Abstract
e18010 Background: TK is an enzyme supporting DNA synthesis under conditions of increased cell proliferation. The prognostic significance of TK1 activity in hematological malignancies and early stage solid cancers are well studied but little is known about the prognostic significance of TK1 activity in metastatic NSCL cancer. Methods: TK1 activity was measured by means of novel high sensitive non radioactive DIVITUM assay. We prospectively measured serum TK1 activity immediately before the first and second cycle of the treatment in 48 consecutive metastatic NSCL cancer patients. 10 healthy volunteers were also included as a control group. We aimed to evaluate the value of prognostic significance of TK1 activity. In addition, the clinical significance of the difference between the two serum TK1 activity levels was also assessed. Results: The mean TK1 level in the study group was significantly higher than the controls (respectively 325.6±63.46 vs. 32.97±7.307; p<0.0001). TK1 levels were positively correlated with weight loss (p=0.039). TK1 activity levels in the squamous subtype were higher than the adenocarcinoma but this difference was not significant. (respectively 444.2 ± 143.4 vs. 225.1 ± 59.77; p=0.108). A cut off value of 156 Du/l (AUC 0.77 %95 CI 0.62-0.92; sensitivity %56,1-specifity %14) was determined by ROC curve analysis. High TK1 values were associated with decreased PFS and OS. In multivariate analysis TK1 levels continued to be an independent prognostic factor for patients with metastatic NSCLC (p value for OS was found to be 0.02). Although the difference was not clinically significant, the mean TK1 levels before second cycle of chemotherapy was higher than baseline TK1 levels before the start of chemotherapy (respectively 620±35.3Du/L vs. 325.6±63.46 Du/l p). Conclusions: TK1 levels serve as a good independent prognostic factor in the metastatic setting for NSCLC. Early evaluation of TK1 levels during chemotherapy can not be used for monitoring treatment response. In addition TK1 can be a valuable molecular molecular therapeutic target for metastatic NSCLC.
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