Distinguishing true progression from treatment effects in glioblastoma: a practical, evidence-graded imaging framework for the multidisciplinary team.

BACKGROUND: Distinguishing true progression (TP) from treatment effects-pseudoprogression (PsP) and radiation necrosis (RN)-after chemoradiation for glioblastoma (GBM) is a consequential, unresolved decision that conventional MRI cannot reliably make in 30-40% of cases, and that is rarely made by any single specialty alone. METHODS: We synthesized and graded evidence from RANO 2.0, advanced MRI (perfusion, diffusion, and spectroscopy), amino acid PET (per PET RANO 1.0), and radiomics, based on a literature search of PubMed/MEDLINE, Embase, and Cochrane (2010-2025). RESULTS: In selected cohorts, combined MRI plus amino acid PET reports areas under the curve of 0.90-0.95 versus 0.65-0.72 for conventional MRI alone; however, these figures come from cohorts spanning the full range of post-treatment enhancement-including easily classified cases-rather than the ambiguous subset in which advanced imaging is actually used, and therefore likely overstate real-world accuracy. We organize the evidence around clinical modifiers of pretest probability-MGMT methylation, interval since chemoradiation, neurologic trajectory, antiangiogenic or immunotherapy exposure, reirradiation, and lesion location-that determine how heavily each imaging tier should be weighted. For amino acid PET, we address U.S. access, including recently published prospective and multicenter diagnostic-accuracy data for 18F-fluciclovine. CONCLUSIONS: We propose a tiered imaging framework-RANO 2.0 MRI → perfusion MRI → amino acid PET → tissue sampling or empirical therapy-explicitly as a structure for prospective evaluation, not a validated clinical decision tool. The principal unresolved gap is amino acid PET performance conditional on an equivocal perfusion MRI, which ongoing trials should address.