scholarly journals Complete remission of heavily treated ovarian clear cell carcinoma with ARID1A mutations after pembrolizumab and bevacizumab combination therapy: a case report

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yu-Chien Lin ◽  
Kuo-Chang Wen ◽  
Pi-Lin Sung ◽  
Yu-Ting Chou ◽  
Phui-Ly Liew ◽  
...  
Keyword(s):  
Complete Remission ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Checkpoint Inhibitors ◽  
Genomic Analysis ◽  
Angiogenesis Inhibitors ◽  
Ca 125 ◽  
Ovarian Clear Cell Carcinoma ◽  
Platinum Based Chemotherapy

Abstract Background Patients with ovarian clear cell carcinoma (OCCC) have a poor prognosis because they show low sensitivity to platinum-based chemotherapy. New treatments for refractory OCCC are urgently needed. Case presentation We present a patient with refractory OCCC in whom conventional chemotherapy failed. Cachexia was induced by the disseminating recurrent tumors. Tumor tissue staining and genomic analysis revealed PD-L1 negativity, a low tumor burden, stable microsatellite instability, and two mutations in ARID1A. The patient was administered pembrolizumab combined with bevacizumab triweekly. Her serum CA-125 level decreased dramatically after the first cycle. A computerized tomography scan showed marked regression of the recurrent masses after 3 cycles, and the patient reached complete remission after 9 cycles. She showed good recovery from cachexia. We observed no marked side effects except for mild polyarthritis of the small joints. Conclusions The therapeutic effect of checkpoint inhibitors combined with angiogenesis inhibitors is very promising in our patient with OCCC. Further clinical trials of tumors including ARID1A mutations are warranted.

scholarly journals Serum D-dimer, Albumin and Systemic Inflammatory Response Markers in Ovarian Clear Cell Carcinoma and Their Prognostic Implications

2020 ◽  
Author(s):  
Wei Chen ◽  
Siyuan Zhong ◽  
Boer Shan ◽  
Shuling Zhou ◽  
Xiaohua Wu ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Inflammatory Response ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Systemic Inflammatory Response ◽  
Ca 125 ◽  
Chemotherapy Response ◽  
Ovarian Clear Cell Carcinoma ◽  
D Dimer

Abstract Background: This study attempts to evaluate whether preoperative systemic inflammatory response (SIR) markers or other hematological variables, such as albumin, D-dimer, and carbohydrate antigen 125, play roles in predicting chemotherapy response and survival outcome in patients with ovarian clear cell carcinoma (OCCC).Methods: Preoperative leukocyte differential counts, as well as platelet, serum albumin, plasma D-dimer and CA-125 levels, were measured in patients with FIGO IC-IV ovarian clear cell cancer. The correlations of these hematological biomarkers with clinicopathological features, chemotherapy response, and survival outcomes were further analyzed. Survival time was estimated using the Kaplan-Meier model, whereas Cox regression was conducted for multivariate analysis.Results: Among the 84 patients, 28.6% were classified as platinum resistant, and 69.0% were platinum sensitive. Preoperative CA125, albumin, and D-dimer levels; neutrophil to lymphocyte ratios (NLR); and monocyte to lymphocyte ratios were significantly correlated with FIGO stage, residual tumor, and platinum response. Platelet to lymphocyte ratio was not related to platinum response (P=0.060). The median follow-up time was 28 months (range, 1 to 128 months). Preoperative CA125, albumin, and D-dimer levels were significant prognostic factors for overall survival (OS) and progression-free survival (PFS). In the univariate analysis, only NLR exhibited prognostic significance for PFS (P = 0.007). Multivariate analysis indicated that D-dimer > 3.27 (P = 0.001 for OS; P = 0.040 for PFS) and albumin <39.6 (P = 0.005 for OS and P = 0.041 for PFS) retained significance.Conclusions: Preoperative NLR has some predictive value for platinum resistance in patients with IC-IV stage OCCC but has little predictive effect on prognosis. Elevated D-dimer and reduced albumin might be potential biomarkers for worse response to first-line platinum-based chemotherapy and poor clinical outcomes.

scholarly journals The prognostic value of pretreatment CA-125 levels and CA-125 normalization in ovarian clear cell carcinoma: a two-academic-institute study

Oncotarget ◽  
2016 ◽  
Vol 7 (13) ◽  
pp. 15566-15576 ◽  
Author(s):  
Huimin Bai ◽  
Guisha Sha ◽  
Meizhu Xiao ◽  
Huiqiao Gao ◽  
Dongyan Cao ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Prognostic Value ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ca 125 ◽  
Ovarian Clear Cell Carcinoma

Prognostic Value of Serum CA19-9 and Perioperative CA-125 Levels in Ovarian Clear Cell Carcinoma

2018 ◽  
Vol 28 (6) ◽  
pp. 1108-1116
Author(s):  
Jun Zhu ◽  
Long Jiang ◽  
Hao Wen ◽  
Rui Bi ◽  
Xiaohua Wu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Prognostic Value ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ca 125 ◽  
Ovarian Clear Cell Carcinoma

HERV-K Hypomethylation in Ovarian Clear Cell Carcinoma Is Associated With a Poor Prognosis and Platinum Resistance

2011 ◽  
Vol 21 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Kanokwan Iramaneerat ◽  
Prakasit Rattanatunyong ◽  
Nipon Khemapech ◽  
Surang Triratanachat ◽  
Apiwat Mutirangura
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Treatment Response ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Platinum Resistance ◽  
Ovarian Clear Cell Carcinoma ◽  
Platinum Based Chemotherapy

Introduction:In general, ovarian clear cell carcinoma (OCCC) has a history of poor response to standard platinum-based chemotherapy regimens, and advanced cases have short survival periods. Therefore, the discovery of a biomarker for the pretreatment prediction of OCCC is crucial. Loss of methylation of a retrotransposable sequence, such as long interspersed repetitive sequence 1 (LINE-1), frequently occurs in cancers, including ovarian cancer, and it has been proven to be associated with poor survival. The expressions of human endogenous retrovirus (HERV) K and E were found to be increased in tissues from patients with OCCC. Here, we propose that methylation levels of HERV are associated with treatment response and prognosis of OCCC.Methods:Twenty-nine patients with OCCC were enrolled. Methylation levels of HERV-K, HERV-E, and LINE-1 were measured from microdissected cancer and normal ovarian tissues. The methylation levels were correlated with stage, treatment response, and prognosis.Results:Methylation levels of HERV-K, HERV-E, and LINE-1 were decreased in tissues from patients with advanced stage cancer (P= 0.0179,P= 0.0021, andP= 0.0307, respectively). Human endogenous retrovirus K demonstrated significantly lower methylation levels in the platinum-resistant group (P= 0.0004). Patients with lower levels of methylated (hypomethylated) HERV-K had a shorter mean overall survival (P= 0.006). In advanced OCCC cases, patients with hypomethylated HERV-K had shorter mean progression-free survival (P= 0.018) and mean overall survival (P= 0.018) than did patients with higher methylation levels of HERV-K.Conclusions:Methylation levels of HERV-K, HERV-E, and LINE-1 are decreased during OCCC multistep carcinogenesis. Moreover, HERV-K hypomethylation is a promising biomarker for predicting OCCC treatment response and prognosis.

Complete remission of recurrent ovarian clear cell carcinoma by chemotherapy with bevacizumab, trabectedin and oxaliplatin

2012 ◽  
Vol 39 (4) ◽  
pp. 872-875 ◽  
Author(s):  
Masashi Takano ◽  
Yuji Ikeda ◽  
Kazuya Kudoh ◽  
Tsunekazu Kita ◽  
Naoki Sasaki ◽  
...  
Keyword(s):  
Complete Remission ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ovarian Clear Cell Carcinoma

scholarly journals Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1769
Author(s):  
Kazuaki Takahashi ◽  
Masataka Takenaka ◽  
Aikou Okamoto ◽  
David D. L. Bowtell ◽  
Takashi Kohno
Keyword(s):  
Ovarian Cancer ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Immune Checkpoint Blockade ◽  
Serous Carcinoma ◽  
Histological Subtype ◽  
Ovarian Clear Cell Carcinoma ◽  
Chemotherapeutic Regimen ◽  
Platinum Based Chemotherapy

Ovarian clear cell carcinoma (OCCC) is a histological subtype of ovarian cancer that is more frequent in Asian countries (~25% of ovarian cancers) than in US/European countries (less than 10%). OCCC is refractory to conventional platinum-based chemotherapy, which is effective against high-grade serous carcinoma (HGSC), a major histological subtype of ovarian cancer. Notably, deleterious mutations in SWI/SNF chromatin remodeling genes, such as ARID1A, are common in OCCC but rare in HGSC. Because this complex regulates multiple cellular processes, including transcription and DNA repair, molecularly targeted therapies that exploit the consequences of SWI/SNF deficiency may have clinical efficacy against OCCC. Three such strategies have been proposed to date: prioritizing a gemcitabine-based chemotherapeutic regimen, synthetic lethal therapy targeting vulnerabilities conferred by SWI/SNF deficiency, and immune checkpoint blockade therapy that exploits the high mutational burden of ARID1A-deficient tumor. Thus, ARID1A deficiency has potential as a biomarker for precision medicine of ovarian cancer.

scholarly journals Serum D-dimer, Albumin and Systemic Inflammatory Response Markers in Ovarian Clear Cell Carcinoma and Their Prognostic Implications

2020 ◽  
Author(s):  
Wei Chen ◽  
Siyuan Zhong ◽  
Boer Shan ◽  
Shuling Zhou ◽  
Xiaohua Wu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Systemic Inflammatory Response ◽  
Ca 125 ◽  
Chemotherapy Response ◽  
Ovarian Clear Cell Carcinoma ◽  
Lymphocyte Ratio ◽  
D Dimer

Abstract Background The study aims to evaluate whether preoperative systemic inflammatory response (SIR) markers or other hematologic variables, such as albumin, D-dimer, carbohydrate antigen 125 play a role in predicting chemotherapy response and survival outcome in patients with ovarian clear cell carcinoma (OCCC). Methods Preoperative leukocyte differential counts, platelet, serum albumin, plasma D-dimer and CA-125 levels were measured in patients with FIGO IC-IV ovarian clear cell cancer. The correlations of these hematologic biomarkers with clinicopathological features, chemotherapy response, and survival outcomes were further analyzed. Survival time was estimated using the Kaplan-Meier model, whereas Cox regression was conducted for multivariate analysis.Results Among the 84 patients, 28.6% were classified as platinum-resistant and 69.0% as platinum sensitive. Preoperative CA125, albumin, D-dimer, and neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio were significantly correlated with FIGO stage, residual tumor, and platinum response. Platelet to lymphocyte ratio was not related to platinum response ( P =0.060). The median follow-up time was 28 months (range, 1 to 128 months). Preoperative CA125, albumin, and D-dimer were significant prognostic factors for overall survival (OS) and progression-free survival (PFS). In the univariate analysis, only NLR had prognostic significance for PFS ( P =0.007). Multivariate analysis indicated that D-dimer > 3.27 ( P = 0.001 for OS; P = 0.040 for PFS) and albumin <39.6 ( P = 0.005 for OS and P = 0.041 for PFS) retained significance.Conclusions Preoperative NLR has some predictive value for platinum resistance in patients with IC-IV stage OCCC, but has little predictive effect on prognosis. Elevated D-dimer and reduced albumin might be potential biomarkers for worse response to first-line platinum-based chemotherapy and poor clinical outcomes.

scholarly journals Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell Carcinoma: A Two Center Cohort Study

2016 ◽  
Vol 48 (1) ◽  
pp. 250-258 ◽  
Author(s):  
Hee Seung Kim ◽  
Hwa-Young Choi ◽  
Maria Lee ◽  
Dong Hoon Suh ◽  
Kidong Kim ◽  
...  
Keyword(s):  
Cohort Study ◽  
Inflammatory Response ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Systemic Inflammatory Response ◽  
Ca 125 ◽  
Ovarian Clear Cell Carcinoma

scholarly journals Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: a Retrospective Study of 112 Patients in Beijing

2020 ◽  
Author(s):  
Huimei Zhou ◽  
Qian Liu ◽  
Xiaohua Shi ◽  
Jiaxin Yang ◽  
Dongyan Cao ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Cell Carcinoma ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Stage I ◽  
Stage Iii ◽  
Ca 125 ◽  
Ovarian Clear Cell Carcinoma

Abstract ObjectivesThis retrospective study aimed to evaluate the clinical characteristics and prognosis of ovarian clear cell carcinoma (OCCC) and to further explore the monitoring value of cancer antigen 125 (CA-125).MethodsThe medical records of 112 OCCC patients who were treated in Peking Union Medical College Hospital (PUMCH) between 2014 and 2019 were collected and reviewed, and data such as age, Federation of Gynecology and Obstetrics (FIGO) stage, CA-125 level, treatment, recurrence, and death were extracted.OutcomesThe median patient age was 50 (45, 57) years. Sixty (53.57%) patients were in stage I, 13 (11.61%) patients were in stage II, 22 (28.57%) patients were in stage III, and 7 (6.25%) patients were in stage IV. In total, 109 (97.32%) patients received adjuvant chemotherapy. The median chemotherapy cycles of CA-125 normalization was 2 (0, 3). The 1-year and 3-year progression-free survival (PFS) rates were 87.85% and 72.90%, respectively. The median PFS1 duration was 19 (11, 35) months, and the median overall survival (OS) duration was 24 (13, 40) months. Recurrence occurred in 32 patients, of whom 7 (21.88%) developed platinum-resistant recurrence. Fifty percent of relapsed patients had a CA-125 level<35 IU/ml at the time of relapse. Nine (28.13%) patients experienced a second recurrence. In the multivariate Cox regression analysis, the Chemotherapy cycles of CA-125 normalization remained nonsignificant for stage I (P=0.003, HR 4.287, 95% CI=1.632–11.258) and stage III (P=0.003, HR 4.287, 95% CI=1.632–11.258) disease. Multivariate Cox regression showed that platinum resistance was an independent factor for PFS2 (P=0.008, HR 11.562, 95% CI=1.873–71.353).ConclusionsFIGO stage and chemotherapy resistance are independent risk factors for prognosis. CA-125 levels following treatment are a valid indicator for treatment monitoring. Regardless of chemosensitivity to CA-125, CA-125 normalization before chemotherapy cycle 2 may not be a distinct inflection point for PFS and OS.

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