The impact of lymphadenectomy on survival outcomes of ovarian clear cell carcinoma: a systematic review and meta-analysis

Background: The treatment strategies for ovarian clear cell carcinoma (OCCC) are the same as those for epithelial ovarian cancer. Due to the rarity of OCCC, no prospective studies of its surgery have been reported. Therefore, the therapeutic significance of lymphadenectomy for OCCC needs to be further clarified. Objectives: To assess the effectiveness of lymphadenectomy in patients with ovarian clear cell carcinoma by a meta-analysis. Search Strategy: The Web of Science, Scopus, PubMed, and other sources (e.g. Google Scholar) were searched from each database’s earliest inception to June 2021. Selection Criteria: English-language publications of observational studies that investigated the role of lymphadenectomy in patients with OCCC were included. Data Collection and Analysis: The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated. Main Results: The analysis demonstrated that lymphadenectomy is associated with significantly improved disease-specific survival (DSS) (HR=0.76; 95%CI=0.60-0.95; P=0.02; I2= 0.0%) and disease-free survival (DFS) (HR=0.58; 95%CI=0.33-1.00; P=0.05; I2=61%), but not for overall survival (OS) (HR=0.80; 95%CI=0.60-1.06; P=0.12; I2= 19%) and progression-free survival (PFS) (HR=0.95; 95%CI=0.64-1.42; P=0.79; I2= 0.0%). But it is worth noting that several single studies indicated a tendency of improved OS, PFS, DFS, DSS with lymphadenectomy. Conclusions: Lymphadenectomy could not significantly improve OS and PFS for OCCC, but is associated with improved DFS and DSS. Gynecologic oncologists should tailor treatment to patients to achieve optimal outcomes. And further studies are necessary to validate the impact of lymphadenectomy on OCCC. Keywords: ovarian clear cell carcinoma, lymphadenectomy, survival, systematic review, meta- analysis

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Outcomes in patients with early stage uterine clear cell carcinoma treated with chemotherapy and radiotherapy: A systematic review and meta-analysis

10.21203/rs.2.20417/v1 ◽

2020 ◽

Author(s):

Xia Yin ◽

Jie Cheng ◽

Yi Zhang ◽

Chee Wai Chua ◽

Cheng Zhou ◽

...

Keyword(s):

Systematic Review ◽

Cell Carcinoma ◽

Odds Ratio ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Early Stage ◽

Meta Analysis ◽

Treatment Strategies ◽

Progression Free Survival ◽

Uterine Clear Cell Carcinoma

Abstract Background : Uterine clear cell carcinoma (UCCC) is a rare histological type of endometrial cancer with poor prognosis and high risk of tumor relapse. Although adjuvant chemotherapy (CT) and/or radiotherapy (RT) are often recommended for early stage UCCC patients, the effectiveness of these treatment strategies remains unclear. Methods : Systematic review and meta-analysis were applied to evaluate treatment-related outcomes of stage I-II UCCC patients. Search strategy was applied using electronic databases until June 1st, 2019. Inclusion criteria were retrospective, observational and prospective studies that reported outcome of UCCC patients receiving adjuvant therapy. Clinical endpoints like overall survival (OS) and progression-free survival (PFS) were evaluated. Data were extracted by two independent reviewers and a meta-analysis was performed. Results : 13 articles with a total of 3967 patients were analyzed. Overall, adjuvant CT after surgery could improve 5 year-OS significantly compared to patients without CT (odds ratio 0.75, 95% confidence interval [CI] 0.58-0.96; p=0.02). In comparison, RT could also improve OS in UCCC patients of early stage (odds ratio 0.58, 95% CI 0.44-0.77; p=0.0002) compared to the patients without RT, especially in US and Europe patients. Lastly, when comparing the patients undergoing both CT and RT with those receiving CT or RT alone, no further improvement in OS was observed (odds ratio 1.12, 95% CI 0.63-1.99; P=0.70). Conclusions : Either CT or RT after surgery could improve the OS of early stage of UCCC patients. However, combinatorial CT and RT treatment did not improve the OS compared with CT or RT treatment alone.

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Outcomes in patients with early stage uterine clear cell carcinoma treated with chemotherapy and radiotherapy: A systematic review and meta-analysis

10.21203/rs.2.20417/v3 ◽

2020 ◽

Author(s):

Jie Cheng ◽

Guanglei Zhuang ◽

Cheng Zhou ◽

Chee Wai Chua ◽

Yi Zhang ◽

...

Keyword(s):

Systematic Review ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Early Stage ◽

Meta Analysis ◽

Treatment Strategies ◽

Progression Free Survival ◽

Clinical Endpoints ◽

Uterine Clear Cell Carcinoma

Abstract Background: Uterine clear cell carcinoma (UCCC) is a rare histological type of endometrial cancer with poor prognosis and high risk of tumor relapse. Although adjuvant chemotherapy (CT) and/or radiotherapy (RT) are often recommended for early stage UCCC patients, the effectiveness of these treatment strategies remains unclear. Methods: Systematic review and meta-analysis were applied to evaluate treatment-related outcomes of stage I-II UCCC patients. Search strategy was applied using electronic databases until June 1st, 2019. Inclusion criteria were retrospective, observational and prospective studies that reported outcome of UCCC patients receiving adjuvant therapy. Clinical endpoints like overall survival (OS) and progression-free survival (PFS) were evaluated. Data were extracted by two independent reviewers and a meta-analysis was performed. Results: 12 articles with a total of 3845 patients were analyzed. Overall, adjuvant CT after surgery could improve 5 year-OS significantly compared to patients without CT (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.58-0.95; p=0.02). In comparison, RT could also improve OS in UCCC patients of early stage (OR: 0.61, 95% CI: 0.46-0.82; p=0.001) compared to the patients without RT, in US and Europe patients. Lastly, when comparing the patients undergoing both CT and RT with those receiving CT or RT alone, no further improvement in OS was observed (OR: 0.95, 95% CI: 0.53-1.72; P=0.88). Conclusions: Either CT or RT after surgery could improve the OS of early stage of UCCC patients. However, combinatorial CT and RT treatment did not improve the OS compared with CT or RT treatment alone.

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Outcomes in patients with early stage uterine clear cell carcinoma treated with chemotherapy and radiotherapy: A systematic review and meta-analysis

10.21203/rs.2.20417/v2 ◽

2020 ◽

Author(s):

Jie Cheng ◽

Guanglei Zhuang ◽

Cheng Zhou ◽

Chee Wai Chua ◽

Yi Zhang ◽

...

Keyword(s):

Systematic Review ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Early Stage ◽

Meta Analysis ◽

Treatment Strategies ◽

Progression Free Survival ◽

Clinical Endpoints ◽

Uterine Clear Cell Carcinoma

Abstract Background : Uterine clear cell carcinoma (UCCC) is a rare histological type of endometrial cancer with poor prognosis and high risk of tumor relapse. Although adjuvant chemotherapy (CT) and/or radiotherapy (RT) are often recommended for early stage UCCC patients, the effectiveness of these treatment strategies remains unclear. Methods : Systematic review and meta-analysis were applied to evaluate treatment-related outcomes of stage I-II UCCC patients. Search strategy was applied using electronic databases until June 1st, 2019. Inclusion criteria were retrospective, observational and prospective studies that reported outcome of UCCC patients receiving adjuvant therapy. Clinical endpoints like overall survival (OS) and progression-free survival (PFS) were evaluated. Data were extracted by two independent reviewers and a meta-analysis was performed. Results : 12 articles with a total of 3845 patients were analyzed. Overall, adjuvant CT after surgery could improve 5 year-OS significantly compared to patients without CT (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.58-0.95; p=0.02). In comparison, RT could also improve OS in UCCC patients of early stage (OR: 0.61, 95% CI: 0.46-0.82; p=0.001) compared to the patients without RT, in US and Europe patients. Lastly, when comparing the patients undergoing both CT and RT with those receiving CT or RT alone, no further improvement in OS was observed (OR: 0.95, 95% CI: 0.53-1.72; P=0.88). Conclusions : Either CT or RT after surgery could improve the OS of early stage of UCCC patients. However, combinatorial CT and RT treatment did not improve the OS compared with CT or RT treatment alone.

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A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician’s choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA)

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001604 ◽

2020 ◽

Vol 30 (8) ◽

pp. 1239-1242

Author(s):

Natalie YL Ngoi ◽

Valerie Heong ◽

Samuel Ow ◽

Wen Yee Chay ◽

Hee Seung Kim ◽

...

Keyword(s):

Sample Size ◽

Cell Carcinoma ◽

Disease Progression ◽

Immune Checkpoint ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Progression Free Survival ◽

Oncology Group ◽

Ovarian Clear Cell Carcinoma ◽

Free Survival

BackgroundThe optimal treatment of recurrent ovarian clear cell carcinoma remains unknown. There is increasing rationale to support the role of immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in ovarian clear cell carcinoma.Primary objectiveTo evaluate the efficacy of durvalumab (MEDI-4736) compared with standard chemotherapy in patients with recurrent ovarian clear cell carcinoma.Study hypothesisPatients with recurrent ovarian clear cell carcinoma treated with durvalumab will have improved progression-free survival compared with those treated with chemotherapy of physician’s choice.Trial designThe MOCCA study is a multicenter, open-label, randomized phase II trial in patients with recurrent ovarian clear cell carcinoma, which recruited from eight sites across Gynecologic Cancer Group Singapore (GCGS), Korean Gynecologic-Oncology Group (KGOG), and Australia New Zealand Gynecological Oncology Group (ANZGOG). Enrolled patients were randomized in a 2:1 ratio to receive durvalumab or physician’s choice of chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent.Major inclusion/exclusion criteriaEligible patients required histologically documented diagnosis of recurrent ovarian clear cell carcinoma, as evidenced by WT1 negativity. All patients must have been of Eastern Cooperative Oncology Group (ECOG) performance status 2 or better, and have had previous treatment with, and progressed or recurred after prior platinum-based chemotherapy. No more than four prior lines of treatment were allowed and prior immune checkpoint inhibitor treatment was not permitted.Primary endpointsThe primary endpoint was the median progression-free survival following treatment with durvalumab, compared with physician’s choice of chemotherapy. Progression-free survival was defined as the time from the first day of treatment to the first observation of disease progression, or death due to any cause, or last follow-up.Sample sizeThe target sample size was 46 patients.Estimated dates for completing accrual and presenting resultsAccrual has been completed and results are expected to be presented by mid-2021.Trial registrationClinicaltrials.gov: NCT03405454.

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Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: A meta-analysis

Gynecologic Oncology ◽

10.1016/j.ygyno.2011.05.009 ◽

2011 ◽

Vol 122 (3) ◽

pp. 541-547 ◽

Cited By ~ 54

Author(s):

Yoo-Young Lee ◽

Tae-Joong Kim ◽

Min-Ji Kim ◽

Ha-Jeong Kim ◽

Taejong Song ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Meta Analysis ◽

Ovarian Clear Cell Carcinoma ◽

Histological Subtypes

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Adjuvant Chemotherapy for Stage I Ovarian Clear Cell Carcinoma: Is it Necessary for Stage IA?

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31825c7cbe ◽

2012 ◽

Vol 22 (7) ◽

pp. 1143-1149 ◽

Cited By ~ 17

Author(s):

Mika Mizuno ◽

Hiroaki Kajiyama ◽

Kiyosumi Shibata ◽

Kimio Mizuno ◽

Osamu Yamamuro ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Stage I ◽

Surgical Staging ◽

Recurrence Free Survival ◽

Ovarian Clear Cell Carcinoma ◽

Free Survival ◽

Stage Ia

BackgroundIt is controversial whether patients with stage I ovarian clear cell carcinoma (CCC) benefit from postoperative chemotherapy. This study was designed to evaluate the postoperative outcomes associated with the inclusion or exclusion of adjuvant therapy in these patients.MethodsA total of 185 patients who were treated for stage I CCC between 1991 and 2007 were retrospectively evaluated. All of the patients had received comprehensive surgical staging, and their condition had been diagnosed by a central pathological review system. Only one patient with stage IB was excluded from this study.ResultsMedian follow-up time was 62 months (range 7–191 months). Median age was 52 years (30–75 years). There were 41, 93, and 50 patients in stage IA, intraoperative capsule ruptured IC (rupture-IC), and all other-IC groups, respectively. The 5-year recurrence-free survival rates for the substage were 97.6%, 87.8%, and 70.4% (P < 0.001), respectively. Among 134 patients consisting of those in the stage IA and rupture-IC groups, 91 patients received adjuvant chemotherapy (AC) and 43 patients did not (non-AC). There was no significant survival difference in each substage group between the non-AC and AC groups in 5-year recurrence-free survival rate (stage IA, 100% vs 93.8%; rupture-IC, 94.1% vs 86.6%). Multivariate analysis demonstrated that there was no significant prognostic factor for both recurrence and survival among the IA and rupture-IC groups. Postoperative therapy, regimen, and chemotherapy cycles were not significantly affected.ConclusionsThis study indicates that adjuvant chemotherapy does not contribute to the improving prognosis of stage IA ovarian CCC. Whereas the histological type is CCC, the routine adjuvant chemotherapy after comprehensive surgical staging may be unnecessary for patients with at least stage IA.

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Fertility sparing surgery for patients with FIGO stage I clear cell ovarian carcinoma: a database analysis and systematic review of the literature

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001716 ◽

2020 ◽

Vol 30 (9) ◽

pp. 1372-1377 ◽

Cited By ~ 1

Author(s):

Dimitrios Nasioudis ◽

Lakeisha Mulugeta-Gordon ◽

Erin McMinn ◽

Melissa K Frey ◽

Eloise Chapman-Davis ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Cell Carcinoma ◽

Clear Cell ◽

Radical Surgery ◽

Clear Cell Carcinoma ◽

Stage I ◽

Ovarian Clear Cell Carcinoma ◽

Fertility Sparing Surgery ◽

Fertility Sparing

ObjectiveFertility sparing surgery for patients with early stage ovarian clear cell carcinoma is controversial. We aimed to investigate the impact of fertility sparing surgery on the oncologic outcomes of young patients with stage I ovarian clear cell carcinoma.MethodsThe National Cancer Database was accessed and patients with pathological stage IA or IC ovarian clear cell carcinoma, aged <45 years, were selected. Based on site specific surgery codes, patients who underwent fertility sparing or radical surgery were identified. Overall survival was evaluated following generation of Kaplan–Meier curves, and compared with the log rank test. Multivariate Cox analysis was performed to control for possible confounders. A systematic review of literature of the Pubmed, EMBASE and Web of Science databases was also performed to summarize all reported cases.ResultsA total of 57 (35.8%) and 102 (64.2%) patients underwent fertility sparing and radical surgery. There was no difference in overall survival between patients who had fertility sparing and radical surgery (p=0.92); 5 year overall survival rates were 89% and 87.9%, respectively. After controlling for the performance of lymphadenectomy and disease substage, fertility sparing surgery was not associated with worse survival (hazard ratio 0.83, 95% confidence interval 0.30 to 2.32). A systematic review of the literature identified 132 patients with stage I disease who underwent fertility sparing surgery; a total of 20 patients (15.2%) experienced a relapse at a median of 18 months from surgery.ConclusionsIn a large cohort of young patients with stage I ovarian clear cell carcinoma, fertility sparing surgery was not associated with worse survival.

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The impact of systematic retroperitoneal lymphadenectomy on long-term oncologic outcome of women with advanced ovarian clear-cell carcinoma

Journal of Gynecologic Oncology ◽

10.3802/jgo.2020.31.e47 ◽

2020 ◽

Vol 31 (4) ◽

Cited By ~ 2

Author(s):

Hiroaki Kajiyama ◽

Shiro Suzuki ◽

Nobuhisa Yoshikawa ◽

Satoshi Tamauchi ◽

Kiyosumi Shibata ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Oncologic Outcome ◽

Ovarian Clear Cell Carcinoma ◽

Retroperitoneal Lymphadenectomy ◽

The Impact

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Vasohibin-1 is a new predictor of disease-free survival in operated patients with renal cell carcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2013-201444 ◽

2013 ◽

Vol 66 (7) ◽

pp. 613-619 ◽

Cited By ~ 17

Author(s):

Naoki Kanomata ◽

Yasufumi Sato ◽

Yoshiyuki Miyaji ◽

Atsushi Nagai ◽

Takuya Moriya

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Disease Free Survival ◽

Vegf Receptor ◽

Clinicopathological Factors ◽

Free Survival ◽

Disease Free

BackgroundVasohibin-1 (VASH1) is an endothelium-produced angiogenesis inhibitor. Renal cell carcinoma is highly vascularised, but the significance of endogenous VASH1 in renal cell carcinoma has not been defined.AimsTo identify VASH1 expression and its possible relationship with various clinicopathological factors and prognosis in renal cell carcinoma.MethodsA retrospective analysis of 122 tumours obtained from 118 consecutive patients with renal cell carcinoma was performed. The expression patterns of VASH1, CD31, vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2) were examined immunohistochemically and their relationships with clinicopathological factors were analysed.ResultsMicrovessel density, VASH1 and VEGFR2 expression were significantly higher in clear cell carcinoma than in other subtypes. The VEGF expression pattern differed significantly between clear cell carcinoma and other histological subtypes. VASH1, pT factor and TNM stage were significantly associated with disease-free survival (p=0.030, p = 0.0012 and p = 0.0018, respectively). Cox models of multivariable disease-free survival analyses indicated that VASH1 and stage are independent prognostic factors (p=0.019 and p = 0.024).ConclusionsVASH1 expression may be useful for estimating the prognosis of renal cell carcinoma. Further studies of the role of VASH1 in renal cell carcinoma involving larger sample sizes are warranted.

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