Early prediction of treatment resistance in low-risk gestational trophoblastic neoplasia using population kinetic modelling of hCG measurements.

Abstract

BACKGROUND:

In low-risk gestational trophoblastic neoplasia (GTN) patients, a predictive marker for early identification of methotrexate (MTX) resistance would be useful. We previously demonstrated that kinetic modelling of human chorionic gonadotrophin (hCG) measurements could provide such a marker. Here we validate this approach in a large independent patient cohort.

METHODS:

Serum hCG measurements of 800 low-risk GTN patients treated with MTX were analysed. The cohort was divided into Model and Test data sets. hCG kinetics were described from initial treatment day to day 50 using: '(hCG(time))=hCG0*exp(-k*time)+hCGres', where hCGres is the modelled residual production, hCG0 is the baseline hCG level, and k is the rate constant. HCGres-predictive value was investigated against previously reported predictors of MTX resistance.

RESULTS:

Declining hCG measurements were well fitted by the model. The best discriminator of MTX resistance in the Model data set was hCGres, categorised by an optimal cut-off value of >20.44 IU l(-1): receiver-operating characteristic (ROC) area under the curve (AUC)=0.87; Se=0.91; Sp=0.83. The predictive value of hCGres was reproducible using the Test data set: ROC AUC=0.87; Se=0.88; Sp=0.86. Multivariate analyses revealed hCGres as a better predictor of MTX resistance (HR=1.01, P<0.0001) and MTX failure-free survival (HR=13.25, P<0.0001) than other reported predictive factors.

CONCLUSION:

hCGres, a modelled kinetic parameter calculated after fully dosed three MTX cycles, has a reproducible value for identifying patients with MTX resistance.

• Authors: B You, R Harvey, E Henin, H Mitchell, F Golfier, P M Savage, M Tod, M Wilbaux, G Freyer, M J Seckl
• Journal: British journal of cancer (Br J Cancer) Vol. 108 Issue 9 Pg. 1810-6 (May 14 2013) ISSN: 1532-1827 [Electronic] England
• PMID: 23591194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Biomarkers, Tumor
• Chorionic Gonadotropin
• Methotrexate

Topics

• Adult
• Antimetabolites, Antineoplastic (therapeutic use)
• Biomarkers, Tumor
• Chorionic Gonadotropin (blood)
• Drug Resistance, Neoplasm
• Female
• Gestational Trophoblastic Disease (drug therapy)
• Humans
• Methotrexate (therapeutic use)
• Multivariate Analysis
• Pregnancy
• ROC Curve
• Treatment Failure