CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients

Abstract

The purpose of this study was to determine the prognostic significance of a high pretreatment serum CYFRA 21-1 level (a cytokeratin 19 fragment) adjusted for the effects of well-known co-variables in non-small-cell lung cancer (NSCLC). This meta-analysis based on individual updated data gathered comprehensive databases from published or unpublished controlled studies dealing with the prognostic effect of serum CYFRA 21-1 level at presentation in NSCLC of any stage (nine institutions, 2063 patients). Multivariate regression was carried out with the Cox model. The proportional hazard assumption for each of the selected variables retained in the final model was originally checked by log minus log plots baseline hazard ratio. The follow-up ranged from 25 to 78 months. A total of 1616 events were recorded. In the multivariate analysis performed at the 1-year end point, a high pretreatment CYFRA 21-1 level was an unfavourable prognostic determinant in all centres except one (Hazard ratio (95% confidence interval): 1.88 (1.64 -2.15), Po10 À4 ). Other significant variables were stage of the disease, age and performance status. Within the first 18 months, the procedure disclosed a nearly similar hazard ratio for patients having a high pretreatment serum CYFRA 21-1 level (1.62 (1.42 -1.86), Po10 À4 ). For patients who did not undergo surgery, the hazard ratio during the first year of follow-up was 1.78 (1.54 -2.07), Po10À4 . Finally, in the surgically treated population, at the 2-year end point, a high pretreatment CYFRA 21-1 and a locally advanced stage remained unfavourable prognostic determinants. In conclusion CYFRA 21-1 might be regarded as a putative co-variable in analysing NSCLC outcome inasmuch as a high serum level is a significant determinant of poor prognosis whatever the planned treatment.

Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer: association of marker changes after two chemotherapy cycles with different measures of clinical response and survival

“…In addition to known unfavourable prognostic implication of high pretreatment CYFRA 21-1 in advanced NSCLC (Pujol et al, 2004), we have observed that therapy-induced 2-CYFRA 21-1 impacts survival even more. Inclusion of 2-CYFRA 21-1 and NP in the Cox model replaced pretreatment CYFRA 21-1, PS and stage of disease, becoming the major determinants of survival with relative risks 0.40 and 0.55, respectively.…”

CYFRA 21-1 level predicts survival in non-small-cell lung cancer patients receiving gefitinib as third-line therapy

“…Using commercial kit, CYFRA 21-1 is easily assessable and its role as prognostic marker alone (Pujol et al, 2004) or in combination (Barlési et al, 2004) has been demonstrated. Furthermore, the prognostic value of CYFRA 21-1 in the present study was higher than that of clinical (performance status, weight loss) or biological (leucocytes, liver enzymes) traditional prognostic markers.…”

“…The prognostic value of CYFRA 21-1 for non-small-cell lung cancer (NSCLC) patients was recently definitively demonstrated in a meta-analysis in 2063 patients (Pujol et al, 2004). In the same time, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) as gefitinib emerged as an accepted treatment in second-or third-line setting in NSCLC (Pfister et al, 2004).…”

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung

“…More extensive studies with clinically relevant models are required to prove the merit of the proposed A high pretreatment CYFRA 21-1 level emerged as an unfavorable prognostic determinant at the 1-year end point, and, remained an unfavorable prognostic determinant at the 2-year end point (together with a locally advanced stage). 9 Au et al 26 submitted a panel of 18 immunomarkers to unsupervised hierarchical clustering analysis to investigate the possibility of identifying different subgroups in a series of 284 patients with nonsmall cell lung cancers. These authors report that the analysis of the three different World Health Organization (WHO) subtypes (namely, adenocarcinomas, squamous cell carcinomas and large cell carcinomas) showed that different markers were significant in different subtypes, but did not behave as significant prognostic predictors in the case of these carcinomas as a group.…”

“…4 Modern literature accordingly emphasizes the search for new biological prognostic markers in order to refine the prognostic value contributed by tumor staging and histopathological analyses. [4][5][6][7][8][9] Among the biological markers whose diagnostic and prognostic values have already been demonstrated in various types of cancers are galectins in general, [10][11][12] and galectin-3 in particular. 13,14 In all, 14 galectins have been identified to date 10,11 which function as cell receptors for the N-acetyl-lactosamine (LacNAC) moieties present on most of the extracellular matrix components.…”