Nucleosomes and CYFRA 21-1 indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer.
The increasing panel of systemic therapies enables the individual management of cancer patients, even in advanced stages. However, diagnostic tools indicating early the efficacy of therapy are still needed. In prospectively collected sera of 161 patients with recurrent non-small cell lung cancer (NSCLC) receiving second-line chemotherapy, the courses of nucleosomes, 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. At high specificity for detection of progressive disease, most sensitive biomarkers were identified and included in a combination model. High levels and insufficient decreases of nucleosomes and CYFRA 21-1 during the first cycle of therapy indicated poor outcome. Combination of nucleosome concentrations at day 8 and CYFRA 21-1 before start of the second cycle enabled the early detection of progressive disease with a sensitivity of 34.4% at 95% specificity (AUC 0.79) prior to imaging techniques. When cutoffs were fixed at the 90th percentile of responding patients, the combination model achieved sensitivities of 19% at 100% specificity and of 52% at 88% specificity. Thus, nucleosomes and CYFRA 21-1 showed to be valuable for the individual management of patients with recurrent NSCLC.
Institute of Clinical Chemistry, University Hospital Munich, Marchioninistr. 15, D-81366 Munich, Germany. Stefan.Hodenrieder@med.uni-muenchen.de
Stefan
S
Holdenrieder
Joachim
J
von Pawel
Elke
E
Dankelmann
Thomas
T
Duell
Bernhard
B
Faderl
Andreas
A
Markus
Maria
M
Siakavara
Horst
H
Wagner
Knut
K
Feldmann
Harald
H
Hoffmann
Hannelore
H
Raith
Dorothea
D
Nagel
Petra
P
Stieber
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D053539:Keratin-19; D007633:Keratins / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000378:metabolism*; D010455:Peptides / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D012008:Recurrence
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; D009707:Nucleosomes; D010455:Peptides; D011498:Protein Precursors; C102012:antigen CYFRA21.1; C047897:gastrin-releasing peptide precursor; D007633:Keratins; D010751:Phosphopyruvate Hydratase