Fédération Internationale De Gynécologie Et d'Obstétrique Research Articles

The Role of Lymphovascular Space Invasion and Cytology in the Prognosis of Endometrial Cancer.

Lymphovascular space invasion (LVSI) and cytology are both independent and strong prognostic factors in endometrial cancer. This study aims to highlight the impact of LVSI and cytology positivity on prognosis, in addition to molecular classification. A retrospective review was conducted on the records of 223 patients with endometrial cancer diagnosed between January 2011 and January 2021. The inclusion criteria stipulated that the patients were diagnosed with endometrial cancer by endometrial biopsy and were operated in the clinic. The exclusion criteria included sarcoma in the postoperative pathology report results or synchronous tumor. Staging was performed according to the Fédération internationale de gynécologie et d'obstétrique (FIGO) 2009 criteria. Cytology (using 50 cc saline) was obtained upon entry into the peritoneal cavity. In 20 patients, saline was not used due to the presence of ascites in the abdomen. The Kaplan-Meier method was employed to evaluate overall survival and progression-free survival. Survival rates were compared in terms of cytology and LVSI. After analyzing the postoperative pathology results, it was found that the mean tumor size was 4.03 ± 2.3 cm. The most common histological type was endometrioid carcinoma, with stage IA being the most common stage. Out of 223 patients with endometrial cancer, the overall survival rate was 82.4%, and the progression-free survival rate was 88.3%. For patients negative for LVSI, the progression-free survival rate was 93%, while for LVSI-positive patients, it was 77.3% (p < 0.001). Additionally, the progression-free survival rate for patients negative for cytology was 90.4%, whereas for cytology-positive patients, it was 77.1% (p < 0.05). In our study, we observed that LVSI positivity and cytology positivity also reduced the overall survival rate. We aimed to highlight that, in addition to molecular classification, cytology positivity and LVSI positivity are still highly significant and independent factors in prognosis.

A Machine Learning Framework Integrating Electronic Health Records for Survival Prognostication in Cervix Cancer

Recent advances in Machine learning (ML) have led to promising clinical applications in oncology, such as improved detection on imaging, predicting emergency department visits, and predicting survival. The hypothesis of this study is a machine learning model using features extracted from electronic health records can be created to improve individual prognostication in patients with cervix cancer managed with radiotherapy in a binary higher and lower risk group model. This study used a single-institution retrospective dataset. Electronic records of patients treated for cervix cancer with definitive radiotherapy from 2003-2014 were queried. Features were selected for model building were based on relevant clinical variables and ease of abstraction from records: age, race, smoking status, parity, self-reported unintentional weight loss, histology, revised 2018 Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging, tumor size, number of enlarged lymph nodes, involved node location, presence of metastases, radiotherapy duration, and concurrent chemotherapy. The dataset was split into training and testing cohorts, with multivariable Cox regression with Lasso regularization performed to predict hazard ratios (HR), and internal 5-fold cross-validation (training set) to determine the regularization parameter. For each patient, a partial HR using all variables was predicted. A cut-off value maximally splitting the training dataset into higher and lower risk cohorts was calculated in the training dataset using Kaplan-Meier estimates and log-rank tests, and this predicted cut-off value was evaluated in the test dataset. A total of 226 patients were included in study, with a median follow-up of 55.1 months; 226 patients in training cohort, and 57 in testing cohort. Feature concordance indices of 0.74 and 0.75 were obtained in the testing and training datasets, respectively, with minimal over-fitting. The three variables that contributed most to the model (with Log HR, 95% CI, p-value) were FIGO stage (0.38, 0.1-0.66, p = 0.01), presence of metastases (0.26, -0.02-0.53, p = 0.07), and unintentional weight loss (-0.34, -0.54-0.14, p<0.01), and FIGO IIB maximally divided the cohort into higher and lower risk stage groupings. A partial HR of 1.15 threshold using all features predicted the largest survival separation between higher and lower risk patients, more so than stage alone (p = 1.18 × 10-3 separated by stage alone vs p = 8.97 × 10-7 separated by partial hazard). A machine learning approach was able to improve prognostication of survival in cervix cancer using additional features from electronic health records. Future work should explore prognostication using large scale datasets and pre-treatment variables for potential incorporation into patient discussions and shared decision making.

Feasibility and Surgical Outcomes of Hysteroscopic Myomectomy of FIGO Type 3 Myoma: A Systematic Review.

The latest classification from the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) has reclassified type 3 myomas, changing their classification from intramural to submucosal. While hysteroscopic myomectomy is considered the gold standard treatment for patients experiencing symptoms from submucosal myomas, there are currently no specific guidelines available for managing type 3 myomas, and the optimal surgical approach remains uncertain. Methods: The search for suitable articles published in English was carried out using the following databases (PROSPERO ID CRD42023418602): MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), Health Technology Assessment Database, Web of Science and search register. Only original studies reporting data on hysteroscopic myomectomy of type 3 myoma were considered eligible. The main outcomes investigated were the effectiveness and feasibility of hysteroscopic myomectomy and reproductive outcomes after surgical treatment. Results: Two hundred and sixty-one studies were screened and nineteen of these were read for eligibility. Three studies encompassing 56 patients in total were included. Among the overall population studied, three patients needed an additional procedure to completely remove the myoma and five cases of post-surgical synechiae were recorded. No complications were reported. Of 42 patients wishing for pregnancy, the cumulative live birth rates before and after the hysteroscopic myomectomy were 14.3% and 42.9%, respectively. Conclusions: Hysteroscopic myomectomy appears to be a safe and feasible approach. Nevertheless, data reported in the literature are extremely scarce and based on studies with few patients enrolled. New evidence is needed to assess the safety and effectiveness of hysteroscopic treatment for FIGO type 3 myomas.

Tumor-stroma interaction in cervical cancer: The prognostic importance of desmoplasia.

e17519 Background: During tumor growth, cancer cells can induce the formation of new extracellular matrix, mainly by activating peritumoral fibroblasts. This stromal reconfiguration has been termed desmoplasia. In pancreatic and ovarian cancer models, targeting desmoplasia therapeutically to normalize the microenvironment has recently shown promising results. We investigated the frequency and prognostic relevance of peritumoral desmoplasia, as well as its association with other prognostic factors such as lymph node involvement and parametrial tumor extension in cervical cancer patients. Methods: A retrospective cohort study based on data from the prospective monocentric observational Leipzig School Mesometrial Resection study was conducted. Cervical cancer patients staged IB1 to IVA according to the Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) who underwent primary surgery between 1999 and 2017 were included. Information regarding desmoplastic tumor reaction was retrospectively retrieved from the pathology reports. All other data had been collected prospectively during the trial period. Using non-parametric tests, we calculated the association of peritumoral desmoplasia with other common risk factors. To determine the prognostic significance of desmoplasia, we used the Kaplan-Meier estimator and performed multivariable Cox-regression modelling. Results: Overall, 355 patients were included. Desmoplasia was present in 298 cases and was associated with a significantly higher likelihood of lymphovascular space involvement (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.4 – 5.1, p = 0.001) and venous infiltration (OR 5.1, 95%-CI 1.3 – 44.9, p = 0.01). Lymph node metastasis was more common in patients with desmoplasia (OR 2.4, 95%-CI 1.2 – 5.0, p = 0.01), as was parametrial involvement (OR 3.5, 95%-CI 1.7 – 7.9, p = 0.0002). Interestingly, the presence of desmoplasia was not associated with larger tumor size. Patients with desmoplastic tissue reaction were significantly older than those without desmoplasia (median 41 years [inter quartile range 34 – 51] vs. 47 years [IQR 39-56], p = 0.009). These prognostically negative parameters in patients with desmoplastic disease translated into inferior overall (94.5% vs 80.5%, OR 3.9 [95%-CI 1.2 – 12.5], p = 0.02) and recurrence-free survival (86.8% vs. 74.2%, OR 2.3 [95%-CI 1.0 – 4.9], p = 0.04). A multivariable Cox-regression model including tumor size, patient age, and nodal status indicated that desmoplasia was an independent risk factor for overall death (OR 4.2, 95%-CI 1.03 – 17.5, p = 0.04). Conclusions: Desmoplastic stromal remodeling is associated with a more aggressive phenotype of cervical cancer and inferior survival. Targeting desmoplasia, especially in advanced disease when surgical treatment is not feasible, might be a promising treatment approach in the future.

Expression of selected molecular factors in two types of endometrial cancer

Endometrial cancers (EC) are a heterogeneous group of malignant neoplasms differing in etiology, clinical-pathological features and prognosis. To determine the differences between the expression of selected molecular factors and find connections between them in order to isolate possible biomarkers influencing treatment options. The investigated data involved archival histological preparations obtained from uterine EC samples taken from 137 patients, treated surgically between 2007 and 2014. The immunohistochemical Dako EnVisionTM Flex+ method was applied. The expression of ERβ, MLH1 and BRCA1 was lower in ECI than in ECII patients. The ERα expression was higher in early Fédération internationale de gynécologie et d'obstétrique (FIGO) (IA) stages than in advanced (IB-IV) stages, while ERβ expression was significantly higher in advanced stages compared to stage IA and increased with grading. The BRCA1 expression also increased with grading. In both type I and type II EC patients, ERα expression correlated with MYH9 and BRCA1, while ERβ expression correlated with BAP expression. High expression of BRCA1 correlated with several proteins: BAP, MYH9 and FAK. High BAP expression also correlated with high MYH9 expression. A correlation in the expression of these proteins was also demonstrated in the group consisting only of patients with ECI. A significant correlation was found between BAP expression and MYH9 among patients diagnosed with ECI. In the ECII group, no correlation was found between the tested proteins. The ECI and ECII patients differed in the studied molecular factors, mainly in terms of ER and BRCA1 expression. Changes in BRCA1 expression were linked to alterations in BAP expression, but were also associated with the proteins MYH9 and FAK.

Lymph Node Staging with a Combined Protocol of 18F-FDG PET/MRI and Sentinel Node SPECT/CT: A Prospective Study in Patients with FIGO I/II Cervical Carcinoma.

Lymph node metastasis (LNM) is present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes. Therefore, the aim of this prospective study was to analyze the impact of 18F-FDG PET/MRI in addition to sentinel lymph node (SLN) biopsy on lymph node (LN) status. Methods: Forty-two women with an initial diagnosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IA-IIB cervical carcinoma were included between March 2016 and April 2019. Each patient underwent preoperative whole-body 18F-FDG PET/MRI and SLN imaging with SPECT/CT after intracervical injection of 99mTc-labeled nanocolloid. Systematic lymphadenectomy and SLN biopsy served as the reference standard. Staging using PET/MRI was performed by nuclear medicine and radiology experts working in consensus. Results: One patient was excluded from surgical staging because of liver metastases newly diagnosed on PET/MRI. The overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). Five of 12 patients with LNM had solely small metastases with a maximum diameter of 5 mm. The consensus interpretation showed PET/MRI to have a specificity of 100% (29/29; 95% CI, 88.3%-100%) for LNM staging but a low sensitivity, 33.3% (4/12; 95% CI, 12.8%-60.9%). LN size was the most important factor for the detectability of metastases, since only LNMs larger than 5 mm could be identified by PET/MRI (sensitivity, 57.1% for >5 mm and 0% for ≤5 mm). Paraaortic LNM was evaluated accurately in 3 of the 4 patients with paraaortic LN metastasis. SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of the hemipelves. In cases with an undetectable SLN on SPECT/CT, the malignancy rate was considerably higher (31.2% vs. 19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. Conclusion:18F-FDG PET/MRI is a highly specific N-staging method and improves LNM detection. Because of the limited sensitivity in frequently occurring small LNMs, PET/MRI should be combined with SLN mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.

Conditional Probability of Survival and Prognostic Factors in Long-Term Survivors of High-Grade Serous Ovarian Cancer.

Objective: High-grade serous ovarian cancers (HGSOC) are heterogeneous, often diagnosed at an advanced stage, and associated with poor overall survival (OS, 39% at five years). There are few data about the prognostic factors of late relapses in HGSOC patients who survived ≥five years, long-term survivors (LTS). The aim of our study is to assess the probability of survival according to the already survived time from diagnosis. Methods: Data from HGSOC patients treated between 1995 and 2016 were retrospectively collected to estimate the conditional probability of survival (CPS), probability of surviving Y years after diagnosis when the patient had already survived X years, and to determine the LTS prognostic factors. The primary endpoint was OS. Results: 404 patients were included; 120 of them were LTS. Patients were aged 61 years (range: 20–89), WHO performance status 0–1 in 86.9% and 2 in 13.1%, and Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) staging III and IV in 82.7% and 17.3% patients. Breast cancer (BRCA) status was available in 116 patients (33% mutated), including 58 LTS (36% mutated). No macroscopic residual disease was observed in 58.4% patients. First-line platinum-based chemotherapy plus paclitaxel was administered in 80.4% of patients (median: six cycles (range: 1–14)). After a 9 point 3-year follow-up, median OS was four years (95% CI: 3.6–4.5). The CPS at five years after surviving one year was 42.8% (95% CI: 35.3–48.3); it increased to 81.7% (95% CI: 75.5–87.8) after four survived years. Progression-free interval>18 months was the only LTS prognostic factor in the multivariable analysis (hazard ratio (HR) = 0.23; 95% CI: 0.13–0.40; p < 0.001). Conclusion: The CPS provided relevant and encouraging clinical information on the life expectancy of HGSOC patients who already survived a period of time after diagnosis. LTS prognostic factors are useful for clinicians and patients.

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients.

The chemokine CCL22 recruits regulatory T (T-reg) cells into tumor tissues and is expressed in many human tumors. However, the prognostic role of CCL22 in cervical cancer (CC) has not been determined. This study retrospectively analyzed the clinical significance of the expression of CCL22 and FOXP3 in 230 cervical cancer patients. Immunohistochemical staining analyses of CCL22 and FOXP3 were performed with a tissue microarray. Double immunofluorescence staining, cell coculture, and ELISA were used to determine CCL22 expressing cells and mechanisms. The higher number of infiltrating CCL22+ cells (CCL22high) group was associated with lymph node metastasis (p = 0.004), Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stages (p = 0.010), therapeutic strategies (p = 0.007), and survival status (p = 0.002). The number of infiltrating CCL22+ cells was positively correlated with that of infiltrating FOXP3+ cells (r = 0.210, p = 0.001). The CCL22high group had a lower overall survival rate (OS), compared to the CCL22low group (p = 0.001). However, no significant differences in progression free survival (PFS) were noted between the two groups. CCL22high was an independent predictor of shorter OS (HR, 4.985; p = 0.0001). The OS of the combination group CCL22highFOXP3high was significantly lower than that of the combination group CCL22lowFOXP3low regardless of the FIGO stage and disease subtype. CCL22highFOXP3high was an independent indictor of shorter OS (HR, 5.284; p = 0.009). The PFS of group CCL22highFOXP3high was significantly lower than that of group CCL22lowFOXP3low in cervical adenocarcinoma, but CCL22highFOXP3high was not an independent indicator (HR, 3.018; p = 0.068). CCL22 was primarily expressed in M2-like macrophages in CC and induced by cervical cancer cells. The findings of our study indicate that cervical cancer patients with elevated CCL22+ infiltrating cells require more aggressive treatment. Moreover, the results provide a basis for subsequent, comprehensive studies to advance the design of immunotherapy for cervical cancer.

Clinical study of nimotuzumab combined with concurrent radiochemotherapy for treatment of locally advanced cervical cancer.

PurposeNimotuzumab is a humanized monoclonal antibody that targets the epidermal growth factor receptor (EGFR) to inhibit tumor growth. Nimotuzumab has demonstrated desirable therapeutic activity in various types of tumors. However, the benefit of nimotuzumab for the treatment of cervical cancer is not entirely clear. The present study aimed to investigate the effects of nimotuzumab in the presence of CCRT in the first-line treatment of locally advanced cervical cancer (LACC).MethodsThe therapeutic efficacy and side effects of nimotuzumab combined with concurrent radiochemotherapy (CCRT) were retrospectively assessed in inoperable patients with LACC (stage IIb-IIIb) who were treated using CCRT with or without nimotuzumab.ResultsThe complete response rate of study group was significantly better than control group (78.3% vs 50%, P=0.035). The difference in median progression-free survival (PFS) in the two groups was statistically significan (not reach vs 27 months, P=0.037). Multivariate comparisons of prognostic factors in the two groups indicated that both the Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage and combined nimotuzumab treatment affected PFS (P<0.05). Although generally tolerable, grade 3–4 toxicities including leukopenia (P=0.025) and hemoglobin (P=0.026) reduction were more frequent in the control group than those in the study group.ConclusionThese data suggest that combining nimotuzumab with CCRT for the treatment of LACC resulted in extended PFS and higher complete remission rates, without an increased incidence of adverse events.

Prognostic factors in Asian and white American patients with cervical cancer, considering competing risks.

Cervical cancer is the 2nd most common malignant tumour in women worldwide. Previous research studies have given little attention to its prognostic factors in the rapidly growing Asian American population. In the present study, we explored prognostic factors in Asian and white American patients with cervical cancer, considering competing risks. The study included 58,780 patients with cervical cancer, of whom 54,827 were white and 3953 were Asian American, and for all of whom complete clinical information was available in the U.S. Surveillance, Epidemiology, and End Results database. Death from cervical cancer was considered to be the event of interest, and deaths from other causes were defined as competing risks. The cumulative incidence function and the Fine-Gray method were applied for univariate and multivariate analysis respectively. We found that, for all patients (white and Asian American combined), the cumulative incidence function was associated with several factors, such as age at diagnosis, figo (Fédération internationale de Gynécologie et d'Obstétrique) stage, registry area, and lymph node metastasis. Similar results were found when considering white patients only. However, for Asian American patients, registry area was not associated with the cumulative incidence function, but the other factors (for example, figo stage) remained statistically significant. Similarly, in multivariate analyses, we found that age at diagnosis, figo stage, lymph node metastasis, tumour histology, treatment method, and race were all associated with prognosis. Survival status differs for white and Asian American patients with cervical cancer. Our results could guide the treatment of, and facilitate prognostic judgments about, white and Asian American patients with cervical cancer.

Is there uniformity in definitions and treatment of gestational trophoblastic disease in Europe?

Because gestational trophoblastic disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe. To provide a basis for international standardization of definitions, treatment and follow-up protocols in gestational trophoblastic disease, we evaluated differences and similarities between protocols in EOTTD countries. Members from each EOTTD country were asked to complete an online structured questionnaire comprising multiple-choice and multiple-answer questions. The following themes were discussed: incidence of gestational trophoblastic disease and gestational trophoblastic neoplasia, definitions, guidelines, classification system, treatment, recurrence, and follow-up. Forty-four respondents from 17 countries participated in this study. Guidelines were present in 80% of the countries and the FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) staging and risk classification was often used to estimate risks. Agreement about when to start chemotherapy for post-molar gestational trophoblastic neoplasia was present among 66% of the respondents. Preferred first-line treatments in low- and high-risk gestational trophoblastic neoplasia were methotrexate (81%) and EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (93%), respectively. The definition of human chorionic gonadotropin normalization after hydatidiform mole evacuation was two consecutive normal values for nine countries. The FIGO definition of post-molar gestational trophoblastic neoplasia based on human chorionic gonadotropin plateau or rise was agreed on by 69% of respondents, and only 69% and 74% defined low-risk and high-risk disease, respectively, using FIGO criteria. There were major differences in definitions of recurrence, chemotherapy resistance and follow-up protocols among countries, despite EOTTD consensus statements. This questionnaire provides a good overview of current clinical practices in different countries. Based on the survey results, it is clear that there are several gestationaltrophoblastic disease-related topics that need urgent attention within the EOTTD community to create more uniformity and to aid the development of uniform guidelines in Europe.

L1CAM as a Negative Prognostic Factor in Endometrioid Endometrial Adenocarcinoma FIGO Stage IA-IB.

In this study, we aimed to investigate how positivity for L1 cell adhesion molecule (L1CAM) was associated with outcome and relapse pattern in patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IA-IB endometrial cancer. This retrospective study included 358 patients who underwent surgical treatment for endometrial carcinoma. Tumor samples from 312 patients (87.2%) were available for L1CAM analysis by immunohistochemistry. Of the 312 tumor samples analyzed, 93 (29.8%) were L1CAM-positive. L1CAM positivity was significantly more common in grade 3 compared to grade 1-2 carcinomas (p=0.02). Patients with L1CAM positivity more commonly experienced disease progression. Distant metastasis was significantly associated with L1CAM positivity (p=0.01). Progression-free interval and overall survival did not significantly differ between L1CAM-positive and L1CAM-negative cases. L1CAM is a promising independent prognostic marker associated with aggressive tumor behavior and recurrence risk, but not with overall survival.

Global Consultation on Cancer Staging: To Promote Consistent Understanding and Use of Cancer Stage Terminology

Background and context: Although the TNM stage schema has been the traditional means to classify anatomic extent of disease, in recent years confusion and uncertainty have emerged which underpinned by lack of familiarity concerning underlying rules of staging and their application. In turn such lack of clarity has led increased risk of miscommunication regarding patient care, research, cancer surveillance, epidemiology and cancer control. The UICC TNM Committee has confirmed a lack of uniformity in the application of cancer stage and its rules. In addition to stage, numerous other factors influence the outcome of patients as relate to tumor characteristics, patient descriptors, and the environment where any treatment is administered. A particularly a frequent problem is mixing disease extent and biology which has promoted additional misunderstanding about the importance and relevance of different individual prognostic elements and to what degree biology vs disease burden contribute to outcome. Aim: To ensure uniformity of staging systems, rules and classifications, the TNM Committee developed a global consensus on cancer staging. Strategy/Tactics: A selected literature review of twelve high impact oncology journals was performed and results will be summarized. There was inconsistent understanding and use of cancer stage classification terminology evident in up to 20% of the literature. A survey was developed and found that only 12.5% of those surveyed thought that the application of the TNM staging terminology was consistent and uniform in the literature. Respondents believed that complete T, N and M data should be recorded in cancer registries, 71% considered that other predictive and prognostic factors should also be collected by central cancer registries but that anatomic disease extent should be collected as a separate variable (85%). The Global Consultation on Cancer Staging was held under the auspices of the Union for International Cancer Control (UICC) and Lancet Oncology with support from the United States (US) National Cancer Institute (NCI) and the US Centers for Disease Control and Prevention (CDC). Experts from these organizations and FIGO (Fédération Internationale de Gynécologie et d´Obstétrique), IACR (International Association of Cancer Registries), IARC (International Agency for Research in Cancer), and the ICCR (International Collaboration on Cancer Reporting) attended. Program/Policy process: The purpose of the staging classification was reaffirmed. Important issues about staging processes were annunciated, and inconsistencies in terminology and use were acknowledged. Definitions of frequently misused staging terms were clarified. What was learned: It was determined that methodologies need to be explored to identify and include necessary data elements relevant to personalized treatment. Selection of factors should particularly include attention to their inclusion in cancer registries where appropriate.

Prognostic value of preoperative hyponatremia and thrombocytosis in patients with epithelial ovarian cancer

Preoperative hyponatremia and thrombocytosis are associated with perioperative morbidity in patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate preoperative hyponatremia and thrombocytosis as prognostic parameters in patients with EOC. In aretrospective cohort study, serum levels of sodium and thrombocyte counts were evaluated in 498 patients with EOC. Data were extracted from the prospectively maintained database. Results were correlated with clinicopathological parameters and patient survival. Mean (standard deviation) overall pretherapeutic serum sodium levels and thrombocyte counts in patients with EOC were 138.8 (2.9) mmol/l and 340.1 (122.6) × 103/µl, respectively. Hyponatremia (serum sodium levels ≤ 134 mmol/l) was found in 33 (6.7%) patients and thrombocytosis (thrombocytes ≥ 450/µl) in 88 (17.7%) patients. Serum sodium levels were associated with the presence or absence of residual tumor tissue after primary surgery. Thrombocyte counts were associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) tumor stage, presence/absence of residual tumor, histological grade and histological type. Patients with thrombocytosis presented with advanced tumor stage, ahigher rate of postoperative residual tumor mass, higher tumor grade, and ahigher rate of serous ovarian cancer. In amultivariate logistic regression analysis, only the established clinicopathological parameters but not serum sodium and thrombocyte count were independent predictors of patient overall survival. Preoperative hyponatremia and thrombocytosis are not useful as additional independent prognostic parameters in patients with EOC.

Neoadjuvant chemotherapy and the complexity of operative procedure in advanced epithelial ovarian cancer: a retrospective analysis

Introduction: Complete tumor resection for epithelial ovarian cancer (EOC) generally incorporates complex surgical maneuvers, especially bowel resection. This study retrospectively analyzed the impact of neoadjuvant chemotherapy (NAC) on complexity of surgical procedures for EOC (represented by bowel resection) and postoperative morbidity. Methods: We retrospectively recruited all patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages IIIC–IVB EOC who were treated in our center between 2011 and 2016. Patients were divided into those who received primary debulking followed by chemotherapy (group A), and those who received NAC followed by interval debulking (group B). Patient age, tumor stage, grade, dates of commencement and completion of therapy, intraoperative events, completion of surgical resection, and postoperative events were evaluated. Results: Of 92 patients, 42 were assigned to group A and 50 to group B. Their FIGO stages were group A—stages IIIC: 34 (80.9%), IVA: 6 (14.3%), and IVB: 2 (4.8%); and group B—stages IIIC: 45 (90%), IVA: 5 (10%), and IVB: 0 (0%). The 2 groups did not significantly differ in completeness of surgical cytoreduction or rates of bowel resection, intraoperative complications, or postoperative morbidities. Conclusion: NAC did not reduce rates of bowel resection, intraoperative complications, and postoperative morbidity in advanced EOC compared with primary surgical cytoreduction. Future prospective studies will be required to corroborate our results.

The Prostaglandin EP3 Receptor Is an Independent Negative Prognostic Factor for Cervical Cancer Patients.

We know that one of the main risk factors for cervical cancer is an infection with high-risk human papillomavirus (HR-HPV). Prostaglandins and their receptors are very important for the tumour growth and tumour-associated angiogenesis. Little is known about the expression of the Prostaglandin E receptor type 3 (EP3) or the Prostaglandin (PG)E2-EP3 signalling in cervical cancer, so the aim of the study was to analyse the expression of the EP3 receptor in cervical cancer and find prognostic factors in relation to survival; EP3 immunohistological staining of 250 cervical cancer slides was performed and analysed with a semi-quantitative score. The statistical evaluation was performed with Statistical Package for the Social Sciences (SPSS) to evaluate the staining results and the survival analyses of the cervical cancer cases. A significant difference was observed in EP3 expression in Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stadium I versus FIGO stadium II–IV cases. High expression of EP3 (IRS ≥ 1.5) in cervical cancer patients was correlated with poor prognosis in overall survival rates. Survival in adenocarcinoma (AC) of the cervix was lower than in squamous cell carcinoma (SCC). Cox regression analysis shows that EP3 is an independent prognosticator. In this study we could show that the membrane-bound prostaglandin receptor EP3 is an independent prognosticator for cervical cancer patient survival. Targeting the EP3 receptor seems to be an interesting candidate for endocrine therapy. Therefore, more research is needed on the influence of the receptor system and its influence on cervical cancer growth.

Diagnostic value of whole body diffusion-weighted MRI compared to computed tomography for pre-operative assessment of patients suspected for ovarian cancer

BackgroundDespite excellent per-lesion performance for peritoneal staging, the additional clinical value of diffusion-weighted magnetic resonance imaging (DWI/MRI) compared to computed tomography (CT) remains to be established in ovarian cancer.Our purpose was to evaluate whole body (WB)-DWI/MRI for diagnosis, staging and operability assessment of patients suspected for ovarian cancer compared to CT. MethodsOne hundred and sixty-one patients suspected for ovarian carcinoma underwent 3 T WB-DWI/MRI and contrast-enhanced CT. WB-DWI/MRI and CT were compared for confirmation of the malignant nature and primary origin of the ovarian mass, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging and prediction of incomplete resection using institutional operability criteria. Interobserver agreement between two readers was determined for WB-DWI/MRI and CT. ResultsWB-DWI/MRI showed a significantly higher accuracy than CT (93 versus 82%, p = 0.001) to confirm the malignant nature of the ovarian mass and correctly identified 26 of 32 (81%) cancers of non-ovarian origin compared to 10/32 (31%) for CT (p < 0.001). WB-DWI/MRI assigned more ovarian carcinoma patients to the correct FIGO stage (82/94, 87%) compared with CT (33/94, 35%). For prediction of incomplete resection, WB-DWI/MRI showed significantly higher sensitivity (94 versus 66%), specificity (97.7 versus 77.3%) and accuracy (95.7 versus 71.3%) compared to CT (p < 0.001). Interobserver agreement was almost perfect (κ = 0.90) for WB-DWI/MRI and moderate (κ = 0.52) for CT for prediction of incomplete resection. ConclusionsWB-DWI/MRI was superior to CT for primary tumour characterisation, staging and prediction of incomplete resection in patients suspected for ovarian cancer.

Should ovarian carcinoma metastatic to the inguinal nodes be assigned stage IVB?

Objective: According to the recently revised Fédération Internationale de Gynécologie et d' Obstétrique (FIGO) staging classification, women with ovarian carcinoma and inguinal lymph nodes (LN) metastases, formerly stage III, are now considered stage IVB. The prognostic significance of this classification has yet to be evaluated. In this retrospective study we compare the survival of these patients to that of women with stage III (with aortic and/or pelvic LN metastases) and stage IV (due to distant metastasis) disease.

Efficacy and Safety of AEZS-108 (LHRH Agonist Linked to Doxorubicin) in Women With Advanced or Recurrent Endometrial Cancer Expressing LHRH Receptors: A Multicenter Phase 2 Trial (AGO-GYN5)

ObjectiveAdvanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone–releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients.MethodsPatients had FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) III or IV or recurrent EC, LHRH receptor–positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors.ResultsFrom April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%).ConclusionsAEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor–positive EC, supporting the principle of receptor-mediated targeted chemotherapy.

L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation

Despite the excellent prognosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome. We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan-Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death. Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). In the L1CAM-negative cancers FIGO stage I subdivision, grading and risk assessment were irrelevant for predicting disease-free and overall survival. The prognostic relevance of these parameters was related strictly to L1CAM positivity. A classification and regression decision tree (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89). To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.