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Furthermore, LDH contributes to prognostic models in malignancies such as renal cell cancer, germ cell tumours, and non-Hodgkin's lymphomas. We have therefore decided to select LDH as a promising factor on which we perform a pilot study investigating methodological aspects the following site of biomarker studies in patients with brain metastases, before embarking on large-scale studies that will look at a larger number of candidate markers in an expanded patient cohort.2. Material and MethodsWe analyzed patients from a previously described brain metastases database, which is maintained and updated at the first author's institution [8, 9]. For this retrospective pilot study, 100 patients with available information on LDH treated with palliative whole-brain radiotherapy (WBRT; total dose 30Gy in 10 fractions; no surgery or radiosurgery) during the last 5 years were selected.

A backward inclusion was used starting with all patients treated in 2011. Patients were entered on a year-by-year basis until the target group size of 100 was reached. All patients were treated at two different institutions in northern Norway. LDH was part of routine blood chemistry and imaging assessment in patients with newly detected brain metastases treated Temsirolimus mTOR inhibitor in these institutions. LDH measurement no older than 2 weeks before the first fraction of WBRT was required. Elevated LDH was defined as ��205 U/l according to the hospitals' reference value. The prognostic impact of LDH was tested in various fashions (comparison of normal versus elevated LDH; normal versus 1.

5x upper limit of normal (ULN) as cut-off; by quartiles and by kinetics) in univariate analyses (log-rank test). Actuarial survival was calculated with the Kaplan-Meier method and compared between different groups with the log-rank Axitinib test. For multivariate analysis of survival Cox regression analysis was used. A P value �� 0.05 was considered statistically significant. Sixteen patients were alive at last follow-up (June 01, 2011) with a median follow-up of 8 months (range 1�C42). The patient characteristics are shown in Table 1.Table 1Pretreatment characteristics of all 100 patients included in this study.3. Results3.1. Univariate AnalysesPatients with normal LDH (<205 U/l) had significantly longer survival (median 4.0 months) as compared to those with elevated LDH (median 3.1 months), P = 0.037 (Figure 1). With a different cut-off (1.

5x ULN, i.e., LDH <307 U/l), a P value of 0.013 was found (median survival 3.0 versus 4.0 months), (Figure 2). When evaluated by quartiles, median survival was 5.5 months in patients with the lowest LDH, 3.4 months in those with intermediate LDH, and 2.8 months in those with the highest LDH, P = 0.017 (Figure 3). Given that the lowest P value was found when discriminating between patients with LDH higher versus lower 1.5x ULN, this cut-off was chosen for confirmatory analyses stratified by primary tumour type. Consistent trends were seen for all primary tumour types despite low numbers of patients. Regarding lung cancer, median survival was 3.1 months in patients with elevated LDH and 5.6 months in others; P = 0.145.