Early Stage Epithelial Ovarian Carcinoma Research Articles

Survival Outcomes in the Patients of Ovarian Epithelial Carcinomas Treated with Fertility-Sparing Surgery: A Study from a Developing Country

Objective: To assess the outcomes of fertility-sparing surgery in patients with ovarian epithelial carcinoma treated at our centre.
 Study Design: Retrospective longitudinal study.
 Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore Pakistan, from Jul 2001 to Aug 2015.
 Methodology: We studied 31 patients with ovarian epithelial carcinoma who underwent fertility-sparing surgery at Shaukat Khanum Memorial Hospital. The detail regarding patients and tumour characteristics, along with outcomes of the intervention, was obtained from secondary data kept in the electronic hospital information system.
 Results: A total of 132 patients with ovarian epithelial carcinoma were identified; 31 patients underwent fertility-sparing surgery (Stage-IA, n=19; Stage-IC, n=12). By histopathology, 14(45.0%) had mucinous cystadenocarcinoma, 7(22.6%) serous adenocarcinoma, 6(19.4%) endometroid, and 4(12.9%) with clear cell pathology. The mean duration of follow-up was 52.6±2.3 months (18-118 months) after fertility-sparing surgery. Five-year recurrence-free survival was 81.0%. (Three-year=89.0%), using the Kaplan-Meier graph. Three patients had successful pregnancies, with one having a twin pregnancy.
 Conclusion: Fertility-sparing surgery should be considered for children of early-stage epithelial ovarian carcinoma patients as it preserves fertility and endocrine function while avoiding recurrence.

Abstract 775: Evaluation of Erb-B2 expression from archival tumor tissue in early stage epithelial ovarian carcinoma patient prognosis

Abstract In this retrospective study, Erb-B2 expression was assessed in 106 patients using Paraffin-Embedded Tissue (PET) to determine the prognostic value in Epithelial Ovarian Carcinoma (EOC) patients diagnosed at Saskatoon Cancer Center between the years 1983-1995. Relationship between Erb-B2 positivity and patient tumor characteristics was assessed for Overall Survival (OS) and Relapse-Free Survival (RFS) by Kaplan-Meier method. Based on the intensity of stain with a polyclonal antibody (A485, 1/400 dilution), cases with markedly intense cytoplasmic and membranous immunoreactivity were classified as Erb-B2 over-expressors. Erb-B2 was overexpressed in 13 (12%) cases. The mean age of the patients was 56 years (range 18-84 years). The patient population consisted of 64 Stage I and II, Early Stage (ES) and 36 cases with Stage III and IV Advanced Stage (AS). Data on histologic grade was available in 81 cases. 58 patients received platinum-containing regimen, 13 melphalan, and in 9 cases combination chemotherapy. Erb-B2 expression did not influence OS and RFS in these patients. Similarly, there was no significant relation to OS and RFS between Erb-B2 and age, grade, and patients with No Evidence of Disease (NED). Of the 64 cases with ES disease, 16 cases had Grade 2 tumor with Erb-B2 over-expression in 4 cases. Grade 2 tumors with Erb-B2 overexpression indicated significant relationship to OS and RFS, p=0.01, (median = 30 months, CI: 26 - 68) and p=0.05, (median = 15 months, CI: 13 - 68). Furthermore, in 21 cases with ES, Endometrioid histology and Erb-B2 expressors 6/21 (28%) experienced significantly shorter OS compared to non-expressors p=0.005, (median = 48 months, CI: 22 - 74) (mean = 134 months, CI: 124 - 144). In conclusion, Erb-B2 overexpression could be detected in only limited EOC cases in PET and appears to have no prognostic influence. Additionally, endometrioid carcinoma and grade 2, ES certainly reflect the importance of sub-group analysis. In ovarian carcinoma distribution of stage, histology, and grading of tumor cells are conventional markers for prognosis. Finally, Erb-B2 status detected by immunohistochemistry, in a subgroup of patients with high-degree of HER2 positivity/focal amplification may likely have better clinical outcome with anti-HER2 agents. Citation Format: Kavitha Advikolanu Rao, Anthony Magliocco, Andrew Maksymiuk. Evaluation of Erb-B2 expression from archival tumor tissue in early stage epithelial ovarian carcinoma patient prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 775.

Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis

ObjectiveIn young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients’ survival.MethodsBetween 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts.ResultsDuring 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234–1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330–2.669), P = 0.905}.ConclusionsEven after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

Exploration of Potential Diagnostic Value of Protein Content in Serum Small Extracellular Vesicles for Early-Stage Epithelial Ovarian Carcinoma.

Epithelial ovarian carcinoma (EOC) is one of the most common gynecologic malignancies with a high mortality rate. Serum biomarkers and imaging approaches are insufficient in identifying EOC patients at an early stage. This study is to set up a combination of proteins from serum small extracellular vesicles (sEVs) for the diagnosis of early-stage EOC and to determine its performance. A biomarker for early-stage ovarian cancer (BESOC) cohort was used as a Chinese multi-center population-based biomarker study and registered as a Chinese Clinical Trial ChiCTR2000040136. The sEV protein levels of CA125, HE4, and C5a were measured in 299 subjects. Logistic regression was exploited to calculate the odds ratio and to create the sEV protein model for the predicted probability and subsequently receiver-operating characteristic (ROC) analysis. The combined sEV marker panel of CA125, HE4, and C5a as a sEV model obtained an area under curve (AUC) of 0.912, which was greater than the serum model (0.809), by ROC analysis to identify EOC patients from the whole cohort. With the cutoff of 0.370, the sensitivity and specificity of the sEV model were 0.80 and 0.89, which were much better performance than the serum markers (sensitivity: 0.55~0.66; specificity: 0.59~0.68) and the risk of ovarian malignancy algorithm (ROMA) index approved by the U.S. Food and Drug Administration (sensitivity: 0.65; specificity: 0.61), to identify EOC patients from patients with benign ovarian diseases or other controls. The sEV levels of CA125 significantly differed among early-stage and late-stage EOC (p < 0.001). Moreover, the AUC of ROC to identify early-stage EOC patients was 0.888. Further investigation revealed that the sEV levels of these 3 proteins significantly decreased after cytoreductive surgery (CA125, p = 0.008; HE4, p = 0.025; C5a, p = 0.044). In summary, our study showed that CA125, HE4, and C5a levels in serum sEVs can identify EOC patients at the early stage, elucidating the possibility of using a sEV model for the diagnosis of early-stage EOC.

Delay in adjuvant chemotherapy administration for patients with FIGO stage I epithelial ovarian carcinoma is associated with worse survival

<h3>Objectives:</h3> Administration of adjuvant chemotherapy within 42 days from surgery is one of the quality measures for ovarian cancer per SGO. The aim of the present study was to evaluate the impact of chemotherapy delay on the survival of patients with FIGO stage I epithelial ovarian carcinoma (EOC). <h3>Methods:</h3> The National Cancer Database (NCDB) was accessed and patients diagnosed between 2004-2015 with pathological stage I EOC without a history of another tumor who received multi-agent chemotherapy with known surgery-chemotherapy interval and had at least one month of follow-up were identified. Overall survival (OS) was compared between patients who received multi-agent chemotherapy 1-6 weeks and 6-12 weeks from staging surgery with the log-rank test following generation of Kaplan-Meier curves. A Cox multivariate model was constructed to control for confounders. <h3>Results:</h3> A total of 8549 patients who met the inclusion criteria and received adjuvant chemotherapy at a median 35 days from surgery were identified; 67.7% received adjuvant chemotherapy 1-6 weeks from staging surgery while 32.3% experienced a delay. Patients who experienced a delay were more likely to be older than 65 years (21.8% vs 18%, p<0.001), with comorbidities (18.4% vs 14.9%, p<0.001), be managed in non-academic facilities (57.1% vs 53.2%, p=0.001), have government-issued insurance (32.7% vs 25.6%, p<0.001), stage IA (44.7% vs 40.1%, p<0.001), low-grade tumors (49.2% vs 45.6%, p=0.004), have a prolonged hospital stay (>10 days) (6.2% vs 2.3%, p<0.001) and an unplanned re-admission within 30-days from surgery (4.3% vs 2.7%, p<0.001). They were also less likely to be White (85.3% vs 89%, p<0.001), and undergo lymphadenectomy (80.7% vs 87.2%, p<0.001). Patients who experienced a delay had worse OS compared to those who did not, p<0.001; 5-year OS rates were 85.7% and 89.7% respectively. For patients with high-grade serous tumors, those who experienced a delay had a 5-yr OS of 81.9% compared to 88.6% for those who did not, p<0.001. After controlling for patient age, race, presence of comorbidities, insurance status, tumor histology and grade, performance of lymphadenectomy and substage, chemotherapy delay was associated with a worse survival (HR: 1.27, 95% CI: 1.12, 1.44). <h3>Conclusions:</h3> For patients with early stage EOC administration of adjuvant chemotherapy within 6 weeks from surgery was associated with better survival.

Outcomes after Fertility-sparing Surgery for Women with Ovarian Cancer: A Systematic Review of the Literature

To compare reproductive and oncologic outcomes of patients diagnosed with early-stage epithelial ovarian carcinoma, borderline ovarian tumors, or nonepithelial ovarian carcinoma according to receipt of fertility-sparing surgery or conventional surgery. PubMed was searched from January 1, 1995, to May 29, 2020. Studies were included if they (1) enrolled women of childbearing age diagnosed with ovarian cancer between the ages of 18 years and 50 years, (2) reported on oncologic and/or reproductive outcomes after fertility-sparing surgery for ovarian cancer, and (3) included at least 20 patients. The initial search identified 995 studies. After duplicates were removed, we abstracted 980 unique citations. Of those screened, 167 publications were identified as potentially relevant, and evaluated for inclusion and exclusion criteria. The final review included 44 studies in epithelial ovarian cancer, 42 in borderline ovarian tumors, and 31 in nonepithelial ovarian carcinoma. The narrative synthesis demonstrated that overall survival does not seem to be compromised in patients undergoing fertility-sparing surgery compared with those undergoing conventional surgery, although long-term data are limited. Areas of controversy include safety of fertility-sparing surgery in the setting of high-risk factors (stage IC, grade 3, and clear cell histology), as well as type of surgery (salpingo-oophorectomy vs cystectomy). It seems that although there may be some fertility compromise after surgery, pregnancy and live-birth rates are encouraging. Fertility-sparing surgery is safe and feasible in women with early-stage low-risk ovarian cancer. Pregnancy outcomes for these patients also seem to be similar to those of the general population.

Oncological and Reproductive Outcomes of Fertility-sparing Surgery in Women with Early-stage Epithelial Ovarian Carcinoma: A Multicenter Retrospective Study.

With delayed childbearing in women, preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma (EOC). Fertility-sparing surgery (FSS) can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life. In order to evaluate oncological safety, attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS, this multicenter retrospective study was conducted. Between January 2005 and December 2014, total of 87 young women with FIGO stage I EOC were included, with their clinicopathologic parameters in relation to disease-free survival (DFS) and overall survival (OS) assessed. Attitudes toward childbearing, ovarian function and fertility were studied in women undergoing FSS (n=36). As a result, in contrast to radical surgery, FSS did not affect prognosis by Kaplan-Meier curves (log-rank test; DFS: P=0.484; OS: P=0.125). However, two of the three recurrence cases and both death cases were in FSS group stage IC. All women undergoing FSS resumed regular menstrual periods after chemotherapy. Only 16 (44.44%) had tried to conceive, and 17 pregnancies occurred in 15 (93.75%) women. Among 20 women who did not attempt conception, the most common reason was not being married (70%), followed by already having children (15%). In summary, FSS is considered safe in young women with stage IA EOC. Regular menstruation and good obstetric outcomes can be achieved. This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.

Mismatch Repair Deficiency in Ovarian Carcinoma: Frequency, Causes, and Consequences.

Mismatch repair deficiency (MMRD) is involved in the initiation of both hereditary and sporadic tumors. MMRD has been extensively studied in colorectal cancer and endometrial cancer, but not so in other tumors, such as ovarian carcinoma. We have determined the expression of mismatch repair proteins in a large cohort of 502 early-stage epithelial ovarian carcinoma entailing all the 5 main subtypes: high-grade serous carcinoma, endometrioid ovarian carcinoma (EOC), clear cell carcinoma (CCC), mucinous carcinoma, and low-grade serous carcinoma. We studied the association of MMRD with clinicopathologic and immunohistochemical features, including tumor-infiltrating lymphocytes in EOC, the histologic type in which MMRD is most frequent. In addition, MLH1 promoter methylation status and massive parallel sequencing were used to evaluate the proportion of sporadic and Lynch syndrome-associated tumors, and the most frequently mutated genes in MMRD EOCs. MMRD occurred only in endometriosis-associated histologic types, and it was much more frequent in EOC (18%) than in CCC (2%). The most frequent immunohistochemical pattern was loss of MLH1/PMS2, and in this group, 80% of the cases were sporadic and secondary to MLH1 promoter hypermethylation. The presence of somatic mutations in mismatch repair genes was the other mechanism of MMRD in sporadic tumors. In this series, the minimum estimated frequency of Lynch syndrome was 35% and it was due to germline mutations in MLH1, MSH2, and MSH6. ARID1A, PTEN, KTM2B, and PIK3CA were the most common mutated genes in this series. Interestingly, possible actionable mutations in ERRB2 were found in 5 tumors, but no TP53 mutations were detected. MMRD was associated with younger age and increased tumor-infiltrating lymphocytes. Universal screening in EOC and mixed EOC/CCC is recommended for the high frequency of MMRD detected; however, for CCC, additional clinical and pathologic criteria should be evaluated to help select cases for analysis.

Is standard radical surgery necessary for elderly patients with early-stage epithelial ovarian carcinoma? ~Propensity score matched analysis~.

The impact of 'standard full-staged radical surgery (SRS)' on overall survival (OS) in elderly patients with early-stage epithelial ovarian cancer (EOC) remains unclear. In the current study, we investigated the impact of SRS on OS in elderly patients with early-stage EOC in a multicentric analysis using a propensity score (PS)-matching technique. Between 1986 and 2017, 3227 patients with EOC were registered and accumulated by the Tokai Ovarian Tumor Study Group, consisting of 14 collaborating institutions, after a central pathological review. Among them, 204 elderly patients aged older than or equal to 65years who had a stage I EOC were analyzed, including 72 patients who had received SRS (Group I) and 132 who had undergone non-SRS limited surgery (Group II). Oncologic outcomes were compared between the two groups using a PS-matching technique to adjust for various clinicopathologic risk factors. The median follow-up duration of all surviving patients was 55.9months. Consequently, 54 patients (26.5%) developed recurrence. In addition, 33 patients (16.2%) died of the disease. In the original cohort, the 5-year OS rates of Groups I and II were 95.8 and 82.3%, respectively. We identified a marginally significant difference between the two groups (Log-rank: P=0.086). In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in OS between the two groups [OS (Group I vs. II), HR: 0.766 (95% CI: 0.271-2.165), P=0.615]. After adjustment for clinicopathologic factors, non-SRS limited surgery may not worsen the oncologic outcome in elderly women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

The value of surgical staging in patients with apparent early stage epithelial ovarian carcinoma

ObjectiveThe value of surgical staging of apparent early stage epithelial ovarian carcinoma (EOC) is unclear. The aim of this study was to evaluate the importance of surgical staging on the stage of disease and treatment plan. Material and methodsAll patients with apparent stage I EOC undergoing staging from 01/01/2005 to 30/06/2017 in all Danish hospitals and in the Radboud University Hospital Nijmegen, the Netherlands, were evaluated to identify the pathological findings responsible for upstaging and changes in treatment plans. ResultsWe included 1234 patients with apparent stage I EOC. The staging steps often missed were the biopsy from the right diaphragmatic surface (missed in 96.9% of all patients) and lymph node (LN) sampling or lymphadenectomy (missed in 65.5% of all patients). Upstaging occurred in 393 patients (31.8%) due to microscopic spread to both ovaries (0.8%); ovarian surface (5.8%); positive cytology (10.0%); fallopian tubes (3.1%), ovary (1.5%) and/or uterus serosa (1.2%); pelvic peritoneum (4.3%); LNs (4.7%); omentum (3.7%); abdominal peritoneum (0.6%) and right diaphragmatic surface (2.6%). Of the 393 upstaged patients, 138 (35.1%) had an altered treatment plan due to metastases found by surgical staging. ConclusionStaging was incomplete in most patients, mainly because a biopsy of the diaphragm was omitted. However, surgical staging led to adjuvant treatment in 35.1% of the upstaged patients. Peritoneal biopsies (para-colic gutters and right diaphragm) were of little value, since few patients had an adjustment of treatment plan due to these biopsies. Omitting these biopsies, in the absence of peritoneal abnormalities, is justifiable.

Prognostic Factors of Early Stage Epithelial Ovarian Carcinoma.

We aimed to determine prognostic factors of early stage (I/II) epithelial ovarian carcinoma (EOC) including clinicopathologic and chemotherapeutic regimens. Four hundred and thirty-seven women who underwent primary staging surgery with adjuvant chemotherapy between January 1, 2000 and December 31, 2010 were retrospectively reviewed and analyzed from two medical centers. The prognostic factors were determined from multivariate survival analyses using Cox regression models. The majority of women were diagnosed with stage Ic (244/437, 55.8%). The histopathologic types were clear cell (37.5%), endometrioid (27.2%), serous (14.0%), and mucinous (13.3%). Fifty-seven percent (249/437) of the women received taxane-based (platinum plus paclitaxel) regimens and 43.0% received non-taxane (platinum plus cyclophosphamide) regimens as frontline adjuvant chemotherapy. Clear cell tumors (adjusted Hazard ratio (aHR) 0.37, 95% confidence interval (CI) 0.21–0.73, p = 0.001) showed better 5-year disease-free survival (DFS) than serous tumors. Women diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage II (aHR 5.97, 95% CI = 2.47–14.39, p < 0.001), grade 3 tumor without clear cell (aHR 2.28, 95% CI = 1.02–5.07, p = 0.004) and who received 3–5 cycles of non-taxane regimens (aHR 3.29, 95% CI = 1.47–7.34, p = 0.004) had worse 5-year overall survival (OS). Clear cell histology treated with taxane-based regimens showed significantly higher 5-year DFS (91.2% vs. 82.0%, aHR = 0.45, 95% CI = 0.21–0.93, p = 0.043) and 5-year OS (93.5% vs. 79.0%, aHR = 0.30, 95% CI = 0.13–0.70, p = 0.005) than those treated with non-taxane-based regimens. We conclude that stage, tumor grade, and chemotherapeutic regimens/cycles are independent prognostic factors for early stage ovarian cancer.

Identification of six serum antigens and autoantibodies for the detection of early stage epithelial ovarian carcinoma by bioinformatics analysis and liquid chip analysis.

The early detection of ovarian cancer is critical for improving the prognosis of patients, but there are currently insufficient tumor biomarkers for early detection owing to their low diagnostic sensitivity and specificity. The aim of the present study was to investigate the use of the serum antigens C-C motif chemokine ligand 18 and C-X-C motif chemokine ligand 1, and autoantibodies C1D, transmembrane 4 L six family member 1, zinc finger protein 675 and fragile X mental retardation 1 autosomal homolog 1, for the early screening of epithelial ovarian cancer (EOC). The expression of these sex genes/proteins in ovarian cancer and normal ovarian tissue was examined, and the potential functions of the six genes/proteins in ovarian cancer were analyzed by bioinformatics. Finally, these data were verified in clinical samples, and the multi-analyte suspension array method was compared with the ELISA method. Taken together, these data indicated that these six genes/proteins may serve as potential biomarkers for the early detection of EOC.

Detection of OPCML methylation, a possible epigenetic marker, from free serum circulating DNA to improve the diagnosis of early-stage ovarian epithelial cancer.

The aim of the present study was to identify the appropriate DNA sequence and design high-quality primers for methylation-specific polymerase chain reaction (MSP). These primers may be used to examine and identify patients with early-stage epithelial ovarian carcinoma (EOC). Opioid binding protein/cell adhesion molecule like (OPCML), Runt-related transcription factor 3 and tissue factor pathway inhibitor 2 were selected as possible molecular markers. MSP primer sets were designed to monitor the methylation of the three markers. Free circulating DNA (fcDNA) from 194 patients with epithelial ovarian carcinoma and healthy donors were templates in the nested MSP. OPCML MSP was effective with respect to screening methylated fcDNA. One-way ANOVA P-values indicated that the difference in cancer antigen 125 (CA125), a biomarker for EOC diagnosis, level between early EOC and healthy donors was not significant. The methylation of OPCML was significantly altered in early-stage EOC compared with healthy donors (P<0.0001), and this supported the hypothesis that specific fcDNA methylation was able to distinguish patients with early-stage EOC from healthy donors. With respect to detecting early EOC, compared with the results of the CA125 test, MSP increased the κ coefficient from 0.140 to 0.757. Therefore, OPCML combined with fcDNA may be used to establish an improved clinical assay compared with the current CA125 test.

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.

Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC). A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions. Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months. As histologic grade increased, overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined. Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS. Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group. Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups. Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients. The surgical procedure and surgical route might not significantly influence the prognosis. Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

High-Resolution Genomic Profiling of Carboplatin Resistance in Early-Stage Epithelial Ovarian Carcinoma

Chemotherapy resistance remains a major obstacle to successful treatment of ovarian cancer patients. Therefore, increased knowledge of underlying mechanisms and identification of predictive factors are of great importance. Standard treatment for ovarian carcinoma is surgery followed by platinum-based chemotherapy. In this study, we aimed to search for genes or genomic regions involved in platinum resistance in ovarian carcinoma. Array-based comparative genomic hybridization (CGH) was used to identify genetic alterations in 32 early-stage epithelial ovarian carcinomas homogeneously treated with single-agent carboplatin. The arrays contain 33,370 bacterial artificial chromosome (BAC) clones and form a contiguous and tiling coverage of the human genome with an average resolution of ∼100 kb. We found certain genetic changes associated with carboplatin response. Gains in 1q25.1–q41 were significantly more frequent in carboplatin-resistant tumours. In this region, we further detected two smallest regions of overlap (SRO) at 1q25.2 and 1q32.2 (∼690 and ∼830 kb in size, respectively). Interestingly, we found some regions that were lost exclusively in the sensitive tumours 17q24.1, Xq21.33–q22.1, and 6 regions in 15q. We also detected genetic differences with regard to histologic subtype. Gain in 8q was found highly associated with serous and clear cell subtypes, and an SRO was identified at 8q24.22–q24.23. The genomic regions found altered in this study confirm some of our previous metaphase CGH results. The alteration found in chromosome arm 1q was verified and specified, and is therefore of great interest as a candidate for predictive markers. Identifying predictive markers of chemosensitive and chemoresistant disease would greatly help in the choice of chemotherapy in the clinic, and thus improve treatment of women with ovarian cancer.

Adjuvant chemotherapy with carboplatin and taxane compared with single drug carboplatin in early stage epithelial ovarian carcinoma

The objective of the present study was to compare recurrence-free survival (RFS) in early stages (FIGO stages I-II) of epithelial ovarian cancer after adjuvant chemotherapy with carboplatin and a taxane (113 patients) and with carboplatin alone (27 patients). The distribution of clinical and pathological prognostic factors as well as type of primary surgery were comparable in the two groups. Recurrence rate was 21% and RFS was 79% in the series of patients treated with taxane-based chemotherapy and 19% and 81%, respectively, in the series of patients who received single drug carboplatin. Thus, no significant differences were recorded. The major toxicities in the present study were myelosuppression (46%) and neuro-toxicity (26%). Neuro-toxicity was more frequently (P=0.007) recorded and of higher grade (P=0.011) for patients in the carboplatin-taxane series compared with patients in the carboplatin series. RFS for patients in FIGO-stage I was 85% and for patients in FIGO-stage II only 47%. In a multivariate logistic regression analysis of predictive factors for tumor recurrence in the complete series (n=140) the FIGO stage was the only independent and significant (P=0.0006) predictive factor with an odds ratio of 6.4 (95% CI: 2.2-18.9) for stage II versus IA-C. Age, tumor grade and type of adjuvant chemotherapy (+/- taxane) were not significant predictive factors. In the present study, although based on a limited number of patients, we could not find any improvement in recurrence rate or recurrence-free survival for patients treated with a carboplatin-taxane combination regimen compared with patients treated with carboplatin monotherapy. The spectrum of side effects was also in favor of the monotherapy regimen. Further, larger randomized studies are needed to give a final and fully conclusive answer to this question.

Response to Dr. Markman's letter “Re: ‘Randomized phase III trial of three versus six cycles of carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: A Gynecologic Oncology Group Study’”

Response to Dr. Markman's letter “Re: ‘Randomized phase III trial of three versus six cycles of carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: A Gynecologic Oncology Group Study’”

Occult metastasis in early ovarian cancers: risk factors and associated prognosis

The purpose of this study was to define risk factors associated with the occult metastasis in early stage epithelial ovarian carcinoma (EOC), and to compare the survivals in respect to occult metastasis. A retrospective review of 169 patients with clinically early stage EOC was performed. Overall, 53 patients (53/169, 31.4%) were upstaged. The most common occult metastasis was the lymphatic involvement (22/53; 41.5%). Overall, 64.1% (34/53) of these upstaged patients had unrecognized disease in the upper abdomen or retroperitoneal space. Multivariable analysis revealed 3 factors to be associated with occult metastasis: Ca-125 levels > or = 500 U/mL (P = .04), positive peritoneal cytology (P = .001), and grade III disease (P = .04). Five-year survival rates were 61.83% and 88.25%, respectively, in patients with or without occult metastasis. Among the upstaged patients, omental or peritoneal metastasis revealed the worst prognosis. Proper surgical staging is an important issue in early stage ovarian cancers, particularly in patients with high Ca-125 levels, positive cytology, and high grade tumor.

Survival and prognostic factors in early-stage epithelial ovarian carcinoma treated with taxane-based adjuvant chemotherapy

The present study was undertaken with the question about the outcome (recurrence-free survival, [RFS]) after adjuvant chemotherapy with taxane and carboplatin in the early stages of epithelial ovarian cancer after primary surgery. Treatment-related toxicity was also evaluated. A total of 113 patients were included in this study. The 5-year RFS rate for all 113 patients treated with adjuvant chemotherapy including taxane and carboplatin after primary surgery was 79%. The 5-year RFS rate for 85 patients in FIGO stage I was 85% and for 18 patients in FIGO stage II, it was 44%. For clear-cell carcinomas, the RFS was 87%. In univariate analysis, recurrent disease was associated with both FIGO stage and tumor grade, but in multivariate logistic regression analysis of prognostic factors for tumor recurrences, only FIGO stage (stage I versus stage II) was a significant and independent prognostic factor. However, an odds ratio (OR) of 1.9 for tumor grade (grade 3 versus grades 1-2) demonstrated two times increased risk for recurrence in a patient with a grade 3 tumor compared with grade 1-2 tumors. Furthermore, an OR of 0.39 for lymph node sampling versus no sampling meant 61% reduced risk for recurrence for a patient who had undergone lymph node sampling at surgical staging laparotomy. The major toxicities in the present study were myelosuppression (46%) and neurotoxicity (34%). Despite the use of prophylaxis, severe paclitaxel-related hypersensitivity occurred in three patients (3%).