Early-stage Epithelial Ovarian Cancer Research Articles

Laparoscopic versus open surgery in the treatment of apparently early stage epithelial ovarian cancer: Case-control and case-matched study of Korean Gynecologic Oncology Group.

5560Background: The efficacy and safety of laparoscopic surgery in the treatment of apparently early stage epithelial ovarian cancer is controversial. The aim of this study was to evaluate the long...

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer

Background: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. Methods: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Results: Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Conclusions: Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome.

Laparoscopic surgical staging in women with early stage epithelial ovarian cancer performed by recently certified gynecologic oncologists

ObjectiveTo compare the surgical and oncological outcomes of laparoscopic versus open surgical staging in patients with early stage ovarian cancer performed by recently certified gynecologic oncologists. Study designA retrospective comparative observational study was performed, which included women who had undergone laparoscopic comprehensive surgical staging for early stage epithelial ovarian cancer between June, 2008 and January, 2014. Patients were compared with women who had undergone laparotomic staging between June, 2006 and January, 2014. ResultsA total of 50 and 58 patients underwent, laparoscopic and laparotomy surgical staging, respectively. The patients’ baseline characteristics were similar in both groups. Women in the laparoscopy group had a significantly lower preoperative CA-125 value (p=0.01). The operative time was similar between groups. The patients in the laparotomy group had significantly higher estimated blood loss (p≤0.001) and larger ovarian masses (p=0.001). Estimated blood loss was significantly higher in laparotomy versus laparoscopy; median (IQ range) 200 (200–225) ml and 500 (300–1000) ml (p≤0.0001). Intraoperative complications and postoperative complication rate was similar in both groups regardless of the type of surgical procedure; and laparoscopy was associated with a significantly shorter length of the hospital stay (p≤0.001). The number of lymph node retrieved and upstaging rate, as well as progression free survival and overall survival rates, were similar in both groups. ConclusionsLaparoscopic surgical staging of apparent early stage ovarian cancer has similar surgical and oncological outcomes to laparotomy when recently certified gynecologic oncologists perform the procedures.

Fertility-sparing surgery in epithelial ovarian cancer.

Since the last two decades, the feasibility of fertility-sparing surgery in early-stage epithelial ovarian cancer has been explored by several teams. Despite the impossibility of conducting a randomized trial to validate this management, evidence-based data suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. Conservative surgery maintains organ function, enables patients of childbearing age to preserve their fertility and improves their quality of life. In this review, we analyze the main series in the literature on this topic in order to highlight the selected criteria for conservative management and to summarize oncological and fertility outcomes.

Use of Plasma Metabolomics to Identify Diagnostic Biomarkers for Early Stage Epithelial Ovarian Cancer.

The early detection of ovarian carcinoma is difficult due to the absence of recognizable physical symptoms and a lack of sensitive screening methods. The currently available biomarkers (such as CA125 and HE4) are insufficiently reliable to distinguish early stage (I/II) epithelial ovarian cancer (EOC) patients from normal individuals because they possess a relatively poor sensitivity and specificity. To evaluate the application of metabolomics to biomarker discovery in the early stages of epithelial ovarian cancer (EOC), plasma samples from 21 early stage EOC patients and 31 healthy controls were analyzed with ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof/MS) in conjunction with multivariate statistical analysis. Eighteen metabolites, including lysophospholipids, 2-piperidone and MG (18:2), were found to be disturbed in early stage EOC with satisfactory diagnostic accuracy (AUC=0.920). These biomarkers were specifically validated in the EOC nude mouse model, and five of the biomarkers (lysophospholipids, adrenoyl ethanolamide et al.) were highly suspected of being associated with EOC because they were differentially expressed with the same tendency in the EOC nude mice versus normal controls. In conclusion, the selected metabolic biomarkers have considerable utility and significant potential for diagnosing early ovarian cancer and investigating its underlying mechanisms.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

ObjectiveFertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC.MethodsWe retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated.ResultsA total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease.ConclusionFSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer: Updated Guidelines From the European Group on Tumor Markers.

ObjectiveTo present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer.MethodsSystematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation.ResultsBecause of its low sensitivity (50–62% for early stage epithelial ovarian cancer) and limited specificity (94–98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended for the differential diagnosis of a pelvic mass. Because human epididymis protein 4 has been reported to have superior specificity to CA125, especially in premenopausal women, it may be considered either alone or as part of the risk of ovarian malignancy algorithm, in the differential diagnosis of pelvic masses, especially in such women. CA125 should be used to monitor response to first-line chemotherapy using the previously published criteria of the Gynecological Cancer Intergroup, that is, at least a 50% reduction of a pretreatment sample of 70 kU/L or greater. The value of CA125 in posttherapy surveillance is less clear. Although a prospective randomized trial concluded that early administration of chemotherapy based on increasing CA125 levels had no effect on survival, European Group on Tumor Markers state that monitoring with CA125 in this situation should occur, especially if the patient is a candidate for secondary cytoreductive surgery.ConclusionsAt present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.

Individualized Treatment of Patients With Early-Stage Epithelial Ovarian Cancer After Incomplete Initial Surgery.

Incomplete initial surgery complicates subsequent management of early-stage epithelial ovarian carcinoma (ESEOC). This study aimed to determine the most appropriate strategies for individualized treatment of these patients. Medical records of ESEOC patients treated at our hospital between 2000 and 2011 were reviewed, and 246 patients initially treated by incomplete surgery were included. A scoring system was established to assess the quality of initial surgery (QOIS). Of 246 patients, 130 underwent restaging surgery and 116 received chemotherapy only. Follow-up duration ranged from 4 to 148 months (median, 72 months). The 5-year overall survival (OS) rates were 87.5% and 74.7% in the restaging and chemotherapy groups, respectively. Survival analysis showed significantly better recurrence-free survival (RFS) and OS in the restaging group (P = 0.043 and P = 0.029, respectively). Multivariate analysis showed that histologic grade was an independent predictor for RFS and OS in the restaging group (P = 0.035 and P = 0.038, respectively), and histologic grade (P = 0.005 and P = 0.015, respectively) and QOIS (P = 0.044 and P = 0.024, respectively) were independent predictors for RFS and OS in the chemotherapy group. Subgroup analysis showed that restaging surgery produced better RFS and OS than chemotherapy in patients with low QOIS and unfavorable histology (5-year RFS, 58.5% vs 33.4%, P = 0.007; 5-year OS, 82.2% vs 54.4%, P = 0.011), whereas the outcomes between the treatment options were comparable in patients with high QOIS or favorable histology. Our results support individualized treatment of ESEOC patients initially treated by incomplete surgery. Restaging surgery is recommended only for patients with low QOIS and unfavorable histology.

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

This is the second update of the review first published in the Cochrane Database of Systematic Reviews in 2009, Issue 1. Epithelial ovarian cancer is diagnosed in over 200,000 women worldwide each year. Ten to 20% of women are diagnosed early, when there is still a good possibility of cure. The treatment of early-stage (stage I and IIa) disease involves surgery to remove the disease, often followed by chemotherapy (adjuvant chemotherapy). The largest clinical trials of adjuvant chemotherapy show an overall survival (OS) advantage with platinum-based chemotherapy; however the precise role and type of this treatment in subgroups of women with differing prognoses needs to be defined. To undertake a systematic review of the evidence for adjuvant chemotherapy in early-stage epithelial ovarian cancer to determine whether chemotherapy following surgery offers a survival advantage over the policy of observation following surgery (with chemotherapy reserved for treatment of disease recurrence); and to determine if clinical subgroups of women with differing prognoses, based on histological subtype or completeness of surgical staging, have more or less to gain from adjuvant chemotherapy. We performed an electronic search using the Cochrane Gynaecological Cancer Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 3), MEDLINE (1948 to March week 5, 2015), and EMBASE (1980 to week 14, 2015). We developed the search strategy using free-text and medical subject headings (MeSH). We also searched registers of clinical trials and citation lists of included studies for potentially relevant studies. We included randomised clinical trials (RCTs) of women with early stage (I/IIa) epithelial ovarian cancer staged at laparotomy. Two review authors independently extracted data and assessed study quality of included RCTs. We resolved any disagreements by discussion with a third review author. We used random-effects methods for all meta-analyses, including subgroup analyses. The original version of this Cochrane review included five RCTs involving 1277 women. In this 2015 update, no new studies met the inclusion criteria but we included an additional paper with mature data (10-year follow-up) relating to a previously included study (ICON1).We included four studies in the meta-analyses and considered them to be at a low risk of bias. Most study participants (> 95%) had stage I ovarian cancer. Meta-analysis of five-year data from three studies indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (Hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.93; 1008 women; 3 studies; I² statistic = 0%; high quality evidence). Likewise, meta-analysis of five-year data from four studies indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (HR 0.67, 95% CI 0.53 to 0.84; 1170 women, 4 studies; I² statistic = 0%; high quality evidence). These findings were robust over time, with 10-year HR estimates of 0.72 (95% CI 0.57 to 0.92; 925 women, 2 studies) and 0.67 (95% CI 0.53 to 0.83; 925 women, 2 studies) for OS and PFS, respectively (high quality evidence). The risk of death at 10 years follow-up favoured the adjuvant chemotherapy arm (0.76, 95% CI 0.62 to 0.94; 923 women, 2 studies; I² statistic = 0%), as did the findings for risk of progression at 10 years (RR 0.72, 95% CI 0.60 to 0.87; 925 women, 2 studies; I² statistic = 0%). Low quality evidence suggested that women with high-risk disease may have the most to gain from adjuvant chemotherapy. However, subgroup analyses could neither confirm nor exclude survival benefits in lower risk disease or in optimally staged disease. We found insufficient data to compare adverse events and long term risks between chemotherapy and observation groups. High-quality evidence indicates that adjuvant platinum-based chemotherapy is effective in prolonging survival in women with early stage (FIGO stage I/IIa) epithelial ovarian cancer. It remains uncertain whether women with low- and intermediate-risk early stage disease will benefit as much from adjuvant chemotherapy as women with high-risk disease. Decisions to use adjuvant chemotherapy (AC) in these women should be mindful of this uncertainty, and the uncertainty regarding adverse events. Treatment of women with lower risk disease should be individualised to take into account individual factors.

Modification of cut-off values for HE4, CA125 and the ROMA algorithm for early-stage epithelial ovarian cancer detection: Results from 1021 cases in South China

ObjectivesThe purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) in early stage epithelial ovarian cancer (EOC) detection in patients in southern China. Additionally, this study proposes a possible ideal cut-off value for each marker to its own population in South China. Design and methodsSerum HE4 and CA125 were measured in 756 patients with pelvic masses (275 malignancies, 53 borderline tumors and 428 benign diseases), and their ROMA values were calculated. Areas under the receiver operator characteristic (ROC) curves (AUC) were assessed for HE4, CA125, ROMA and combinations of these biomarkers. ResultsBoth HE4 and ROMA performed better diagnostically than CA125 alone for early stage EOC, with AUCs ranging from 0.714 for HE4, 0.699 for ROMA, and 0.463 for CA125 in premenopausal subjects, and 0.902 for ROMA, 0.880 for HE4, and 0.256 for CA125 in postmenopausal subjects. ConclusionsHE4 and ROMA alone were found to be better than CA125 for detecting borderline tumors and early-stage EOC. The optimal cut-off values (HE4: 70pmol/l for all; CA125: 60U/ml for pre- and 35U/ml for postmenopausal women) could notably improve diagnostic performance in EOC detection in patients in southern China.

Abstract 1579: Circulating cell-free DNA as a diagnostic marker for epithelial ovarian cancer and an association with epithelial-mesenchymal transition

Abstract Objectives: Although technologies continue to develop, there are still many limitations on detecting circulating tumor cells in blood. In addition, the great genetic heterogeneity in ovarian cancer is one of the major concerns. Therefore, we aimed to investigate the cell-free DNA (cfDNA) as a diagnostic marker for epithelial ovarian cancer (EOC) and evaluate the cfDNA level of epithelial-mesenchymal transition markers. Methods: Blood was preoperatively collected from women who were assigned to surgery for pelvic mass. DNA was extracted using Qiagen DNA Mini kit and quantification of total cfDNA was performed using real-time PCR with TaqMan Assay with primers directed to the following genes: GAPDH, β-globin, β-actin, E-cadherin, and fibronectin. Results: A total of 32 patients with EOC and 17 patients of benign ovarian disease (controls) were included. The median cfDNA level of β-globin was 0 (range, 0-0.35)GE/ml in EOC and 0.41 (range, 0-33.5)GE/ml in control (p = 0.04). The sensitivity of β-globin cfDNA (>0.4 GE/ml) was 51.9%, which was lower than that of CA-125 (96.3%, if CA-125 >35IU/ml). cfDNA was significantly higher in advanced stage of EOC than early stage EOC (p = 0.02). Plasma E-cadherin level was significantly related with β-globin cfDNA (coefficient 0.886, p<0.001). However, there was no significant association with cfDNA amount and survival outcomes. Conclusions: Circulating cfDNA can be a promising target for early detection of EOC. The levels of epithelial-mesenchymal transition markers showed a different pattern in plasma and were associated with other cfDNA amounts. Citation Format: Yu-Jin Koo, Kyung-Jin Min, Jin-Hwa Hong, Jae-Kwan Lee. Circulating cell-free DNA as a diagnostic marker for epithelial ovarian cancer and an association with epithelial-mesenchymal transition. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1579. doi:10.1158/1538-7445.AM2015-1579

Identification of novel candidate biomarkers of epithelial ovarian cancer by profiling the secretomes of three-dimensional genetic models of ovarian carcinogenesis.

Epithelial ovarian cancer (EOC) is still considered the most lethal gynecological malignancy and improved early detection of ovarian cancer is crucial to improving patient prognoses. To address this need, we tested whether candidate EOC biomarkers can be identified using three-dimensional (3D) in vitro models. We quantified changes in the abundance of secreted proteins in a 3D genetic model of early-stage EOC, generated by expressing CMYC and KRAS(G) (12) (V) in TERT-immortalized normal ovarian epithelial cells. Cellular proteins were labeled in live cells using stable isotopic amino acid analogues, and secreted proteins identified and quantified using liquid chromatography-tandem mass spectrometry. Thirty-seven and 55 proteins were differentially expressed by CMYC and CMYC+KRAS(G) (12) (V) expressing cells respectively (p < 0.05; >2-fold). We evaluated expression of the top candidate biomarkers in ∼210 primary EOCs: CHI3L1 and FKBP4 are both expressed by >96% of primary EOCs, and FASN and API5 are expressed by 86 and 75% of cases. High expression of CHI3L1 and FKBP4 was associated with worse patient survival (p = 0.042 and p = 0.002, respectively). Expression of LGALS3BP was positively associated with recurrence (p = 0.0001) and suboptimal debulking (p = 0.018) suggesting that these proteins may be novel prognostic biomarkers. Furthermore, within early stage tumours (I/II), high expression of API5, CHI3L1 and FASN was associated with high tumour grade (p = 3 × 10(-4) , p = 0.016, p = 0.010, respectively). We show in vitro cell biology models of early-stage cancer development can be used to identify novel candidate biomarkers for disease, and report the identification of proteins that represent novel potential candidate diagnostic and prognostic biomarkers for this highly lethal disease.

Novel directions in adjuvant chemotherapy for early stage epithelial ovarian cancer.

Treatment of early stage ovarian cancer remains controversial despite advances in chemotherapeutic options. Over the past 30 years, molecular and clinicopathologic studies accelerated and treatment of ovarian cancer has undoubtedly improved although there is a debate as to whether this impacts outcome or not. More recently, the introduction of targeted therapy started a new era. Probably it is because early stage disease comprises a small portion of the epithelial ovarian cancer, studies have mostly ignored this group and still there is no clear consensus regarding systemic treatment of early-stage lesions. However this group of patients has the best chance of cure. In this review, we focus on current developments in the treatment of early stage ovarian cancer and query the options.

Long-term safety of fertility sparing surgery in early stage ovarian cancer: Comparison to standard radical surgical procedures

ObjectiveFertility-sparing surgery (FSS) is a strategy often considered in young patients with low-grade (G1–2) early-stage epithelial ovarian cancer (eEOC), while is still controversial in high-risk patients. We investigated the role of FSS in low and high-risk eEOC patients undergoing comprehensive surgical staging. MethodsWe analyzed data from patients operated for an eEOC from 1975 to 2011, focusing on patients submitted to FSS. Seventy patients out of 307 with eEOC were identified. Patients underwent FSS were compared with 237 patients underwent radical-comprehensive-staging (RCS) in the same period. Disease free (DFS) and overall (OS) survivals were evaluated using Kaplan–Meier and Cox models. ResultsOverall, 307 patients had surgery for eEOC: 70 (22.8%) and 237 (77.2%) women had FSS and RCS, respectively. At univariate analysis, the execution of FSS not influenced DFS (HR:1.06 (95%CI: 0.56,2.02); p=0.84) and OS (HR:1.94 (95%CI: 0.75,4.98); p=0.16). Stage of disease was the only factor correlating with DFS (HR:4.73; 95%CI: 2.01,11.11; p<0.001). Independently, increased age (HR per 1-unit of age:1.06 (95%CI: 1.03,1.11); p<0.001) and high risk disease (HR:3.26; 95%CI: 1.23,8.62; p=0.01) remained associated with worse OS. Focusing on the high risk group (stage IAG3 or more) we observed that type of surgery (FSS v. RCS) did not influence DFS (p=0.77, log-rank test) and OS (p=0.08, log-rank test). ConclusionsFSS upholds oncologic effectiveness of RCS, preserving reproductive and endocrine functions. FSS does not increase risk of recurrence among high risk eEOC patients. Further prospective studies on this issue are warranted to improve patients' care.

Validation of LRG1 as a potential biomarker for detection of epithelial ovarian cancer by a blinded study.

BackgroundLeucine-rich alpha-2-glycoprotein (LRG1) was found to be differentially expressed in sera from patients with Epithelial Ovarian Cancer (EOC). The aim of this study is to investigate the performance of LRG1 for detection of EOC, including early stage EOC, and to evaluate if LRG1 can complement CA125 in order to improve EOC detection using two independent blinded sample sets.Methods and ResultsSerum LRG1 and CA125 were measured by immunoassays. All assays were performed blinded to clinical data. Using the two independent sample sets (156 participants for sample set 1, and 233 for sample set 2), LRG1 was differentially expressed in EOC cases as compared to healthy, surgical, and benign controls, and its performance was not affected by the conditions of blood collection. The areas under the ROC curve (AUC) for LRG1 in differentiating EOC cases from non-cases were 0.797 and 0.786 for sample set 1 and 2. For differentiating EOC cases from healthy controls, the AUC values for LRG1 were 0.792 and 0.794. At a fixed specificity of 95%, LRG1 detects 52%, and 53.5% of EOC cases from healthy controls for sample set 1 and 2. When combining LRG1 and CA125, the AUC value increased to 0.927, which was improved compared to CA125 (AUC=0.916) (p=0.008) alone in distinguishing EOC cases from non-cases. More importantly, LRG1 also showed potential performance in differentiating early stage EOC from non-cases with an AUC of 0.715 for sample set 1, and 0.690 for sample set 2. The combination of LRG1 and CA125 resulted in an AUC of 0.838, which outperforms CA125 (AUC=0.785) (p=0.018) in detecting early stage EOC cases from non-cases using the larger sample set.ConclusionsLRG1 could be a useful biomarker alone or in combination with CA125 for the diagnosis of ovarian cancer.

Plasma immune analytes in patients with epithelial ovarian cancer

ObjectivesInflammation is a common feature of epithelial ovarian cancer (EOC), and measurement of plasma markers of inflammation might identify candidate markers for use in screening or presurgical evaluation of patients with adnexal masses. MethodsPlasma specimens from cohorts of 100 patients with advanced EOC (AJCC Stage III and IV), 50 patients with early stage EOC (Stage I and II), and 50 patients with benign surgical conditions were assayed for concentrations of multiple cytokines, toll-like receptor agonists, and vascular growth factors via ELISA and electrochemiluminescence. Immune proteins were then analyzed for association with EOC. Differences in plasma protein levels between benign, early, and advanced EOC patient groups were assessed with and without adjustment for plasma cancer antigen 125 (CA-125) levels. ResultsOut of 23 proteins tested, six—including interferon gamma (IFNγ), interleukin 6 (IL-6), IL-8, IL-10, tumor necrosis factor alpha (TNFα), and placental growth factor (PlGF)—were univariately associated with EOC (all p<0.005), and one—IL-6—was associated with early stage EOC (p<0.0001). Heat shock protein 90kDa beta member 1 (HSP90B1, gp96) was associated with EOC and early stage EOC with borderline statistical significance (p=0.039 and p=0.026, respectively). However, when adjusted for (CA-125), only HSP90B1 independently predicted EOC (p=0.008), as well as early stage EOC (p=0.014). ConclusionsMultiple plasma cytokines, including IFNγ, IL-6, IL-8, IL-10, TNFα, PlGF, and HSP90B1 are associated with EOC. Of these, HSP90B1 is associated with EOC independent from the biomarker CA-125.

Impact of guideline adherence on patient outcomes in early-stage epithelial ovarian cancer

AimThe aim of this study was to evaluate the effects of adherence to National Comprehensive Cancer Network (NCCN) guidelines on survival outcomes in patients with early-stage epithelial ovarian cancer. MethodsOur institutional cancer registry data on 266 patients with Stage I epithelial ovarian cancer was reviewed retrospectively and compliance with treatment guidelines for surgery and adjuvant treatment was determined. Patients were categorized according to adherence or non-adherence. The primary endpoints were recurrence-free survival and disease-specific survival. Hazard ratios (HRs) for survival were estimated with a Cox proportional hazards model. ResultsOf the 266 patients, 71 (26.7%) underwent adequate surgical staging in accordance with the guidelines. The guidelines for adjuvant chemotherapy were followed adequately in all 71 patients that were adherent to surgical staging and in 163 of the 195 patients with non-adherence to surgical staging (83.6%). Multivariate analysis, adjusted for prognostic factors, identified higher recurrence-free survival (HR, 0.36; 95% CI, 0.15–0.88) and disease-specific survival (HR, 0.42; 95% CI, 0.16–1.12) among patients whose treatment adhered to both surgical and chemotherapy guidelines, although disease-specific survival was not statistically significant. When excluding clear cell histology from the cohort, the guideline-adherent group had significantly better disease-specific survival than the non-adherent group (HR, 0.13; 95% CI, 0.02–0.94). ConclusionThe results of this study suggest that adherence to NCCN guidelines may improve survival outcomes in patients with early-stage epithelial ovarian cancer, particularly in cases other than clear cell histology.

Lymph node dissection (lymphadenectomy) for presumed early stage epithelial ovarian cancer

Lymph node dissection (lymphadenectomy) for presumed early stage epithelial ovarian cancer

Systematic lymphadenectomy in the treatment of epithelial ovarian cancer: a meta-analysis of multiple epidemiology studies.

To evaluate the role of systematic lymphadenectomy in epithelial ovarian cancer by comparing 5-year overall survival rates between systematic and unsystematic lymphadenectomies. A literature search of the Pubmed, Embase and Cochrane Library databases was performed up to 2014. Two authors independently determined the eligibility of the articles and extracted the available data. The role of systematic lymphadenectomy in epithelial ovarian cancer was analyzed by combining all qualified individual studies using a fixed-effect model. Then, subgroup analysis was performed by dividing articles according to type, cancer stage and residual tumor. Finally, heterogeneity and publication bias in all enrolled studies were assessed using Higgins I(2) statistics and funnel plots, respectively. Fourteen relevant studies including 3488 subjects were included in the analysis. The value of pooled relative ratios of all qualified studies revealed that the 5-year overall survival rate in the lymphadenectomy group was higher than that in the unsystematic lymphadenectomy group (relative ratio = 1.08; P = 0.001), which was duplicated in the subgroup analysis of observational studies (relative ratio = 1.07; P = 0.002) and advanced stage (relative ratio = 1.21; P = 0.012) epithelial ovarian cancer. No significant differences were observed in randomized controlled trials (relative ratio = 1.01; P = 0.858), early stage epithelial ovarian cancer (relative ratio = 1.06; P = 0.064) or patients with residual tumor ≤2 cm (relative ratio = 1.05; P = 0.125). The heterogeneity and publication bias in the enrolled studies were within acceptable thresholds. Lymphadenectomy can improve the 5-year overall survival rate in advanced stage epithelial ovarian cancer but not in early stage epithelial ovarian cancer or in patients with residual tumor ≤2 cm.

Impact of adjuvant chemotherapy for stage I ovarian carcinoma with intraoperative tumor capsule rupture.

Adjuvant chemotherapy is generally recommended for early stage epithelial ovarian cancer. However, it remains uncertain which histological subtypes and substages of stage I disease should receive adjuvant chemotherapy. The objective of this study is to determine the impact of chemotherapy among stage I epithelial ovarian cancer. Of the 267 patients with stage I epithelial ovarian cancer analyzed in this study, 152 patients received adjuvant chemotherapy (AC-positive group) and 115 patients did not (AC-negative group). Survival analysis was retrospectively performed to determine the effectiveness of adjuvant chemotherapy in stage I epithelial ovarian cancer patients. Recurrence was observed in 14 patients in the AC-negative group and 20 patients in the AC-positive group. There were no statistically significant differences in disease-free survival (DFS) and overall survival between the two groups. In stage IA and IB patients, there was no statistically significant difference in DFS and overall survival based on adjuvant chemotherapy status. However, in patients with intraoperative tumor capsule rupture, the AC-positive group had significantly better DFS than the AC-negative group (P = 0.01). Patients with clear cell carcinoma who received adjuvant chemotherapy had better DFS than patients who did not (P = 0.004). Adjuvant chemotherapy may not be necessary for patients with stage IA or IB epithelial ovarian cancer, but may be beneficial for clear cell carcinoma patients with intraoperative tumor rupture.