Elevated citrate in pediatric astrocytomas with malignant progression.

Area of Science:

• Neuro-oncology
• Metabolic imaging
• Pediatric oncology

Background:

• In vivo magnetic resonance spectroscopy (MRS) measures tissue metabolite concentrations.
• Citrate, a tricarboxylic acid (TCA) cycle intermediate, accumulates when glycolysis exceeds TCA activity, a hallmark of malignancy.
• Predicting malignant progression in pediatric World Health Organization (WHO) grade II astrocytomas remains challenging.

Purpose of the Study:

• To investigate the role of citrate as a potential biomarker for predicting malignant progression in pediatric astrocytomas.
• To correlate citrate concentrations measured by MRS with tumor grade and clinical behavior.

Main Methods:

• Retrospective review of medical records and in vivo MRS data from 29 pediatric astrocytomas.
• Categorization of tumors into indolent and aggressive grade II astrocytomas, anaplastic astrocytomas (WHO III), and glioblastoma (WHO IV).
• Quantification of citrate concentrations using MRS and statistical analysis to compare groups.

Main Results:

• Citrate was detected in all aggressive grade II astrocytomas.
• Mean citrate concentration was significantly higher in aggressive grade II astrocytomas compared to indolent ones (4.1 ± 1.1 vs 0.6 ± 0.8 mmol/kg; P < .0001).
• Citrate levels showed no consistent pattern in anaplastic astrocytoma and glioblastoma.

Conclusions:

• Prominent citrate levels identified a subgroup of pediatric grade II astrocytomas with aggressive behavior.
• Citrate is not specific for poor outcomes as it was not detected in all high-grade astrocytomas.
• In high-grade astrocytomas, prominent citrate may define a distinct metabolic subclass.