PURPOSE: We investigated the potential of circulating, nucleosomal DNA for the early prediction of the efficacy of chemotherapy in patients with advanced lung cancer. EXPERIMENTAL DESIGN: In serum of 212 patients with newly diagnosed non-small cell lung cancer (stages III and IV) undergoing chemotherapy, nucleosomes (ELISA, Roche) were measured at days 1, 3, 5, and 8 of the first cycle and before each new therapeutic cycle. Additionally, carcinoembryonic antigen and cytokeratin 19 fragments (CYFRA 21-1; Elecsys, Roche) were determined before each cycle. The therapeutic success was classified by computed tomography before start of the third cycle according to the World Health Organization criteria. RESULTS: In univariate analysis, responders (patients with remission) showed significantly (P < 0.05) lower values for the area under the curve of days 1 to 8 (AUC 1-8) of nucleosomes, the pretherapeutic baseline values of cycle 2 (BV2) and cycle 3 (BV3) of nucleosomes, and higher decreases of the baseline values from cycle 1 to 2 (BV1-2) and from cycle 1 to 3 (BV1-3) compared with nonresponders (patients with stable or progressive disease). Additionally, CYFRA 21-1 (BV1, BV2, BV3, BV1-2, BV1-3) and carcinoembryonic antigen (BV1-2) discriminated significantly between both groups. In multivariate analysis including all parameters available until end of the first therapeutic cycle, nucleosomes (AUC 1-8), CYFRA 21-1 (BV1), stage, and age were independent predictors of therapy response with nucleosomes (AUC 1-8) having the strongest impact. CONCLUSION: Circulating nucleosomes in combination with oncological biomarkers are valuable for the early estimation of the efficacy of chemotherapy in patients with lung cancer.
PURPOSE: We investigated the potential of circulating, nucleosomal DNA for the early prediction of the efficacy of chemotherapy in patients with advanced lung cancer. EXPERIMENTAL DESIGN: In serum of 212 patients with newly diagnosed non-small cell lung cancer (stages III and IV) undergoing chemotherapy, nucleosomes (ELISA, Roche) were measured at days 1, 3, 5, and 8 of the first cycle and before each new therapeutic cycle. Additionally, carcinoembryonic antigen and cytokeratin 19 fragments (CYFRA 21-1; Elecsys, Roche) were determined before each cycle. The therapeutic success was classified by computed tomography before start of the third cycle according to the World Health Organization criteria. RESULTS: In univariate analysis, responders (patients with remission) showed significantly (P < 0.05) lower values for the area under the curve of days 1 to 8 (AUC 1-8) of nucleosomes, the pretherapeutic baseline values of cycle 2 (BV2) and cycle 3 (BV3) of nucleosomes, and higher decreases of the baseline values from cycle 1 to 2 (BV1-2) and from cycle 1 to 3 (BV1-3) compared with nonresponders (patients with stable or progressive disease). Additionally, CYFRA 21-1 (BV1, BV2, BV3, BV1-2, BV1-3) and carcinoembryonic antigen (BV1-2) discriminated significantly between both groups. In multivariate analysis including all parameters available until end of the first therapeutic cycle, nucleosomes (AUC 1-8), CYFRA 21-1 (BV1), stage, and age were independent predictors of therapy response with nucleosomes (AUC 1-8) having the strongest impact. CONCLUSION: Circulating nucleosomes in combination with oncological biomarkers are valuable for the early estimation of the efficacy of chemotherapy in patients with lung cancer.
Authors: Takuji Mori; Steven J O'Day; Naoyuki Umetani; Steve R Martinez; Minoru Kitago; Kazuo Koyanagi; Christine Kuo; Teh-Ling Takeshima; Robert Milford; He-Jing Wang; Vu D Vu; Sandy L Nguyen; Dave S B Hoon Journal: J Clin Oncol Date: 2005-12-20 Impact factor: 44.544
Authors: Oliver J Stoetzer; Debora M I Fersching; Christoph Salat; Oliver Steinkohl; Christian J Gabka; Ulrich Hamann; Michael Braun; Axel-Mario Feller; Volker Heinemann; Barbara Siegele; Dorothea Nagel; Stefan Holdenrieder Journal: Tumour Biol Date: 2012-09-15