High GMFG expression correlates with poor prognosis and promotes cell migration and invasion in epithelial ovarian cancer

Objective

The aim of this study was to characterize the clinical significance of GMFG, a novel ADF/cofilin superfamily protein, and investigate its role in cell migration and invasion in epithelial ovarian cancer (EOC).

Methods

The expression of GMFG in EOC tissues and ovarian cancer cell lines was evaluated by immunohistochemistry and immunoblotting respectively. The data were statistically analyzed for the associations of GMFG expression with clinicopathologic parameters and survival. In vitro cell migration and invasion assays were performed to determine the role of GMFG in cell migratory behaviors. The effect of GMFG on reorganization of actin cytoskeleton was investigated by immunostaining.

Results

GMFG was overexpressed in EOC. Up-regulated GMFG expression was closely correlated with advanced FIGO stage and chemoresistance of the disease. EOC patients with higher GMFG expression showed poorer progression-free survival (PFS) and overall survival (OS). In vitro cellular assays revealed that GMFG promoted cell migration and invasion. GMFG expression altered actin cytoskeleton organization probably by interacting with the Arp2/3 complex.

Conclusion

GMFG expression independently predicts poorer prognosis in patients with EOC. Ectopic overexpression of GMFG contributes to the malignant biological behavior of ovarian cancer cells.     

Prognostic analysis of invasive circulating tumor cells (iCTCs) in epithelial ovarian cancer

Goals

Circulating tumor cells (CTCs) have been introduced as a biomarker in detecting advanced epithelial ovarian cancer (EOC). The goals are to examine the prevalence of the invasive subpopulation of CTCs (iCTCs) in patients at high risk of EOC and to compare this biomarker to serum CA125.

Methods

We used a unique cell adhesion matrix (CAM)-based, functional cell enrichment and identification platform to isolate iCTCs from 129 preoperative patients. We confirmed the identity of iCTCs using positive epithelial (Epi +) markers and negative hematopoietic lineage (HL −) markers. Sensitivity and specificity of the assays were examined and iCTCs/CA125 were correlated with overall survival (OS), progression-free survival (PFS) and clinical parameters.

Results

We found a 41.2% sensitivity, 95.1% specificity and 77.8% positive predictive value (PPV) of the iCTC assay in detecting patients with stage I and II EOC malignancy, and a 83% sensitivity and 97.3% PPV in detecting all stages of EOC malignancy. However, a positive CA125 test provided weak evidence to detect stage I and II malignancy (61.6% PPV) and all EOC (92.1% PPV), because of its 76.2% specificity. A significantly stronger concordance in OS and PFS of clinical factors (tumor stage, debulking and platinum sensitivity) was noted for elevated iCTCs than for serum CA125.

Conclusion

The CAM-initiated CTC enrichment/identification method enabled the detection of early stage EOC. iCTCs were better correlated with worse OS and PFS, more specific and better PPV than CA125 in detecting EOC malignancy in patients at high risk of EOC.     

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma

Background

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored.

Method

We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months.

Results

Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients.

Conclusions

EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

     

Overexpression of c-Abl predicts unfavorable outcome in epithelial ovarian cancer

Objectives

Abelson tyrosine kinase (c-Abl) has been shown to promote solid tumor invasion and metastasis. However, little is known regarding whether c-Abl contributes to the development or progression of epithelial ovarian cancer (EOC). The aims of this study are to determine the expression of c-Abl and investigate a possible relationship between c-Abl and prognosis in EOC.

Methods

c-Abl protein level was evaluated in 137 EOC specimens by immunohistochemical staining and 32 EOC specimens by Western blot analysis. Expression of c-Abl in ovarian cancer cell lines was measured by Western blot analysis and immunofluorescence. Survival analysis was performed to assess the correlation between c-Abl expression and survival.

Results

Immunohistochemical staining and Western blot analysis revealed that c-Abl was overexpressed in EOC compared with samples from a non-invasive ovarian tumor and normal ovaries (P < 0.05). Furthermore, expression of c-Abl was significantly associated with advanced FIGO stage, poor grade, serum Ca-125 and residual tumor size (P < 0.05). By Western blot analysis, c-Abl expression was examined in four ovarian cancer cell lines. Meanwhile, immunofluorescence was performed to show c-Abl expression in SKOV3 and 3AO cell lines. Survival analysis demonstrated that patients with low c-Abl staining had a significantly better survival compared to patients with high c-Abl staining (P < 0.05). In multivariate analysis, c-Abl overexpression, poor grade, advanced stage and suboptimal surgical debulking were independent prognostic factors of poor survival.

Conclusions

Our present study finds that c-Abl overexpression is associated with an unfavorable outcome. c-Abl may be a crucial predictor for EOC metastasis.     

The prognostic significance of preoperative leukocytosis in epithelial ovarian carcinoma: A retrospective cohort study

Objective

Preoperative leukocytosis is known to be a negative prognostic factor for several gynecologic malignancies, but its relationship with epithelial ovarian carcinoma (EOC) is unknown. We sought to evaluate the prognostic implications of preoperative leukocytosis for women with EOC.

Methods

We retrospectively reviewed the medical records of patients who underwent primary debulking surgery and adjuvant platinum-based chemotherapy for EOC between January 1993 and October 2011. Associations between leukocytosis and recurrence-free survival (RFS) and overall survival (OS) were determined by univariate analyses. Multivariate Cox proportional hazards regression was used to identify independent prognostic factors for RFS and OS.

Results

Of 155 women, 23 (14.8%) had leukocytosis and 132 (85.2%) did not have leukocytosis. RFS and OS were significantly shorter for women with leukocytosis than for women without leukocytosis (P = 0.009 and P < 0.0001, respectively). The mortality rate was also higher among women with leukocytosis (P < 0.0001). Multivariate analysis revealed that preoperative leukocytosis (hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.55–4.41; P = 0.009), advanced stage (HR: 3.12; 95% CI: 1.44–6.75; P = 0.004), and optimal cytoreduction (HR: 0.38; 95% CI: 0.14-0.70; P = 0.031) were independent prognostic factors for RFS. Additionally, preoperative leukocytosis was independently associated with decreased OS (HR: 7.66; 95% CI: 2.78–21.16; P < 0.0001).

Conclusions

Among women with EOC, preoperative leukocytosis might be an independent prognostic factor for RFS and OS. A larger-scaled, prospective study is needed to verify these results.     

Retrospective analysis of prognostic variables and clinical outcomes in surgically staged intermediate risk endometrial carcinoma

Objective

To identify independent prognostic variables for surgically staged intermediate risk endometrial carcinoma as defined by the Gynecologic Oncology Group 99 (GOG99) criteria.

Study design

Retrospective study of 239 patients with FIGO stage IB-occult IIB endometrioid type endometrial cancer, who were primarily treated with comprehensive staging surgery. Data were collected on clinicopathological variables, extent of primary surgery, postoperative adjuvant treatment, and patterns of recurrences. Kaplan–Meier survival curves were used to estimate disease free survival (DFS) and overall survival (OS), and multivariate Cox regression models were used to identify independent prognostic variables. The median follow-up time was 67 months (range, 12–183 months).

Results

The 5-year DFS and OS were 91.0% and 93.0%, respectively. On univariate Kaplan–Meier analysis, age > 60 years, deep myometrial invasion (MI), presence of lymph vascular invasion (LVSI), and negative progesterone receptor (PR) status were significantly associated with diminished 5-year DFS and OS. The univariate analysis on patterns of failures demonstrated that patients with older age or positive LVSI were more inclined to develop locoregional recurrence, while PR status and the depth of MI had a statistically significant impact on distant failure. On multivariate analysis, PR status, age, and the depth of MI were independent prognostic variables for 5-year DFS, and age was the only independent prognostic variable for 5-year OS. LVSI and age were independent prognostic variables for locoregional recurrence, while PR status and depth of MI were independent prognostic variables for distant recurrence.

Conclusions

Age, depth of MI, PR status and presence of LVSI are of independent prognostic value for intermediate risk endometrial cancer. The presence of these variables warrants consideration when deciding upon treatment strategies.     

Diabetes mellitus and ovarian cancer: More complex than just increasing risk

Objective

Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC.

Methods

A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan–Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients.

Results

62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p = 0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7 kg/m², p < 0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3 months, p = 0.024) and OS (26.1 vs. 42.2 months, p = 0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS.

Conclusions

EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.     

A validation study of new risk grouping criteria for postoperative treatment in stage IB cervical cancers without high-risk factors: Rethinking the Gynecologic Oncology Group criteria

Objective

The aim of this study was to verify whether the Gynecologic Oncology Group (GOG) criteria are valid in a different cohort of patients and to investigate simplified new criteria tailoring adjuvant radiation therapy in patients with intermediate-risk factors after radical hysterectomy.

Study design

We analyzed the data of 332 patients with FIGO stage IB cervical cancer who underwent radical hysterectomy between 1994 and 2007. Two hundred and twenty-five patients without high-risk factors (lymph node metastasis, parametrial invasion, or positive surgical margins) were identified and were classified into low-risk and high-risk groups according to the GOG criteria and new criteria based on combinations of intermediate-risk factors (large tumor size, deep stromal invasion, lymph-vascular space invasion). We evaluated the prognostic significance of both criteria.

Results

We identified 140 low-risk patients and 85 high-risk patients in the application of the GOG criteria. Low-risk patients had significantly better disease-free survival (DFS) (P = 0.001) and overall survival (OS) (P = 0.013) than high-risk patients. There were 145 low-risk patients and 80 high-risk patients on applying the new criteria. Low-risk patients had significantly better DFS (P = 0.001) and OS (P = 0.013) than high-risk patients. The receiver operating characteristic (ROC) curves showed that both criteria had similar performance for predicting which patients would have help from adjuvant therapy.

Conclusion

This study demonstrated that the GOG criteria were still valid in the different population, the simplified new criteria were convenient to apply in practice, and the performance of the new criteria was as good as the GOGs.     

Defective expression of Protein 4.1N is correlated to tumor progression,aggressive behaviors and chemotherapy resistance in epithelial ovarian cancer

Objective

Protein 4.1N (4.1N) is a member of the Protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. In this study, we evaluated the expression of 4.1N protein and its potential roles in epithelial ovarian cancer (EOC) tumorigenesis and progression.

Methods

4.1N protein expression was investigated in a total of 280 samples including 74 normal tissues, 35 benign, 30 borderline and 141 malignant epithelial ovarian tumors by immunohistochemistry. Correlation between 4.1N expression levels and clinicopathologic features was statistically analyzed. The expression of 4.1N in EOC cell lines was examined by western blotting.

Results

Immunohistochemistry analysis revealed that, although there was no loss of 4.1N expression in normal tissues and benign tumors, absence of Protein 4.1N was significantly more common in EOCs (44.0%) than in borderline tumors (3.3%) (p < 0.001). Furthermore, loss or decreased expression of 4.1N protein expression was correlated with malignant potential of the tumors (14.3% in benign tumors, 56.7% in borderline tumors and 92.9% in malignancy) (p < 0.001). In EOC samples, loss of 4.1N protein was significantly associated with advanced-stage (p = 0.004), ascites (p = 0.009), omental metastasis (p = 0.018), suboptimal debulking (p = 0.024), poorly histological differentiation (p = 0.009), high-grade serous carcinoma (p = 0.001), short progression-free-survival (p = 0.018) and poor chemosensitivity to first-line chemotherapy (p = 0.029). Moreover, western blotting analysis revealed that expression of 4.1N protein was lost in 4/8 (50%) EOC cell lines.

Conclusions

4.1N protein expression level was significantly decreased during malignant transformation of epithelial ovarian tumors and that loss of 4.1N expression was closely correlated to poorly differentiated and biologically aggressive EOCs.     

Reasons for failure to deliver National Comprehensive Cancer Network (NCCN)-adherent care in the treatment of epithelial ovarian cancer at an NCCN cancer center

Objective

The National Comprehensive Cancer Network (NCCN) has established guidelines for treating epithelial ovarian cancer (EOC) which includes cytoreductive surgery and platinum and taxane-based chemotherapy (CT). The objective of this study was to determine the reasons for failure to deliver NCCN-adherent care at an NCCN cancer center serving a diverse racial and socioeconomic population.

Methods

Medical records of women with EOC diagnosed between 2004 and 2009 were reviewed for demographic, clinical, tumor, treatment, and survival data. Independent reviewers determined if their treatment met criteria for being NCCN-adherent. Progression-free survival (PFS) and overall survival (OS) were calculated with Kaplan–Meier estimates and compared with the log-rank test.

Results

367 patients were identified. 79 (21.5%) did not receive NCCN-adherent care. Non-adherent CT in 75 patients was the most common reason for failure to receive NCCN-adherent care. 39 patients did not complete CT due to treatment toxicities or disease progression. 12 patients received single agent CT only and 4 received no CT due to comorbidities. 2 patients declined CT. 18 patients died in the postoperative period without receiving CT. 8 patients did not undergo cytoreduction due to disease progression or comorbidities. PFS and OS were improved in the NCCN-adherent cohort (PFS: 5.7 vs. 18.3 months, p < .005) (OS: 11.4 vs. 49.5 months, p < .005).

Conclusions

The vast majority of patients at an NCCN cancer center received NCCN-adherent treatment. Reasons for failure to receive NCCN-adherent care were variable, but most did not receive chemotherapy in accordance with guidelines due to comorbidities or disease progression.     

nm23 gene polymorphisms are associated with survival of patients with epithelial ovarian cancer but not with susceptibility to disease

Objective

nm23, a tumor metastasis suppressor gene, has been linked to protection against tumorigenesis and tumor metastasis. This study evaluated whether genetic variants in the nm23 gene were associated with susceptibility to epithelial ovarian cancer (EOC) or the clinical outcome of patients.

Methods

A case-control study was performed with 302 patients with epithelial ovarian cancer and 302 control women. According to the genotypes, the outcome in 213 EOC patients was compared. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier plots and Cox models adjusted for clinical factors.

Results

The case-control analysis showed that the rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter were not associated with the risk of developing EOC. In contrast, survival analysis showed that the rs2302254 C/T polymorphism was related to the prognosis of EOC patients. Compared with patients carrying the C/C genotype, patients carrying the T/T genotype had a shorter median PFS and median OS by Kaplan-Meier plots and Cox models adjusted for clinical factors. For rs16949649 T/C polymorphisms, Kaplan-Meier analysis indicated that patients carrying the homozygous C/C genotype had shorter PFS and OS than those carrying the T allele (T/T + T/C genotype). The Cox proportional hazard model analysis suggested that this relationship was only retained in OS when adjusted for clinical factors.

Conclusion

Our studies suggest that rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter may influence the prognosis of patients with epithelial ovarian cancer.     

Outcome of 6 fractions of 5.3 Gray HDR brachytherapy in combination with external beam radiotherapy for treatment of cervical cancer

Objective

To review the characteristics, outcomes and toxicities of cervical cancer patients treated with 6 fractions of brachytherapy after external beam radiotherapy (EBRT).

Methods

All patients diagnosed with cervical cancer from 2000 to 2009 who were referred for radical treatment and who received 6 fractions of brachytherapy were retrospectively reviewed. Overall survival (OS), disease free survival (DFS), local control (LC), distant control (DC) rate, acute and late toxicities were the primary endpoints.

Results

Thirty-two patients with mainly advanced stage squamous cell carcinoma were identified and reviewed. Patients received EBRT of 45 to 50.4 Gy in 1.8 Gy daily fractions followed by 6 sessions of 3 channel brachytherapy of 5.3 Gy prescribed to point H. Response rates to treatment were good, with no residual disease in 84% six weeks after the completion of treatment. With a median follow up time of 8.1 years, the five-year OS, DFS, LC and distant control rates were 75%, 68.5%, 92.8% and 76.9% respectively. None of the patients developed any G3-4 acute toxicity but one patient who had advanced disease developed G3-4 proctitis with a fistula formation.

Conclusions

HDR brachytherapy utilizing 6 fractions of 5.3 Gy prescribed to point H with concurrent chemo-radiation is superior in terms of OS and LC to regimens that deliver a lower EQD2 dose to point A/H and is associated with very low rates of toxicities.     

LINE1 and Alu repetitive element DNA methylation in tumors and white blood cells from epithelial ovarian cancer patients

Objective

We determined whether DNA methylation of repetitive elements (RE) is altered in epithelial ovarian cancer (EOC) patient tumors and white blood cells (WBC), compared to normal tissue controls.

Methods

Two different quantitative measures of RE methylation (LINE1 and Alu bisulfite pyrosequencing) were used in normal and tumor tissues from EOC cases and controls. Tissues analyzed included: i) EOC, ii) normal ovarian surface epithelia (OSE), iii) normal fallopian tube surface epithelia (FTE), iv) WBC from EOC patients, obtained before and after treatment, and v) WBC from demographically-matched controls.

Results

REs were significantly hypomethylated in EOC compared to OSE and FTE, and LINE1 and Alu methylation showed a significant direct association in these tissues. In contrast, WBC RE methylation was significantly higher in EOC cases compared to controls. RE methylation in patient-matched EOC tumors and pre-treatment WBC did not correlate.

Conclusions

EOC shows robust RE hypomethylation compared to normal tissues from which the disease arises. In contrast, RE are generally hypermethylated in EOC patient WBC compared to controls. EOC tumor and WBC methylation did not correlate in matched patients, suggesting that RE methylation is independently controlled in tumor and normal tissues. Despite the significant differences observed over the population, the range of RE methylation in patient and control WBC overlapped, limiting their specific utility as an EOC biomarker. However, our data demonstrate that DNA methylation is deranged in normal tissues from EOC patients, supporting further investigation of WBC DNA methylation biomarkers suitable for EOC risk assessment.     

Preoperative 18F-FDG PET/CT in the management of advanced epithelial ovarian cancer

Objective

The introduction of 18-FDG-PET/CT during preoperative evaluation of patients with epithelial ovarian cancer (EOC) has led to an increase of the detection of extra-abdominal metastases. However, the clinical impact of this upstage remains unclear.

Methods

Patients with suspected advanced EOC underwent 18-FDG-PET/CT within two weeks prior to debulking surgery.

Results

Between 2006 and 2011 95 patients met the inclusion criteria. Based on the concordance or the discrepancy of clinical and PET/CT stage, patients were divided into 3 groups (A: clinical and PET III; B: clinical III and PET IV; C: clinical and PET IV). Twenty-five patients were upstaged from FIGO stage III to stage IV by PET/CT. The proportion of patients who achieved a residual tumor < 1 cm in group B and C was similar, whereas it was significantly lower compared to group A. Similarly, complete response to adjuvant chemotherapy was achieved more frequently in patients in group A. PFS was similar in the three groups (17, 17 and 12 months in group A, B and C), as well as OS (51, 41 and 35 months).

Conclusions

PET/CT is able to detect distant metastases in EOC patients. The presence of extra-abdominal disease probably indicates a more aggressive disease which also shows a lower response to standard chemotherapy. However, upstaged patients have a similar prognosis compared to stage III patients, probably because intra-abdominal disease is more likely to lead patients to death. This might also explain why residual tumor is the most important prognostic factor for advanced EOC patients.     

Surgical outcomes and national comprehensive cancer network compliance in advanced ovarian cancer surgery in a low volume military treatment facility

Objective

To evaluate the optimal cytoreduction (OPT) rate, National Comprehensive Cancer Network (NCCN) treatment guideline compliance rate and patient outcomes for advanced stage epithelial ovarian cancer (EOC) patients at our low volume institution.

Methods

Following IRB approval, records of patients with Stage III-IV EOC, primary peritoneal, or fallopian tube carcinoma completing both primary surgery and adjuvant chemotherapy were reviewed. Patient demographics, clinicopathologic variables, cytoreduction status (optimal or suboptimal), NCCN treatment guideline compliance, and survival were reviewed. Standard statistical tests including the t-test, Chi-square or Fisher's exact test and Kaplan–Meier Survival curves were utilized.

Results

Overall, 48 patients met all inclusion criteria. 35(73%) and 13 (27%) achieved optimal and suboptimal cytoreduction, respectively. Median overall survival (OS) for all patients was 37.1 months (95% CI 23.2 – 51.1 months) and NCCN treatment guideline compliance was 85.4%. Compared to sub-optimally cytoreduced patients the optimally cytoreduced patients were significantly older (62.2 vs. 53.5 yrs; p = 0.015); no other significant clinicopathologic differences were observed between the two groups. 19 of 48 (39.6%) patients enrolled in an upfront cooperative group trial. Median OS was 43.4 months for optimally compared to 15.6 months in sub-optimally cytoreduced patients (p = 0.012).

Conclusions

NCCN treatment guideline compliance, OPT, and median OS rates in our low volume institution are similar to those reported nationally, and argue against using volume alone as a rationale for centralization of care.     

Survival impact of capsule rupture in stage I clear cell carcinoma of the ovary in comparison with other histological types

Objective

We analyzed a large number of stage I clear cell carcinoma of the ovary (CCC) patients to estimate the survival impact of the capsule status in stage I CCC patients, particularly in comparison with non-CCC patients.

Methods

Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer (EOC) collected under the central pathological review system were subjected to uni- and multivariable analyses to evaluate the disease-free survival (DFS) and overall survival (OS).

Results

There was no significant difference in both the OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture) {IA vs. IC(ir); OS: P = 0.1402, DFS: P = 0.2701}. In contrast, CCC patients at IC(non-ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive ascites/washing, and surface involvement} showed a poorer OS and DFS than those at IC(ir), or those at the corresponding stage in non-CCC. In multivariable analysis, the capsule status was an independent prognostic factor of a poor OS and DFS {OS: HR, 2.832; 95% CI 1.156-6.938; P = 0.023; DFS: HR, 4.327; 95% CI, 1.937-9.667; P = 0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in CCC patients, intraperitoneal recurrences were more frequently observed in IC(non-ir) CCC than IA or IC(ir) CCC (P = 0.0083) {In contrast, non-CCC: N.S.}.

Conclusion

This study suggests that CCC patients other than those with intraoperative capsule rupture show a considerable risk for mortality despite adjuvant chemotherapy.     

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.     

Adjuvant chemotherapy in stage I–II uterine leiomyosarcoma: A multicentric retrospective study of 140 patients

Objective

About 50–60% of patients with stage I–II uterine leiomyosarcoma (ULMS), primarily treated with surgery, relapse and die from progressive disease. In this retrospective study we describe the impact of adjuvant chemotherapy in this subset of patients.

Methods

140 women treated from 1976 to 2011 were included in the study. Univariate and multivariate analysis were used to test the association of clinical features and adjuvant treatments with overall survival (OS) and disease-free survival (DFS).

Results

62 women did not receive any further treatment after hysterectomy, 14 had radiotherapy (RT), 52 chemotherapy and 12 chemo-radiotherapy. Chemotherapy based on doxorubicin and ifosfamide combination was used in 54 cases. After a median follow-up of 63 months, 87 women (62%) have relapsed, and 62 (44%) have died. The vast majority of patients who relapsed had distant recurrences (72%).The 5 year median DFS and OS were 43% and 64% respectively. After 5 years of follow up 68.7% of women treated with chemotherapy (± RT) vs 65.6% of patients only observed were alive (p = 0.521). In the univariate analysis no factors had a statistical impact on DFS, while number of mitosis (> 20 × 10HPF), age (> 60 years) and adjuvant radiotherapy were found as negative prognostic factors for OS. In the multivariate analysis only mitosis and age remained significant for OS.

Conclusion

Adjuvant chemotherapy was not associated with a significant survival benefit and should not be considered as standard of care for patients with stage I–II ULMS until randomized clinical studies will give further information.     

Interferon-gamma in ascites could be a predictive biomarker of outcome in ovarian carcinoma

Objective

The ovarian cancer-associated ascites is an ideal material for evaluating the interaction between the host immune system and cancer cells in the tumor micro-environment. The aim of this study was to investigate whether the selected target cytokine expression levels in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer.

Methods

Eighty-eight specimens of ovarian cancer-associated ascites were evaluated to select the target cytokine by a cytokine profiling kit. The 144 total samples were subsequently analyzed for this target cytokine. The correlation between the target cytokine and clinical characteristics was analyzed.

Results

Interferon-gamma (IFN-γ) was identified as the target cytokine. Higher levels of IFN-γ in the ascites of the tumor micro-environment were associated with advanced disease (p = 0.012), higher tumor histological grading (p = 0.004), and sub-optimal surgical status (p = 0.040). By multivariate analysis, the adjusted hazard ratios (HRs) were 2.74 (95% confidence interval (CI) 1.85–4.05, p < 0.001) for disease-free survival (DFS) and 1.72 (95% CI 1.01–2.93, p = 0.048) for overall survival (OS) for a 10-fold increase in IFN-γ concentration in the ascites. An inverse dose–response relationship between IFN-γ level and survival was also noted (P_trend < 0.001 for DFS and P_trend < 0.042 for OS).

Conclusions

Patients with ovarian cancer and higher IFN-γ expression levels in cancer-associated ascites will have shorter DFS and OS. IFN-γ levels in the ascites may be a prognostic marker and a potential reference for immunotherapy targeting IFN-γ.     

A comparison of primary intraperitoneal chemotherapy to consolidation intraperitoneal chemotherapy in optimally resected advanced ovarian cancer

Objective

To compare survival outcomes for patients with advanced epithelial ovarian cancer (EOC) who received primary intravenous/intraperitoneal (IV/IP) chemotherapy to those who received IV followed by consolidation (treatment given to patients in remission) IP chemotherapy.

Methods

Data were analyzed and compared for all patients with stage III–IV EOC who underwent optimal primary cytoreduction (residual disease ≤ 1 cm) followed by cisplatin-based consolidation IP chemotherapy (1/2001–12/2005) or primary IV/IP chemotherapy (1/2005–7/2011).

Results

We identified 224 patients; 62 (28%) received IV followed by consolidation IP chemotherapy and 162 (72%) received primary IV/IP chemotherapy. The primary IP group had significantly more patients with serous tumors. The consolidation IP group had a significantly greater median preoperative platelet count, CA-125, and amount of ascites. There were no differences in residual disease at the end of cytoreduction between both groups. The median progression-free survival (PFS) was greater for the primary IP group; however, this did not reach statistical significance (23.7 months vs 19.7 months; HR 0.78; 95% CI, 0.57–1.06; p = 0.11). The median overall survival (OS) was significantly greater for the primary IP group (78.8 months vs 57.5 months; HR 0.56; 95% CI, 0.38–0.83; p = 0.004). On multivariate analysis, after adjusting for confounders, the difference in PFS was not significant (HR 0.78; 95% CI, 0.56–1.11; p = 0.17), while the difference in OS remained significant (HR 0.59; 95% CI, 0.39–0.89; p = 0.01).

Conclusions

In our study, primary IV/IP chemotherapy was associated with improved OS compared to IV followed by consolidation IP chemotherapy in patients with optimally cytoreduced advanced EOC.