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Biomedical subjects

W Sauerbrei

Publications and source records attributed to W Sauerbrei.

At least 37 records · Page 2Linked to original sources
PubMed2000

Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients: an update based on 10 years' follow-up. German Breast Cancer Study Group.

PURPOSE: In 1984, the German Breast Cancer Study Group started a multicenter randomized trial to compare six versus three cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) starting perioperatively and to investigate the additional effect of tamoxifen as adjuvant treatment in node-positive breast cancer patients treated with mastectomy. PATIENTS AND METHODS: From 1984 to 1989, 473 patients were randomized from 41 institutions. After a median follow-up of approximately 10 years for overall survival (OS) and 9 years for event-free survival (EFS), the treatment groups were compared with respect to OS and EFS. Results based on a median follow-up of 56 months have been published earlier. RESULTS: Estimated cumulative locoregional incidence rate after 10 years was 19.9%; the corresponding rate of distant recurrences was 41.3%. Concerning duration of chemotherapy, we did not find any difference between six and three cycles of CMF (EFS: relative risk [RR] in multivariate analysis = 0.95; 95% confidence interval [CI], 0.74 to 1.21 OS: RR = 0.90; 95% CI, = 0.69 to 1.18). Treatment with tamoxifen resulted in an improvement in outcome (EFS: RR = 0.81; 95% CI, 0.61 to 1.07, OS: RR = 0.74; 95% CI, 0.55 to 1.0) although it proved not significant. Number of positive lymph nodes and progesterone receptor were the dominant prognostic factors. CONCLUSION: In this study, we observed some tendency in favor of hormonal treatment, which is in agreement with the literature. Concerning duration of chemotherapy, the results of this study provide further evidence that a reduction to three cycles of CMF is possible without increasing the risk of recurrence or death. For a definitive conclusion, however, further investigations are required.

Adult↗
PubMed2000

Role of isolated locoregional recurrence of breast cancer: results of four prospective studies.

PURPOSE: We evaluated the effect on future prognosis of an isolated locoregional recurrence (ILRR) after the primary diagnosis of breast cancer. Using data from four prospective studies of the German Breast Cancer Study Group, we investigated factors influencing prognosis after ILRR and defined a simple classification of patients into groups with different prognoses. PATIENTS AND METHODS: From 1983 to 1989, 2,746 patients were recruited into four studies comparing different treatments in primary breast cancer. After a median follow-up time of 8 years, 337 patients developed an ILRR as the first event. The influence of ILRRs on disease progression was examined. The effects of different prognostic factors on progression-free survival (PFS) and overall survival after ILRR were analyzed after a median follow-up time of 4.5 years. RESULTS: ILRRs increased the risk with respect to distant recurrence and death. After ILRR, 185 events occurred with respect to the PFS end point, and 171 patients died. Primary nodal status, tumor grade, estrogen receptor status of the primary tumor, and length of the disease-free interval (DFI) until the time of the ILRR had a significant prognostic impact. CONCLUSION: Determinants of prognosis after the ILRR should be taken into account for designing future risk-adapted clinical studies for these patients. Risk strata can be defined by a simple classification scheme based on primary nodal status and DFI.

Adult↗
PubMed1999

Modelling the effects of standard prognostic factors in node-positive breast cancer. German Breast Cancer Study Group (GBSG).

Prognostic models that predict the clinical course of a breast cancer patient are important in oncology. We propose an approach to constructing such models based on fractional polynomials in which useful transformations of the continuous factors are determined. The idea may be applied with all types of regression model, including Cox regression, the method of choice for survival-time data. We analyse a prospective study of node-positive breast cancer. Seven standard prognostic factors--age, menopausal status, tumour size, tumour grade, number of positive lymph nodes, progesterone and oestrogen receptor concentrations--were investigated in 686 patients, of whom 299 had an event for recurrence-free survival and 171 died. We determine a final model with transformations of prognostic factors and compare it with the more traditional approaches using categorized variables or assuming a straight line relationship. We conclude that analysis using fractional polynomials can extract important prognostic information which the traditional approaches may miss.

Breast Neoplasms↗
PubMed1999

Traditional reviews, meta-analyses and pooled analyses in epidemiology.

BACKGROUND: The use of review articles and meta-analysis has become an important part of epidemiological research, mainly for reconciling previously conducted studies that have inconsistent results. Numerous methodologic issues particularly with respect to biases and the use of meta-analysis are still controversial. METHODS: Four methods summarizing data from epidemiological studies are described. The rationale for meta-analysis and the statistical methods used are outlined. The strengths and limitations of these methods are compared particularly with respect to their ability to investigate heterogeneity between studies and to provide quantitative risk estimation. RESULTS: Meta-analyses from published data are in general insufficient to calculate a pooled estimate since published estimates are based on heterogeneous populations, different study designs and mainly different statistical models. More reliable results can be expected if individual data are available for a pooled analysis, although some heterogeneity still remains. Large prospective planned meta-analysis of multicentre studies would be preferable to investigate small risk factors, however this type of meta-analysis is expensive and time-consuming. CONCLUSION: For a full assessment of risk factors with a high prevalence in the general population, pooling of data will become increasingly important. Future research needs to focus on the deficiencies of review methods, in particular, the errors and biases that can be produced when studies are combined that have used different designs, methods and analytic models.

Breast Neoplasms↗
PubMed1999

The use of fractional polynomials to model continuous risk variables in epidemiology.

BACKGROUND: The traditional method of analysing continuous or ordinal risk factors by categorization or linear models may be improved. METHODS: We propose an approach based on transformation and fractional polynomials which yields simple regression models with interpretable curves. We suggest a way of presenting the results from such models which involves tabulating the risks estimated from the model at convenient values of the risk factor. We discuss how to incorporate several continuous risk and confounding variables within a single model. The approach is exemplified with data from the Whitehall I study of British Civil Servants. We discuss the approach in relation to categorization and non-parametric regression models. RESULTS: We show that non-linear risk models fit the data better than linear models. We discuss the difficulties introduced by categorization and the advantages of the new approach. CONCLUSIONS: Our approach based on fractional polynomials should be considered as an important alternative to the traditional approaches for the analysis of continuous variables in epidemiological studies.

Coronary Disease↗
PubMed1998

[Meta-analysis of epidemiologic studies].

BACKGROUND: A metaanalysis is often performed if risk assessment with available epidemiological data is not sensible. The results of these analyses serve mainly to quantify the risk of weak associations. MATERIAL AND METHODS: In this paper we describe methodologic issues of this approach with emphasis on the difference between metaanalysis from published data and from individual patient records. As an example we discuss studies on oral contraceptives and breast cancer. Limits of metaanalysis from published data are given. CONCLUSION: Although metaanalysis with individual data may be cost- and time-consuming their results are more reliable.

Breast Neoplasms↗
PubMed1998

Eight-year results of a prospective non-randomised study on therapy of small breast cancer. The German Breast Cancer Study Group (GBSG).

In this report, the results of the first controlled clinical trial on breast cancer in Germany, begun in 1983, are presented after a median follow-up of 8 years. Four-year results have been previously published. In pT1 N0 M0 breast cancer, mastectomy as the standard treatment was to be compared with tumorectomy plus radiotherapy to the remaining breast tissue. The study design, originally planned as a comprehensive cohort study including randomised and non-randomised patients, had to be changed into a prospective observation study due to the low randomisation rate. 1036 out of 1119 recruited patients were evaluable. After a median follow-up of 97 months, 237 events (local recurrence, regional recurrence, distant metastases, contralateral breast cancer or death of the patient without previous recurrence) occurred. With the exception of death without recurrence, the events were evenly distributed among the two treatment groups. The 8-year local recurrence rate of the whole patient population is 8.8%. Out of all prognostic factors examined, only tumour size and grade had a significant influence on recurrent disease. Event-free survival decreased in cases with 'uncertain' tumour margins, whereas the width of the margin has no influence on disease recurrence. Based on 151 deaths observed so far, there was no significant difference in overall survival between the two treatment groups. The 8-year results of this study are in accordance with the 4-year results reported previously and with those of other breast-conserving treatment trials. There was no significant difference between the two treatment groups with regard to event-free and overall survival. Incomplete tumorectomy had a negative influence on recurrence.

Adult↗
PubMed1998

The effect of oral contraceptive use on the prognosis of node positive breast cancer patients. German Breast Cancer Study Group.

The effect of oral contraceptive (OC) use as a risk factor for breast cancer was recently assessed in a large meta-analysis, but currently available data on the prognostic effect are still insufficient. We investigated the relationship between OC use and standard prognostic factors and the effect of OC use on recurrence-free survival (RFS) and overall survival (OS) in 422 premenopausal pT1a-3aN + M0 patients from two trials of the German Breast Cancer Study Group (GBSG). 137 patients (32.5%) were OC users. They were younger on average (mean age 41.5 years versus 45 years for non-OC users) and the percentage of patients with smaller tumours was higher in the group of OC users. Based on 163 events for RFS and 103 events for OS, no significant effect of OC use on RFS and OS could be demonstrated in univariate and multivariate analyses. In our study of node positive breast cancer cases, OC users were younger and had smaller tumours. This may be an effect of earlier detection of breast cancer, but OC users did not have a better prognosis, both before and after adjustment for tumour size and other prognostic factors.

Adult↗
PubMed1998

Differentiation of benign and malignant breast tumors by logistic regression and a classification tree using Doppler flow signals.

In breast examinations with Doppler, an increased flow is found in malignant tumors. With the relatively new color Doppler, we measured different flow values in 133 cancer patients and in 325 women with benign disease. These measurements were used to develop diagnostic rules. For the highly correlated flow values, we used a stepwise procedure to select a final logistic regression model and a tree-based approach, which is a different way of modeling. With both approaches we developed simple diagnostic rules of which the sensitivity and the specificity exceeded 90%. There are no differences between the two approaches concerning discriminative ability. As complex statistical modeling leads to an overoptimism in the assessment of the error rates, we applied sensitivity analysis, investigated the stability of the selected logistic regression model, and estimated the magnitude of the overoptimism of the diagnostic rules with resampling methods. The results indicate that the estimates of sensitivity and specificity are probably close to realistic values for a clinical setting.

Blood Flow Velocity↗
PubMed1997

Resampling and cross-validation techniques: a tool to reduce bias caused by model building?

The process of model building involved in the analysis of many medical studies may lead to a considerable amount of over-optimism with respect to the predictive ability of the 'final' regression model. In this paper we illustrate this phenomenon in a simple cutpoint model and explore to what extent bias can be reduced by using cross-validation and bootstrap resampling. These computer intensive methods are compared to an ad hoc approach and to a heuristic method. Besides illustrating all proposals with the data from a breast cancer study we perform a simulation study in order to assess the quality of the methods.

Bias↗
PubMed1997

Color Doppler and duplex flow analysis for classification of breast lesions.

The purpose of this study was to evaluate the differences of blood supply in benign and malignant breast tumors by color Doppler flow measurements. The study included 471 patients, 133 with carcinomas, 325 with benign breast lesions, and 13 with mastitis. An ATL UM9/HDI was used with an electronic 10-MHz linear array broadband transducer. The following flow data were analyzed: Presence of vascularity; number of tumor arteries; the mean, minimum, maximum RI index, and AB ratio; the mean, minimum, and maximum peak systolic flow velocity and the sum of all peak systolic flow velocities in each tumor. In all cancers and in most benign pathologies vascularity was found. Highly significant differences between benign and malignant were found for all quantitative flow data such as number of tumor arteries and blood flow velocity (P < 0.0001). Flow profiles analyzed by RI index and AB ratio showed a trend for increased flow resistance in malignancies. However, due to the wide overlap between benign and malignant, indices did not allow a sufficient differentiation. The study showed that standardization of the Doppler examination technique and equipment parameters is essential for vascularity assessment of tumors.

Adult↗
PubMed1997

Randomized study comparing carboplatin/cyclophosphamide and cisplatin/cyclophosphamide as first-line treatment in patients with stage III/IV epithelial ovarian cancer and small volume disease. German Ovarian Cancer Study Group (GOCA).

UNLABELLED: Several randomized studies in patients with advanced ovarian cancer have dealt with the comparison of cisplatin and carboplatin when given as either a single drug or in combination. The German Ovarian Cancer Study Group (GOCA) performed a prospective randomized trial in a subgroup of patients specified by a successful cytoreductive operation before the start of chemotherapy. From February 1987 to May 1990, 173 previously untreated patients with stage III and IV disease and limited tumor bulk of <2 cm postoperatively received either cyclophosphamide 600 mg/m2 plus carboplatin 350 mg/m2 or cyclophosphamide 1000 mg/m2 plus cisplatin 80 mg/m2. The drugs had to be administered on Day 1 every 28 days for six subsequent courses. RESULTS: In 158 assessable patients no significant differences in pathologically confirmed CR rates (pCR: 14% vs 16%), median time to progression (PFI: 19 months vs 26 months), and overall survival (OS: 35 months vs 37 months) were observed. Refusal of therapy due to toxicity was more frequent in the cisplatin arm, whereas patients with progressive disease predominated in the carboplatin arm. Nonhematologic adverse effects were more likely to occur with cisplatin whereas carboplatin patients experienced more myelosuppression. As prognostic factors associated with an increased risk of progressive disease and shorter overall survival time, stage of disease and amount of residual tumor after first surgery were determined. CONCLUSIONS: Carboplatin proved to be effective in patients with optimally debulked ovarian cancer. However, neither regimen used in this trial is sufficiently active to prevent tumor progression in the majority of patients.

Adult↗
PubMed1997

[Limitations of meta-analysis from published data in epidemiological research].

Metaanalyses of epidemiological studies have increased during the last years and are often used to evaluate the effect of risk factors which are inconsistent in different studies, mainly for small risk factors. Very often a metaanalysis is performed from published data. In this article we discuss this form of a metaanalysis and investigate whether the requirement to get reliable information is achievable with it. We mainly ask questions whether qualitative and quantitative dose-response analysis can be performed. We point out the differences between metaanalysis from experimental data and clinical randomized studies and epidemiological studies. We discuss different arguments that were given for performing metaanalysis in clinical trials and investigate whether they are also valid in observational studies. We mainly concentrate on the problem of estimating a single pooled risk estimate. Two examples from literature are used to show problems with metaanalysis from published data.

Bias↗
PubMed1997

Diagnostic formula for the differentiation of adnexal tumors by transvaginal sonography.

OBJECTIVE: To create a strategy for sonographic differentiation of benign and malignant adnexal tumors in premenopausal and postmenopausal patients. METHODS: Multiple sonomorphologic criteria were analyzed prospectively in 754 tumors. Four hundred were found in premenopausal and 354 in postmenopausal women. In a logistic regression model, relevant criteria were selected, and a diagnostic formula for tumor differentiation was derived. RESULTS: There were 165 malignant tumors, of which 37 (9.2%) were found in premenopausal and 128 (36.2%) in postmenopausal women. In both groups, the criteria of solid phase and ascites were the most significant. Further important diagnostic criteria were structure and tumor size in premenopausal women and cyst architecture and tumor surface in postmenopausal women. These results allowed an estimation of the probability of malignancy. Using a cutoff point of 10% for the probability to classify tumors as malignant, the sensitivity and specificity in premenopausal patients were 86.5% and 92.6%, respectively, with an accuracy of 92%. In postmenopausal women, the sensitivity, specificity, and accuracy were 93%, 82.7%, and 86.6%, respectively. Assuming a prevalence as given in the study, the positive and negative predictive values were 54.4% and 98.5% in premenopausal and 75.3% and 95.4% in postmenopausal women. CONCLUSIONS: With four binary criteria, a useful diagnostic formula for tumor differentiation was obtained. However, estimates for sensitivity, specificity, and accuracy may be too optimistic because they were derived from the same data that were already used for model selection.

Adnexa Uteri↗
PubMed1997

Validation of existing and development of new prognostic classification schemes in node negative breast cancer. German Breast Cancer Study Group.

Several prognostic classification schemes in node negative breast cancer are proposed, but only the Nottingham Prognostic Index (NPI) seems to be sufficiently validated. Validation, which is a prerequisite for a sensible assessment, is not published for two recent proposals according to Glick et al. [1] and Rubens [2]. The German Breast Cancer Study Group (GBSG) entered 662 eligible patients in a prospective observational study. 603 of them had complete data for seven 'standard' prognostic factors and median follow-up is about 5 years. As there is no accepted and informative measure of separation for classification schemes presently available, we propose a new one and use it additionally to the well known logrank-test and Kaplan-Meier estimates to investigate the predictive power of the three schemes. significant differences in survival and recurrence-free survival could be established for the NPI subgroups but not for others where even the ordering of the groups was different. With the Cox model and the classification and regression tree approach we develop two new proposals for the differentiation of subgroups of node negative patients. As in the NPI, tumor size and grade are the most important factors, but with a different weighting scheme. Young age (< or = 40 years) and very high estrogen receptor values (> 300 fmol) in a small subgroup of patients were associated with worse prognosis. The new proposals showed a better degree of separation, which demonstrates that an improvement seems possible using standard factors. Because the measures of separation give an overoptimistic impression for the new proposals, a validation with other studies is necessary before a general recommendation can be given.

Adult↗
PubMed1997

Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer.

PURPOSE: We investigated quality and efficacy criteria of an autologous, physically and immunologically purified, Newcastle disease virus (NDV)-modified, irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a through c) of patients vaccinated between 1991 and 1995. MATERIALS AND METHODS: Included were 63 patients with primary breast cancer (a), 27 with metastatic pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy as supportive treatment. After cryoconservation and purification, the vaccines varied in applied numbers of viable cells and dead cell contaminations. We retrospectively hypothesized that an immunogenic vaccine should contain at least 1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort was thus divided into two groups; one that received vaccine type A (A), fulfilling both criteria; and the other type B (B), missing one or both criteria. RESULTS: Conventional prognostic factors were wall balanced between A and B in cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and disease-free survival (P = .089) for A. In addition, in cohort a, the relative risk of dying in the group that received A as compared with B was 0.2 (univariate Cox model). There were also survival trends in favor of A versus B (P = .18 and P = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42, respectively. In cohort b, the survival benefit could not be ascribed to vaccine quality alone, because of prognostic imbalance in favor of A. CONCLUSION: In cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV-NDV vaccine quality, since prognostic factors were not biased. This could imply clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality vaccine. Furthermore, the data provide clinically relevant information for standardization and quality control of autologous tumor-cell vaccines. A randomized study is urgently needed.

Breast Neoplasms↗