Clinical correlation between metabolic biomarkers and chemoresistance in gestational trophoblastic neoplasia

The objective of this study was to develop and validate a metabolic-lipid nomogram that refines the International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system, thereby enhancing the predictive capacity for primary chemoresistance and informing therapeutic decision-making in patients with low-risk gestational trophoblastic neoplasia.

A cohort of 83 consecutive patients with gestational trophoblastic neoplasia receiving first-line single-agent chemotherapy was retrospectively enrolled. Measurements of fasting blood glucose, full lipid profile, and serum beta-human chorionic gonadotropin (β-hCG) were obtained prior to the first cycle and before every subsequent cycle. A logistic nomogram, designated as the novel model, was constructed using 4 baseline variables: total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and β-hCG. Its predictive performance was compared to that of the FIGO score alone and a model combining both.

Compared to responders, patients with chemoresistance presented with elevated baseline β-hCG (p =.023) and fasting blood glucose (p =.004), reduced total cholesterol and low-density lipoprotein cholesterol (p =.009), and higher FIGO scores (3-6; p =.004). Multi-variate analysis confirmed low-density lipoprotein cholesterol (odds ratio [OR] 0.085, 95% confidence interval [CI] 0.012 to 0.621), fasting blood glucose (OR 3.793, 95% CI 1.359 to 10.588), and β-hCG >5000 IU/L (OR 7.229, 95% CI 1.484 to 35.209) as independent resistance predictors. The resulting nomogram showed superior predictive performance (area under the curve [AUC] 0.81, 95% CI 0.697 to 0.922), which was further enhanced upon integration with the FIGO score (AUC 0.833, 95% CI 0.738 to 0.929), markedly surpassing the FIGO score alone (AUC 0.704, 95% CI 0.55 to 0.858).

Our findings indicate that elevated fasting blood glucose, low-density lipoprotein cholesterol, and β-hCG > 5000 IU/L are key risk factors for chemoresistance in patients with gestational trophoblastic neoplasia. The integration of low-density lipoprotein cholesterol and fasting blood glucose into the FIGO framework significantly enhances the pre-therapeutic prediction of treatment failure, representing a readily translatable, cost-effective strategy for personalizing primary chemotherapy. External validation in diverse, multi-center populations should be encouraged.