Characterizing long- and short-survival glioblastoma patients with FLT-PET/MRI and metabolomics.

Background: Glioblastoma is the most aggressive and malignant brain tumor, characterized by a high degree of heterogeneity, invasiveness, and resistance to treatment. Patients with glioblastoma have a very poor prognosis despite multimodal interventions. In this study, we investigated how ¹⁸F-fluorothymidine (¹⁸F-FLT) PET combined with contrast-enhanced MRI and blood metabolomics can contribute to evaluate prognosis and treatment response for patients with glioblastoma.

Methods: Patients, scheduled for surgery due to suspected high-grade glioma were included in this clinical study and underwent four ¹⁸F-FLT-PET/MRI examinations prior to surgery and during standard treatment. Blood samples were collected and analyzed by metabolomics. Patients were grouped according to survival as long-time survivors (>3 years) and short-time survivors (<500 days).

Results: Both 2 and 6 weeks into treatment, short-time survivors displayed a significantly larger tumor volume than long-time survivors. When comparing MRI findings during treatment, long-time survivors displayed a substantial tumor decrease, whereas the short-time survivors showed minor or no effect. Regarding ¹⁸F-FLT-PET the results were not as unambiguous. Furthermore, there was a clear and significant separation in the metabolomic pattern in blood between the survival groups and across treatment time points.

Conclusions: MRI measures of tumor volume and growth during treatment appear to be prognostic clinical factors that affect outcome. Metabolomic patterns in blood differ significantly between the defined survival groups and may serve as support for an early forecast of prognosis. We also observe a clear separation in metabolite levels between different time points during treatment, which likely reflects treatment effects.