Early and specific prediction of the therapeutic efficacy in non-small cell lung cancer patients by nucleosomal DNA and cytokeratin-19 fragments.
Facing an era of promising new antitumor therapies, predictors of therapy response are needed for the individual management of treatment. In sera collected prospectively from 311 patients with advanced non-small cell lung cancer receiving first-line chemotherapy, changes in nucleosomal DNA fragments, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) were investigated and correlated with therapy response. In univariate analysis, high levels, slower and incomplete decline in nucleosomal DNA, CYFRA 21-1, and CEA predicted poor outcome. DNA concentrations at day 8 of the first therapeutic cycle and CYFRA 21-1 before start of the second cycle were identified as best predictive variables. In multivariate analysis, they predicted progression with a specificity of 100% in 29% of the cases earlier than imaging techniques. Thus, nucleosomal DNA and CYFRA 21-1 specifically identify a subgroup of patients with insufficient therapy response at the early treatment phase and showed to be valuable for disease management.
Holdenrieder
Stefan
S
Institute of Clinical Chemistry, University Hospital of Munich-Grosshadern, Munich, Germany. Stefan.Holdenrieder@med.uni-muenchen.de
Stieber
Petra
P
VON Pawel
Joachim
J
Raith
Hannelore
H
Nagel
Dorothea
D
Feldmann
Knut
K
Seidel
Dietrich
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism*; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053539:Keratin-19; D009707:Nucleosomes; D010446:Peptide Fragments; C102012:antigen CYFRA21.1; D007633:Keratins