Functional connectivity between tumor region and resting-state networks as imaging biomarker for overall survival in recurrent gliomas diagnosed by O-(2-[<SUP>18</SUP>F]fluoroethyl)-l-tyrosine PET

Background. Amino acid PET using the tracer O-(2-[ ¹⁸F]fluoroethyl)-l-tyrosine (FET) is one of the most reliable imaging methods for detecting glioma recurrence. Here, we hypothesized that functional MR connectivity between the metabolic active recurrent tumor region and resting-state networks of the brain could serve as a prognostic imaging biomarker for overall survival (OS). Methods. The study included 82 patients (26–81 years; median Eastern Cooperative Oncology Group performance score, 0) with recurrent gliomas following therapy (WHO-CNS 2021 grade 4 glioblastoma, n = 57; grade 3 or 4 astrocytoma, n = 12; grade 2 or 3 oligodendroglioma, n = 13) diagnosed by FET PET simultaneously acquired with functional resting-state MR. Functional connectivity (FC) was assessed between tumor regions and 7 canonical resting-state networks. Results. WHO tumor grade and IDH mutation status were strong predictors of OS after recurrence (P < .001). Overall FC between tumor regions and networks was highest in oligodendrogliomas and was inversely related to tumor grade (P = .031). FC between the tumor region and the dorsal attention network was associated with longer OS (HR, 0.88; 95%CI, 0.80–0.97; P = .007), and showed an independent association with OS (HR, 0.90; 95%CI, 0.81–0.99; P = .033) in a model including clinical factors, tumor volume and MGMT. In the glioblastoma subgroup, tumor volume and FC between the tumor and the visual network (HR, 0.90; 95%CI, 0.82–0.99, P = .031) were independent predictors of survival. Conclusions. Recurrent gliomas exhibit significant FC to resting-state networks of the brain. Besides tumor type and grade, high FC between the tumor and distinct networks could serve as independent prognostic factors for improved OS in these patients.