Purpose: Among oligodendrogliomas, World Health Organization (WHO) grade 2 tumors have relatively more favorable prognosis compared to the grade 3. However, heterogeneity in tumoral behavior exists in grade 2 oligodendrogliomas, with some exhibiting an aggressive course. The authors applied [18F]FET-PET in oligodendrogliomas and extended its utility in predicting prognosis of low-grade oligodendrogliomas.
Methods: Twelve consecutive patients with oligodendrogliomas treated at our institution (Oligo-WHO2: n = 8; Oligo-WHO3: n = 4) were enrolled. All patients underwent contrast-enhanced MRI and [18F]FET-PET/MR before surgery. Maximum and mean target-to-background ratios (TBRmax, TBRmean) were evaluated, and progression-free survival (PFS) was recorded. Bulk RNA sequencing and immunohistochemical(IHC) staining were performed for the verification of [18F]FET-PET findings.
Results: All grade-3 oligodendrogliomas presented high [18F]FET uptake on PET and contrast-enhancement on MRI. Although all grade-2 tumors were non-enhanced, only 50% showed low uptake of [18F]FET, which thus dissected grade-2 oligodendrogliomas into two subgroups: Oligo-WHO2-Low-Uptake and Oligo-WHO2-High-Uptake tumors. Using cutoff of TBRmax = 2.5, [18F]FET-PET based stratification was more correlated with PFS, compared to the WHO grade classification, with all of 4 recurrent oligodendrogliomas (2/4 were grade-2) being [18F]FET high-uptake. Transcriptional results revealed clear discrimination: Oligo-WHO2-High-Uptake tumors were enriched with pathways of energy metabolism and tumor chemotaxis, while the Oligo-WHO2-High-Uptake group displayed upregulation of myelin formation-related pathways. Representative protein markers were selected for validation, with IHC staining unveiling AK4, CXCL5, and IL-33 highly expressed in Oligo-WHO2-High-Uptake oligodendrogliomas and SOX10 enriched in Oligo-WHO2-Low-Uptake tumors.
Conclusion: WHO grade 2 oligodendrogliomas is a heterogeneous composition of tumors with distinct prognosis and molecular characteristics. [18F]FET-PET represents a promising radiological tool for dissecting these tumors.
Keywords: Low-grade glioma; Oligodendroglioma; Prognosis; Progression-free survival; [18F]FET-PET.