Tumor Forkhead Box Q1 Is Elevated, Correlates with Increased Tumor Size, International Federation of Gynecology and Obstetrics Stage but Worse Overall Survival in Epithelial Ovarian Cancer Patients

PURPOSE: In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS: The site of stage IV–defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV–defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION: Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.

Download Full-text

Prognostic implications of forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) in epithelial ovarian cancer

BMC Cancer ◽

10.1186/s12885-019-6406-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Gwan Hee Han ◽

Doo Byung Chay ◽

Sanghee Nam ◽

Hanbyoul Cho ◽

Joon-Yong Chung ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Epithelial Ovarian Cancer ◽

Hazard Ratio ◽

Ovarian Tumors ◽

High Expression ◽

Epithelial Tissues ◽

Forkhead Box ◽

High Hazard Ratio

Abstract Background Transcription factors forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) have been reported to play important roles in various cancers. However, their role in epithelial ovarian cancer (EOC) has not been elucidated yet. Therefore, we evaluated the expression and clinical significance of FOXO1 and PAX3 in EOC. Methods Immunohistochemical analyses of FOXO1 and PAX3 in 212 EOCs, 57 borderline ovarian tumors, 153 benign epithelial ovarian tumors, and 79 nonadjacent normal epithelial tissues were performed using tissue microarray. Various clinicopathological variables, including the survival of EOC patients, were compared. In addition, the effect of FOXO1 on cell growth was assessed in EOC cell lines. Results FOXO1 and PAX3 protein expression levels were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues, and borderline tumors (all p < 0.001). In EOC tissues, FOXO1 expression was positively correlated with PAX3 expression (Spearman’s rho = 0.118, p = 0.149). Multivariate survival analysis revealed that high FOXO1 expression (hazard ratio = 2.77 [95% CI, 1.48–5.18], p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed a high hazard ratio (4.60 [95% CI, 2.00–10.55], p < 0.001) for overall survival. Also in vitro results demonstrated that knockdown of FOXO1 was associated with decreased cell viability, migration, and colony formation. Conclusions This study revealed that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results suggest the promising potential of FOXO1 and PAX3 as prognostic and therapeutic markers. The possible link between biological functions of FOXO1 and PAX3 in EOC warrants further studies.

Download Full-text

An open-label, multicenter, randomized Phase II Study to compare the effects of Paclitaxel/Carboplatin and Lonafarnib to those of Paclitaxel/Carboplatin for 1st line Treatment of patients with epithelial ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) Stages IIB-IV

http://isrctn.org/> ◽

10.1186/isrctn51315091 ◽

2013 ◽

Author(s):

Gabriele Elser

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

International Federation ◽

Line Treatment ◽

Open Label ◽

Gynecology And Obstetrics ◽

Randomized Phase Ii

Download Full-text

Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.7.2426 ◽

1998 ◽

Vol 16 (7) ◽

pp. 2426-2434 ◽

Cited By ~ 97

Author(s):

M Gore ◽

P Mainwaring ◽

R A'Hern ◽

V MacFarlane ◽

M Slevin ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Epithelial Ovarian Cancer ◽

Total Dose ◽

Single Agent ◽

Dose Intensity ◽

Hematologic Toxicity ◽

Dose Increase ◽

Gynecology And Obstetrics ◽

Carboplatin Auc

PURPOSE We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy. PATIENTS AND METHODS Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer. RESULTS The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001). CONCLUSION We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.

Download Full-text

Impact of nonspecific death on overall survival in early-stage epithelial ovarian cancer patients

Current Problems in Cancer ◽

10.1016/j.currproblcancer.2020.100621 ◽

2020 ◽

pp. 100621

Author(s):

Danian Dai ◽

Ting Deng ◽

Bin Wang ◽

Shangqiu Chen ◽

Zhimin Liu ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Epithelial Ovarian Cancer ◽

Cancer Patients ◽

Early Stage

Download Full-text

Improved Classification of Epithelial Ovarian Cancer: Results of 3 Danish Cohorts

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31822a0f6b ◽

2011 ◽

Vol 21 (9) ◽

pp. 1592-1600 ◽

Cited By ~ 28

Author(s):

Karina Dahl Steffensen ◽

Marianne Waldstrøm ◽

Anni Grove ◽

Bente Lund ◽

Niels Pallisgård ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Epithelial Ovarian Cancer ◽

P53 Protein ◽

Benign Tumors ◽

Braf Mutations ◽

P53 Expression ◽

Gynecology And Obstetrics

ObjectiveAn increasing body of evidence has suggested that epithelial ovarian cancer (EOC) patients can broadly be divided into 2 groups on the basis of histopathologic parameters and molecular profiles. Type 1 tumors are slow-growing tumors with inherent mutations such as KRAS or BRAF mutations, whereas type 2 tumors are more rapidly growing tumors of which many contain TP53 mutations. In the present study, we performed a comprehensive study in a large Danish material to evaluate the clinical importance.Materials and MethodsA total of 512 tissue samples were included (430 EOCs, 34 borderline, 28 benign tumors, and 20 normal ovaries). KRAS mutations (codon 12/13) and BRAF codon 600 mutations were analyzed from formalin-fixed paraffin-embedded tissue by ARMS qPCR. p53 expression was examined by immunohistochemistry.ResultsOf the EOC patients, 25% had histopathologically classified type 1 tumors, and of these, 44% were either KRAS or BRAF mutated. Of patients with histopathologic type 2 tumors, 66% showed p53 protein overexpression, whereas 4 (1.5%) patients contained a KRAS mutation. In a univariate survival analysis, a large difference in survival was seen between patients with type 1 and type 2 tumors. Patients with type histologic 2 tumors had significantly worse survival compared with patients with type 1 tumors (P< 10−5). International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, residual tumor, and KRAS/BRAF mutation were independent predictors of overall survival in the multivariate analysis. Patients with KRAS/BRAF mutated carcinomas showed independent decreased overall survival with a hazard ratio of 2.01 (95% confidence interval, 1.13–3.57;P= 0.018).ConclusionsKRAS/BRAF mutations are with very few exceptions constrained to patients with histopathologic type 1 tumors, whereas p53 overexpression is very frequent in type 2 tumors. KRAS/BRAF mutations had independent prognostic importance. The classification presented here should have a major therapeutic implication and serve as a hallmark of future clinical trials.

Download Full-text

Stage IIA1 Versus Stage IIA2 Cervical Cancer: Does the New Staging Criteria Predict Survival?

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182138648 ◽

2011 ◽

Vol 21 (4) ◽

pp. 711-716 ◽

Cited By ~ 10

Author(s):

Gunjal Garg ◽

Jay P. Shah ◽

Eugene P. Toy ◽

Carl Christensen ◽

Gunter Deppe ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Radical Hysterectomy ◽

Tumor Size ◽

International Federation ◽

Primary Radiation ◽

Adjuvant Radiation ◽

Patient Age ◽

Gynecology And Obstetrics ◽

Patient Âgé

Objective:(1) To determine the correlation of 2008 International Federation of Gynecology and Obstetrics staging system with survival in patients with stage IIA cervical cancer, (2) to elucidate the treatment patterns in stage IIA1 and stage IIA2 cervical cancer, and (3) to investigate whether radical hysterectomy or radiation influenced overall survival.Methods:Data were extracted from the Surveillance, Epidemiology and End Results database between 1988 and 2005. Statistical analysis usedχ2test, Kaplan-Meier method, Cox regression, and logistic regression.Results:Of the 560 women, 271 (48.4%) had stage IIA1, and 289 (51.6%) had stage IIA2 cervical cancer. Stage IIA2 patients were younger than stage IIA1 patients (mean age, 49 years vs 54 years;P= 0.01). Stage IIA1, compared with stage IIA2, differed significantly regarding the administration of primary radiation (47.2% vs 64.7%,P< 0.001) and adjuvant radiation (60.5% vs 77.5%,P= 0.006). The following variables were significantly associated with the performance of radical hysterectomy: patient age, 65 years or younger, tumor size, ≤2 cm or lesser, high tumor grade, and nonsquamous tumor histology. The incidence of adjuvant radiation after radical hysterectomy was high (48% [tumor size, ≤2 cm] to 86% [tumor size, >6 cm]). The 5-year overall survival was not significantly different between stages IIA1 and IIA2 (65.8% vs 59.5%,P= 0.2). Only patient age (P= 0.01), tumor size (P= 0.02), and lymph node status (P= 0.002) were independent predictors of survival. When controlled for other contributing factors, there was no significant difference in survival between patients treated by radical hysterectomy and primary radiation.Conclusions:The 2008 International Federation of Gynecology and Obstetrics staging criteria is not an independent predictor of survival in stage IIA cervical cancer. Given the equivalent efficacy of radical hysterectomy and radiation, attention should be paid to the high risk of adjuvant radiation in these patients.

Download Full-text