title: Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer.
abstract: This retrospective study aimed at determining the prognostic significance of neuroendocrine markers chromogranin A (CgA), pro-gastrin releasing peptide (ProGRP) and neuron-specific enolase (NSE), together with the cytokeratin 19 marker CYFRA 21-1 in small cell lung cancer (SCLC). A total of 148 histologically proven and previously untreated SCLC patients were included. Among them 118 patients received a cisplatin-etoposide combination or cisplatin-etoposide-cyclophosphamide-4'-epidoxorubicin combination. All tumour markers were tested using immunoradiometric assays except for ProGRP which was tested using an enzyme-linked immunosorbent assay. The thresholds for marker serum titrations were 53 pg/ml, 65, 17, and 3.6 ng/ml for ProGRP, CgA, NSE and CYFRA 21-1 respectively. Univariate analysis showed that patients affected by one of the following characteristics proved to have a significant shorter survival in comparison with the opposite status of each variable: age over 63 years, extensive-stage, serum LDH level higher than 600 U/l, serum NSE level higher than 17 ng/ml, serum CgA level higher than 65 ng/ml and serum CYFRA 21-1 level higher than 3.6 ng/ml. In addition, there was a trend towards a statistical significance for a high serum alkaline phosphatase level and a performance status equal to or worse than two. The following variables were independent determinants of a poor outcome: a poor performance status (hazard ratio [95% confidence interval]: 1.51 [1.02-2.22]), a high CgA level (HR: 1.61 [1.06-2.45]), a high CYFRA 21-1 level (HR: 2.10 [1.40-3.14]) and an age older than 63 years (HR: 1.68 [1.14-2.48]). When the multivariate analysis was restricted to patients receiving a cisplatin-etoposide-based chemotherapy, the same variables were prognostic determinants with nearly similar hazard ratios. In conclusion, aside classical variables such as age and performance status, high serum CYFRA 21-1 and high serum CgA level in SCLC are both prognostic determinants of prognosis, in particular in patients receiving conventional chemotherapy consisting of cisplatin and etoposide-based combinations.
authors.affiliation: Department of Thoracic Oncology of Montpellier University Hospital, Avenue du Doyen Giraud, 34295 Montpellier Cedex 5, France. pujol@cyber-sante.org
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pujol
authors.forename: Xavier
authors.initials: X
authors.lastname: Quantin
authors.forename: William
authors.initials: W
authors.lastname: Jacot
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boher
authors.forename: Jean
authors.initials: J
authors.lastname: Grenier
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Lamy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018288:Carcinoma, Small Cell / Q000097:blood* / Q000175:diagnosis; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood; D005260:Female; D006801:Humans; D053539:Keratin-19; D007633:Keratins / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011379:Prognosis; D011994:Recombinant Proteins / Q000097:blood; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins; D053539:Keratin-19; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D010455:Peptides; D011994:Recombinant Proteins; C102012:antigen CYFRA21.1; C087079:pro-gastrin-releasing peptide (31-98); D007633:Keratins; D010751:Phosphopyruvate Hydratase