Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients.

BACKGROUND: Patients with metastatic colorectal cancer are usually offered systemic chemotherapy as palliative treatment. A multivariate analysis was performed in order to identify predictors and their constellation that allow a valid prediction of the outcome in patients treated with 5-fluorouracil (5-FU)-based therapy. PATIENTS AND METHODS: A total of 3825 patients treated with 5-FU within 19 prospective randomised and three phase II trials were separated into learning (n = 2549) and validation (n = 1276) samples. Data were analysed by tree analysis using the recursive partition and amalgamation method (RECPAM). A predictor could only enter the RECPAM analysis if the number of patients with missing values was < 33.3% within a node, and the minimal node size was set to 50 patients. Twenty-three potential predictors were grouped into subsets of laboratory variables (11 parameters), tumour-related variables (seven parameters) and clinical variables (five parameters). In the first step, tree analysis was performed separately for each predictor subset. The selected prognostic parameters of the resulting partial models (the 'winners') were entered into the general model. The classification rule from the data of the learning set was applied to the independent validation set. RESULTS: Winners of the subgroup analysis for laboratory variables were: platelets > or = 400 x 10(9)/l, alkaline phosphatase > or = 300 U/l, white blood cell (WBC) count > or = 10 x 10(9)/l and haemoglobin < 11 x 10(9)/l, and all predicted a worse outcome. Negative predictors within the subgroup of tumour parameters were: number of tumour sites more than one or more than two, presence of liver metastases or peritoneal carcinomatosis, which predicted a worse outcome. Furthermore, presence of lung metastases, a primary rectal cancer and presence of lymph node metastases all predicted a better outcome in the multivariate setting. Among the clinical parameters only performance status of ECOG 0 or 1 predicted better outcome. In the final regression tree, three risk groups could be identified: low risk group (n = 1111) with a median survival of 15 months for patients with ECOG 0/1 and only one tumour site; intermediate risk group (n = 904) with a median survival of 10.7 months for patients with ECOG 0/1 and more than one tumour site and alkaline phosphatase < 300 U/l or patients with ECOG > 1, WBC count < 10 x 10(9)/l and only one tumour site; high risk group (n = 534) with a median survival of 6.1 months for patients with ECOG 0/1 and more than one tumour site and alkaline phosphatase of > or = 300 U/l or patients with ECOG > 1 and more than one tumour site or WBC count > 10 x 10(9)/l. The median survival times for the good, intermediate and high risk groups in the validation sample were 14.7, 10.5 and 6.4 months, respectively. CONCLUSIONS: Patients can be divided into at least three risk groups depending on the four baseline clinical parameters: performance status, WBC count, alkaline phosphatase and number of metastatic sites. Any molecular or biological marker should be validated against these clinical parameters and decisions for more or less intensive treatments may be studied separately in these three risk groups. Also, clinical trials should be stratified according to the three risk groups.

[In-vitro research on the marginal adaptation of composites with the use of different dentin adhesives]. / In-vitro-Untersuchungen zur marginalen Adaptation von Komposits bei Anwendung verschiedener Dentinhaftmittel.

The aim of this investigation was the check and evaluation of 7 various dentin adhesives regarding their influence on the connection between dentin resp. enamel and composite filling. For that cylindrical cavities in dental crowns (enamel cavities) and roots (dentin cavities) were prepared and treated with dentin adhesives and composite materials. One part of the test teeth was subjected to loads storage in aqueous solution and thermocycling. The marginal adaptation of the composite filling was checked by means of the dye penetration test. The evaluation was made after cutting the teeth in the stereo microscope TECHNIVAL 2 (Carl Zeiss Jena) at 16-resp. 25 magnifications and defined criteria. The fillings in cavities bound by enamel exhibited a very good marginal adaptation of the composite. The location of the dentin cavity (crown or root dentin) had no significant influence on the fitting of the filling. A clear penetration of dye could be observed with the fillings in the dentin with and without adhesives, which considerably intensified after thermocycling. Best results with regard to the marginal adaptation were obtained with Scotchbond 2, Mirage-Bond and Cavex-Clearfil-Newbond. A restoration without a marginal gap was not possible.