aim of this study was to investigate the clinicopathological prognostic factors of malignant ovarian germ cell tumors (MOGCT) and evaluate the survival trends of MOGCT by histotype. <b><i>Methods:</i></b> We extracted data on 1,963 MOGCT cases diagnosed between 2000 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database and the histological classification of MOGCT, including 5 categories: dysgerminoma, embryonal carcinoma (EC), yolk sac tumor, malignant teratoma, and mixed germ cell tumor. We examined overall and disease-specific survival of the 5 histological types. Kaplan-Meier and Cox proportional hazards regression models were used to estimate survival curves and prognostic factors. We also estimated survival curves of MOGCT according to different treatments. <b><i>Results:</i></b> There was a significant difference in prognosis among different histological classifications. Age, histotype, grade, SEER stage, and surgery were independent prognostic factors for survival of patients with MOGCT. For all histotypes, 1-, 3-, and 5-year survival rate estimates were >85%, except for EC, which had the worst outcomes at 1 year (55.6%), 3 years (44.4%), and 5 years (33.3%). In the distant SEER stage, both chemotherapy and surgery were associated with improved survival outcomes compared with surgery- and chemotherapy-only groups. <b><i>Conclusions:</i></b> Dysgerminoma patients had the most favorable outcomes, whereas EC patients had the worst survival. A young age, low grade, and surgery were all significant predictors for improved survival. In contrast, a distant SEER stage was a risk factor for poor survival. Chemotherapy combined with surgery contributed to longer survival times of patients with MOGCT in the distant SEER stage.

Effect of Adjuvant Chemotherapy in Stage III Cervical Cancer Patients Treated with Concurrent Chemoradiation: A Multicenter Study

Introduction: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. Methods: We performed a multicenter, retrospective analysis of 139 International Federation of Gynecology and Obstetrics stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. Results: Five-year progression-free survival (PFS) was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p = 0.008). Median PFS was 30.9 months (CI 95% 14.8–46.9) and 16.6 months (CI 95% 9.3–23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival (OS) was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p < 0.001). Median OS was 132.2 months (CI 95, %66.5–197.8) and 34.9 months (CI 95% 23.1–46.7) in patients receiving CCRT with and without AC, respectively. Conclusion: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.

Patient-Reported Outcome in Metastatic Breast Cancer and Platinum-Resistant Recurrent Ovarian Cancer Patients Treated with Metronomic Cyclophosphamide ± Methotrexate: PROmetronomic

Introduction: Maintenance of subjective well-being and health-related quality of life (HRQoL) play a crucial role in the treatment of metastatic cancer. The metronomic chemotherapy (MCT) may be a favorable treatment option in metastatic breast cancer (MBC) and platinum-resistant recurrent ovarian cancer (ROC). The aim of this study was to evaluate the HRQoL of MBC and ROC patients treated with MCT. Methods: PROmetronomic was a prospective, monocentric study evaluating the HRQoL in MBC and ROC patients treated with oral cyclophosphamide 50 mg daily (+ oral methotrexate 2.5 mg every other day for MBC) from August 2020 to August 2022. The data were obtained using EORTC QLQ-C30, BR23, OV28, and HADS-D via the eHealth-based platform CANKADO. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 5 MBC patients and 9 ROC patients were evaluated. The mean global health status was 47.2 at baseline and 36.1 at the end of MCT (p = 0.350). Functional scales and symptoms remained stable during MCT except for the significant increase of fatigue (51.9 vs. 77.8, p = 0.038). Anxiety and depression were without significant alteration (9.1 and 8.1 at baseline vs. 9.3 and 8.1 after MCT). The median PFS and OS were 10.0 weeks and 28.0 weeks, respectively. No ≥grade 3 toxicities were reported. Conclusion: MCT had no significant impact on HRQoL of our small cohort of heavily pretreated MBC and ROC patients and may represent a valuable treatment option for maintaining HRQoL in selected patients.

Prognostic Significance of HER2 Positivity in Endometrium Cancer

Introduction: Endometrium cancer is the most common gynecological malignancy in developed countries. In this study, we aimed to investigate the effect of HER2 positivity on prognosis in endometrial cancer. Methods: In our study, patients admitted to our clinic with a diagnosis of endometrial cancer between September 2019 and December 2023 were retrospectively evaluated. Human epidermal growth factor receptor 2 (HER2) immunohistochemistry was performed in 121 patients. HER2-low group (HER2 score: 0 and 1) and HER2-high group (HER2 score: 2 and 3) were defined according to the HER2 immunohistochemistry score in the pathology, and patients were compared accordingly. Results: We observed that 97 (80.2%) of the patients were in the HER2-low group, while 24 (19.8%) were in the HER2-high group. In the OS analysis, age (p = 0.381), menopausal status (p = 0.511), ECOG performance status (p = 0.087), histological type of tumor (p = 0.727), pathological grade (p = 0.206), serum LDH (p = 0.091), and albumin (p = 0.315) levels did not affect the prognosis. Patients with lower FIGO stage (p = 0.003) and HER2-high patients (p = 0.040) had better survival outcomes. Multivariable analysis showed that FIGO stage (p = 0.004) and HER2 status (p = 0.040) were independent risk factors affecting survival in endometrial cancer. Conclusion: As a result of our study, it was observed that FIGO stage and HER2 status were independent risk factors affecting OS in endometrial cancer patients. HER2-high group had a better prognosis than HER2-low group.

Navigating Gynecological Oncology with Different Versions of ChatGPT: A Transformative Breakthrough or the Next Black Box Challenge?

Introduction: The study evaluates the performance of large language model versions of ChatGPT – ChatGPT-3.5, ChatGPT-4, and ChatGPT-Omni – in addressing inquiries related to the diagnosis and treatment of gynecological cancers, including ovarian, endometrial, and cervical cancers. Methods: A total of 804 questions were equally distributed across four categories: true/false, multiple-choice, open-ended, and case-scenario, with each question type representing varying levels of complexity. Performance was assessed using a six-point Likert scale, focusing on accuracy, completeness, and alignment with established clinical guidelines. Results: For true/false queries, ChatGPT-Omni achieved accuracy rates of 100% for easy, 98% for medium, and 97% for complicated questions, higher than ChatGPT-4 (94%, 90%, 85%) and ChatGPT-3.5 (90%, 85%, 80%) (p = 0.041, 0.023, 0.014, respectively). In multiple-choice, ChatGPT-Omni maintained superior accuracy with 100% for easy, 98% for medium, and 93% for complicated queries, compared to ChatGPT-4 (92%, 88%, 80%) and ChatGPT-3.5 (85%, 80%, 70%) (p = 0.035, 0.028, 0.011). For open-ended questions, ChatGPT-Omni had mean Likert scores of 5.8 for easy, 5.5 for medium, and 5.2 for complex levels, outperforming ChatGPT-4 (5.4, 5.0, 4.5) and ChatGPT-3.5 (5.0, 4.5, 4.0) (p = 0.037, 0.026, 0.015). Similar trends were observed in case-scenario questions, where ChatGPT-Omni achieved scores of 5.6, 5.3, and 4.9 for easy, medium, and hard levels, respectively (p = 0.017, 0.008, 0.012). Conclusions: ChatGPT-Omni exhibited superior performance in responding to clinical queries related to gynecological cancers, underscoring its potential utility as a decision support tool and an educational resource in clinical practice.

Curative Polyendocrine Therapy in a 21-year-Old Patient with Endometrial Carcinoma: Case Report and Review of the Literature

Introduction: As the numbers of young patients diagnosed with early-stage endometrial carcinoma continue to rise, the question regarding fertility-preserving therapeutic options will increasingly gain significance in the future. Case Presentation: Here, we present the case of a 21-year-old patient diagnosed with symptomatic atypical endometrial hyperplasia. After 4 months of treatment with medroxyprogesterone acetate, a follow-up dilatation and curettage revealed early-stage, well-differentiated endometrioid endometrial carcinoma. Despite national guidelines recommending hysterectomy, the nulliparous patient expressed a desire to preserve her fertility. Subsequently, she underwent polyendocrine therapy with letrozole, everolimus, metformin, and Zoladex. Forty-three months after diagnosis, the patient successfully gave birth to a healthy child, and there have been no indications of recurrence thus far. Discussion: This case suggests that triple endocrine therapy may be an option for selected patients with early endometrial cancer and a desire for fertility-sparing therapy.

Epidemiology, Real-World Treatment Patterns, and Patient Outcomes of Primary Advanced or Recurrent Endometrial Cancer in Germany between 2015 and 2021

Introduction: The aim of this study was to describe the epidemiology of primary advanced or recurrent endometrial cancer and the outcomes from real-world treatment patterns of patients affected in Germany between 2015 and 2021. Methods: In this retrospective cohort study covering the period from 1 January 2015 to 31 December 2021, data from patients with primary advanced or recurrent endometrial cancer who initiated systemic treatment for their disease were extracted from an anonymized claims dataset from a regional health insurance fund in the German states of Saxony and Thuringia. Epidemiologic outcomes were cumulative incidence of endometrial cancer and point prevalence. Overall survival after the index date was assessed, with all-cause death used as an event. Endometrial cancer-related real-world treatment patterns were described for the post-index period. Results: The incidence of primary advanced or recurrent endometrial cancer in 2021 was 4.77 cases/100,000 persons, with no substantial change over time (4.63 in 2018; 4.93 in 2019; 4.45 in 2020). The point prevalence on 1 January 2022 was 0.023%, with a slight increase in prevalence observed from 1 January 2019 onwards. Among 466 patients with confirmed endometrial cancer, the mean (standard deviation) age was 68.0 (11.6) years; the tumor material from 86 patients (18.5%) underwent immunohistochemistry or polymerase chain reaction testing. Median overall survival was estimated to be 47.5 months (95% CI: 35.1–70.4) and the 5-year survival probability was 46.2%. The most frequent first-line systemic therapies were carboplatin (45.7%) and paclitaxel (43.1%). Second-line therapy was received by 153 patients (32.8%). Conclusion: The analysis of the German claims data produced contemporary epidemiologic estimates for advanced or recurrent endometrial cancer. Treatments were aligned with guideline recommendations during the study period, with tumor testing yet to enter mainstream practice.

Effect of Statin Use on Survival Outcomes in Patients Diagnosed with Epithelial Ovarian Cancer

Introduction: Patients diagnosed with epithelial ovarian cancer (EOC) usually experience a poor prognosis with a 5-year survival rate of approximately 40%. Thus, there would be an interest in a new perspective on the anticancer action of statins on survival outcomes in patients with EOC. This study aimed to assess the effect of statin on survival outcomes in patients diagnosed with EOC. Methods: A retrospective cohort study was conducted on EOC patients scheduled for cytoreductive surgery at Rajavithi Hospital between January 2012 and December 2016. Data on statin use before being diagnosed with EOC and cancer treatment were extracted from medical records. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using the Kaplan-Meier method and log-rank test, comparing statin users and non-users. The Cox proportional hazards model was employed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) to determine the association between statin use and survival outcomes. Results: A total of 477 EOC patients met the inclusion criteria. Among them, 76 (15.9%) were statin users, while 401 (84.1%) were non-users. Over a median follow-up of 59 months, 210 patients (44%) experienced disease recurrence, and 197 (41.3%) succumbed to EOC. There was no statistically significant difference between statin users and non-users between 5-year PFS (45.1% vs. 56.1%, p = 0.295) and 5-year OS (50.8% vs. 55.3%, p = 0.590). Multivariate Cox analysis identified advanced cancer stage and optimal surgery as independent prognostic factors for PFS and OS. However, statin uses did not significantly impact PFS (adjusted HR 1.09; 95% CI 0.73, 1.64) or OS (adjusted HR 0.84; 95% CI 0.56, 1.27). Conclusion: Statin use was not associated with improved survival outcomes in patients with EOC. Future research, preferably through prospective randomized control trials, is warranted to minimize selection bias and further explore the potential benefits of statin in this context.

Durable Response after Olaparib Treatment for Perihilar Cholangiocarcinoma with Germline BRCA2 Mutation

Introduction: Despite major advances in surveillance and management, advanced cholangiocarcinoma (CCA) still carries a dismal prognosis. In recent years, several actionable genomic alterations in pancreatobiliary malignancies have been identified. For instance, homologous recombination deficiency (HRD) has been considered a predictive biomarker of clinical response to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors. Case Report: A 53-year-old man with a stage 3 (T4N0M0) BRCA2-mutant CCA developed intolerable toxicity after 44 cycles of gemcitabine/cisplatin. In light of his HRD positivity, treatment was switched to single-agent olaparib. The patient showed a partial radiological response, which was maintained after 8 months of olaparib discontinuation (progression-free survival >36 months). Conclusion: Given the durable response observed, olaparib can be a valuable therapeutic tool in BRCA-mutant CCAs. Ongoing and future clinical trials are needed to confirm the role of PARP inhibition in similar patients and to define the clinicopathological and molecular profile of the individuals most likely to benefit.

A Phase 1 Study of a CDH6-Targeting Antibody-Drug Conjugate in Patients with Advanced Solid Tumors with Evaluation of Inflammatory and Neurological Adverse Events

<b><i>Purpose:</i></b> This first-in-human study (NCT02947152) evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of HKT288, a first-in-class CDH6-targeting antibody-drug conjugate (ADC). <b><i>Experimental Design:</i></b> HKT288 was administered intravenously (IV) every 3 weeks until patients experienced unacceptable toxicity or progressive disease (PD). The starting dose of 0.3 mg/kg was determined based on the highest nonseverely toxic dose in monkeys, which was 2 mg/kg IV weekly. Based on preclinical toxicology, skin, eyes, bone marrow, and liver were expected targets of toxicity. <b><i>Results:</i></b> Nine patients were enrolled: 5 with renal cell carcinoma and 4 with epithelial ovarian cancer. The best overall response on the 0.3 mg/kg cohort in patients with measurable disease was RECIST v1.1 stable disease in 3 patients and PD in 2 patients. The most frequent adverse events (AEs) regardless of causality were pyrexia (44.4%), constipation (44.4%), fatigue (33.3%), and vomiting (33.3%). Three suspected-related neurologic AEs (Grade 2) were reported on the 0.75 mg/kg cohort: seizure in 1 patient and another patient with aphasia and encephalopathy. Further studies were unable to identify the underlying mechanism of the neurologic AEs, and the study was terminated early. <b><i>Conclusions:</i></b> Preclinical toxicology did not predict the neurotoxicity observed with HKT288, and a comprehensive assessment performed post hoc did not identify the mechanism of toxicity. The development of further CDH6-targeting ADCs should be pursued with caution.

Clinical Efficacy and Safety of Apatinib for the Treatment of Patients with Metastatic, Recurrent Cervical Cancer after Failure of Radiotherapy and First-Line Chemotherapy: A Prospective Study

<b><i>Purpose:</i></b> As a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), apatinib has shown a survival benefit in multiple solid tumors. This study aims to evaluate the efficacy and safety of apatinib in patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy. <b><i>Methods:</i></b> A total of 42 patients between June 2018 and March 2019 were involved in this study. All patients orally received apatinib once daily in a 4-week cycle until disease progression or adverse events that prohibit further therapy. The primary endpoint was progression-free survival (PFS), the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), health-related quality of life (HRQoL) and adverse events. <b><i>Results:</i></b> During a median follow-up of 13 months, 8 patients achieved a partial response and 24 cases achieved stable disease. None of them reported a complete response. The ORR and DCR were 19.0 and 76.2%, respectively. The median PFS was 6.0 months (95% CI 4.9–7.1), and the median OS was 12.0 months (95% CI 10.1–13.9). The global health score/HRQoL improved significantly following 3-cycle treatment (50.4 ± 12.5 vs. 60.1 ± 11.8; <i>p</i> < 0.01). The most frequent grade 3–4 adverse events were hand-foot syndrome, hypertension and fatigue. <b><i>Conclusion:</i></b> Apatinib should be an effective and tolerable treatment option for patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy.

An Abnormal Precone Endocervical Curettage Result Is an Independent Risk Factor for Positive Margins in Conization Specimens

<b><i>Objective:</i></b> This study aimed to identify risk factors associated with the presence of positive surgical margins in cervical conization specimens. <b><i>Methods:</i></b> This study is a retrospective analysis of data from women who had undergone conization for cervical intraepithelial neoplasia (CIN) from 2012 to 2018 at Fujian Maternity and Child Health Hospital. Factors extracted from the database included age, gravidity, parity, menopausal status, precone Thinprep cytology test, human papillomavirus (HPV) test, precone biopsy, precone endocervical curettage (ECC) result, conization method, operating surgeon, cone dimension, and pathology of the conization specimen, including grade of CIN, margin status and glandular involvement. Univariate and multivariate analyses were performed to identify risk factors associated with positive margins. <b><i>Results:</i></b> Data from 495 women were analysed. The proportion of positive margins was 24.85% overall, which varied according to the conization method (27.22% for loop electrosurgical excision procedure vs. 18.52% for cold-knife conization, <i>p</i> = 0.047) and was increased as the severity of the treated lesion increased (10.07% for CIN2 vs. 30.62% for CIN3, <i>p</i> < 0.001). HPV-16 genotype infection, abnormal precone ECC result, higher grade of biopsy, larger cone length and volume, and glandular involvement were significantly associated with positive margins on univariable analysis. After logistic regression analysis, only an abnormal precone ECC result (odds ratio 1.952; 95% confidence interval 1.037–3.676; <i>p</i> = 0.038) remained significant. <b><i>Conclusions:</i></b> In the present study, an abnormal precone ECC result was identified as an independent risk factor for positive margins in cervical conization specimens. More aggressive treatment may be considered in patients with abnormal precone ECC results in clinical practice.

Artificial Intelligence and Gynecological Oncology: A Comparative Study of ChatGPT Omni and Gemini Pro across Repeated Intervals with Case-Scenario and Open-Ended Queries

Introduction: Artificial intelligence (AI) models offer potential benefits in supporting clinical decision-making, diagnosis, and treatment. The study aimed to compare the performance of ChatGPT-4o (Omni) and Gemini Pro in answering clinical questions and case scenarios related to gynecological oncology and to assess the consistency of their long-term responses. Methods: A two-phase comparative analysis was conducted. 700 clinical questions (350 per model) were developed and categorized into open-ended and case-scenario questions. Three months later, the same set of questions was presented again to evaluate any changes in performance for accuracy, completeness, and guideline adherence. Results: Omni outperformed Gemini Pro across all question types (p = 0.001). Omni achieved a mean score of 5.9 for the basic open-ended questions, higher than Gemini, which had 5.1 (p = 0.001). It also maintained a clear advantage in complex, open-ended questions, scoring a mean of 5.6 than Gemini AI’s 4.2 (p = 0.001). Omni scored a mean of 5.7 for basic case scenarios, while Gemini AI lagged with a mean score of 5 (p = 0.001). Omni showed a modest improvement in complex, open-ended queries, with an increase of 0.2 points (+3.57%) (p = 0.001). Omni provided more accurate and comprehensive responses in guideline adherence than Gemini, particularly in complex cases requiring nuanced judgment and adherence to oncology protocols. Its responses aligned with the latest guidelines, including the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Conclusion: Omni is a more reliable and consistent model for answering questions related to gynecological cancers than Gemini. The stability of Omni’s performance over time highlights its potential as an effective tool for clinical applications requiring high accuracy and consistency.

Impact of Poor Preoperative Glycemic Control on Outcomes among Patients with Cervical Cancer Undergoing a Radical Hysterectomy

Background: The impact of preoperative glycemic control on the survival outcomes of patients undergoing a radical hysterectomy (RH) for cervical cancer has not been investigated. Patients and Methods: We reviewed patients who underwent a type III RH for cervical cancer between January 2004 and June 2011 in our institution. Results: A total of 431 patients were included and 83 (19.3%) were diagnosed with diabetes mellitus (DM). Poorly controlled DM (preoperative hemoglobin A1c [HbA1c] ≥7.0%) was observed in 49 (59.0%) diabetic patients. Compared to patients without DM and diabetic patients with good glycemic control (preoperative HbA1c <7.0%), diabetic patients with poor glycemic control had significantly higher risks of tumor recurrence, cervical cancer-specific death, and overall death. In multivariate analysis, DM with poor glycemic control independently predicted recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). We excluded patients without DM and performed a sensitivity analysis. When HbA1c levels were treated as a dichotomous variable, preoperative HbA1c ≥7.0% was independently associated with RFS, CSS, and OS. When HbA1c level was treated as a continuous variable, it remained an independent predictor of RFS, CSS, and OS. Conclusion: DM with poor glycemic control prior to RH was significantly associated with an increased risk of recurrence and mortality in cervical cancer patients. These results underscore the importance of intensive glycemic control and close follow-up for diabetic patients.

Is the Oncological Outcome of Early Stage Uterine Carcinosarcoma Different from That of Grade 3 Endometrioid Adenocarcinoma?

<b><i>Aim:</i></b> The clinicopathologic characteristics, recurrence patterns, and survival of patients with grade 3 endometrial cancer (G3-EAC) and uterine carcinosarcoma (UCS) were compared. <b><i>Materials and Methods:</i></b> The medical records of patients treated for G3-EAC and UCS between January 1996 and December 2016 at 11 gynecologic oncology centers in Turkey and Germany were analyzed. <b><i>Results:</i></b> Of all patients included in the study, 161 (45.1%) were diagnosed with UCS and 196 (54.9%) with G3-EAC at FIGO stage I–II (early stage) disease. The recurrence rate was higher in patients with UCS than in those with G3-EAC (17.4 vs. 9.2%, <i>p</i> = 0.02). The 5-year disease-free survival (DFS; 75.2 and 80.8%, respectively; <i>p</i> = 0.03) and overall survival (OS; 79.4 and 83.4%, respectively; <i>p</i> = 0.04) rates were significantly lower in the UCS group compared to the G3-EAC group. UCS histology was an independent prognostic factor for decreased 5-year DFS (HR 1.8, 95% CI 1.2–3.2; <i>p</i> = 0.034) and OS (HR 2.7, 95% CI 1.3–6.9; <i>p</i> = 0.041) rates. <b><i>Conclusions:</i></b> The recurrence rate was higher in UCS patients than in G3-EAC patients, regardless of disease stage. DFS and OS were of shorter duration in UCS than in G3-EAC patients. Adequate systematic lymphadenectomy and omentectomy were an independent prognostic factor for increased 5-year DFS and OS rates.