The occurrence of endometriosis with ovarian carcinomas is not purely coincidental

Objective

To explore the association between epithelial ovarian cancer (EOC) and common benign gynecological disorders.

Study design

The medical records of 226 patients with EOC treated at Peking Union Medical College Hospital between March 2011 and March 2012 were reviewed. Histological evaluations had been performed to determine the presence of coexisting pelvic endometriosis (n = 17), uterine leiomyoma (n = 66), adenomyosis (n = 22), or endometrial polyps (n = 17).

Results

Coexistence of endometriosis occurred in 35.3% and 36.4% of cases of the clear cell and endometrioid subtypes of EOC histology, respectively. Endometriosis was more likely associated with clear cell or endometrioid ovarian carcinoma, but less likely with high grade serous cancer. No differences were observed in the concurrence of uterine myoma, adenomyosis or endometrial polyps among the different subtypes of EOC.

Conclusions

In contrast to other common benign gynecological disorders, endometriosis showed close relationships with the clear cell and endometrioid subtypes of EOC specifically.     

Comparison of clinical outcomes of patients with clear cell and endometrioid ovarian cancer associated with endometriosis to papillary serous carcinoma of the ovary

Objective

The aim of this investigation was to compare outcomes of patients with clear cell carcinoma (CCC) and endometrioid carcinoma (EC) of the ovary associated with endometriosis to patients with ovarian papillary serous carcinoma (PSC).

Methods

Patients with CCC and EC of the ovary associated with endometriosis were identified and matched by age and stage to PSC controls. Student's t test and chi square test were used to analyze continuous and categorical data. The Kaplan–Meier method was used for survival analysis.

Results

67 cases associated with endometriosis were identified, of which 45 were arising in endometriosis. Cases were matched to 134 PSC controls. 27 patients with tumors associated with endometriosis presented at stage I (40.3%), 27 at stage II (40.3%), ten at stage III (14.9%) and three at stage IV (4.5%). There was no difference in rate of optimal cytoreduction or response to chemotherapy in cases vs. PSC controls. There was a significant increase in synchronous endometrial cancer in tumors associated with endometriosis compared to PSC (25.4% vs. 3.7%; P < 0.001). 18 cases (26.9%) had recurrent disease vs. 55 (41%) controls (P = 0.03). The 5-year disease-free survival (DFS) and overall survival (OS) of patients with tumors associated with endometriosis compared to PSC controls were 75% vs. 55% (P = 0.03) and 85% vs. 77% (P = 0.2), respectively.

Conclusions

Patients with tumors associated with endometriosis had a higher rate of synchronous endometrial cancer. Cases also demonstrated a lower rate of recurrence and improved 5 year DFS; however, this did not translate into a difference in OS.     

Lynch Syndrome in patients with clear cell and endometrioid cancers of the ovary

Objective

Patients with Lynch Syndrome are at an increased risk for a variety of malignancies, including ovarian cancer. Ovarian cancers associated with Lynch Syndrome are predominantly clear cell or endometrioid in histology. Lynch Syndrome is characterized by germline mutations in mismatch repair (MMR) genes. The current study aims to assess the prevalence of loss of MMR expression in patients with endometrioid and clear cell ovarian carcinoma.

Methods

A retrospective review identified 90 patients with endometrioid and/or clear cell carcinomas. Slides made from tumor tissue microarray blocks were evaluated using immunohistochemical stains with antibodies against MLH1, PMS2, MSH2, and MSH6. Statistical analysis was performed.

Results

Seven of the 90 cases (7.8%) had loss of MMR expression. The mean age of patients with loss of MMR expression (47 years) was significantly younger than those with retained MMR expression (p = 0.014). Loss of MMR expression was present in 20% of patients under the age of 53 with clear cell or endometrioid cancers. Genetic studies found that 3 of the 5 patients with loss of MMR expression carried mutations consistent with Lynch Syndrome; acquired hypermethylation of MLH1 was noted in one patient. Six of 7 patients (86%) whose tumors lacked MMR expression had synchronous or metachronous primary malignancies, a significantly greater prevalence than those with retained MMR expression (p < 0.001).

Conclusion

Patients under the age of 53 with clear cell or endometrioid ovarian carcinomas are at a clinically significant risk for loss of MMR expression and Lynch Syndrome; routine screening with immunohistochemical staining should be considered.     

Prognostic analysis for Chinese patients with stage I ovarian endometrioid carcinoma

Background

This study aimed to identify the clinical and pathological characteristics and the possible prognostic factors for Chinese patients with early-stage ovarian endometrioid carcinoma.

Methods

The present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of ovarian endometrioid carcinoma at our center. In all, 78 patients had stage I ovarian endometrioid carcinoma.

Results

In this series, the 5-year overall survival rate and 5-year disease-free survival (DFS) rates of patients with stage I ovarian endometrioid carcinoma was 98.7% and 87.2%, respectively. Univariate analysis showed the factors that influence the DFS rates include menopausal status, FIGO stage, histological grade, lymphadenectomy, cytology of ascites. Multivariate analysis showed that grade 3 and lymphadenectomy were the independent prognostic factors of DFS for Stage I ovarian endometrioid carcinoma (P = 0.0259, 0.0276 respectively). However, the coexisting endometriosis, concomitant endometrial disorders, dissection of para-aortic lymph node and more courses of thermotherapy had no influence on DFS. Besides, it was found that 19.3% of patients in this series had synchronous early stage and well-to-moderate differentiated endometrial carcinoma.

Conclusions

Grade 3 and lymphadenectomy were indicated as the independent factors of DFS for stage I patients with ovarian endometrioid carcinoma. The endometrial changes should be considered seriously when fertility-sparing surgery was planned.

     

Characteristics of clear cell ovarian cancer arising from endometriosis: A two center cohort study

Objective

Endometrioid and clear cell ovarian tumors have been referred to as “endometriosis associated ovarian cancers”. However, very few studies have compared clinical and prognostic features of endometriosis-associated cancers or cancers not associated with endometriosis according to specific histotypes. We have investigated clinical and histological features of the largest published series of clear cell ovarian cancers arising in endometriosis using a retrospective database.

Methods

Seventy three patients with a primary diagnosis of either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer have been divided into two groups according to the detection of cancer strictly arising from ovarian endometriosis or not (n = 27 and n = 46, respectively). Clinical and pathological data have been compared.

Results

Patients with clear cell carcinomas arising from endometriosis tend to be significantly younger (51.4 ± 10.0 and 58.4 ± 11.2 years, p = 0.02). FIGO stage, laterality, prevalence of pure versus mixed histology, and presence of synchronous endometrial carcinoma were not significantly different between the two groups. Unilateral ovarian involvement was more frequent in cases arising in endometriosis (85% vs 63%, p = 0.04). Ascites was not found in any of the endometriosis-associated cancer cases vs 19.5% in patients without endometriosis. The presence of endometriosis did not affect 5-year overall survival rates.

Conclusions

Endometriosis per se does not appear to be associated with a lower stage tumor or to predict prognosis in ovarian clear cell cancers. Unilateral involvement and reduced presence of ascites may be linked to the cystic nature of endometriosis which frequently presents as monolateral and in which associated tumors are more likely to be longer confined to the ovary before spreading.     

Unraveling the two entities of endometrioid ovarian cancer: a single center clinical experience

Objective

Due to the increasing prevalence of the benign condition, ovarian carcinoma arising from endometriosis is emerging as a relevant clinical entity with an unclear biological signature. We have investigated clinical and histologic features of endometriosis-associated endometrioid ovarian cancer using an institutional retrospective database.

Methods

Patients diagnosed with endometrioid ovarian cancer at our institution were divided into two groups according to the fulfillment or not of Sampson's and Scott's criteria for the detection of endometriosis-associated ovarian cancer. Clinical and histological data were reported and compared. Survival analysis was obtained using the log-rank test in an unadjusted Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model to establish independent factors associated with endometriosis-associated endometrioid ovarian cancer and to identify predictors of survival. The degree of concordance was evaluated by Cohen's Kappa measures.

Results

Patients with endometriosis-associated endometrioid ovarian cancer were significantly younger, had a lower disease stage (62% vs 23%; p = 0.003), a less prevalent high grade tumor (38% vs 82%; p = 0.002) and a higher prevalence of squamous and mucinous metaplasia. The rate of endometrial cancer diagnosis was significantly higher in women with endometriosis-associated endometrioid ovarian cancer (33%) than in other patients (11%) (p = 0.04) with a 92% concordance between ovarian and endometrial histologic tumor grade. A significant difference in survival rate could not be demonstrated between patients with or without endometriosis.

Conclusions

The analysis of a retrospective endometrioid ovarian cancer database may allow to suggest a 40 molecular, morphological and clinical parallelism between endometrial and endometrioid ovarian cancers.     

Venous thromboembolism in ovarian cancer: incidence,risk factors and impact on survival

Objectives

Ovarian cancer has a higher incidence of venous thromboembolism (VTE) than other cancers. Clear cell cancers carry the highest risk at 11–27%. The aim of this study was to identify the predisposing factors for VTE in a population of ovarian cancer patients and to determine the influence of VTE on overall survival.

Study design

VTE events were identified from hospital and general practice/community care records for all patients with ovarian cancer who were diagnosed and treated in a tertiary cancer center between 2006 and 2010.

Results

The overall incidence of VTE was 9.7% (33) in 344 patients. Sixteen (48%) had pulmonary embolism. Six (18%) presented with VTE. Five (15%) had VTE diagnosed during pre-treatment routine CT scanning. Eleven (33%) developed VTE following surgery and eleven (33%) developed VTE during chemotherapy. Risk factors associated with the occurrence of VTE were BMI ≥ 30 (p < 0.01), clear cell carcinoma (p < 0.05), advanced stage (p < 0.01), high grade (p < 0.01) and CA125 > 500 IU/ml (p < 0.001). The occurrence of VTE was associated with decreased overall survival time (p < 0.001).

Conclusion

The incidence of VTE is high in ovarian cancer especially in the clear cell subtype. VTE adversely affects survival in ovarian cancer. Obesity, high grade and stage of cancer, clear cell subtype and high CA 125 level should be incorporated into protocols of VTE prophylaxis in women with ovarian cancer.     

Src as a novel therapeutic target for endometriosis

Background

Endometriosis is a common condition that is associated with an increased risk of developing ovarian carcinoma. Improved in vitro models of this disease are needed to better understand how endometriosis, a benign disease, can undergo neoplastic transformation, and for the development of novel treatment strategies to prevent this progression.

Methods

We describe the generation and in vitro characterization of novel TERT immortalized ovarian endometriosis epithelial cell lines (EEC16-TERT).

Results

Expression of TERT alone was sufficient to immortalize endometriosis epithelial cells. TERT immortalization induces an epithelial-to-mesenchymal transition and perturbation in the expression of genes involved in the development of ovarian cancer. EEC16-TERT was non-tumorigenic when xenografted into immunocompromised mice but grew in anchorage-independent growth assays in an epidermal growth factor and hydrocortisone dependent manner. Colony formation in agar was abolished by inhibition of Src, and the Src pathway was found to be activated in human endometriosis lesions.

Conclusions

This new in vitro model system mimics endometriosis and the early stages of neoplastic transformation in the development of endometriosis associated ovarian cancer. We demonstrate the potential clinical relevance of this model by identifying Src activation as a novel pathway in endometriosis that could be targeted therapeutically, perhaps as a novel strategy to manage endometriosis clinically, or to prevent the development of endometriosis-associated ovarian cancer.     

Prognostic significance of lymphadenectomy and prevalence of lymph node metastasis in clinically-apparent stage I endometrioid and mucinous ovarian carcinoma

Objective

The aim of the present study was to investigate the prevalence of lymph node (LN) metastasis in women with apparent stage I ovarian carcinoma of endometrioid or mucinous histology and to examine the prognostic significance of LN sampling/dissection (LND) on patient survival.

BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer

Objective

Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its often late diagnosis and its chemoresistance. We identified a set of microRNAs whose expression is altered upon BAG3 knockdown. Our primary objective was to examine the relationships between BAG3, miR-29b and Mcl-1, an antiapoptotic Bcl-2 family protein, in ovarian cancer cells.

Methods

Ovarian cancer cells were cultured and their responsiveness to paclitaxel was tested. Microarray analysis was performed to identify microRNAs differentially expressed in ES2 BAG3 knockdown ovarian cancer cells and their control cells. Primary ovarian cancer tissues were obtained from 56 patients operated on for ovarian cancer. The patients' clinical and pathological data were obtained from their medical records.

Results

BAG3 knockdown increased the chemosensitivity to paclitaxel of ES2 ovarian clear cell carcinoma cells to a greater degree than AMOC2 serous adenocarcinoma cells. qRT-PCR analysis showed that miR-29b expression was significantly upregulated in primary cancer tissue expressing low levels of BAG3, as compared to tissue expressing high levels. Moreover, levels of miR-29b correlated significantly with progression-free survival. Upregulation of miR-29b also reduced levels of Mcl-1 and sensitized ES2 cells to low-dose paclitaxel.

Conclusions

BAG3 knockdown appears to downregulate expression of Mcl-1 through upregulation of miR-29b, thereby increasing the chemosensitivity of ovarian clear cell carcinoma cells. This suggests that BAG3 is a key determinant of the responsiveness of ovarian cancer cells, especially clear cell carcinoma, to paclitaxel and that BAG3 may be a useful therapeutic target for the treatment of ovarian cancer.     

Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: A SEER analysis

Objective

The aims of this study are to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from women with high grade papillary serous ovarian carcinoma when compared by stage as well as to identify any associated clinico-pathologic factors.

Methods

The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1998 to 2009 was reviewed to identify women with OCS and high grade papillary serous carcinoma of the ovary. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan–Meier method. Factors predictive of outcome were compared using the Cox proportional hazard model.

Results

The final study group consisted of 14,753 women. 1334 (9.04%) had OCS and 13,419 (90.96%) had high grade papillary serous carcinoma of the ovary. Overall, women with OCS had a worse five-year, disease specific survival rate, 28.2% vs. 38.4% (P < 0.001). This difference persisted for each FIGO disease stages I–IV, with five year survival consistently worse for women with OCS compared with papillary serous carcinoma. Over the entire study period, after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, lymph node dissection, and history of secondary malignancy after the diagnosis of ovarian cancer, carcinosarcoma histology was associated with decreased cancer-specific survival.

Conclusions

OCS is associated with a poor prognosis compared to high grade papillary serous carcinoma of the ovary. This difference was noted across all FIGO stages.     

Clear cell carcinoma of the ovary: a review of the literature

Objective

Different histologic types of epithelial ovarian cancer may represent different diseases with unique clinical and molecular characteristics. Clear cell carcinoma (CCC) of the ovary has been reported as having a worse prognosis than high grade serous epithelial ovarian cancer (EOC). This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with ovarian CCC.

Methods

MEDLINE was searched for all research articles published in English between January 01, 1977 and January 30, 2012 which reported on patients diagnosed with ovarian CCC. Given the rarity of this tumor, studies were not limited by design or number of reported patients.

Results

Ovarian CCC tumors represent 5-25% of ovarian cancers. Its histologic diagnosis can be challenging, resulting often times in misclassification of these tumors. Ovarian CCC tends to present at earlier stages and has been associated with endometriosis, ARID1A and PIK3CA mutations. When compared to stage-matched controls, patients with early-stage ovarian CCCs may have a better prognosis than patients with high-grade serous tumors. For those with advanced stage disease, high-grade serous histology confers a better prognosis than ovarian CCC. Patients with Stage IC-IV have a relatively poor prognosis and efforts should center in discovery of more effective treatment strategies.

Conclusions

Ovarian CCC is a biologically distinct entity, different from high-grade serous EOC. Future studies should explore the role of targeted therapies in the management of ovarian CCC.     

A two-stage,single-arm,phase II study of EGCG-enriched green tea drink as a maintenance therapy in women with advanced stage ovarian cancer

Objectives

A two-stage, single-arm, phase II study was conducted to assess the effectiveness and safety of an epigallocatechin gallate (EGCG)-enriched tea drink, the double-brewed green tea (DBGT), as a maintenance treatment in women with advanced stage serous or endometrioid ovarian cancer (clinicaltrials.gov, NCT00721890).

Methods

Eligible women had FIGO stage III-IV serous or endometrioid ovarian cancer. They had to undergo complete response after debulking surgery followed by 6 to 8 cycles of platinum/taxane chemotherapy at the Centre Hospitalier Universitaire de Québec. They all had to drink the DBGT, 500 mL daily until recurrence or during a follow-up of 18 months. The primary endpoint was the absence of recurrence at 18 months. Statistical analyses were done according to the principle of intention to treat. Using a two-stage design, the first stage consisted of 16 enrolled patients. At the end of the follow-up, if 7 or fewer patients were free of recurrence, the trial stopped. Otherwise, accrual would continue to a total of 46 patients.

Results

During the first stage of the study, only 5 of the 16 women remained free of recurrence 18 months after complete response. Accordingly, the clinical trial was terminated. Women's adherence to DBGT was high (median daily intake during intervention, 98.1%, interquartile range: 89.7–100%), but 6 women discontinued the intervention before the end of their follow-up. No severe toxicity was reported.

Conclusions

DBGT supplementation does not appear to be a promising maintenance intervention in women with advanced stage ovarian cancer after standard treatment.     

Adjuvant radiation in early stage,unfavorable histology endometrial carcinoma is associated with improved local control and survival

Objective

Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer.

Methods

We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival.

Results

The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local–regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local–regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p = 0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p = 0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value = 0.018) was associated with a significant increase in local relapse free survival.

Conclusions

Adjuvant radiation therapy was significantly associated with an improvement in local–regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.     

Mucinous differentiation does not impact stage or risk of recurrence among patients with grade 1, endometrioid type,endometrial carcinoma

Objective

To evaluate whether the presence of mucinous differentiation influences histopathologic findings, stage distribution, or rate of recurrence among women with grade 1, endometrioid type, endometrial carcinoma.

Methods

This was a retrospective cohort study of all patients with grade 1, endometrioid type, endometrial carcinoma between January 2005 and December 2012. Patients were separated by the presence or absence of mucinous differentiation and then compared.

Results

Of 655 patients, mucinous differentiation was present in 137 (20.9%) and absent in 518 (79.1%) patients. Compared to the group without mucinous differentiation, the group containing mucinous differentiation was older at diagnosis (mean: 61.1 vs. 58.5 years, OR, 95% CI; 1.03, 1.01–1.05) and more likely to have myometrial invasion (61.3% vs. 51.5%, OR, 95% CI; 1.49, 1.01–2.19). Additional histopathologic findings including: tumor size, cervical stromal invasion, adnexal involvement, LVI and/or the presence of positive lymph nodes were similar between groups. Mucinous differentiation did not affect stage distribution, as most patients were stage 1A (85.4% vs. 86.3%). The median PFS for the entire group has yet to be reached. The mean PFS for the entire study sample was 94.7 months. There was no difference in mean PFS when comparing the group with mucinous differentiation to the group without mucinous differentiation (98 vs. 93.4 months, p = 0.07).

Conclusions

In the setting of grade 1, endometrioid type, endometrial carcinoma, mucinous differentiation is more common in older patients and is associated with an increased likelihood of myometrial invasion. However, stage distribution and risk of recurrence are not affected.     

Ovarian endometriosis associated with ovarian carcinoma: a clinicopathological and immunohistochemical study

OBJECTIVE: The purpose of this study was to demonstrate the incidence, the histopathological characteristics, and the proliferation activity of endometriosis and atypical endometriosis associated with ovarian carcinoma. METHODS: Microscopic slides of primary lesions from 127 patients with primary ovarian carcinoma were reviewed. The presence or absence of endometriosis and the transitions from typical endometriosis to atypical endometriosis and from atypical endometriosis to carcinoma were also histologically evaluated. Ki-67 immunoreactivity of typical and atypical endometriosis and carcinoma was examined. In addition, endometrial metaplasias were also evaluated. RESULTS: Of the 127 patients, 37 had endometriosis: 70% (30/43) had clear cell adenocarcinoma, 43% (3/7) had endometrioid adenocarcinoma, 7% (4/60) had serous adenocarcinoma, and none (0/17) had mucinous adenocarcinoma. Thirty-three cases showed typical endometriosis and 29 cases had atypical endometriosis (25 cases had both). Tufting and the stratification of the lining epithelium were observed in 25 and 23 cases, respectively. The transition from typical endometriosis to atypical endometriosis was observed in 22 cases, and the transition from atypical endometriosis to carcinoma, in 23 cases. Only one case showed a direct transition from typical endometriosis to carcinoma. The mean Ki-67 indices were as follows: ovarian carcinoma, 23.1; atypical endometriosis, 9.9; typical endometriosis, 2.7. In 18 cases with metaplasia in endometriosis, eosinophilic metaplasia and ciliated metaplasia were the most common types. Five cases had two types of metaplasia. CONCLUSIONS: Ovarian carcinomas, especially clear cell and endometrioid adenocarcinomas, are highly associated with endometriosis. Atypical endometriosis shows proliferation activity intermediate to those of typical endometriosis and ovarian carcinoma, suggesting it is a precancerous status.     

The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations

Objective

This article represents a review of histologic and genetic findings in endometriosis and describes the mechanisms whereby genetic and non-genetic factors potentially contribute to the neoplastic progression of endometriosis.

Methods

Literature review of the English language literature based on searching in the MEDLINE (PubMed) database and additional collection of reports by systematically reviewing all references from retrieved papers.

Results

Atypical endometriosis seems to represent a transition from benign endometriosis to carcinoma. Endometriosis is characterized by genetic instability: like neoplasms endometriosis seems to be monoclonal in origin, several studies have documented loss of heterozygosity (LOH) in endometriosis, data suggest that mutation of the tumor suppressor gene PTEN play a part in the malignant transformation of endometriosis, some studies have revealed TP53 mutations in endometriotic lesions, and mutation of ARID1A seems to be an important early event in the malignant transformation of endometriosis to endometrioid and clear cell carcinomas. Heme and iron induced oxidative stress, inflammation, and hyperestrogenism are possible links between endometriosis and cancer.

Conclusions

The histological and genetic alterations in endometriosis seem to explain why endometriosis can be a precursor of some ovarian cancers, especially clear cell and endometrioid carcinomas. However, the exact molecular mechanisms that may lead to this malignant transformation of endometriosis are not completely understood. More and larger studies are needed to clarify how exactly endometriotic tissue undergoes malignant transformation.     

A phase II study of combination chemotherapy using docetaxel and irinotecan for TC-refractory or TC-resistant ovarian carcinomas (GOGO-OV2 study) and for primary clear or mucinous ovarian carcinomas (GOGO-OV3 Study)

Objective

To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas.

Study design

Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study.

Results

A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable.

Conclusion

Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma.     

Peritoneal cytology: A risk factor of recurrence for non-endometrioid endometrial cancer

Objective

We compared the impact of positive peritoneal cytology on prognosis between patients with endometrioid and non-endometrioid endometrial carcinoma.

Methods

We retrospectively reviewed the medical records of 490 patients diagnosed with endometrial cancer between 2000 and 2012. These patients were divided into two groups: endometrioid and non-endometrioid histologies. We compared the patients' baseline characteristics, tumor recurrence patterns, and survival to determine the prognostic factors and how they differed between the two groups.

Results

Of the included patients, 448 had endometrioid histology and 42 had non-endometrioid histology. A total of 27 patients experienced tumor recurrence: 17 with endometrioid histology (4.0%) and 10 with non-endometrioid histology (23.8%). Compared to endometrioid type, non-endometrioid type exhibited higher rates of recurrence (p < 0.01). Recurrence sites of the non-endometrioid group were mainly peritoneal seeding (p < 0.01) and distant organ metastasis (p = 0.02). Risk factors for tumor recurrence included patient age, stage of disease, and adjuvant treatment for endometrioid type. On the other hand, in cases of non-endometrioid endometrial cancer, positive peritoneal cytology was an independent prognostic factor regardless of tumor stage (HR, 15.34; 95% CI, 3.55–66.25; p < 0.01). Among cases with non-endometrioid histology, median recurrence-free survival significantly differed between the negative peritoneal cytology group and the positive peritoneal cytology group (120 months versus 22 months, respectively; p < 0.01).

Conclusions

Positive peritoneal cytology is an independent prognostic factor for patients with non-endometrioid endometrial cancer.