Introduction
Recurrent glioblastoma remains one of the most formidable challenges in clinical oncology. Despite aggressive initial therapy involving maximal safe resection followed by radiochemotherapy, nearly all patients experience disease progression. When recurrence occurs, treatment options are limited and often include systemic therapies, re-operation, or re-irradiation. Re-irradiation, in particular, requires precise target volume delineation to maximize tumor control while minimizing the risk of radionecrosis in previously irradiated brain tissue.
Traditionally, contrast-enhanced T1-weighted MRI (CE-T1MRI) has been the standard for defining radiotherapy volumes. However, MRI is limited by its inability to reliably distinguish between treatment-related changes (such as pseudoprogression) and true tumor recurrence. Amino acid PET imaging, specifically using O-(2-[18F]fluoroethyl)-L-tyrosine (FET), has emerged as a promising adjunct due to its higher specificity for neoplastic tissue. The GLIAA/NOA-10 (ARO2013-01) trial was designed to determine if this superior specificity translates into improved clinical outcomes when used to guide re-irradiation.