Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125).
OBJECTIVE
To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients.


METHODS
From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed.


RESULTS
At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2-0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001).


CONCLUSIONS
Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.
Gronlund
B
B
Department of Oncology, Finsen Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark. bo.gronlund@dadlnet.dk
Høgdall
E V S
EV
Christensen
I J
IJ
Johansen
J S
JS
Nørgaard-Pedersen
B
B
Engelholm
S A
SA
Høgdall
C
C
D054392:Adipokines; D000951:Antigens, Neoplasm / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D000071451:Chitinase-3-Like Protein 1; D019008:Drug Resistance, Neoplasm; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D037102:Lectins; D037181:Lectins, C-Type / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy*; D011237:Predictive Value of Tests; D012008:Recurrence
D054392:Adipokines; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C121307:CASA antigen; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D037181:Lectins, C-Type; C048648:tetranectin