Early-stage Ovarian Cancer Research Articles

Minimally Invasive Staging of Early-Stage Epithelial Ovarian Cancer versus Open Surgery in Terms of Feasibility and Safety: A Systematic Review and Meta-Analysis.

Epithelial ovarian cancer is women's fourth most common oncological cause of death. One of the main prognostic factors in ovarian cancer is the tumor stage. For instance, surgical staging of the disease is focal when choosing the best therapeutic option for each case. Although open surgery is the prevalent approach for staging and treating ovarian cancer, the use of minimally invasive surgery (MIS) has found recent application in staging or restaging cases of early disease. Our work compares oncological outcomes after MIS staging for FIGO I epithelial ovarian cancer with the laparotomic approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations, we systematically searched the Pub Med and Scopus databases in February 2023. No temporal nor geographical limitation was made. We included the articles containing data about Disease-Free Survival (DFS) and Overall Survival (OS), Recurrence Rates (RR), and Upstaging Rates (UpR). We used comparative studies for the meta-analysis. After the database search and article selection, 19 works matched the inclusion criteria for the systematic review. Eleven of these were comparative studies between MIS and Open Surgical Staging (OSS) approaches for ovarian cancer staging and were included in the meta-analysis. The meta-analysis did not show a statistically significant difference between the MIS and the OSS group concerning DFS, OS, and RR. Only Upstaging Rate ≥ FIGO Stage II was statistically significative higher in the OSS group. Likewise, MIS is confirmed to be an approach with a lower profile of surgical complications. In conclusion, our study did not show one approach to be safer than the other. However, the lack of dedicated studies limits the evidence of our study. For instance, we recommend adequately selecting the specimen, minimizing the risk of spillage, and optimizing surgical staging.

Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage ovarian cancer: A prospective multicentre study (SELLY).

e17579 Background: Comprehensive surgical staging of early epithelial ovarian cancer includes systematic paraaortic and bilateral pelvic lymphadenectomy but its therapeutic role is controversial and it is associated with potential severe morbidity. The feasibility of sentinel lymph-node (SLN) identification in early stage ovarian cancer has been shown only. We did a prospective multicenter study to assess the feasibility, detection rate and diagnostic accuracy of the SLN procedure in predicting the pathological pelvic-node status in patients with early stage ovarian cancer. Methods: This is a phase II single arm study (EUDRACT 2019-001088-58) including patients with presumed stage I-II epithelial ovarian cancer planned for immediate or delayed minimally-invasive comprehensive staging. The ovarian pedicle is injected with 2 mL of a 1.25 mg/mL indocyanine green (ICG) solution. The pelvic and lumbo-aortic retroperitoneum is then accessed and inspected to identify and remove SLNs. Staging is then completed including systematic pelvic and para-aortic lymphadenectomy and an histopathological examination of all nodes is performed. The primary endpoint was estimation of the sensitivity and sensibility of SLN in predicting nodal status. Assuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (i.e. the maximum marginal error) d=5%, a type I error α = 0.05, a sample size of 141 patients is needed to test the general hypothesis (i.e. to answer whether SLN(s) identified with ICG can accurately predict nodal status at histology of patients with apparently early EOC). Assuming a drop-out rate of 20%, a total of 176 patients will be enrolled in the study. Results: One-hundred and seventy-six patients were included with a drop-out rate of 22%. Sentinel node was identified in 102 patients (detection rate, 58%, [95% CI: 51-65]). There were no clinical differences between patients with successful or unsuccessful mapping. Both the infundibolopelvic ligament and the legamentum ovarii proprium were injected in 29.0% of cases. Twenty-one patients had positive nodes and 71% of them showed successful mapping. Among the latter, a negative sentinel node was identified in 3 patients (Sensitivity 78.6% [95% CI: 57-100]; Specificity 100%; Accuracy 97% [95% CI: 94-100]; PPV 100%; NPV 96,6% [95% CI: 93-100]). Twenty-two (12.5%) intra- and 25 (14.2%) postoperative complications occurred (12 G1; 9 G2; 2 G3, 2 G4). Clinical trial information: EUCTR2019-001088-58 .

Is laparoscopic approach feasible in early-stage ovarian cancer? A retrospective study in single tertiary center.

e17560 Background: Laparoscopic approach for early-stage ovarian cancer is a controversy. Current studies showed no negative impacts on these patients. However, some limitations were noted, such as small case numbers, heterogeneity, and retrospective study. Methods: We retrospectively reviewed our cases who was diagnosed as early-stage ovarian cancer and received staging surgery from 2009 through 2017. There patients were divided into two groups, via laparoscopic staging or laparotomy. The primary outcome was progression-free survival. The secondary outcomes were overall survival and intra-operative rupture rate. We performed the Kaplan-Meier method and chi-square test for analyzing survival outcome and factors, in order to evaluate impacts on different surgical methods. Results: Total 520 patients (2014 FIGO stage IA-IC3) were enrolled, including 355 patients who underwent open surgery and 165 patients who underwent laparoscopic surgery. The median follow-up time for survivors was 71(range,39.7-102.3）months. The progression-free survival was similar between two groups and all subgroups. The overall survival was also similar between two surgical methods and all subgroups, except subgroup of clear cell carcinoma. The p-value of overall survival in clear cell carcinoma patients was 0.05. However, the case numbers of clear cell carcinoma 81 in laparotomy group and 31 in laparoscopy group, respectively. The intra-operative rupture rate was increased in laparoscopic group. The relative risk and p-value were 1.139 and 0.043, respectively. Conclusions: Laparoscopic may be feasible in early-stage ovarian cancer in selected patients and expert surgeon due to higher intra-operative rupture rate. If clear cell carcinoma of ovary was highly suspected, the surgeon should be alerted because poorer overall survival in clear cell carcinoma of ovary patients was observed.

GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of ovarian cancer.

e17604 Background: Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers but they have never before been quantified in OC. We investigated the diagnostic utility GD2 and GD3 for diagnosis of all subtypes and stages of OC. Methods: This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299), and in two cohorts of serum samples by quantitative ELISA. A Discovery Cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent Model Cohort (n=200) was used to train and cross-validate a diagnostic model. Results: GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A novel diagnostic model that included serum levels of GD2 and GD3 was superior to the standard of care (CA125, p<0.001) at detecting OC, as well as, in early-stage (I/II) OC samples. Conclusions: GD2 and GD3 are high value candidates for building a novel diagnostic panel. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early-stage. Further research exploring the utility GD2 and GD3 for diagnosis of OC is warranted. Future work will aim to validate these biomarkers in independent prospective studies. [Table: see text]

Profiling the metabolome of uterine fluid for early detection of ovarian cancer

Ovarian cancer (OC) causes high mortality in women because of ineffective biomarkers for early diagnosis. Here, we perform metabolomics analysis on an initial training set of uterine fluid from 96 gynecological patients. A seven-metabolite-marker panel consisting of vanillylmandelic acid, norepinephrine, phenylalanine, beta-alanine, tyrosine, 12-S-hydroxy-5,8,10-heptadecatrienoic acid, and crithmumdiol is established for detecting early-stage OC. The panel is further validated in an independent sample set from 123 patients, discriminating early OC from controls with an area under the curve (AUC) of 0.957 (95% confidence interval [CI], 0.894-1). Interestingly, we find elevated norepinephrine and decreased vanillylmandelic acid in most OC cells, resulting from excess 4-hydroxyestradiol that antagonizes the catabolism of norepinephrine by catechol-O-methyltransferase. Moreover, exposure to 4-hydroxyestradiol induces cellular DNA damage and genomic instability that could lead to tumorigenesis. Thus, this study not only reveals metabolic features in uterine fluid of gynecological patients but also establishes a noninvasive approach for the early diagnosis of OC.

Affinity-based electrochemical biosensor with antifouling properties for detection of lysophosphatidic acid, a promising early-stage ovarian cancer biomarker

Electrochemical techniques are considered to be highly sensitive, capable of fast response and can be easily miniaturized, properties which can aid with regard to the fabrication of compact point-of-care medical devices; however, the main challenge in developing such a tool is overcoming a ubiquitous, problematic phenomenon known as non-specific adsorption (NSA). NSA is due to the fouling of non-target molecules in the blood on the recognition surface of the device. To overcome NSA, we have developed an affinity-based electrochemical biosensor using medical-grade stainless steel electrodes and following a unique and novel strategy using silane-based interfacial chemistry to detect lysophosphatidic acid (LPA), a highly promising biomarker, which was found to be elevated in 90 % of stage I OC patients and gradually increases as the disease progresses to later stages. The biorecognition surface was developed using the affinity-based gelsolin-actin system, which was previously investigated by our group to detect LPA using fluorescence spectroscopy. We demonstrate the capability of this label-free biosensor to detect LPA in goat serum with a detection limit of 0.7 µM as a proof-of-concept for the early diagnosis of ovarian cancer.

The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in Fancd2-KO Mice.

Ovarian cancer (OC) has the highest mortality rate of all gynaecological malignancies. The asymptomatic nature and limited understanding of early disease hamper research into early-stage OC. Therefore, there is an urgent need for models of early-stage OC to be characterised to improve the understanding of early neoplastic transformations. This study sought to validate a unique mouse model for early OC development. The homozygous Fanconi anaemia complementation group D2 knock-out mice (Fancd2-/-) develop multiple ovarian tumour phenotypes in a sequential manner as they age. Using immunohistochemistry, our group previously identified purported initiating precursor cells, termed 'sex cords', that are hypothesised to progress into epithelial OC in this model. To validate this hypothesis, the sex cords, tubulostromal adenomas and equivalent controls were isolated using laser capture microdissection for downstream multiplexed gene expression analyses using the Genome Lab GeXP Genetic Analysis System. Principal component analysis and unbiased hierarchical clustering of the resultant expression data from approximately 90 OC-related genes determined that cells from the sex cords and late-stage tumours clustered together, confirming the identity of the precursor lesion in this model. This study, therefore, provides a novel model for the investigation of initiating neoplastic events that can accelerate progress in understanding early OC.

A single institution’s experience with minimally invasive surgery for ovarian cancer, and a systematic meta-analysis of the literature

BackgroundThis study assesses the feasibility of minimally invasive surgery (MIS) for well-selected epithelial ovarian cancer (EOC) patients.MethodsWe performed a review of data prospectively collected from a single center from 2017 to 2022. Only patients with histologically confirmed EOC, with a tumor diameter of less than 10 cm, were eligible. We also performed a meta-analysis of similar studies comparing the outcomes of laparoscopy and laparotomy. We used MINORS (Methodological Index for Non-Randomized Studies) to assess the risk of bias and calculated the odds ratio or mean difference.ResultsEighteen patients were included; 13 in re-staging group, four in PDS group, and one in IDS group. All achieved complete cytoreduction. One case was converted to laparotomy. The median number of removed pelvic lymph nodes was 25 (range 16–34), and 32 (range 19–44) for para-aortic nodes. There were two (15.4%) intraoperative urinary tract injuries. The median follow-up was 35 months (range 1–53). Recurrence was observed in one case (7.7%). Thirteen articles for early-stage ovarian cancer were included in our meta-analysis. Analysis of the pooled results found that MIS had a higher frequency of spillage (OR, 2.15; 95% CI 1.27–3.64). No differences were observed in recurrence, complications, or up-staging.ConclusionsOur experience supports the possibility of conducting MIS for EOC in well-selected patients. Except for spillage, our meta-analysis findings are consistent with previous reports, the majority of which were also retrospective. Ultimately, randomized clinical trials will be needed to authenticate the safety.

Could uterine conservation be an option in presumed early-stage epithelial ovarian cancer?

In early-stage epithelial ovarian cancer (EOC), patients usually undergo a hysterectomy. However, in fertility sparing surgery (FSS), carefully selected patients could conserve their uterus. The aim of our study was to evaluate the incidence and epidemiologic characteristics associated with uterine involvement in patients with early-stage EOC, outside of FSS. We conducted a retrospective, monocentric, study from 2003 to 2019 and included all patients with a presumed early-stage EOC (FIGO I) who underwent a hysterectomy. The incidence of uterine involvement, predictive factors of uterine involvement, and the impact of uterine involvement on survival (recurrence-free survival and overall survival) were analyzed. Eighty-five patients had an early-stage EOC. Of these, six had an uterine involvement (7%). The populations of patients with or without uterine involvement did not differ except for CA 125 at diagnosis (136 ± 138 versus 356 ± 723, p = 0.04, respectively). No patient or tumor characteristics were predictive of uterine involvement. Uterine involvement was not associated with recurrence-free survival (HR = 1.26, IC95% 0.36-4.4, p = 0.72) or overall survival (HR = 0.7, IC95% 0.1-6.1, p = 0.77). Due to the small size of our sample, no conclusion can be drawn, yet it could be hypothesized that, for selected patients, a systematic hysterectomy could be discussed, notably in restaging surgery.

Abstract 5396: Early detection of ovarian cancer using mRNA sample data to investigate the correlation of specific gene mutations with ovarian cancer

Abstract Introduction: Ovarian cancer (OC) is the second most common gynecologic cancer in the U.S, and is the deadliest cancer of the female reproductive system. Because of the complex nature of OC, diagnoses are often by display of symptoms at late stages of disease. Identifying OC at early stages can increase the 5-year survival rate from 40% in stage IV to 94% in stage I. Therefore, effective screening and detection of OC at early stages is imperative. The main objective of this study is to develop a diagnostic panel of markers that correlate with early-stage OC, and ultimately, improve the survival rate of patients. Background: Approaches in the past several years to detect malignant OC have focused on processing relevant images or screening genomic data. These studies use liquid-based biopsies, sonographic images, cyst images, CT images, MR imaging and genomics data. Some studies have focused on distinguishing malignant tumors versus benign tumor cells. In addition to statistical methods to examine available genomic datasets, Machine Learning models including K-Nearest Neighbor, K-means, Convolutional Neural Networks, Deep Learning, Support Vector Machine, Random Forest, and Fuzzy algorithms have been used. Methods: In this study we proposed a method to determine a possible correlation between some actively expressed genes and OC, using publicly available mRNA data sets. The samples were retrieved from the GSE106817 dataset via the NCBI GEO site, with 333 cancerous and 2759 Non-cancerous samples. The objective is to define a set of genes which is able to illustrate prediction of correlation through the use of PCA, NMF and SVD. We further verified our findings by testing on one additional different mRNA datasets. For this, we compared several machine learning algorithms to potentially correlate active genes and OC stages, from the available data. Results and Discussions: Through our study we have developed Machine Learning models valuable to identify patterns of disease at different stages, thus, potentially be useful in developing predictive models. Our initial experimental results have been demonstrated with a set of mRNA signatures, which may be used to create a panel of biomarkers valuable for detecting early-stage OC. Our results confirm the correlation between OC and PAX8, PEG3, and BIRC5, and MYB and RAC2. Continuation of this study highlights methods towards the early detection of OC and to improve disease identification outcome. Citation Format: Zahra Saghaie, Christine Richardson, M. Taghi Mostafavi. Early detection of ovarian cancer using mRNA sample data to investigate the correlation of specific gene mutations with ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5396.

Abstract 5556: Lemur tyrosine kinase 3 serves as a predictor of patient outcome and a target for the treatment of ovarian cancer

Abstract The objective of these in vitro and in vivo studies was to validate Lemur Tyrosine Kinase 3 (LMTK3) as a specific target and predictor of clinical outcome in ovarian cancer. LMTK3 belongs to a family of regulated tyrosine kinases with three structurally related isoforms, LMTK1, LMTK2, and LMTK3. Both nuclear and cytoplasmic LMTK3 expressions correlated with tumor grade and patient survival in cancers such as breast and colorectal cancer. We tested the clinical significance of the LMTK3 gene by immunohistochemistry (IHC) using LMTK3 monoclonal antibody on formalin-fixed paraffin-embedded sections (FFPE) collected from 204 early-stage (stage I-II) ovarian cancer patients. Results from this IHC LMTK3 study revealed a higher cytoplasmic to nuclear localization of LMTK3 correlated with worse overall survival (P<0.01). Further investigation of LMTK3’s prognostic value by screening LMTK3 signaling in 270 stage III-IV ovarian cancer patients is ongoing. We utilized the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay for testing the killing efficacy of targeting LMTK3 by a monoclonal antibody, siRNA, and specific LMTK3 binding peptides (LMTK3BP) in ovarian cancer cell lines SKOV3, MDAH-2774, A2780, and TOV-21G. Treatment with LMTK3 specific monoclonal antibody, siRNA, and LMTK3BP significantly induced killing of both chemosensitive and chemoresistant ovarian cancer cells without affecting normal cells in vitro. Moreover, we observed this killing as synergistic with both Cisplatin and Taxotere treatment in vitro. Lastly, we used an A2780 cell line derived orthotopic xenograft mouse model of ovarian cancer to test the efficacy of specific LMTK3BP in vivo. Strikingly, LMTK3BP 20 mg/kg IV dose given three times a week for three weeks showed a 35% tumor reduction. Furthermore, in vivo safety studies showed no signs of toxicity of the LMTK3BP, even at a very high dose of 40 mg/kg. Thus, with dose optimization in ongoing experiments, we could expect a higher efficacy. In conclusion, this study highlighted the importance of LMTK3 as a predictor of patient clinical outcome and potential target for treatment in ovarian cancer. Citation Format: Thea K. Kirsch-Mangu, Axel S. Tullberg, Anna Portela, Khalil Helou, Ghassan M. Saed. Lemur tyrosine kinase 3 serves as a predictor of patient outcome and a target for the treatment of ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5556.

Abstract 3333: Exosomal non-coding RNAs as a biomarker to improve early ovarian cancer detection

Abstract Purpose: There is no consensus on screening for ovarian cancer in high-risk women because no effective biomarker or screening method exists, especially for early-stage cancer patients. The available methods, such as monitoring of CA125 levels, transvaginal ultrasound, and combination of pelvic examination are associated with high false-positive results, leading to additional unnecessary imaging tests, emotional burdens, and risk of invasive surgery for women without cancer. An effective, reliable, and non-invasive method for early detection of ovarian cancer is thus critically needed. In this research, weThus, we aim to identify a distinctive signature of exosomal small RNAs to serve as a novel biomarker for detecting early-stage ovarian cancer in high-risk population. Methods: Women of all ages and ethnical backgrounds were included in this study. Blood samples were collected in the clinic from women with germline BRCA mutations. A total of 30 patients with ovarian cancer before surgery, and 30 age-matched (mean age = 55) healthy women as controls were used. Among the 30 thirty cases, 11 patients had early (stage I) ovarian cancer. Identification of differential exosome small non-coding RNA copy numbers in plasma samples from BRCA1 mutation carriers with and without ovarian cancer was performed by next-generation RNA-Sseq. We randomly split 60 samples into two groups: training set (20 cancer, 20 normal) and , testing set (10 cancer, 10 normal). We apply 10-fold cross-validation to determine hyperparameter of five machine learning models and use the ensemble learning method to evaluate the predictive value of the small RNAs in the exosome by integrating the five machine learning models. Results: The ensemble learning model achieved the testing accuracy of 85% with the sensitivity of 70% and the specificity of 100% by using small RNA and CA125 abundance level as input features. While uUsing CA125 alone, the testing accuracy equals to 90% with the sensitivity of 80% and the specificity of 100%. For the 11 eleven early-stage patient samples, our ensemble learning model made 2 false negative predictions with a total accuracy of 95.1% (sensitivity=81.8%, specificity=100%) while using CA125 alone had five 5 false negative predictions with a total accuracy of 87.8% (sensitivity=54.5%, specificity=100%). All 30 control samples had been correctly classified. Conclusions: We found that ensemble learning model using combining both exosome small RNAs and CA125 will not improve the prediction accuracy for late-stage cancer patients compared to CA125 alone but will significantly improve the prediction accuracy for early-stage patients. Our research findings may indicate a two-pronged strategy in assessing ovarian cancer risks using existing CA125 test followed by small RNA features to detect early-stage ovarian cancer. We are now collecting a larger number of early-stage cancer patient samples for validation. Citation Format: Yuliang Cao, Cun Han, Jianting Sheng, Samuel Mok, Stephen T.C. Wong. Exosomal non-coding RNAs as a biomarker to improve early ovarian cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3333.

Impact of complete surgical staging on survival of patients with early-stage (FIGO I or II) ovarian cancer: Data from the Cote d'Or Registry of Gynecological Cancers from 1998 to 2015.

Early-stage ovarian cancer represents 20 to 33% of all ovarian cancers and is thus quite rare in France, with around 1200 new cases per year. No study to date has convincingly demonstrated the utility of lymphadenectomy in early-stage ovarian cancer. We sought to evaluate the impact on overall survival of complete surgical staging in patients management for FIGO stage I and II ovarian cancer. We performed a retrospective observational study using data from the Cote d'Or Registry of Gynecological Cancers. We included patients with invasive early stage epithelial ovarian cancer (FIGO stages I and II), diagnosed between 1 January 1998 and 31 December 2015. A total of 179 patients were included in the study. Patients who had lymphadenectomy were younger on average (P<0.001) and had fewer comorbidities (P=0.03). Lymphadenectomy was performed during the first surgery in 59.2% of cases (58 patients) and during a second, re-staging surgery in 40.8% (n=40). When complete surgical staging was performed, the rate of up-staging (to at least FIGO stage III) was 11.2% (11/98). The median follow-up was 8.4 years. At the study, 31.6% patients with complete surgical staging had died and 48.4% patients also died in the group without lymphadenectomy, HR 0.59 CI [0.36-0.97] P<0.04. In patients with early-stage ovarian cancer, complete surgical staging appears to yield a benefit in terms of overall survival. In 10 to 15% of cases, it leads to upstaging, with the resultant indication for maintenance therapy, which has also shown a survival benefit.

Ovarian clear cell carcinoma with or without endometriosis origin in a single institution cohort

BackgroundAs ovarian clear cell carcinoma (OCCC) has distinct clinical features, biology, genetic characteristics and mechanisms of pathogenesis, and whether the origin of endometriosis or not affects the prognosis of OCCC remains controversial.MethodsWe retrospectively collected medical records and follow-up data of patients with OCCC treated at the Obstetrics and Gynecology Hospital of Fudan University from January 2009 to December 2019. Further, we divided patients into 2 groups. Group 1: non-endometriosis origin; Group 2: endometriosis origin. Clinicopathological characteristics and survival outcomes were compared between the 2 groups.ResultsA total of one hundred and twenty-five patients with ovarian clear cell carcinoma were identified and included. In the overall patients’ population, the 5 year overall survival was 84.8%, the mean overall survival was 85.9 months. The results of the stratified analysis showed that early stage (FIGO stage I/II) OCCC had a good prognosis. The results of univariate analyses indicated that a statistically significant relationship between overall survival (OS) and FIGO stage, lymph node metastasis, peritoneum metastasis, chemotherapy administration methods, Chinese herbal treatment, molecular target therapy. As for progression-free survival (PFS), a significant relationship between PFS and child-bearing history, largest residual tumor size, FIGO stage, tumor maximum diameter, lymph node metastasis was found, respectively. FIGO stage and lymph node metastasis are common poor prognostic factors affecting OS and PFS. The multivariate regression analysis revealed that FIGO stage (p = 0.028; HR, 1.944; 95% CI 1.073–3.52) and treatment by Chinese herbs (p = 0.018; HR, 0.141; 95% CI 0.028–0.716) were identified as influencing factors with regard to survival. The presence or absence of lymphadenectomy did not affect OS of 125 OCCC patients (p = 0.851; HR, 0.825; 95% CI 0.111–6.153).There was a trend towards a better prognosis for patients with OCCC of endometriosis origin than those with OCCC of non-endometriosis origin (p = 0.062; HR, 0.432; 95% CI 0.179–1.045). The two groups differed with respect to several clinicopathological factors. And the proportion of patients with disease relapse was higher in Group 1 (46.9%) than in Group 2 (25.0%), with a statistically significant difference (p = 0.048).ConclusionsSurgical staging and treatment by Chinese herbs postoperatively are two independent prognostic factors affecting the OS of OCCC, early detection and Chinese herbal medicine combined with chemotherapy postoperatively may be a good choice. Tumor with endometriosis-origin was found less likely to relapse. While the non-necessity of lymphadenectomy in advanced ovarian cancer has been proven, the need for lymphadenectomy in the early stage ovarian cancer, including early stage OCCC, still deserved to be explored.

Recurrence rate in early-stage epithelial ovarian cancer: Is there a role for upfront maintenance with PARP inhibitors in stages I and II?

ObjectiveTo determine the recurrence rate and survival among early-stage epithelial ovarian cancer cases considering homologous recombination deficiency (HRD) status. MethodsSingle institution retrospective study of stage I/II EOC patients from 2017 to 2020. HRD was defined as evidence of germline or somatic BRCA mutation, or loss of heterozygosity (LOH)/genomic instability (GIS) as determined by companion diagnostic tests. Kaplan-Meier analyses were performed. Results89 stage I/II cases were included. 4/89 (4.5%) had a germline BRCA1/2mutation, 8 (9%) were germline negative but had a somatic BRCA mutation, and 8 (9%) were BRCA wild-type but had evidence of LOH/GIS on somatic testing; these 20/89 (22%) cases comprised the HRD group. The remaining tumors were confirmed homologous recombination proficient (HRP, 35/89, 39%) or homologous recombination unknown (HRU, 34/89, 38%). The overall recurrence rate was 33/89 (37%). There were more recurrences among HRD cases (14/20, 70%) compared to HRP/HRU cases (19/69, 27.5%, p = 0.0012). Median Recurrence-Free Survival (RFS) was 35 months for HRD cases and 225 months for HRP/HRU cases (p = 0.001). At 2 years, there were 60% HRD cases and 88% HRP/HRU cases recurrence-free. At 5 years there were 29% HRD and 69% HRP/HRU cases recurrence-free (p = 0.001). ConclusionsDespite a high rate of complete surgical staging and six cycles of adjuvant chemotherapy, recurrence rate was high in this early-stage cohort. Higher recurrence rates were seen in the HRD group, however these data are likely biased by the clinical practice of tumor testing primarily at the time of recurrence rather than the upfront setting. RFS was significantly lower for HRD cases.

Early detection of ovarian cancer by wavelet analysis of protein mass spectra.

Accurate and efficient detection of ovarian cancer at early stages is critical to ensure proper treatments for patients. Among the first-line modalities investigated in studies of early diagnosis are features distilled from protein mass spectra. This method, however, considers only a specific subset of spectral responses and ignores the interplay among protein expression levels, which can also contain diagnostic information. We propose a new modality that automatically searches protein mass spectra for discriminatory features by considering the self-similar nature of the spectra. Self-similarity is assessed by taking a wavelet decomposition of protein mass spectra and estimating the rate of level-wise decay in the energies of the resulting wavelet coefficients. Level-wise energies are estimated in a robust manner using distance variance, and rates are estimated locally via a rolling window approach. This results in a collection of rates that can be used to characterize the interplay among proteins, which can be indicative of cancer presence. Discriminatory descriptors are then selected from these evolutionary rates and used as classifying features. The proposed wavelet-based features are used in conjunction with features proposed in the existing literature for early stage diagnosis of ovarian cancer using two datasets published by the American National Cancer Institute. Including the wavelet-based features from the new modality results in improvements in diagnostic performance for early-stage ovarian cancer detection. This demonstrates the ability of the proposed modality to characterize new ovarian cancer diagnostic information.

Current Treatment Practices and Prognostic Factors in Early-Stage Ovarian Cancer—An Analysis of the NOGGO/JAGO

Surgery is the backbone of early-stage ovarian cancer (OC) management. However, in practice, there is disagreement about the extent of surgical staging and whether additional adjuvant treatment should be provided. As omitting relevant diagnostic or therapeutic procedures might lead to undertreatment, we aimed to structurally investigate treatment practice in addition to prognostic factors in a multicentre series of patients (pts) diagnosed with early-stage OC. Within this retrospective, multicentre study, medical records of 379 pts who had undergone surgery for suspected early-stage OC between January 2014 and March 2020 were analysed. Of the 379 patients, 292 had pT stage 1a-2a and had complete data on the extent of surgical staging. At least one surgical step was omitted in 100 pts (34.2%). Complete surgical staging (n = 192; (65.8%)) was more often performed in high-grade serous OC and was independent of the healthcare level of the hospital where the initial diagnosis was made. Missing to take peritoneal biopsies was associated with reduced relapse-free-survival in incompletely staged, pT1 cases (p = 0.03). About every second patient (46.7%) with a final stage lower than FIGO IIB and treated with adjuvant chemotherapy received combination chemotherapy. BRCA1 and BRCA2 testing was only performed in a subset of pts, and mutations were detected in 18% (14/79) and 9% (7/85) pts, respectively. This study helps to increase our understanding of early-stage OC treatment and prognosis. In addition to treating patients in compliance with current guidelines, the need for BRCA testing should also be considered for early-stage OC.

Oncologic and obstetric outcomes of early-stage epithelial ovarian cancer patients who underwent fertility-sparing surgery: A retrospective study.

This study aimed to assess the long-term oncologic and obstetric outcomes of women with epithelial ovarian cancer who underwent fertility-sparing surgery. A total of 68 patients observed between March 2007 and July 2021 were included in this retrospective study. Unilateral salpingo-oophorectomy and uterine preservation with staging surgery were the main procedures for fertility-sparing surgery. Disease-free, overall survival, and obstetric outcomes were measured as primary outcomes. The median age of the patients was 30.5 years. The median follow-up time was 60.5months. Disease recurrence occurred in 15 (22.1%) of the patients. Five-year disease-free survival and overall survival (OS) percentages were 75.6% and 83.3%, respectively, for all stages. The FIGO (International Federation of Gynecology & Obstetrics) stage was the only significant factor that affected OS (P= 0.001). Twenty-three patients tried to conceive, and 15 (65.2%) patients became pregnant. Twelve (80%) pregnancies reached term and resulted in 15 live births. Chemotherapy administration and surgical intervention (cystectomy or unilateral salpingo-oophorectomy) showed no difference in pregnancy results (P= 0.806 and P= 0.066, respectively). Fertility preservation is safe for invasive epithelial ovarian cancer at early stages for women in the reproductive era. Disease recurrence and OS results are similar to standard treatment at early stages with decent obstetric outcomes.

Impact of lymphadenectomy and intra-operative tumor rupture on survival in early-stage mucinous ovarian cancers

ObjectiveMucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical management of clinical stage I mucinous...

A Dual Biomarker TK1 Protein and CA125 or HE4-Based Algorithm as a Better Diagnostic Tool than ROMA Index in Early Detection of Ovarian Cancer

The early detection of ovarian cancer is presently not effective, and it is crucial to establish biomarkers for the early diagnosis of ovarian cancer to improve the survival of patients. The aim of this study was to investigate the role of thymidine kinase 1 (TK1) in combination with CA 125 or HE4 to serve as a potential diagnostic biomarkers for ovarian cancer. In this study, a set of 198 serum samples consisting of 134 ovarian tumor patients and 64 healthy age-matched controls were analyzed. The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA. A combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone in the differentiation of early stage ovarian cancer from the healthy control group, but also a significantly better performance than the ROMA index. However, this was not observed using a TK1 activity test in combination with the other markers. Furthermore, the combination of TK1 protein and CA 125 or HE4 could differentiate early stage disease (stage I, II) more efficiently from advanced-stage (stage III, IV) disease (p < 0.0001). The combination of TK1 protein with CA 125 or HE4 increased the potential of detecting ovarian cancer at early stages.