paywalled: Postrecurrent Oncologic Outcome of Patients With Ovarian Clear Cell Carcinoma

Postrecurrent Oncologic Outcome of Patients With Ovarian Cle... : International Journal of Gynecological Cancer

Abstract

Objectives: 

To estimate the long-term clinical outcome of patients with recurrent clear cell carcinoma (RCCC) of the ovary in comparison with those with recurrent serous adenocarcinoma (RSAC).

Conclusions: The long-term clinical outcome of patients with RCCC was extremely poor. We confirmed that RCCC (recurrent clear cell carcinoma) should be investigated as a different malignancy compared with RSAC.

Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma.

 Blogger's Note: varying studies show different %'s of ARID1A gene expression in clear cell ovarian cancer
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Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma.:

Mod Pathol. 2012 Feb;25(2):282-8

Abstract
Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The current study was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma.

Functional profiling of clear cell ovarian cancer. | 2012 ASCO Annual Meeting Abstracts

Functional profiling of clear cell ovarian cancer. | 2012 ASCO Annual Meeting Abstracts

Abstract:
Background: Clear cell ovarian cancer represents up to 15% of epithelial ovarian cancers. In comparison to other subtypes, clear cell ovarian carcinomas have a poorer prognosis and are relatively resistant to standard platinum based chemotherapy. Recently, loss of function mutations in the tumour suppressor gene ARID1A were identified in up to 50% of ovarian clear cell carcinomas. We have adopted an integral functional and molecular profiling approach as a route to identify new genetic dependencies and therapeutic targets for this disease.

Methods: Clear cell ovarian cancer cell lines were functionally profiled using high throughput screening with chemical and siRNA libraries. This has been integrated with molecular profiling data generated from exome and transcriptome sequencing to aid the discovery of novel targets.

Results: Using functional screens we have now identified critical gene dependencies and potential therapeutics in a series of clear cell ovarian cancer models. The comparison of functional viability profiles for models characterized by ARID1A loss of function mutations is now enabling an analysis of synthetic lethal effects that could be used to target clear cell ovarian cancers carrying these mutations.  

Conclusions: The work undertaken so far provides the framework for the discovery of therapeutic targets for clear cell ovarian cancer using an integrated approach. Revalidation of these preliminary results is now underway to characterize new genetic dependencies for this disease.

JCO search: "clear cell ovarian"

Blogger's Note: these search results are not entirely specific but date back to 1987

 JCO - Searching journal content for clear cell ovarian (all words) in title or abstract.

Displaying results 1-60 of 93

abstract: Low-Stage Ovarian Clear Cell Carcinoma: Population-Based Outcomes in British Columbia, Canada, With Evidence for a Survival Benefit As a Result of Irradiation

Low-Stage Ovarian Clear Cell Carcinoma: Population-Based Outcomes in British Columbia, Canada, With Evidence for a Survival Benefit As a Result of Irradiation

 Abstract

Purpose 

To evaluate the population-based outcomes of stage I and II ovarian clear cell carcinoma (OCCC) in a North American population treated with carboplatin/paclitaxel and abdominopelvic irradiation.

Patients and Methods 

Retrospective analysis was performed of 241 patients referred in the carboplatin/paclitaxel era. Irradiation was to be used with a few defined exceptions. However, because of differing beliefs as to its effectiveness, its use was consistently avoided by specific oncologists, allowing the opportunity to study its possible effect on disease-free survival (DFS) in these concurrent cohorts. 

Results 

Five- and 10-year DFS rates were 84% and 70% for stage IA/B; 67% and 57% for stage IC; and 49% and 44% for stage II, respectively. 

Five- and 10-year DFS rates for those with stage IC disease based purely on rupture were similar to rates for patients with stage IA/B, at 92% and 71%, respectively. 

The remaining patients with stage IC had 48% 5- and 10-year DFS. 

 Multivariate analysis using a decision tree identified positive cytology as the most important factor (72% relapse rate if positive and 27% if negative or unknown). 

If, in addition, the capsule surface was involved, then the relapse rate was 93%. Irradiation had no discernible survival benefit for patients with stage IA and IC (rupture alone), whereas for the remainder of patients with stage IC and stage II, it improved DFS by 20% at 5 years (relative risk, 0.5); the benefit was most evident in the cytologically negative/unknown group. 

Conclusion 

DFS is similar in this North American population with early OCCC to the DFS reported in Asia. A potential benefit from irradiation was evident in a subset.

abstract: Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: A population-based study from 1983 to 2007

 Blogger's Views:
there are a number of interesting subjects here - Japan appears historically to have a higher rate of clear cell than other nations; Japan has also studied clear cell ovarian cancer more extensively than elsewhere (for obvious reasons); increasing incidence rates observed in the Japanese population seems to be contrary to other nation's research (eg. stable/declining incidence rates) however the key is in the data compliation (eg. exclusion of LMP; peritoneal cancers), it can be noted however that there has been reported in the North America's that ovarian cancer rates have been increasing but for some unknown (or unpopular?) reason less is known about the reasons for these discrepancies; past blogs have been posted about increasing incident rates; it is unfortunate that this paper is not open access

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Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: A population-based study from 1983 to 2007 in Niigata:

Abstract

Aim: 
The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan.

Material and Methods: 
Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007.

Results: 
A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid adenocarcinoma showed a steady increasing trend, and those of clear cell and mucinous adenocarcinomas showed significant increasing trends in the total population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in the 50+ age group were significantly increased, especially the incidence of clear cell adenocarcinoma, which strikingly increased by approximately threefold from 1.2 (1983–1989) to 3.5 (2000–2007) per 100 000 females.

Conclusion: 
This prefecture-wide study showed the practical trends in ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan.

abstract: Weekly administration of temsirolimus for heavily pretreated patients with clear cell carcinoma of the ovary: a report of six cases.

"...Among five cases in which responses could be evaluated, partial response was observed in one case (20%) and stabilized disease was seen in another case (20%). There were no toxicities greater than grade 3, and no case developed severe toxicity requiring discontinuation of weekly TEM. The patient who showed a partial response obtained a progression-free period of 14 months. In conclusion, weekly TEM shows a potential therapeutic benefit for patients with CCC of the ovary. Further studies including a translational approach are needed to select candidates for whom TEM therapy would be beneficial."

ASCO 2011 abstract: A North American population-based outcome for early-stage ovarian clear cell (stages 1-11) carcinoma (OCCC). - ASCO 2011 (including w/wo irradiation)

Abstract:

Background: OCCC is regarded as having a poor outcome and being relatively treatment resistant. Recent Japanese data instead have demonstrated high survival in early stage and radiation sensitivity. This study was carried out to reproduce/refute these findings in a North American setting.

Methods: Women with OCCC who had attended one of the four British Columbia Cancer Agency (BCCA) centers have staging, pathological, treatment, and outcome data recorded in a computerized database. Irradiation (XRT) plus platin-based chemotherapy was the standard treatment. XRT usage mandated all such women provincially attending a BCCA centre. However, individual physicians within BCCA differed in their uptake of XRT. Outcomes with or without XRT could be compared. Univariate and multivariate (decision-tree analysis) analyses for disease-free survival (DFS) were performed.

Results: 241 Stage I-II women attended between January 2000 and December 2008 (IA/IB n=64; Ic n=147; II n=30). 5 year and 10 year DFS for stage IA/B; IC and II were 85 and 70%; 64 and 58%; and 43 and 43% respectively. IC subsets faired differently: rupture alone (spontaneous and surgical were equivalent) - 5 yr DFS 80% versus 34% if cytologically positive and 43% with surface involvement. Decision-tree analysis identified cytologic positivity as the most important factor (recurrence 27% if negative, 72% if positive). Surface involvement then further subdivided the cytologically positive: surface involved 93% recurrence, if not involved 60%. XRT had no effect in stage IA (85% DFS at 5 yrs with or without it) but was superior to chemotherapy alone in IC (5 yr DFS 68% vs 58%, 10 yr DFS 63% vs 52%, HR 0.59).
Conclusions: Stage IA OCCC has an excellent long-term outcome as does IC (rupture only). IC otherwise has a poor outcome as does stage II. XRT and chemotherapy improves outcome in stage IC versus chemotherapy alone.

abstract: Genomic Analysis Reveals the Molecular Heterogeneity of Ovarian Clear Cell Carcinomas

CONCLUSIONS:  
OCCCs constitute a heterogeneous disease at the genomic level despite having similar histological features. The pattern of genomic aberrations in subgroups of OCCCs is of clinical significance.