Federation Of Gynecology And Obstetrics Stage Research Articles

Establishment of a risk stratification model based on the combination of post-treatment serum squamous cell carcinoma antigen levels and FIGO stage of cervical cancer for treatment and surveillance decision-making

ObjectiveTo develop a risk stratification model based on the International Federation of Gynecology and Obstetrics (FIGO) staging combined with squamous cell carcinoma antigen (SCC-Ag) for the classification of patients with cervical squamous cell carcinoma (CSCC) into different risk groups.MethodsWe retrospectively reviewed the data of 664 women with stage IIA–IVB CSCC according to the 2018 FIGO staging system who received definitive radiotherapy from March 2013 to December 2017 at the department of radiation oncology of Sun Yat-sen University Cancer Center. Cutoff values for continuous variables were estimated using receiver operating characteristic curve analysis. Using recursive partitioning analysis (RPA) modeling, overall survival was predicted based on the prognostic factors determined via Cox regression analysis. The predictive performance of the RPA model was assessed using the consistency index (C-index). Intergroup survival differences were determined and compared using Kaplan–Meier analysis and the log-rank test.ResultsMultivariate Cox regression analysis identified post-treatment SCC-Ag (< 1.35 ng/mL and > 1.35 ng/mL; hazard ratio (HR), 4.000; 95% confidence interval (CI), 2.911–5.496; P < 0.0001) and FIGO stage (II, III, and IV; HR, 2.582, 95% CI, 1.947–3.426; P < 0.0001) as the independent outcome predictors for overall survival. The RPA model based on the above prognostic factors divided the patients into high-, intermediate-, and low-risk groups. Significant differences in overall survival were observed among the three groups (5-year overall survival: low vs. intermediate vs. high, 91.3% vs. 76.7% vs. 29.5%, P < 0.0001). The predictive performance of the RPA model (C-index, 0.732; 95% CI, 0.701–0.763) was prominently superior to that of post-treatment SCC-Ag (C-index, 0.668; 95% CI, 0.635–0.702; P < 0.0001) and FIGO stage (C-index, 0.663; 95% CI, 0.631–0.695; P < 0.0001).ConclusionsThe RPA model based on FIGO staging and post-treatment SCC-Ag can predict the overall survival of patients with CSCC, thereby providing a guide for the formulation of risk-adaptive treatment and individualized follow-up strategies.

Cell cycle regulatory markers as potential prognostic biomarkers in uterine carcinosarcoma

The relevance of cell cycle regulatory markers with uterine carcinosarcoma was investigated. The immunohistochemical expression of p16, p53, and cyclin D1 were assessed using tissue microarray of 55 eligible patients. p16 and p53 showed a high rate of strong (+3) immune reaction in carcinomatous/sarcomatous components (61.8%/70.9% and 52.7%/56.4%, respectively). Cyclin D1 showed a 14.5%/7.3%of strong immune reaction in the carcinomatous/sarcomatous components. Strong expression of p16 was related to a higher rate of recurrence, lymph node metastasis, and bigger tumor size. Strong expression of cyclin D1 was related to the lower International Federation of Gynecology and Obstetrics (FIGO) stage and recurrence rate. In univariate regression analysis, FIGO stage, lymph node metastasis, p16, and cyclin D1 were prognostic factors for disease-free survival. FIGO stage, p16, p53, and cyclin D1 were prognostic factors for disease specific survival. In a multivariate regression analysis, FIGO stage and p16 in carcinomatous component were independent factors for disease-free survival (odds ratio (OR), 95% confidence interval (CI); 3.2 (1.1–9.6) and 3.5 (1.3–9.7); p = 0.035 and 0.017). p16 was a predictor of lymph node metastasis, tumor size, and prognostic outcome in uterine carcinosarcoma.

Survival Outcomes of Patients with International Federation of Gynecology and Obstetrics Stage IV Ovarian Cancer: Cytoreduction Still Matters.

There is still no consensus on the therapeutic strategies for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV ovarian cancer (OC). We aim to outline the clinical characteristics and optimal therapeutic strategies of patients with FIGO stage IV OC. This single center retrospective study analyzed the clinical features and survival of patients with FIGO stage IV OC that underwent cytoreduction or received at least one course of chemotherapy between January 2014 and December 2020. One hundred and twenty patients were included. Surgery, especially optimal cytoreduction without residual mass improved the overall survival of patients in surgery group (P = .047, HR .432, 95% CI .181-.987). Secondly, the completion of chemotherapy improved median overall survival of patients either with (53.0 months vs 25.0 months, P < .001, HR 7.015, 95% CI 1.372-35.881) or without cytoreduction (43.0 months vs 6.0 months, P = .006, HR 5.969, 95% CI 1.115-31.952). In patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had better survival. In patients with FIGO stage IV, complete resection of intra-abdominal tumor foci and completion of chemotherapy provided considerable survival benefits to patients with FIGO stage IV OC. Among patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had a better prognosis.

Adjuvant chemotherapy in patients with low-risk epithelial ovarian cancer: A Taiwanese cohort study

Background: Whether or not patients with stage I epithelial ovarian cancer (EOC) benefit from postoperative chemotherapy in the Asian population remains unclear. This retrospective cohort study was aimed at investigating the use of adjuvant chemotherapy in clinical practice to treat patients with early-stage EOC considering clinical factors. Materials and Methods: A total of 414 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IA–IC and grade 1 EOC were enrolled from the Taiwan Cancer Registry. We used multivariable Cox proportional-hazards models to control for clinical factors. The overall survival (OS) and disease-free survival (DFS) were estimated with the Kaplan–Meier method. Results: DFS did not improve significantly for patients with FIGO stage IA/IB EOC receiving adjuvant chemotherapy, with a 10-year DFS rate of 98% and 88% for those with and without adjuvant chemotherapy, respectively (hazard ratio [HR] = 0.41, 95% confidence interval [CI]: 0.05–3.36). OS did not improve significantly for patients with FIGO stage IA/IB EOC with adjuvant chemotherapy (HR = 0.86, 95% CI: 0.18–4.22) or stage IC (HR = 0.50, 95% CI: 0.10–2.45). OS did not differ significantly for patients with optimal (10-year OS: 92% with chemotherapy and 86% without chemotherapy in the log-rank test, P = 0.629) or nonoptimal staging (10-year OS: 73% with chemotherapy and 90% without chemotherapy in the log-rank test, P = 0.959). Conclusion: Adjuvant chemotherapy did not improve the prognosis of patients with low to intermediate-risk EOC and optimal/nonoptimal surgery. This result should be considered in clinical practice.

Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro.

Emerging evidence indicates the importance of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in a number of developmental processes. Little is known regarding its biological function in regulating cervical cancer (CC) progression. In this study, we aim to explore the role of HS6ST2 in CC progression. The transcriptome sequencing data of CC tissues from three databases, GSE64217, GSE138080, and GSE63514, was examined for genes with significant changes. The expression profile for HS6ST2 within CC tissue was then assessed through fluorescence quantitative PCR and immunohistochemistry and compared to data from patients with clinicopathological features. A multivariate survival analysis was performed using the COX regression. The real-time quantitative PCR assessed the HS6ST2 expression profile within CC cellular cultures. The results of knocking down HS6ST2, considering the proliferative activity and invasiveness of CC cultures in vitro, were detected through cell viability assay, clonogenic assessment, tumorsphere formation analysis, 3D invasion experiment and transwell assay. The impact of HS6ST2 knockdown in CC proliferation was also evaluated in vivo using a nude mice model. HS6ST2 was severely upregulated within CC tissues across the three explored databases (GSE64217, GSE138080, and GSE63514). Fluorescent quantitative PCR and immunohistochemistry experiments identified HS6ST2 as highly upregulated within patients CC tissues. Survival analysis taking into account the parameters of lymph node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, depth of invasion, pathological grade, and HS6ST2 expression level demonstrated that individuals with downregulated HS6ST2 exhibited considerably extended progression-free survival (PFS) and overall survival (OS) in comparison to upregulated HS6ST2 cases. According to the findings of COX univariate analysis, the parameters lymph node metastasis, FIGO stage, depth of invasion, pathological grade, and HS6ST2 expression level, all showed a statistically significant correlation with effect upon prognosis of CC patients. The FIGO stage, depth of invasion and expression level of HS6ST2 were identified as independent risk variables influencing CC case prognosis within subsequent COX multivariate analysis. Cell function experiments proved that HS6ST2 knockdown can considerably diminish the proliferative potential, stemness and invasive traits of CC cells. Tumor formation experiments in nude mice in vivo demonstrated that knocking down HS6ST2 can significantly thwart CC cellular proliferative properties within animal models. The clinicopathological features and the survival time of the patients significantly correlate with the level of HS6ST2 expression in CC tissue samples.

Clinical utility of pretreatment serum squamous cell carcinoma antigen for prognostication and decision-making in patients with early-stage cervical cancer.

To investigate the prognostic role of pretreatment squamous cell carcinoma antigen (SCCA) in early-stage cervical cancer (CC). We enrolled 487 cases of pathology-proven early-stage [International Federation of Gynecology and Obstetrics (FIGO) I/II] squamous or adenosquamous CC that were treated from 2012 to 2015. Restricted cubic splines (RCS) with a full Cox regression model were used to evaluate the association between SCCA levels and survival outcomes. Recursive partitioning analysis (RPA) was used to construct a risk stratification model for overall survival (OS). The performance of the RPA-based model was assessed using a receiver operating characteristic (ROC) curve. RCS analysis revealed an association between SCCA and OS and disease-free survival (DFS); SCCA ⩾2.5 ng/mL was robust for risk discrimination in our cohort. SCCA had an interaction effect with FIGO classification: Patients with FIGO I and SCCA ⩾2.5 ng/mL overlapped with those with FIGO II and SCCA < 2.5 ng/mL for OS [hazard ratio, 1.04 (95% confidence interval (CI): 0.49-2.24), p = 0.903] and DFS [1.05 (0.56-1.98), p = 0.876]. RPA modeling incorporating SCCA (<2.5 ng/mL and ⩾2.5 ng/mL) and FIGO classification divided CC into three prognostic groups: RPA I, FIGO stage I, and SCCA < 2.5 ng/mL; RPA II, FIGO stage I, and SCCA ⩾ 2.5 ng/mL, or FIGO stage II and SCCA < 2.5 ng/mL; and RPA III, FIGO stage II, and SCCA ⩾ 2.5 ng/mL; with 5-year OS of 94.0%, 85.1%, and 73.5%, respectively (p < 0.001). ROC analysis confirmed that the RPA model outperformed the FIGO 2018 stage with significantly improved accuracy for survival prediction [area under the curve: RPA versus FIGO, 0.663 (95% CI: 0.619-0.705] versus 0.621 (0.576-0.664), p = 0.045]. Importantly, the RPA groupings were associated with the efficacy of treatment regimens. Surgery followed by adjuvant treatment had a higher OS (p < 0.01) and DFS (p = 0.024) than other treatments for RPA III, whereas outcomes were comparable among treatment regimens for RPA I-II. Herein, the role of SCCA for prognostication was confirmed, and a robust clinicomolecular risk stratification system that outperforms conventional FIGO classification in early-stage squamous and adenosquamous CC was presented. The model correlated with the efficacy of different treatment regimes.

Profile of HER2/neu Expression in Surface Epithelial Ovarian Tumours: A Clinicomorphological Study

Introduction: Surface Epithelial Ovarian Tumours (SEOT) are most prevalent tumours and account for about two third of all ovarian cancers. Survival of ovarian carcinoma is poor despite optimal surgical and chemotherapeutic management. Evaluation of new diagnostic and prognostic Immunohistochemical (IHC) markers will be essential in this aspect. Aim: To evaluate quantitatively the profile of Human Epidermal growth factor Receptor 2 (HER2)/neu IHC expression with standard scoring system in SEOTs and their association with various clinicpathologic variables (age, laterality, CA 125 levels, histological subtype and FIGO staging). Materials and Methods: The present ambispective study was done in the Department of Pathology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu, India, from August 2020 to August 2022 with a sample size of 166 cases. All the histopathological samples of SEOT during the study period from August 2020 to August 2022 (prospective) and all borderline, malignant and few benign cases from June 2016 to August 2020 (retrospective) were also included in the study. Cases for which slides and blocks were not available and patient treated with neo adjuvant chemotherapy or radiotherapy were excluded in the study. For prospective cases after getting clinical history and Cancer Antigen 125 (CA 125) level, specimens were fixed, processed and Haematoxylin and Eosin (H&amp;E), IHC staining was done as per standard lab protocol, for retrospective cases clinical history, CA 125 levels, pathological diagnosis and tissue blocks were retrieved, IHC performed and finally both prospective and retrospective cases HER2/neu IHC expression association was studied related to clinicopathological parameters. Results: Out of total sample, SEOT was the most common (n=184, 76.98%) tumour cases, followed by germ cell tumours (n=42, 17.57%) cases and least common was sex cord stromal tumour (n=13, 5.43%). HER2/neu had higher IHC expression in malignant tumours and showed statistically significant positive association with age (p-value=0.001), CA 125 level (p-value0.001), and histological diagnosis (p-value &lt;0.001), but there is no significant association with size of tumour (p-value=0.786), parity (p-value=0.717), laterality (p-value=0.514) and the International Federation of Gynecology and Obstetrics (FIGO) grading (p-value=0.274). Conclusion: Malignant tumours had high HER2/neu IHC expression, thus emphasising its carcinogenic role and helps in the diagnostic differentiation of benign and borderline tumours with malignant potential from actual malignant tumours and can be a therapeutic target in future.

Quantitative evaluation of myelosuppression after chemotherapy for patients with ovarian cancer using material decomposition in dual-energy computed tomography

Objective: To demonstrate feasibility of quantifying myelosuppression after chemother-apy for patients with ovarian cancer (OC) using fat density measurement on material decomposition (MD) images in dual-energy computed tomography (DECT). Materials and methods: Fifty-seven patients with OC after chemotherapy underwent DECT. MD using fat and hydroxyapatite (HAP) as basis material pair was performed. Regions of interest (ROIs) of 20 mm2 were placed on bone marrow of ilia and femoral shafts bilaterally at level of coronal hip joint and the third sagittal lumbar vertebra to measure fat density on FAT (HAP) MD images. Eight characteristics (age, pathological type, International Federation of Gynaecology and Obstetrics (FIGO) stage, unilateral/bilateral, chemotherapy protocol and cycle, days after therapy (DAT), and ROI location) were recorded. Fat densities in ilia and femoral shafts were compared bilaterally with paired sample t tests and among 3 ROI locations with Kruskal-Wallis tests. Regression and correlations were made between fat density and 8 characteristics. Regression equations, correlation coefficients, scatterplot and normal probability plot (P-P) are provided. Results: There were no statistically significant differences in fat density in ilia or femoral shafts bilaterally (p &gt; 0.05). Average fat densities were significantly different with 916.93 ± 9.3 in ilia, 927.04 ± 11.86 in femoral shaft, and 932.18 ± 8.45 in lumbar vertebra (p &lt; 0.001). Regression equation was Y = 923.26 − 0.29 × age + 0.05 × pathological-type − 0.94 × FIGO stage + 0.82 × unilateral/bilateral − 0.54 × chemotherapy-protocol + 0.52 × chemotherapy-cycle + 0.01 × DAT + 7.63 × ROI location, with correlation coefficients with age, DAT and ROI location at −0.23, 0.16 and 0.53, respectively (p &lt; 0.05). Conclusions: Myelosuppression after chemotherapy manifests as fat substitute and can be quantified by measuring fat density on FAT (HAP) images. Fat density was significantly correlated with patient age, DAT and measurement locations.

Clinical characteristics and risk factors analysis for the recurrence of pelvic endodermal sinus tumors

This study investigated the clinicopathological characteristics and factors influencing the recurrence of pelvic endodermal sinus tumor (PEST). 54 cases were retrospectively analyzed from at the Zhejiang Cancer Hospital. Progression-free survival (PFS) and related factors on disease recurrence were evaluated. Six patients had extragonadal endodermal sinus tumor, and four had histological features of endodermal sinus tumor (EST) combined with embryonal carcinoma (EC). 39 patients underwent fertility-preserving surgery, 18 patients had a childbearing history, and eight patients had residual tumor after initial treatment as surgery or chemotherapy. 26 patients had a tumor diameter of more than 15 cm, and 30 patients had a serum αfetoprotein (AFP) level greater than 10,000 ng/mL before initial management. The median follow-up was 47.5 months (range, 14–212 months). During follow-up, 15 patients experience recurrence, with a recurrence rate of 27.8% and a 5-year PFS rate of 61.1%. In univariate analysis, the FIGO (International Federation of Gynecology and Obstetrics) stage (stage III–IV vs. I–II; hazard ratio (HR) = 9.73, p &lt; 0.001), residual tumor (yes vs. no for the first surgery; HR = 4.86, p = 0.001), histological features (EST combined with EC vs. EST; HR = 4.08, p = 0.017), and use of platinum-based chemotherapy (courses ≥3 vs. courses &lt;3; HR = 0.19, p = 0.004) were independent factors influencing recurrence. In multivariate analysis, only stage was an independent risk factor for PFS (stage III–IV vs. I–II; HR = 6.92, p = 0.02). Stage is a prognostic factor for recurrence of PEST. The aim of the initial surgery is to maximally debulk all grossly visible tumor and the post-operative treatment should include a sufficient dose and full course of platinum-based chemotherapy, which may reduce the recurrence rate. Maybe some gene expression that could be associate with PEST.

Preliminary outcomes of five-year survival for ovarian malignancies in profiled Serbian Oncology Centre

ObjectiveThe present study purposed to determine characteristics of ovarian carcinoma and to analyze predictors of survival in patients with ovarian carcinoma. MethodA retrospective cohort study was conducted including the patients with diagnosed ovarian carcinoma treated at the Clinic for Operative Oncology, Oncology Institute of Vojvodina in the period from January 2012 to December 2016. Seventy-two women with ovarian carcinoma were included in the analysis. The data about the histological type of tumor, disease stage, treatment, lymphatic infiltration, and surgical procedure were collected retrospectively, using the database of the institution where the research was conducted (BirPis 21 SRC Infonet DOO ‒ Information System Oncology Institute of Vojvodina). Descriptive statistics and multivariate analysis using Cox proportional hazards model were performed. ResultsThe univariate Cox regression analysis identified histology, tumor grade, FIGO (International Federation of Gynecology and Obstetrics) stage, NACT (Neoadjuvant Chemotherapy), number of therapy cycles, type of surgery, and chemotherapy response as independent predictors of mortality. Finally, the type of tumor and chemotherapy response had an increased hazard ratio for mortality in the multivariate Cox regression model. Herewith, the percentage of high-grade, advanced-stage ovarian cancer patients with complete response to chemotherapy, absence of recurrent disease, and lymphovascular space invasion were significant predictors of survival in patients with ovarian carcinoma. ConclusionsHerein, emerging data regarding precision medicine and molecular-based personalized treatments are promising and will likely modify the way the authors provide multiple lines of treatments in the near future.

Synchronous Primary Carcinoma of Cervix and Ovary-A Rare Case Report

Synchronous malignancies of female genital tract account for less than 3% of all genital tract neoplasms. Amongst synchronous tumours, ovarian with endometrial carcinoma accounts for 51.7% while ovarian with cervix accounts for less than 10% of them. Unusually, they have a favourable prognosis with 5 years survival rate being 73.3%. Authors hereby, present a case of 51-years-old female presented with bleeding per vagina and on examination cervical mass was detected. The cervical mass biopsy confirmed cribriform adenocarcinoma of cervix. Uterus and cervix could not be removed as it was FIGO (The International Federation of Gynecology and Obstetrics) stage III B (inoperable) thus was managed on chemotherapy and radiotherapy. A month later she presented with bilateral ovarian masses for which she had undergone bilateral oophorectomy and omentectomy. Histopathology confirmed moderately differentiated mucinous cystadenocarcinoma of bilateral ovaries. Thus a case of synchronous carcinoma of cervix and ovary was concluded. She tolerated all managements successfully.

Risk factors for and delayed recognition of genitourinary fistula following radical hysterectomy for cervical cancer: a population-based analysis.

This study aimed to identify the risk factors for genitourinary fistulas and delayed fistula recognition after radical hysterectomy for cervical cancer. This study was a retrospective analysis of data collected in the Major Surgical complications of Cervical Cancer in China (MSCCCC) database from 2004-2016. Data on sociodemographic characteristics, clinical characteristics, and hospital characteristics were extracted. Differences in the odds of genitourinary fistula development were investigated with multivariate logistic regression analyses, and differences in the time to recognition of genitourinary fistula were assessed by Kruskal-Wallis test. In this study, 23,404 patients met the inclusion criteria. Surgery in a cancer center, a women's and children's hospital, a facility in a first-tier city, or southwest region, stage IIA, type C1 hysterectomy, laparoscopic surgery and ureteral injury were associated with a higher risk of ureterovaginal fistula (UVF) (p<0.050). Surgery in southwest region, bladder injury and laparoscopic surgery were associated with greater odds of vesicovaginal fistula (VVF) (p<0.050). Surgery at cancer centers and high-volume hospitals was associated with an increase in the median time to UVF recognition (p=0.016; p=0.005). International Federation of Gynecology and Obstetrics (FIGO) stage IIA1-IIB was associated with delayed recognition of VVF (p=0.040). Intraoperative urinary tract injury and surgical approach were associated with differences in the development of UVFs and VVFs. Patients who underwent surgery in cancer centers and high-volume hospitals were more likely to experience delayed recognition of UVF. Patients with FIGO stage IIA1-IIB disease were more likely to experience delayed recognition of VVF.

The prognosis predictive score around primary debulking surgery (PPSP) improves diagnostic efficacy in predicting the prognosis of ovarian cancer

In recent years, the pretreatment inflammatory responses have proven to predict the prognosis, but no report exists analyzing the combined inflammatory response of the pre- and postsurgical treatment. The current study aims to extract the factors predicting the recurrence and create novel predictive scoring. This retrospective study was conducted at our institution between November 2006 and December 2020, with follow-up until September 2022. Demographic and clinicopathological data were collected from women who underwent primary debulking surgery. We created the scoring system named the prognosis predictive score around primary debulking surgery(PPSP) for progression-free survival(PFS). Univariate and multivariate analyses were performed to assess its efficacy in predicting PFS and overall survival(OS). Cox regression analyses were used to assess its time-dependent efficacy. Kaplan–Meier and the log-rank test were used to compare the survival rate. A total of 235 patients were included in the current study. The cut-off value of the scoring system was six. Multivariate analyses revealed that an advanced International Federation of Gynecology and Obstetrics(FIGO) stage (p < 0.001 for PFS; p = 0.038 for OS), the decreased white blood cell count difference (p = 0.026 for PFS) and the high-PPSP (p = 0.004 for PFS; p = 0.002 for OS) were the independent prognostic factors. Cox regression analysis also supported the above results. The PPSP showed good prognostic efficacy not only in predicting the PFS but also OS of ovarian cancer patients comparable to FIGO staging.

XPO1-Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma.

Dysregulation of eukaryotic translation initiation factor 1A, X-linked (EIF1AX), has been implicated in the pathogenesis of some cancers. However, the role of EIF1AX in endometrial carcinoma (EC) remains unknown. We investigated the EIF1AX expression in EC patients and assessed its tumorigenesis-associated function and nucleocytoplasmic transport mechanism in vitro and in vivo. The results indicated that the cytoplasmic EIF1AX expression showed a gradual increase when going from endometrium normal tissue, simple endometrial hyperplasia, complex endometrial hyperplasia, and endometrial atypical hyperplasia to EC, while vice versa for the nuclear EIF1AX expression. In addition, the cytoplasmic EIF1AX expression was positively correlated with histologic type, high International Federation of Gynecology and Obstetrics (FIGO) grade, advanced FIGO stage, deeper infiltration, high Ki67 index, and shorter recurrence-free survival in EC patients. In vitro, short hairpin RNA-mediated EIF1AX depletion or SV40NLS-mediated EIF1AX import into the nucleus in multiple human EC cells potently suppressed cell migration and invasion, epithelial-mesenchymal transition, and lung metastasis. Moreover, exportin 1 induced the transport of EIF1AX from the nucleus to the cytoplasm that could be inhibited by leptomycin B treatment or the mutation in the EIF1AX location sequence. These results demonstrate that cytoplasmic EIF1AX may play a key role in the incidence and promotion of EC, and thus, targeting EIF1AX or its nucleocytoplasmic transport process may offer an effective new therapeutic approach to EC.

Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer

Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. To determine the association of molecular profiling with outcomes among patients with low-grade EC. This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. Molecular testing of the 4 molecular subgroups. The main outcome was disease-specific survival (DSS) within the molecular subgroups. A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS. This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness.

Management of Radiographically Positive Pelvic and/or Para-aortic Lymph Nodes During Primary Chemoradiation Therapy for Cervix Cancer

Advanced imaging in the initial workup of cervix cancer has become standard of care and has led to the need for complex decision making regarding optimal management of locoregional nodal metastases. 1 National Comprehensive Cancer Network. Cervical cancer. National Comprehensive Cancer Network guidelines. 2021;1:1-90. Google Scholar When treating a patient with cervix cancer using primary radiation therapy (RT) or chemoradiation therapy (CRT), radiation oncologists must decide on the total radiation therapy dose and fractionation for radiographically positive pelvic and/or para-aortic lymph nodes. It is evident that nodal involvement negatively affects disease-free survival and risk of developing distant metastases; thus, the updated International Federation of Gynecology and Obstetrics (FIGO) 2018 cervix cancer staging system includes lymph node status. 2 MacDonald KO Chen J Dodson M et al. Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix. Am J Clin Oncol. 2009; 32: 411-416 Crossref PubMed Scopus (77) Google Scholar , 3 Kidd EA Siegel BA Dehdashti F et al. Lymph node staging by positron emission tomography in cervical cancer: Relationship to prognosis. J Clin Oncol. 2010; 28: 2108-2113 Crossref PubMed Scopus (241) Google Scholar , 4 Bhatla N Berek JS Fredes MC et al. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet. 2019; 145: 129-135 Crossref PubMed Scopus (413) Google Scholar This article will first summarize the available data regarding RT dose for positive nodes and then discuss the treatment typically used at our institutions.

Predicting incomplete cytoreduction in patients with advanced ovarian cancer.

The most important prognostic factor for survival in ovarian cancer patients is complete cytoreduction. The preoperative prediction of suboptimal cytoreduction, considered as any residual disease at the end of surgery, could prevent futile surgery and morbidity. Here, we aimed to identify markers in the preoperative abdominal CT scans of an unselected cohort of patients with ovarian cancer that are predictive of incomplete cytoreduction. This is a single-institution retrospective analysis of 105 epithelial ovarian cancer (EOC) patients treated with surgical cytoreduction between 2010 and 2020. Twenty-two variables on preoperative abdominal CT scans were compared to the intraoperative macroscopic findings by Fisher's exact test. Parameters with a significant correlation between intraoperative findings and imaging were analyzed by multivariate binary logistic regression analysis regarding the surgical outcome of complete versus incomplete cytoreduction. Complete cytoreduction (CC), indicated by the absence of macroscopic residual disease, was achieved in 79 (75.2%) of 105 patients and 46 (63.9%) of 72 International Federation of Gynecology and Obstetrics (FIGO) stage III and IV patients. Twenty patients (19%) were incompletely cytoreduced due to miliary carcinomatosis of the small bowel, and six patients (5.7%) had various locations of residual disease. Thirteen variables showed a significant correlation between imaging and surgical findings. Large-volume ascites, absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon in FIGO stage III and IV patients decreased the rate of CC to 26.7% in the multivariate analysis. Large-volume ascites, the absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon are markers in preoperative CT scans predicting a low chance for complete cytoreduction in unselected ovarian cancer patients in a real-world setting.

Addition of Postoperative Radiation Therapy After Preoperative Chemotherapy and Surgery in Patients With Locally Advanced Endometrial Cancer Is Associated With Improved Outcomes

PurposeOur purpose was to examine outcomes of patients with locally advanced endometrial cancer who undergo neoadjuvant chemotherapy followed by surgery (PreCT) with/without postoperative adjuvant radiation therapy. A secondary analysis of down staging and margin clearance was made with reference to those receiving upfront surgery and then adjuvant chemotherapy (PostCT). Methods and MaterialsThe National Cancer Database was queried for FIGO (The International Federation of Gynecology and Obstetrics) stage III/IV locally advanced endometrial cancer cases who underwent definitive surgery from 2010 to 2016 and received chemotherapy as part of their treatment. Cases were classified into 2 cohorts: preoperative chemotherapy +/- postoperative chemotherapy cohort (PreCT) and postoperative chemotherapy cohort (PostCT) for reference for margin assessment. Cases who received preoperative radiation therapy were excluded while those who received postoperative radiation were included in the analysis. Primary endpoints were overall survival (OS), surgical margin status, rate of downstaging, and effect of adjuvant radiation therapy on OS among the PreCT cohort. Univariable (UVA) and multivariable (MVA) Cox regression analyses were performed. ResultsA total of 13,369 cases were identified with 1059 in PreCT and 12,310 in PostCT cohorts. PreCT had lower OS than PostCT (UVA: hazard ratio [HR], 2.18; P < .001; MVA: HR, 1.873; P < .001). PreCT cases with negative margins, who presumably had unresectable tumors initially, also had worse OS compared with PostCT with negative margins (UVA: HR, 2.20; P < .001; MVA: HR, 1.84; P < .001); however, PreCT with negative margins had similar survival to PostCT with positive margins (UVA: HR, 0.825; P < .001; MVA: P = .885). The addition of radiation after surgery in the PreCT cohort was associated with improved survival (5-year OS 20.5% compared with 50%, respectively; UVA: HR, 0.450; P < .001; MVA: HR, 0.337; P < .001). Although fewer cases in PreCT had negative margins compared with PostCT (72% compared with 84%, P < .001), approximately 19% of cases in PreCT had lower pathologic T-stage compared with clinical T-stage and 11% had lower N-stage. ConclusionsNeoadjuvant chemotherapy was given in cases with worse oncologic prognostic factors, many of whom were likely unresectable at outset, compared with those who received postoperative chemotherapy. Although neoadjuvant chemotherapy is associated with tumor downstaging, survival is lower than with primary surgery probably because of these baseline differences. The addition of adjuvant radiation after surgery in cases who received preoperative chemotherapy is associated with improved survival.

Defining the Optimal Treatment Strategy in Patients With Uterine Serous Carcinoma

AimsUterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer with high rates of relapse and death. As adjuvant therapy might be beneficial in early-stage disease, the impact of standard complete surgical staging is questioned. Therefore, we wanted to explore the optimal treatment strategy for women diagnosed with USC. Materials and methodsA retrospective multicentre study of women diagnosed with primary USC in the UK and the Netherlands. Treatment strategy in relation to overall survival and progression-free survival was recorded and evaluated with Kaplan–Meier and Cox regression analysis. Furthermore, primary surgical staging and/or adjuvant treatment in relation to patterns of recurrence were evaluated. ResultsIn total, 272 women with a median age of 70 years were included. Most patients presented with International Federation of Gynecology and Obstetrics (FIGO) stage I disease (44%). Overall, 48% of patients developed recurrent disease, most (58%) with a distant component. Women treated with chemotherapy showed significantly better overall survival (hazard ratio 0.50, 95% confidence interval 0.31–0.81; P = 0.005) and progression-free survival (hazard ratio 0.48, 95% confidence interval 0.28–0.80; P = 0.04) in multivariable analysis. Furthermore, even in surgically staged women with FIGO stage IA disease, a high recurrence rate of 42% was seen. ConclusionWomen with USC who received adjuvant chemotherapy showed better survival rates compared with those who received other or no adjuvant treatment. The benefit of adjuvant chemotherapy was observed across all tumour stages, including surgically staged FIGO stage IA. These data question the role of surgical staging in the absence of macroscopic disease in USC.

Complications of radical hysterectomy with pelvic lymph node dissection for cervical cancer: a 10-year single-centre clinical observational study

Background and purposeThe complications of radical surgery for cervical cancer can increase patient suffering and affect their quality of life. This retrospective study assessed the safety of radical hysterectomy (RH) with pelvic lymph node dissection (PLND) by observing the complications of patients with cervical cancer who underwent this procedure in a single centre over 10 years. Our findings may provide experience and evidence for preventing and reducing complications.MethodsA total of 2226 cervical cancer patients who met the inclusion criteria were enrolled. All patients underwent RH + PLND. Intraoperative injury to adjacent tissues and short-term and long-term complications were recorded to analyze factors associated with the occurrence of complications.ResultsPostoperative complications occurred in 34.41% (766/2226) of patients, including 7.68% of patients with injury to adjacent tissues, 31.45% with short-term complications, and 2.96% with long-term complications. Age, tumor size, invasion depth, parametrial invasion, lymph vascular space invasion (LVSI), lymph node metastasis, International Federation of Gynaecology and Obstetrics (FIGO) stage, and surgical procedure were closely associated with the postoperative complications of RH + PLND (P < 0.05).ConclusionsThe results of this study showed that RH + PLND for cervical cancer is safe and practical. Patients aged 40–60 years, with tumors ≥ 4 cm, invasion depth ≥ 2/3, parametrial invasion, LVSI, lymph node metastasis, FIGO stage > IB2, and who underwent open surgery were more prone to complications.