Factor In Advanced Ovarian Cancer Research Articles

The prognostic effects of performance status and quality of life scores on progression-free survival and overall survival in advanced ovarian cancer

Objective. Performance status (PS) is an important prognostic factor in advanced ovarian cancer. The purpose of this study was to evaluate the prognostic significance of PS and quality of life (QoL) assessment on progression-free survival (PFS) and overall survival (OS) in patients with advanced ovarian cancer. Methods. We studied Canadian patients participating in an intergroup study in ovarian cancer (NCIC-OV10), which randomized patients to receive either standard chemotherapy using cisplatin/cyclophosphamide or cisplatin/paclitaxel chemotherapy. QoL was assessed using the EORTC quality of life questionnaire (QLQ-C30+3). The effects of multiple variables including the relevant clinical variables, PS and QoL scores were analyzed by Cox stepwise regression at baseline and again 3 months after completion of chemotherapy. Results. At baseline and at 3 months after chemotherapy, there were 151 and 93 patients respectively who completed the QLQ-C30+3 questionnaires. Baseline PS, global QoL score and treatment were independent predictors for both PFS and OS. Baseline cognitive functioning score was also an additional independent predictor for OS. At 3 months after completion of chemotherapy global QoL score, PS and grade were significant independent predictors of OS; however, only physical functioning score, emotional functioning score and tumor grade predicted for PFS. Conclusions. Performance status and global quality of life scores at baseline are prognostic factors in advanced ovarian cancer for both PFS and OS. Higher baseline cognitive functioning scores were also associated with improved survival. Global QoL scores at 3 following completion of chemotherapy proved to be of prognostic significance for OS but not PFS.

The prognostic effects of performance status (PS) and quality of life (QoL) scores on progression-free survival (PFS) and overall survival (OS) in advanced ovarian cancer

5066 Background: Performance status is an important prognostic factor in advanced ovarian cancer. We sought to evaluate the relationship between PS and EORTC QLQ-C30 QoL scores and the PFS and OS in advanced ovarian cancer. Methods: Canadian data was analyzed as part of an intergroup randomized trial in ovarian cancer (NCIC-OV10). Patients were randomized to receive either standard chemotherapy using cisplatin/cyclophosphamide or cisplatin/paclitaxel chemotherapy. The EORTC QoL questionnaire QLQ-C30 was administered just prior to starting chemotherapy, at each cycle, and every 3 months thereafter for two years or until disease progression. We determined PS and QoL scores in the following domains: physical, role, emotion, cognitive, social function and global QoL at baseline and 6 months after completing chemotherapy. Effects of multiple variables including treatment, PS, QoL scores, age, stage, grade, residual disease and histology were analyzed by Cox stepwise regression using PFS and OS as the outcome variables. Results: At baseline and at 6 months after chemotherapy, there were 151 and 80 patients respectively who completed QoL assessments. The Cox model revealed that baseline PS, global QoL and treatment were independent predictors for both PFS and OS, and grade and cognitive functioning were additional independent predictors for OS. Physical function at six months after completion of chemotherapy was the only significant independent predictor of both PFS and OS, with age and grade as two additional independent predictors for subsequent OS. Conclusions: Performance status and global quality of life scores at baseline are prognostic factors in advanced ovarian cancer for both PFS and OS. Higher baseline cognitive functioning scores were also associated with improved survival. Higher physical function scores at six months after completing chemotherapy predicted longer PFS and OS. (This research was supported by the NCIC through funds received by the Canadian Cancer Society). No significant financial relationships to disclose.

Role of primary surgery in advanced ovarian cancer

BackgroundMajor issues in surgery for advanced ovarian cancer remain unresolved. Existing treatment guidelines are supported by a few published reports and fewer prospective randomized clinical trials.MethodsWe reviewed published reports on primary surgical treatment, surgical expertise, inadequate primary surgery/quality assurance, neoadjuvant chemotherapy, interval debulking, and surgical prognostic factors in advanced ovarian cancer to help resolve outstanding issues.ResultsThe aim of primary surgery is a well-planned and complete intervention with optimal staging and surgery. Surgical debulking is worthwhile as there are further effective treatments available to control unresectable residual disease. Patients of gynecologic oncology specialist surgeons have better survival rates. This may reflect a working 'culture' rather than better technical skills. One major problem though, is that despite pleas to restrict surgery to experienced surgeons, specialist centers are often left to cope with the results of inadequate primary surgical resections. Patients with primary chemotherapy or those who have had suboptimal debulking may benefit from interval debulking. A proposal for a better classification of residual tumor is given.ConclusionsOptimal surgical interventions have definite role to play in advanced ovarian cancers. Improvements in surgical treatment in the general population will probably improve patients' survival when coupled with improvements in current chemotherapeutic approaches.

Sample size considerations for the evaluation of prognostic factors in survival analysis

When the role of a new prognostic factor is investigated, careful planning of an appropriate study is required. This includes an assessment of the power of the study in terms of sample sizes. An adequate analysis of the independent prognostic effect of a new factor has to be adjusted for the existing standard factors. With survival time as endpoint this will usually be done with the Cox proportional hazards model. Sample size and power formulae in survival analysis have been developed by Schoenfeld for randomized treatment comparisons. In the analysis of prognostic factors the covariates included are expected to be correlated with the factor of primary interest. In this situation, the existing sample size and power formulae are not valid and may not be applied. In this paper, Schoenfeld's formula is first extended to the situation where a correlated factor is included in the analysis. The validity of the resulting approximate asymptotic formula is investigated for its asymptotic behaviour by numerical integration and for its finite behaviour by simulation. Second, an approximate formula for sample size and power is provided to detect an interaction between the interesting and a second correlated factor. This extends the formula for independent effects. Finally, the approach is illustrated by an example on the prognostic impact of DNA ploidy and other factors in advanced ovarian cancer. Copyright © 2000 John Wiley & Sons, Ltd.

Sample size considerations for the evaluation of prognostic factors in survival analysis

When the role of a new prognostic factor is investigated, careful planning of an appropriate study is required. This includes an assessment of the power of the study in terms of sample sizes. An adequate analysis of the independent prognostic effect of a new factor has to be adjusted for the existing standard factors. With survival time as endpoint this will usually be done with the Cox proportional hazards model. Sample size and power formulae in survival analysis have been developed by Schoenfeld for randomized treatment comparisons. In the analysis of prognostic factors the covariates included are expected to be correlated with the factor of primary interest. In this situation, the existing sample size and power formulae are not valid and may not be applied. In this paper, Schoenfeld's formula is first extended to the situation where a correlated factor is included in the analysis. The validity of the resulting approximate asymptotic formula is investigated for its asymptotic behaviour by numerical integration and for its finite behaviour by simulation. Second, an approximate formula for sample size and power is provided to detect an interaction between the interesting and a second correlated factor. This extends the formula for independent effects. Finally, the approach is illustrated by an example on the prognostic impact of DNA ploidy and other factors in advanced ovarian cancer.

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.

Recursive partition methods for the analysis of prognostic factors in advanced ovarian cancer

Recursive partition methods for the analysis of prognostic factors in advanced ovarian cancer

A meta-analysis of prognostic factors in advanced ovarian cancer with median survival and overall survival (measured with the log (relative risk)) as main objectives

We performed a meta-analysis of 38 articles containing 66 treatment groups and 3443 patients in order to evaluate prognostic factors in advanced epithelial ovarian cancer. To evaluate overall survival we designed a method to summarize the overall survival curve into one single figure: the log (relative risk) (LRR). This is the first meta-analysis using overall survival (measured with the LRR) as an objective. We found that the main prognostic factors predicting an improved survival (measured with the LRR) are: chemotherapy including cisplatin as initial treatment, a residual tumour mass of less than 2 cm prior to therapy, FIGO stage II/III and a good performance status. In a multivariate model, the use of cisplatin and the residual tumour were found to be the only factors of prognostic relevance. No relation between median survival and the overall clinical response rate of all patients entered in the denominator, could be demonstrated. Undifferentiated tumours and patients treated with cisplatin regimens had higher response rates to treatment but younger patients and those with endometrioid histology were less likely to respond. A surgical complete remission was encountered more frequently among studies that included a high number of patients with small tumour masses prior to treatment. Trials using cisplatin included more patients with small tumour nodules in their patient material compared to studies not using this drug. The data illustrate the danger of comparing studies with each other. In the trials with a high percentage of patients with small tumour residuals in the study population more toxic deaths were seen. This probably reflects the fact that they had received more intensive treatment. The LRR correlated strongly with the median survival, response and the percentage of surgical complete remissions. We concluded that the introduction of the LRR can be a meaningful addition to the evaluation of the influence of prognostic factors on overall survival.

Tumor ploidy as a major prognostic factor in advanced ovarian cancer.

Tumor ploidy was determined by flowcytometry (FCM) in paraffin-embedded tissue of 74 patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] 2B, 3, 4). Significant differences in survival and progression-free survival were found between classes of tumor ploidy as well as for several clinical parameters, including FIGO stage, histologic grade, diameter of the largest metastases, presence of ascites, peritoneal carcinomatosis, and size of residual tumor. In a Cox regression analysis, tumor ploidy and presence or absence of ascites were the only significant factors for survival, whereas ascites and residual tumor proved to be the significant parameters for progression-free survival. Tumor ploidy was strongly associated with tumor bulk, size of residual tumor, and histologic grade. Tumor ploidy was the same within different tumor sites in the majority of the cases. On the basis of these findings tumor ploidy is considered to be a major prognostic factor for survival in advanced ovarian cancer.