Predictive And Prognostic Biomarker Models In Advanced Lung Cancer
JOURNAL OF CLINICAL ONCOLOGY(2008)
摘要
19010 Background: Biomarker models may be effective for prediction of therapy response and prognosis of overall survival. Methods: 60 clinical factors, “classical” laboratory and oncological biomarkers were prospectively investigated on 300 patients with newly diagnosed advanced NSCLC before and during first-line chemotherapy to test whether i) predictive and prognostic markers are identical, ii) biomarkers have additive prognostic impact to clinical factors, iii) intratherapeutical biomarkers improve prognostic models, iv) biomarkers are useful for early estimation of therapy response? Univariate evaluations were done by Wilcoxon and Logrank tests, multivariate analyses by Cox regression. Results: 30% of patients had progression after 2 cycles of chemotherapy and 57% deceased during observation time (1–29 months). Concerning pretherapeutic markers, strong predictors of therapy response were also highly relevant for prognosis, such as performance score (PS), metastases other than lung (MOL), chemotherapy, WBC, CRP, albumin, CYFRA 21–1, nucleosomes, CA125, CA15–3, and CA72–4. Multivariate analysis revealed PS, MOL, chemotherapy, CRP and CYFRA 21–1 as independent prognostic parameters. When intratherapeutic markers were included, CYFRA 21–1 and nucleosomes before 2nd therapy cycle (BV2), and therapy response also indicated strongly and independently survival and improved the prognostic power of the model. Further, combination of nucleosomes on day 8 and CYFRA 21–1 (BV2) already enabled the detection of insufficient therapy efficacy after one cycle of chemotherapy in 29% of progressive patients with 100% specificity. At 90% specificity, sensitivity rose to 55%. Conclusion: In advanced lung cancer, highly predictive pretherapeutical biomarkers had also high prognostic relevance. Biomarkers determined during 1st therapy cycle improved the prognostic model and enabled the early estimation of therapy response. No significant financial relationships to disclose.
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关键词
prognostic biomarker models,advanced lung cancer,lung cancer,predictive
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