Prognostic significance of DNA index in advanced ovarian cancer

Abstract. Flow cytometric analysis of single cell DNA content was performed in 99 malignant ovarian tumors FIGO stages III and IV. The tumors were divided into two groups with DNA index 1.5 and > 1.5, respectively. The tumor DNA index correlated with histopathological differentiation, frequency of complete pathological remission, and prognosis.     

Prognostic factors in advanced ovarian cancer

In this review, different factors with suspected effect on survival of patients with advanced ovarian cancer are analysed. The volume of residual disease after surgical debulking is one of the most important factors predicting outcome. However, the extent of cytoreduction may not be the only 'responsible' factor indicating a better prognosis; the underlying biology of those debulkable tumors may also play a role in defining the more favorable outcome. Seven reports have studied different prognostic factors by multivariate analysis: performance status, stage, age, grade, histology, tumor size, residual tumor, type of chemotherapy given, and ploidy status are the most common analysed parameters. A meta-analysis indicated that treatment with cisplatin and disease stage are the only independent prognostic variables. Some investigators have developed prognostic indexes with good predictive power, incorporating objective prognostic variables. This approach may be more useful than applying individual factors to each patient. The absolute titer of carbohydrate antigen 125, its decline after several courses of chemotherapy, or its half-life have been correlated with prognosis in some instances, but low sensitivity may be a problem. Other biologic factors with some prognostic potential in ovarian cancer are the expression of lung-resistance protein and the over-expression of c-erbB-2, both perhaps related to resistance to chemotherapy, the product of the metastasis suppressor gene nm23, the epidermal growth factor receptor, heat shock proteins (HSP-60), and plasma or ascites levels of macrophage colony-stimulating factor. Most of these predictors were explored in selected and often small series of patients, and their roles should be confirmed in well-designed confirmatory trials.     

Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer

Objective

The purpose of this study was to evaluate the prognostic significance of serum human epididymis protein 4 (HE4) level in patients with epithelial ovarian cancer.

Study design

A total of 78 women diagnosed with a pelvic mass and operated on in our institute comprised our cohort. Forty-five of these were diagnosed with epithelial ovarian cancer and treated with debulking surgery, followed by taxane and platinum-based chemotherapy as clinically indicated. Preoperatively obtained serum samples were analyzed for levels of HE4 and CA125.

Results

The elevated serum HE4 level was related to advanced stage and serous type of cancer. The median duration of the follow-up was 35.1 months. In advanced stage, the median progression-free survival (PFS) of patients with elevated serum HE4 levels was 20.1 months (95% CI, 15.7–24.6 months), whereas that of patients with normal serum HE4 level was 24.2 months (95% CI, 13.9–34.6 months) (p = 0.029). Independent predictors for PFS in patients with advanced stage EOC included serum HE4 level (hazard ratio 2.24; 95% CI, 1.14 to 6.84; p = 0.048).

Conclusions

Our results demonstrated that an elevated serum HE4 level was related to the advanced stage of epithelial ovarian cancer. An elevated serum level of HE4 is a poor prognostic factor for PFS in patients with epithelial ovarian cancer who were treated with debulking surgery and adjuvant taxane and platinum-based chemotherapy. The serum HE4 level is a promising indicator for the progression of cancer as well as a biomarker for the detection of epithelial ovarian cancer.     

Prognostic value of serial CA125 measurements during chemotherapy for patients with advanced ovarian cancer

Serum CA125 concentrations measured before and during chemotherapy may provide additional information for prognostic assessment of patients with epithelial ovarian cancer (EOC), and enable discrimination between patients who are likely to benefit from further therapy and those who will not. Medical records of 40 patients with advanced EOC, treated at the Department of Obstetrics and Gynecology of the University Hospital Nijmegen between July 1984 and April 1993, were examined. All patients had primary cytoreductive surgery followed by platinum-based chemotherapy. Serum samples were obtained before surgery and during chemotherapy. Follow-up information and patient and tumor characteristics were abstracted from medical records until December 1, 1994. By using multivariate Cox proportional hazards models for disease-free and overall survival it was evaluated whether outcome prediction was improved by inclusion of serum CA125 quantitations.
  Only FIGO stage and extent of residual tumor were significant independent prognostic factors before the start of chemotherapy. When such regression models were constructed after subsequent courses of chemotherapy, serum CA125 measurements conducted after each of the first three chemotherapy courses improved the prediction of disease-free survival. Prediction of overall survival was improved by inclusion of serum CA125 measurements after courses 1–6. Inclusion of serum CA125 measurements during chemotherapy improved prognostic assessment of patients with advanced EOC.     

Correlation of serum and ascitic IL-12 levels with second-look laparotomy results and disease progression in advanced epithelial ovarian cancer patients

Forty-two consecutive patients with advanced epithelial ovarian cancer who underwent primary surgical treatment were evaluated. The control group comprised 21 patients who had undergone surgery associated with benign pathologies. Forty-one patients had stage III disease except one who had stage IV. Optimal debulking (<1 cm) was performed in all the patients who subsequently received chemotherapy. Based on the results of the second-look laparotomy and follow-up, the patients were divided into three groups: the first group had negative second-look laparotomy or no evidence of disease during follow-up (n= 21), the second group had positive second-look laparotomy or progressive disease (n= 21), and the third was the control group (n= 21). Interleukin-12 (IL-12) levels were measured in preoperative serum and intraoperative ascites samples for all the patients. The mean serum IL-12 levels (+/-SD) in serum (S) and ascites (A) were as follows: in the first group, S: 108.44 +/- 76.40 pg/mL and A: 330.93 +/- 125.25 pg/mL; in the second group, S: 51.80 +/- 40.95 pg/mL and A: 206.89 +/- 113.47 pg/mL; and in the control group, S: 36.55 +/- 33.16 pg/mL and A: 93.62 +/- 73.07 pg/mL (P= 0.01). In the patients with advanced ovarian cancer, IL-12 levels in serum and ascites were higher compared to the levels of the controls. Also, there was an inverse relationship between initial serum and ascitic IL-12 levels and disease progression.     

Ⅲ期浆液性卵巢癌存活及复发相关因素分析

目的　探讨影响Ⅲ期浆液性卵巢癌存活及复发的相关因素。方法　回顾性分析 1 982年 1月～2 0 0 2年 6月在我院住院治疗的Ⅲ期浆液性卵巢癌患者的临床资料 ,比较年龄、不同FIGO亚期、病理分级、肿瘤细胞减灭术后残留肿瘤大小、盆腔及腹主动脉旁淋巴结状况及不同化疗情况的缓解率、缓解后的复发率及 3年、5年存活率。结果　 5 8例患者中 ,完全缓解 34例 ,部分缓解 8例 ,未缓解 1 6例。化疗≥ 6疗程者完全缓解率74 % ,<6疗程者无 1例完全缓解 ,二者之间差异有极显著性 (P <0 0 1 ) ;残留肿瘤直径 <2cm者 ,完全缓解率 80 % ,残留肿瘤直径≥ 2cm者 ,完全缓解率 4 7% ,二者之间差异有显著性 (P <0 0 5 ) ;盆腔及腹主动脉旁淋巴结无转移者完全缓解率 93% ,有转移加未切除者完全缓解率 4 7% ,二者之间差异有显著性 (P <0 0 1 )。多因素Logistic回归分析显示 :化疗和淋巴结状况是决定能否完全缓解的重要因素 ;影响 3年生存率及 5年生存率的主要因素首先是化疗 ,其次为淋巴结是否切除及是否转移。去掉淋巴结因素后Logistic回归分析显示 ,化疗是决定能否完全缓解的重要因素 ,影响 3年生存率的主要因素是化疗 ,影响 5年生存率的主要因素首先是化疗 ,其次为残留肿瘤大小。 34例完全缓解病例中 ,1 8例 (5 2 94 % )     

Expression of the c-Met in advanced epithelial ovarian cancer and its prognostic significance

The purpose of this study was to evaluate the prognostic significance of c-Met expression in advanced cases of epithelial ovarian carcinoma. Paraffin-embedded tissues from 41 stage IIIC primary ovarian adenocarcinoma were stained immunohistochemically for c-Met expression. The expression of c-Met was correlated with conventional clinicopathologic parameters and with overall survival of the patients. c-Met expression was found in 60.9% of cases. This clinicopathologic study showed that epithelial ovarian carcinomas with c-Met expression had higher histologic tumor grade and were more frequently associated with para-aortic lymph node metastasis (P < 0.05). In multivariate analysis, c-Met expression remained as a statistically significant predictor for survival with histologic grade. The patients with stage IIIC epithelial ovarian cancers whose tumors expressed c-Met were more likely to have high-grade tumors, have more para-aortic lymph node involvement, and have a significantly worse overall survival than those whose tumors were c-Met negative. In conclusion, c-Met expression might be a potential prognostic marker for patients with advanced-stage epithelial ovarian cancers.     

High-dose medroxyprogesterone acetate in advanced ovarian cancer

Abstract. Quinn MA, Rome RM, Grant P, Planner RS. High-dose medroxyprogesterone acetate in advanced ovarian cancer, int J Gynecol Cancer 1991; 1 : 239-241.
Seventeen patients with advanced ovarian malignancy were treated with high-dose medroxyprogesterone acetate. No objective responses were achieved. Four patients had stable disease, one of whom remains alive with disease at 30+ months.     

Tamoxifen in patients with advanced epithelial ovarian cancer

Tamoxifen was administered to 30 patients with persistent or recurrent epithelial ovarian cancer following initial plantinum-based chemotherapy. Two complete remissions (lasting 41 months and 12 months, respectively) were documented (6.6%), while 10 patients (33.3%) had stabilization of disease for a mean duration of 11.5 months. Tamoxifen was not associated with any significant toxicity and is a reasonable therapeutic option for patients with persistent or recurrent ovarian cancer, although it is only associated with modest activity. This paper reviews our experience with tamoxifen and summarizes the world literature.     

Prognostic significance of systematic lymphadenectomy as part of primary debulking surgery in patients with advanced ovarian cancer

Objective

The objective of this study was to evaluate the impact of systematic pelvic and para-aortic lymphadenectomy on survival in patients with advanced ovarian cancer.

Methods

We retrospectively analyzed the data of 189 consecutive patients with FIGO stage IIIC ovarian cancer between 2000 and 2011, who underwent primary cytoreductive surgery followed by platinum- and taxane-based chemotherapy. All patients were classified into two groups — patients who underwent systematic pelvic and para-aortic lymphadenectomy and those who did not. Progression-free (PFS) and overall survival (OS) times were analyzed using Kaplan-Meier method and Cox proportional hazards model.

Results

Patients who underwent systematic lymphadenectomy had significantly improved PFS (22 versus 9 months, p < 0.01) and OS (66 versus 40 months, p < 0.01). In patients with no gross residual disease (NGR) or residual disease 0.1-1 cm (GR-1), the median OS time of those who had lymphadenectomy was significantly longer than those who did not (86 versus 46 months, p = 0.02). However, in patients with residual disease > 1 cm (GR-B), there was no significant difference in OS according to lymphadenectomy (39 versus 40 months, p = 0.50). Among patients with NGR, the median OS time of those who underwent systematic lymphadenectomy was significantly longer than those who did not undergo lymphadenectomy (not yet reached [> 96] and 56 months, p < 0.01). No significant difference of OS between patients with and without lymphadenectomy was observed in the subgroup of patients with GR-1 (50 versus 38 months, p = 0.44). The performance of lymphadenectomy was a statistically significant and independent predictor of improved OS in addition to the status of residual disease and the performance of radical cytoreductive procedures (hazard ratio, 0.34; [95% CI, 0.23-0.52]; p < 0.01).

Conclusions

Systematic lymphadenectomy may have a therapeutic value and be significantly associated with improved survival in stage IIIC ovarian cancer patients with grossly no visible residual disease.     

Surgery and prognosis in stage III epithelial ovarian cancer

The results of this retrospective case study indicate that a composite of tumor grade, pattern of spread and substage at the time of opening affects the outcome most in the treatment of stage III epithelial tumors of the ovary. The poorest prognosis was associated with grade 3 histology, a pattern of spread requiring extensive and often difficult surgery for removal and a high substage. The best prognosis was usually associated with grade 1, with either very easily removed, isolated spread or low substage.
The extent of tumor defined the degree of primary cytoreduction possible. If the tumor was minimally extensive, primary cytoreduction results were excellent. The same conclusions were reached in the case of secondary cytoreduction at the time of second-look procedure. There was no statistically significant difference ( z = 1.481, P = 0.069) in 5-year survival between patients with microscopic only disease (59%) at second-look, and patients with gross disease not cytoreduced (36%).     

Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer

The immunohistochemical expression of HER-2/neu and cytofluorimetric data were retrospectively analyzed in a group of primary advanced ovarian cancers. Thirty-three out of 94 (35%) cases showed a specific p185/neu immunoreaction. No correlation between p185/neu expression and any of the clinico-pathologic parameters examined was observed. As far as cytofluorimetric data are concerned, 38 out of 69 (55%) of the tumors were diploid (DNA index = 1) while 31 (45%) were aneuploid (DNA index from 1.10 to 2.50 with a median value of 1.50). Ovarian tumors were defined as of low and high S-phase fraction in 68% and 32% of the cases, respectively. Tumor ploidy and S-phase fraction did not correlate with the clinico-pathologic characteristics or p185/neu oncoprotein expression. Aneuploid tumors had a higher S-phase fraction (mean: 15.81 ± 13.44) than diploid tumors (mean: 8.89 ± 7.98) ( P < 0.01). p185/neu expression failed to affect significantly both overall and progression free survival. On the other hand tumor ploidy was found to be related to the prognosis of advanced ovarian cancer patients although the difference was not statistically significant. As far as progression free survival is concerned, the median time to recurrence was not reached for diploid cases whereas it was 21 months for aneuploid cases ( P < 0.05). The 5-year survival for patients with a low S-phase fraction (58%) was significantly higher than for patients with high S-phase fraction tumors (28%) ( P < 0.01). Median time to recurrence was 48 and 17 months for low and high S-phase fraction tumor patients, respectively ( P < 0.05). However, in a multivariate analysis both tumor ploidy and S-phase fraction did not retain their prognostic value. The assessment of the role of the parameters examined in improving the prognostic characterization of ovarian cancer patients should be investigated in large multicenter clinical trials.     

晚期卵巢癌外科治疗中的过度与不足

国内卵巢癌循证医学研究非常少,特别是在卵巢癌手术方面,国际学术领域很少有我国学者的研究报道,因而对卵巢癌手术度的把握,观念上和实践上都非常匮乏。文章分别从卵巢癌外科治疗观念的变更、外科治疗中存在的过度与不足等方面进行讨论。