ONCOLOGY

Evaluation of Clinical Significance of Lymphovascular Space Invasion in Stage IA Endometrial Cancer

<b><i>Introduction:</i></b> The prognostic significance of lymphovascular space invasion (LVSI) in stage IA endometrial cancer remains unclear. The aim of this study was to evaluate the clinical significance of LVSI in stage IA endometrial cancer. <b><i>Methods:</i></b> Clinical data of patients with stage IA endometrial cancer who underwent initial surgery at our institution between January 2008 and December 2018 were reviewed retrospectively. Information of patients, surgery, and characteristics of cancer were obtained from medical records and pathological reports. <b><i>Results:</i></b> Two hundred ninety-seven patients were enrolled in this study. With a median follow-up of 60 months, 15 patients experienced recurrence (5.1%) and 4 patients died of endometrial cancer (1.3%). The recurrence and mortality rates did not differ significantly between the LVSI-positive and -negative groups (<i>p</i> = 0.07 and <i>p</i> = 0.41, respectively). Recurrence-free survival and endometrial cancer-specific survival also did not differ significantly between these groups (<i>p</i> = 0.11 and <i>p</i> = 0.49, respectively). The 5-year endometrial cancer-specific survival rates for tumors with and without LVSI were 97.0% and 98.9%, respectively. Among patients with low-grade tumors, recurrence-free survival and endometrial cancer-specific survival did not differ significantly between patients with tumors with and without LVSI (<i>p</i> = 0.92 and <i>p</i> = 0.72, respectively). The 5-year endometrial cancer-specific survival rates for low-grade tumors with and without LVSI were 100% and 99.3%, respectively. <b><i>Conclusion:</i></b> LVSI was not a prognostic factor of not only stage IA endometrial cancer but also stage IA low-grade cancer.

Does Hormone Replacement Therapy Impact the Prognosis in Endometrial Cancer Survivors? A Systematic Review

Purpose: The objective of this study was to evaluate the impact of hormone replacement therapy (HRT) on the prognosis in endometrial cancer (EC) survivors. Methods: The research was conducted using the following electronic databases: MEDLINE (PubMed), Web of Science, ClinicalTrial.gov, and Cochrane Library. We performed a review of studies published from January 1986 to January 2019. We selected studies that included EC patients submitted to surgery with curative intent and postoperative use of HRT. Result: Seven of 1,332 abstracts considered were eligible: 4 retrospective series, 1 prospective study, 1 randomized controlled trial, and 1 population study. Globally in the observed studies there was not a significant increase in the recurrence rate, measured by the relative risk, in the EC survivors using HRT compared with the controls in tumour stages I and II. The bias was that HRT was prescribed only to low-risk patients, who were young and had a low stage of disease. Conclusion: This systematic review shows that HRT use had no negative effect on prognosis in EC survivors in tumour stages I and II.

Clinical Significance of the TK1-Specific Activity in the Early Detection of Ovarian Cancer

Introduction: Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer. Methods: The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples. Results: The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis. Conclusions: These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer.

Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin in Patients with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer

<b><i>Introduction:</i></b> The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum tolerated dose and recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative (HER2−) MBC and recurrent ovarian cancer (ROC). <b><i>Methods:</i></b> Cohorts of 3–6 patients with HER2− MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1 mg/m<sup>2</sup> or 1.4 mg/m<sup>2</sup> IV on day 1 and day 8) with durvalumab (1.12 g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal. Primary endpoint: the rate of DLTs during cycles 1 and 2 of therapy. Secondary endpoints: AE rate, objective response rate (ORR), progression-free survival (PFS), and OS. <b><i>Results:</i></b> Nine patients with a median of 4 prior therapies for advanced disease were treated: 5 patients with HER2− MBC (1 with triple-negative disease and 4 with hormone-positive disease) and 4 patients with ROC. The RP2D of eribulin was 1.4 mg/m<sup>2</sup> in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 (hepatitis) after 5 cycles of treatment, for which patient came off study. Two other patients discontinued study drug related to toxicity (neutropenia [<i>n</i> = 1], hepatic toxicity [<i>n</i> = 1]). ORR was 55%, and 4 additional patients experienced stable disease. All MBC patients exhibited a response to therapy. Median PFS was 6.2 months. Median OS was 15.0 months. <b><i>Conclusion:</i></b> The combination of eribulin at a dose of 1.4 mg/m<sup>2</sup> with standard dose durvalumab had a favorable AE profile in patients with previously treated HER2− MBC and ROC. The early antitumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.

Impact of Oophorectomy on Survival and Improving Nutritional Status in Ovarian Metastasis from Colorectal Adenocarcinoma

<b><i>Introduction:</i></b> Ovarian metastasis of colorectal cancer is known to have a poor prognosis. This study aimed to elucidate the characteristics of patients who underwent oophorectomy for ovarian metastasis from colorectal cancer. <b><i>Methods:</i></b> This retrospective study included 16 patients who underwent oophorectomy for colorectal cancer metastasis to the ovary from January 2004 to December 2017. Improvement in patient’s symptoms and pre- and postoperative changes in various nutritional and inflammatory indicators were assessed. Survival analysis and identification of prognostic factors were conducted with a median follow-up of 40.7 (5–109) months. <b><i>Results:</i></b> Of 16 patients, 12 had (75%) synchronous and 4 (25%) had metachronous metastasis. Fourteen patients were symptomatic but symptoms resolved postoperatively. Thirteen patients (81.3%) had ascites and 5 (31.3%) had pleural effusion on preoperative computed tomography that disappeared after surgery in all cases. The median value of prognostic nutritional factor was significantly increased postoperatively (36.0 [preoperatively] vs. 47.5, <i>p</i> < 0.0001). The median (interquartile range) values for lymphocyte-C-reactive protein ratio were 715.2 (110–2,607) preoperatively and 6,095.2 (1,612.3–14,431.8) postoperatively (<i>p</i> = 0.0214). The median survival of the entire cohort was 60.4 months. The 3-year survival rates for R0 + R1 and R2 cases were 83% and 24% (<i>p</i> = 0.018), respectively. Univariate analysis showed that R2 resection and low postoperative lymphocyte-C-reactive protein ratio were associated with poor prognosis. <b><i>Conclusions:</i></b> Oophorectomy for ovarian metastasis from colorectal cancers was safely performed. It improved the patients’ symptoms and nutritional status and may result in improved prognosis.

Differences in Clinical Trial Availability vs Distribution of Disease Among Gynecological Cancers

Objective: Given disparities in incidence and outcomes among racial and ethnic groups, and differences in patient characteristics among the 3 main types of gynecologic cancer, we examined whether clinical trial availability at a large, high-enrolling National Cancer Institute–designated Comprehensive Cancer Center reflects the clinical volume of each cancer in the catchment area. We also assessed whether the patients who consented to the trials reflected the racial and ethnic distribution of each cancer type. Methods: Patients who consented to ovarian, uterine, and cervical cancer clinical trials at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles, California, from 2013 through 2018 were included. Clinical trial and patient-level data were collected. Los Angeles County cancer incidence data were used to represent disease burden in the catchment area. χ-Square and Fisher exact tests were used to compare proportions. Results: Twenty-four gynecologic oncology clinical trials were identified: 16 (67%) ovarian, 5 (21%) uterine, and 3 (12%) cervical cancer trials. Compared with corresponding county incidence rates, respectively, the proportion of patients with ovarian (82% vs 25%), uterine (9% vs 59%), or cervical (9% vs 6%) cancer who consented for clinical trials differed significantly ( P  < .001). The racial/ethnic distribution of patients also differed for ovarian ( P  < .001) and cervical cancer trials ( P  = .005). Patients who were Black or Asian were underrepresented in ovarian and cervical cancer trials; Hispanic patients were underrepresented in ovarian trials. Conclusions: The distribution of clinical trials and patients who consented did not reflect the incidence or racial and ethnic makeup of gynecologic cancers in the catchment area. Greater efforts are needed to align trial availability and enrollment with disease burden and population diversity.

Exploration of Extracellular Vesicle Long Non-Coding RNAs in Serum of Patients with Cervical Cancer

<b><i>Introduction:</i></b> Cervical cancer (CC) is the fourth most common cancer type and a leading cause of cancer-related deaths in women worldwide. Its underlying molecular mechanisms are unclear. Cancer cell-derived extracellular vesicles (EVs) are involved in cancer development and progression by delivering regulatory factors, including microRNAs and long non-coding RNAs (lncRNAs). <b><i>Methods:</i></b> Here, we identified the EV lncRNA expression profiles associated with different developmental stages of CC using next-generation sequencing. EVs from the serum of patients with stages I–III CC and healthy donors were characterized using EV marker immunoblotting and transmission electron microscopy. <b><i>Results:</i></b> The EV concentration increases with progression of the disease. Most particles had a 100–250-nm diameter, and their sizes were similar in all groups. We identified many lncRNAs that were uniquely and differentially expressed (DE) in patients with different stages of CC. The pathway analysis results indicated that the upregulated DE EV lncRNAs abundant in stages I and II were associated with cell proliferation and inflammation and cancer progression pathways, respectively. LINC00941, LINC01910, LINC02454, and DSG2-AS1 were highly expressed, suggesting poor overall survival of CC patients. Interestingly, DSG2-AS1 was associated with the human papillomavirus infection pathway through <i>AKT3</i>, <i>DLG1</i>, and <i>COL6A2</i> genes. <b><i>Conclusion:</i></b> This is the first study that reports the levels of EVs and their lncRNA contents change during cancer development, demonstrating the existence of a unique vesicle-mediated cell-to-cell communication network underlying cancer progression.

Development and Validation of a Model Predicting Malignant Potential of Adnexal Masses in Areas with Scarcity of Ultrasound Resources

Introduction: Appropriately stratifying the risk of adnexal masses is of great importance. Many diagnostic algorithms have been devised, most of which rely on ultrasound features. However, some remote areas lack trained sonographers. This study aimed to develop an alternative model to distinguish between malignant and benign adnexal masses in resource-constrained settings using clinical information rather than ultrasound data. Methods: The study included women diagnosed with an adnexal tumor and scheduled for surgery between 2020 and 2023. Participants were divided into two groups based on histopathology reports: those with malignant adnexal masses and those with benign ones. Univariate and multivariate logistic regression analyses were used to identify independent predictors of adnexal mass malignancy. The training set yielded a nomogram model, which was then validated in the validation set. The model’s effectiveness was evaluated using receiver operating characteristic (ROC), calibration, and clinical decision curve analysis (DCA) curves. Results: We randomly assigned 550 participants to the training and the validation sets in an 8:2 ratio. Logistic regression analyses identified age (OR = 1.044, p = 0.003), abdominal distension (OR = 0.139, p < 0.001), serum CA125 (OR = 1.007, p < 0.001), and serum carcinoembryonic antigen (CEA) (OR = 1.291, p = 0.004) as independent risk factors for predicting malignant adnexal tumors. A nomogram was constructed using these factors. The ROC curve showed an area under the curve of 0.846 (95% confidence interval [CI]: 0.783, 0.908) in the training set and 0.817 (95% CI: 0.668, 0.966) in the validation set. The calibration curve showed good consistency between model predictions and actual outcomes. The DCA curve demonstrated a considerable clinical advantage afforded by the model. Conclusion: The logistic regression model can aid gynecologists – particularly those in areas with limited access to skilled sonographers – in identifying patients at high risk and implementing appropriate management strategies.

Comprehensive Analysis of the Relationship between Cuproptosis-Related Gene GCSH and Prognosis, Tumor Microenvironment Infiltration, and Therapy Response in Endometrial Cancer

<b><i>Introduction:</i></b> Cuproptosis is a novel form of cell death regulated by protein lipoylation and implicated in mitochondrial metabolism. However, further research is needed to explore the influence of the cuproptosis-related gene γ-glutamylcysteine synthetase (GCSH) on the prognosis of endometrial cancer (EC), the tumor immune microenvironment, and therapeutic response. <b><i>Methods:</i></b> The differential expression of GCSH between EC and normal tissues was analyzed using multiple public databases. Additionally, cancer and adjacent tissues were prospectively collected from 17 EC patients, and immunohistochemical analysis was performed to further investigate GCSH expression differences. The relationship between GCSH and the prognosis and clinicopathological characteristics of EC patients was evaluated, and a nomogram was constructed to predict patient survival based on GCSH expression. Subsequently, Gene set variation analysis was used to explore the potential biological functions of GCSH in EC. The impact of GCSH on the tumor microenvironment (TME) was estimated. Finally, the effect of GCSH on the response to immunotherapy and chemotherapeutic drugs in EC was investigated. <b><i>Results:</i></b> The expression of GCSH was significantly upregulated in EC. High GCSH expression was associated with poor prognosis in EC patients. Enrichment analysis revealed an association between high GCSH and immune suppression. Furthermore, high GCSH was found to be associated with a non-inflamed TME, leading to decreased infiltration levels of immune cells. Lastly, it was observed that patients with high GCSH exhibited insensitivity to both immunotherapy and chemotherapeutic drugs. <b><i>Conclusion:</i></b> This study revealed the role of GCSH in TME, response to therapy, and clinical prognosis in EC, which provided novel insights for the therapeutic application in EC.

Risk for Second Primary Ovarian Cancer: A Large Population Based on Surveillance, Epidemiology, and End Results Database

Introduction: This study aims to evaluate the likelihood of developing a second primary ovarian cancer (OC) considering factors including age, race, and the types of initial malignancies encountered. Methods: This study employed a retrospective cohort approach, compiling data on individuals diagnosed with OC from the Surveillance, Epidemiology, and End Results (SEER) program databases spanning the years 1975–2019. The analysis used standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) to determine the likelihood of developing OC. The result was further refined by categorizing the data based on patient age, race background, first primary cancer types, the time elapsed since the second primary cancer diagnosis, and radiotherapy treatment. Results: A total of 1,536,151 patients with second primary cancer being OC were included. The SIR of the second primary OC was observed to be elevated among patients between the ages of 18–64 years (SIR: 1.09, 95% CI: 1.06–1.13). In contrast, for patients who were 65 years of age or older, the SIR for a second primary OC was found to be relatively lower (SIR: 0.87, 95% CI: 0.83–0.91). A lowering, however, not statistically significant, of the SIR of the second primary OC in patients with white race was presented. Within 2 months to 1-year diagnosis interval, the SIR of the second primary OC was highest (SIR: 1.48, 95% CI: 1.37–1.61). Liver, gallbladder, intrahepatic, and other bile ducts (SIR: 2.00, 95% CI: 1.38–2.81), and breast cancer (SIR: 1.20, 95% CI: 1.15–1.25) had higher SIRs of second primary OC. Conclusion: This study identifies age, ethnicity, the time span between the diagnoses, and the types of initial cancers as factors correlated with the occurrence of a second primary OC. Our findings suggest that targeted surveillance should be considered for high-risk groups.

Evaluation of Parametrial Status in Locally Advanced Cervical Cancer Patients after Neoadjuvant Chemotherapy: A Prospective Study on Diagnostic Accuracy of Three-Dimensional Transvaginal Ultrasound

<b><i>Objectives:</i></b> To analyze the diagnostic accuracy of two-dimensional (2D) and three-dimensional transvaginal ultrasound (3D TV-US) for evaluation of parametrial status in locally advanced cervical cancer patients after neoadjuvant chemotherapy (NACT), using histology as the gold standard. <b><i>Methods:</i></b> Consecutive patients with histologically confirmed cervical cancer were staged according to FIGO (International Federation of Gynaecology and Obstetrics) criteria. All IB2-IIIB FIGO stage patients were examined by 2D and 3D TV-US and magnetic resonance imaging (MRI) at the diagnosis time (T0) and after NACT. At T0, the US evaluation of parametrial involvement was compared to MRI before treatment. The results of US and MRI examinations of parametrial status after NACT were compared with the histological specimen. <b><i>Results:</i></b> We enroled 51 consecutive patients in the study. Before chemotherapy, clinical examination under anaesthesia identified parametrial involvement in 48 patients, ultrasonography in 46 patients, and MRI in 49 patients. The agreement between US and MRI was 94%. The sensitivity of US for parametrial status was 93.8%, with a positive predictive value of 97.8%, using MRI as the standard. The correlation between US and MRI was statistically significant (<i>p</i> = 0). After chemotherapy, histological examination of surgical specimens identified parametrial involvement in 3 patients. Ultrasonography correctly identified those cases with parametrial infiltration, recording a sensitivity of 100%, specificity of 90.9%, positive predictive value of 50%, and negative predictive value of 100%. The MRI had a sensitivity of 100%, specificity of 45.5%, positive predictive value of 14.3%, and negative predictive value of 100%, respectively. The concordance in the identification of the presence/absence of infiltration between US and MRI with histology was 90% (<i>p</i> = 0.001) and 61%, respectively, after chemotherapy treatment. Particularly, in defining the degree of infiltration, the agreement between US and MRI with histology was 90 and 58%, respectively. <b><i>Conclusion:</i></b> In locally advanced cervical cancer patients, 2D/3D TV-US can be considered accurate in the evaluation of parametrial infiltration to assess the response to NACT. It could be included as a diagnostic method in the preoperative work-up of cervical cancer.

Unraveling the Complexities of Proximal-Type Epithelioid Sarcoma of the Vulva

PURPOSE: To present a rare case of proximal-type epithelioid sarcoma (PES) of the vulva and highlight the importance of a multidisciplinary approach in its diagnosis and treatment, especially in the context of SMARCB1 loss. METHODS: A 41-year-old woman presented with a painless mass in the right labia majora. An MRI, PET/CT, histopathology, and immunohistochemistry confirmed the diagnosis of PES with loss of SMARCB1 expression. The patient underwent wide local excision followed by re-excision and inguinal lymphadenectomy. Adjuvant radiotherapy was initiated but discontinued at 46 Gy due to grade 2 skin reactions and wound dehiscence. RESULTS: Posttreatment PET/CT imaging posed challenges in distinguishing between recurrence and radiation-induced changes. Despite these challenges, the patient remained disease free during the 2-year follow-up period. This case underscores the diagnostic and therapeutic complexities involved in treating PES, particularly in sensitive anatomical regions such as the vulva. The loss of SMARCB1 served as a key molecular marker guiding diagnosis and therapeutic decisions. CONCLUSION: The case underscores the importance of a comprehensive, individualized treatment approach, including surgery, radiotherapy, and advanced imaging, for managing rare malignancies such as vulvar PES.

Treatment of Locally Advanced Cervical Cancer With Kidney Failure and Comorbidities

A woman aged 63 years presented at the gynecological oncology outpatient clinic with the following medical history: smoking history (smoking index of 10); systemic arterial hypertension diagnosed 6 years ago; menarche at 16 years; menopause at 52 years; 4 pregnancies, 4 deliveries; beginning of active sexual life at 18 years; 3 sexual partners; and no early cancer detection method in her life. Her performance status per ECOG criteria was 1. The patient presented with transvaginal bleeding with 5 months of evolution. Upon physical exploration, a 5 x 5 cm tumor in the cervix was detected, with the following characteristics: exophytic, friable, bleeding, with invasion to the lower third of the vagina, affection to the cul-de-sac and parametria, and bilaterally fixed to the pelvic wall. A biopsy of the cervix showed moderately differentiated invasive squamous cell carcinoma.

Adenoid Cystic Carcinoma of Bartholin’s Gland: What Is the Best Approach?

<b><i>Background and summary:</i></b> Among all vulvar cancers, primary adenoid cystic carcinoma (ACC) of Bartholin’s gland is a very rare tumor characterized by a slow growth, a high local aggressiveness, and a remarkable recurrence rate. Due to its rarity, treatment remains a challenge for oncologists and gynecological surgeons. <b><i>Key message:</i></b> The present paper reports clinical, radiological, and histological features of ACC of Bartholin’s gland and reviews the literature data on the treatment options with a particular focus on the potential role of particle radiation therapy.

Life Experience of Survivors of Gynecologic Cancers: A Survey Conducted in Italy

Background: The study of health-related quality of life in survivors of gynecologic cancers is becoming increasingly important as 1.5 million survivors of gynecologic cancer in the United States and more are expected due to advances in diagnosis and treatment. This project investigated the perceived needs and lived experiences of survivors of gynecological cancer to help design supportive activities to be implemented in clinical practice. Methods: Patients were recruited in hospitals or through social media and responded to an online survey that was addressed to patients in Italy, specifically in Sicily, Puglia, and Campania. Patients with ovarian, endometrium, or cervix cancer were recruited among women attending Cannizzaro Hospital and Alleanza Contro il Tumore Ovarico (Alliance Against Ovarian Cancer) members. Results: Body image perception was changed in 82.3% of respondents, whereas familial relationships were described as changed by 27.5% of women. In 69.6% of patients, sexual habits were hindered by changes in the body, depression, pain, and awkwardness. Physicians informed patients about sexuality changes related to cancer extensively in 16.7% of cases and briefly in 19.6% of cases. The advice of a clinical sexologist was considered potentially helpful by 31.4% of patients and not potentially helpful by 47.1%, whereas 21.6% of patients had no opinion. Conclusions: Although sexual habits are often changed by cancer, women surviving gynecological cancer rarely seek medical advice in this area. Physicians should be trained to inform patients and to promote referrals to sexologists. Keywords: Gynecological cancer, quality of life, sexual activity

Late Hepatic Recurrence From Granulosa Cell Tumor: A Case Report

Adult granulosa cell tumor (GCT) of the ovary is a rare sex cord-stromal neoplasm characterized by potential for late recurrence. Hepatic metastases from GCT are exceedingly uncommon. We report a case of late hepatic relapse occurring 15 years post primary treatment. A 66-year-old woman with obesity presented with right upper quadrant pain of 1-month duration. She had a history of stage T1aN0M0 right ovarian GCT treated 15 years prior with total abdominal hysterectomy, bilateral oophorectomy, omentectomy, and adjuvant chemotherapy, with no follow-up. Imaging revealed extensive perihepatic and intrahepatic lesions and a midabdominal mass. Laparotomy confirmed an abdominal mass greater than 15 cm and multiple hepatic lesions. Excisional histopathology demonstrated metastatic GCT of the liver and peritoneum. This case emphasizes the need for lifelong surveillance in patients with GCT due to its latent recurrence potential even beyond a decade.

Synchronous Well-Differentiated Papillary Mesothelioma and Endometrioid Adenocarcinoma Arising From Endometriosis

Well-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumor of uncertain malignant potential. We present a unique case of a woman with synchronous WDPM and well-differentiated endometrioid adenocarcinoma (EA) arising from extraovarian endometriosis. A 56-year-old postmenopausal woman presented with a several-month history of right lower quadrant abdominal pain. She had a history of supracervical hysterectomy and bilateral salpingo-oophorectomy secondary to endometriosis. Imaging reported a mass in the right lower quadrant originating from the distal ileum. At laparotomy, the patient underwent a right colectomy with resection of the terminal ileum and excision of a solitary peritoneal nodule. Pathology was consistent with a diagnosis of well-differentiated EA (arising from extraovarian endometriosis) and WDPM. Further treatment consisted of complete surgical staging/debulking and adjuvant chemotherapy directed toward metastatic well-differentiated EA. Surgeons should be familiar with WDPM as a potential finding in women of reproductive age undergoing abdominal surgery for any indication.

Extreme Case of Surgical Port Metastasis in Ovarian Cancer

Ovarian cancer accounts for more deaths than any other malignancy of the female reproductive system. Early diagnosis of this disease is difficult because there are no systematic opportunistic screening methods. At advanced stages, diagnostic laparoscopy is the first step in confirming disease advancement and obtaining samples for genetic and pathologic examination needed to start chemotherapy. Swiftly starting oncological treatment is crucial for increasing the survival rate in these patients. We present the case of a 51-year-old woman with metastatic International Federation of Gynecology and Obstetrics (FIGO) stage IIIC ovarian cancer who had delayed her therapy after initial laparoscopy due to COVID-19 infection and presented with an extreme case of surgical port metastasis.

Alterations of UHRF Family Expression and UHRF1/ICBP90 Inhibits Phosphatase and Tensin Homolog Expression in Endometrial Cancer

Introduction: The altered protein expression of inverted CCAAT box-binding protein of 90 kDa/ubiquitin-like with PHD and RING finger domains 1 (ICBP90/UHRF1) and Np95-like ring finger protein (NIRF)/UHRF2, which belong to the ubiquitin-like with PHD and RING finger domains (UHRF) family, is linked to tumor malignancy and the progression of various cancers. To determine the role of NIRF and ICBP90 in endometrial tumorigenesis, we evaluated ICBP90 and NIRF expression levels in endometrial cancers. Also molecular alterations of phosphatase and tensin homolog (PTEN) expression are the important event for endometrial carcinogenesis; therefore, we investigated the involvement between ICBP90 and PTEN expression. Methods: We used Western blot for NIRF, ICBP90, and PTEN expression, mutation analysis of NIRF gene, and immunohistochemical staining for the expression of NIRF and ICBP90. For immunohistochemical staining, we examined atypical endometrial hyperplasia, endometrial cancers, and noncancerous samples. Results: Our data showed that the reduced expression of NIRF and overexpression of ICBP90 occurred in atypical endometrial hyperplasia and endometrial cancer compared to the normal endometrium. The decrease in NIRF expression was significantly correlated with histological grade. Expression of ICBP90 was high, especially in the peripheral margin of a cancer nest. Western blot analysis of endometrial cancer cell lines referred an opposite correlation between ICBP90 and PTEN expression. Conclusion: Our findings suggested that continually overexpressed ICBP90 may contribute to the inhibition of PTEN expression, which is a frequent and important event in endometrial carcinogenesis. We propose that the reduced NIRF expression and ICBP90 overexpression is an early event in endometrial carcinogenesis; thus ICBP90 may be useful as a therapeutic target in this disease.

Endometrial Cancer: When Upfront Surgery Is Not an Option

Background and Summary: The management of endometrial cancer, in an ever-older population with considerable comorbidity, remains a challenge for gynecological and radiation oncologists. Key Message: The present paper reviews literature data on treatment options for endometrial cancer patients unfit for surgery.

Intraperitoneal Chemotherapy: A Strategy for the Treatment of Refractory Ascites in Recurrent Endometrial Cancer Patients – Three Case Reports and Review of the Literature

<b><i>Background:</i></b> Endometrial cancer currently represents the most frequent gynecologic malignancy in Western countries, and the seventh most common cancer in women. For advanced-stage disease, the recurrence risk is high, and the site of the relapse is heterogeneous with localized or spread peritoneal disease. There are few therapeutic strategies, and the quality of life is poor. <b><i>Cases Presentation:</i></b> We present 3 cases of peritoneal-spread recurrences of endometrial cancer in patients with advanced stage at diagnosis. The patients had been subjected to multiple lines of chemotherapy including re-challenging with platinum regimens, pegylated liposomal doxorubicin, and taxane, with progression of disease. These patients came to us with abdominal distension, dyspnea, elevated CA 125, and presence of ascites. After paracentesis with a single administration of intraperitoneal chemotherapy based on carboplatin, all 3 patients showed improvement in their quality of life and breathing as well as reduction of fatigue and anorexia. No complications occurred. <b><i>Conclusion:</i></b> Although only 3 cases are reported, the exceptional results and the absence of side effects observed strongly warrant future trials to investigate the role intraperitoneal chemotherapy can have both as palliative treatment of refractory ascites and as salvage therapy in advanced endometrial cancer.

Inflammatory Biomarkers as Promising Predictors of Prognosis in Cervical Cancer Patients

<b><i>Introduction:</i></b> Increasing evidence demonstrates a crucial role of inflammation in inducing and promoting several cancers. Pro-inflammatory upregulation of cytokines such as IL-6 has been implicated in cervical cancer development and progression through several mechanisms, for example, by inducing platelet production, activation, and aggregation. The aim of the study was to evaluate the effective prognostic impact of inflammatory biomarkers such as platelet count, platelet to lymphocyte ratio (PLR), and IL-6 in cervical cancer patients. <b><i>Materials and Methods:</i></b> Between 2016 and 2019, 108 out of 159 patients with cervical cancer have been enrolled. Cutoff level of pretreatment platelet count and PLR was identified by using the ROC curve. IL-6 tumoral and peritumoral expression was analyzed and stratified as low and high (low expression: 0 and +1; marked expression: +2 and +3). <b><i>Results:</i></b> Median follow-up duration was 30 months (range 16–44). Patients with higher platelet counts showed worse DFS and OS (DFS <i>p</i> < 0.001; OS <i>p</i> < 0.001). Cumulative rates of DFS and OS in patients with lower PLR were higher than in patients with higher values of PLR (DFS <i>p</i> = 0.032; OS <i>p</i> < 0.001). Survival analysis showed a better prognosis in patients with lower IL-6 expression (DFS <i>p</i> < 0.001; OS <i>p</i> < 0.001). <b><i>Conclusion:</i></b> Nowadays, causal relationship between inflammation, innate immunity, and cancer is more widely accepted. However, many of the molecular and cellular mechanisms mediating this relationship remain unresolved. Ongoing inflammatory response was associated with poor outcomes in cervical cancer patients. A higher pretreatment platelet count and PLR value associated with higher IL-6 tumoral expression could be used to predict poor prognosis in cervical cancer patients.

Using PARP Inhibitors in Frontline Maintenance Therapy for Ovarian Cancer

Ovarian cancer is the leading cause of mortality among gynecologic cancers in the United States, expected to result in roughly 13,940 deaths in 2020. Between 2008 and 2017, mortality decreased by 2.3% per year. Incidence rates also decreased, with a 1.6% drop per year from 2007 to 2016. In 2020, an estimated 21,750 new cases of ovarian cancer will be diagnosed. The majority (90%) of ovarian cancers are epithelial ovarian cancer-often high-grade serous adenomas, which are associated with a poor prognosis and have the fewest known risk factors.

Decision-Making Analysis for Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer: A Survey by the Executive Committee of the Peritoneal Surface Oncology Group International (PSOGI)

<b><i>Objectives:</i></b> To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. <b><i>Methods:</i></b> The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. <b><i>Results:</i></b> Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria. <b><i>Discussion and Conclusion:</i></b> Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.

Treatment Outcome of Second-Line Chemotherapy for Gynecologic Carcinosarcoma

<b><i>Introduction:</i></b> Carcinosarcoma is a rare cancer, and its prognosis is poor. There are few reports on the prognostic factors of patients with carcinosarcoma who receive second-line chemotherapy. <b><i>Objective:</i></b> To investigate the outcome and prognostic factors of patients who received second-line chemotherapy for gynecologic carcinosarcoma. <b><i>Methods:</i></b> We retrospectively investigated patients with ovarian or uterine carcinosarcoma, who were treated at two institutions from July 2006 to March 2018. All patients who had received second-line chemotherapy for advanced or recurrent disease were eligible. The efficacy of second-line chemotherapy and prognostic factors were evaluated. <b><i>Results:</i></b> Forty-six patients were eligible. Combination chemotherapy was used in approximately half (52.2%) of the patients. The response rate and disease control rate of second-line chemotherapy were 32.6 and 60.9%, respectively. The median follow-up period was 11.0 (range, 8.8–107.5) months. The median progression-free survival and overall survival were 6.3 (95% CI, 3.2–7.5) months and 12.9 (95% CI, 7.8–16.0) months, respectively. In the multivariate analysis of overall survival, a treatment-free interval >180 days was a significant good prognostic factor. The median overall survival was 7.8 (95% CI, 5.1–10.5) months in the <180 days group and 16.4 (95% CI, 13.1–130.6) months in the >180 days group (<i>p</i> = 0.0052; hazard ratio, 0.26; 95% CI, 0.10–0.66), respectively. <b><i>Conclusion:</i></b> The outcome of gynecologic carcinosarcoma in the second-line setting is poor, especially in patients with a short treatment-free interval.

The Role of 2D/3D Ultrasound to Assess the Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer

<b><i>Introduction:</i></b> Different imaging techniques were introduced to improve preoperative clinical staging of locally advanced cervical cancer (LACC) with transvaginal ultrasound (TV-US) or transrectal ultrasound (TR-US) representing a promising staging technique in the evaluation of the local extension of the disease for invasive tumors. The aim of this study was to evaluate the response to neoadjuvant chemotherapy (NACT) in LACC by 2D/3D ultrasound examination. <b><i>Materials and Methods:</i></b> We prospectively enrolled patients affected by histologically and clinically confirmed LACC. All patients were scheduled for 3 cycles of platinum-based NACT followed by radical surgery. The ultrasound examination was performed at every cycle and within 10 days before surgery. The parameters evaluated were: the volume (automatically computed by the VOCAL software) and the mass vascularization. <b><i>Results:</i></b> From March 2010 to March 2019, 157 women were recruited. Among these patients, 12 of them were excluded: 6 for the presence of distant metastases, 4 for rare histology, and 2 for severe comorbidities not allowing the protocol treatment. Seventeen patients after NACT were excluded because they were not amenable to radical surgery. Thus, 128 were considered for the final analysis of whom 106 (83%) were considered responders to NACT by histology. The sensibility and specificity of ultrasound with regard to the response to chemotherapy compared to histological specimen were 94 and 82%, respectively, with an accuracy of 92%. The positive predictive value and negative predictive value were 96 and 75%, respectively. Finally, we found that nonetheless there was a trend towards a continuous response to chemotherapy among patients who were considered responders to NACT at pathological examination; the major volume and vascularization index (VI) reduction were observed during the first 2 cycles (74, 71% and 47, 63%, respectively). On the contrary, non-responders showed an initial reduction of the VI (4.86 consisting of 33%, 95% CI 0.79–8.92, <i>p</i> = 0.013), but no significant modification in tumour volume along NACT. <b><i>Conclusion:</i></b> 2D/3D ultrasound is useful in assessing early response to NACT in patients with LACC.

Is Adjuvant Therapy Necessary for Patients with Intermediate-Risk Cervical Cancer after Open Radical Hysterectomy?

<b><i>Introduction:</i></b> Adjuvant therapy is usually recommended for patients with intermediate-risk cervical cancer (deep stromal invasion [DSI], lymphovascular space invasion [LVSI], and bulky tumor) after radical hysterectomy. However, we previously reported that DSI, LVSI, and bulky squamous cell carcinoma (SCC) were not correlated with prognosis in multivariate analysis; therefore, the indications we use for adjuvant therapy include complete stromal invasion, not DSI or LVSI or bulky SCC. The objective of this study was to evaluate the adequacy of our therapeutic strategy for cervical cancer after radical hysterectomy. <b><i>Methods:</i></b> We performed 321 type III open radical hysterectomies for cervical cancer between 2001 and 2013. Eighty-two patients with DSI, LVSI, or bulky SCC did not receive adjuvant therapy after radical hysterectomy under informed consent. We retrospectively evaluated the prognosis of these 82 patients. <b><i>Results:</i></b> Forty-two patients had >2/3 DSI and 35 patients had 1/3–2/3 DSI. Five patients had LVSI alone. The mean patient age was 43 years (range, 27–72). Six patients (7%) experienced recurrence during a median follow-up period of 84 months (range, 1–206). Two of the 6 patients with recurrence suffered cervical cancer-related deaths, but the remaining 4 cases are alive without evidence of disease after treatment during a follow-up period of 87–165 months. The 5-year disease-free survival rate was 92.6%, and the 5-year overall survival rate was 96.3%. <b><i>Conclusions:</i></b> Adjuvant therapy for DSI, LVSI, or bulky SCC after open radical hysterectomy might not be necessary. Further data collection is warranted to determine the standard of care for patients with intermediate-risk cervical ­cancer.

Comprehensive Genomic Characterization in Ovarian Low-Grade and Chemosensitive and Chemoresistant High-Grade Serous Carcinomas

Introduction: Genomic characterization of serous ovarian carcinoma (SOC), which includes low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), remains necessary to improve efficacy of platinum-based chemotherapy. The aim of this study was to investigate the genomic variations in these SOC groups, also in relation to chemoresponse. Methods: Forty-five samples of SOC were retrospectively analyzed by next-generation sequencing on DNA/RNA extracts from formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained at diagnosis. HGSCs were classified as platinum-resistant and platinum-sensitive. Results: In the LGSC group, 44% of the carcinomas had mutually exclusive variants in the RAS/RAF pathway, while additional likely oncogenic variants in the CDKN2A, SMARCA4, and YAP1 genes were observed in the remaining LGSCs. Tumor mutation burden (TMB) was significantly lower in the intrinsically chemoresistant LGSC group than in the HGSC group. In the HGSC cohort, TP53 variants were found in 90% and homologous recombination repair (HRR) pathway variants in 41% of the neoplasms. HGSCs of the chemoresistant group without classic mutations in the HRR pathway were characterized by additional variants in FGFR2 and with an FGFR3::TACC3 fusion. In addition, HGSCs showed MYC, CCNE1, and AKT2 gains that were almost exclusively observed in the chemosensitive HGSC group. Conclusion: These results suggest that very low TMB and MYC, CCNE1, and AKT2 gains in SOC patients may be biomarkers related to platinum treatment efficacy. Thorough genomic characterization of SOCs prior to treatment might lead to more specific platinum-based chemotherapy strategies.

Racial and Geographic Differences in Endometrial Cancer Death

Introduction: In the USA, endometrial cancer incidence rose by 4.5% annually from 1999 to 2015, reaching 18 per 100,000 women, with a disproportionate impact on African American women. Despite advancements in endometrial cancer research, racial disparities in mortality rates persist. Our retrospective cohort study aimed to investigate the mortality trends and disparities among patients with endometrial cancer in the USA. Methods: Patients with endometrial cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were compared across different races and geographical regions. Results: From 1999 to 2020, endometrial cancer accounted for 90,145 deaths in the USA. Overall, the AAMRs of endometrial cancer increased significantly from 2.50 (95% CI, 2.41–2.58) in 1999 to 3.94 (95% CI, 3.85–4.04) per 100,000 individuals in 2020, with an AAPC of +2.23 (95% CI, 1.39–3.07). The highest AAMR was observed among African Americans (2.69 [95% CI, 2.65–2.74]), followed by whites (1.44 [95% CI, 1.43–1.45]), Hispanics (1.16 [95% CI, 1.13–1.20]), Asians (1.00 [95% CI, 0.96–1.04]), and American Indians (0.99 [95% CI, 0.88–1.10]). The highest AAMR from endometrial cancer was recorded in the Northeast region (1.73 [95% CI, 1.71–1.76]). Conclusion: There was an increasing trend of mortality rates from endometrial cancer in the last 2 decades, which disproportionately affected African Americans. Targeted interventions are warranted to address the mortality disparities among patients with endometrial cancer.

Significance of Ultra-Radical Surgery in Extensive Metastatic Ovarian Growing Teratoma Syndrome

Introduction: The aim of the study was to evaluate the perioperative risks and outcomes of ultra-radical surgery in patients with extensive metastatic ovarian growing teratoma syndrome (GTS). Methods: We conducted a retrospective study of patients with extensive metastatic ovarian GTS treated in our hospital between 2000 and 2022. Patients’ clinical characteristics, surgical treatment, and outcomes were evaluated. Results: Overall, 13 patients were identified, and the median age at diagnosis of ovarian immature teratoma (IT) was 24 years (range: 5–37). The median interval between IT diagnosis and presenting GTS was 8 months (range: 2–60), with a median surgery delay of 5 months (range: 3–300). Peritoneum and liver were the most commonly affected sites (100%), followed by bowel (12 patients, 92.3%), diaphragm (12 patients, 92.3%), adnexa (9 patients, 69.2%), omentum (8 patients, 61.5%), uterus (7 patients, 53.8%), in the descending order. The mean operation time was 316 min (range: 180–625), and the mean blood loss volume was 992 mL (range: 200–5,000). Peritoneal metastasectomy (13 patients, 100%), diaphragmatic metastasectomy (12 patients, 92.3%), metastasis removal from the bowel (8 patients, 61.5%), partial hepatectomy (4 patients, 30.8%), bowel excision and anastomosis (1 patient, 7.7%) were also applied to achieve optimal debulking. R0 was achieved in 9 (69.2%) patients. A high rate of intraoperative blood transfusion (8 patients, 61.5%) and admission to the intensive care unit (9 patients, 69.2%) were observed, and the median postoperative hospitalization time was 8 days (range: 4–22). After a median follow-up of 3.3 years, 9 patients were free of disease, and 4 were alive with stable residual diseases. Conclusion: The survival outcomes in extensive metastatic ovarian GTS were satisfactory after ultra-radical surgery, while a proper therapeutic plan should be established due to the high perioperative risks.