Background: The radiological follow-up of diffuse gliomas is challenged by the difficult distinction of true progression from treatment-related changes. To this end, the Response Assessment in Neuro-Oncology (RANO) Working Group has issued specific recommendation for the standardized evaluation of magnetic resonance imaging (MRI). In addition, positron emission tomography (PET) using radiolabeled amino acids allows for the delineation of metabolically active tumor regions in brain tumors, and guidelines for PET-based response assessment have been recently proposed (PET RANO 1.0). However, well-annotated data on longitudinal PET alterations before and during treatment and follow-up are missing in isocitrate dehydrogenase (IDH)-mutant gliomas, particularly as tumor entities defined by IDH mutations have been established only recently and data on PET imaging mainly rely on previous brain tumor classification frameworks.

Aims: This bicentric, prospective, observational study aims to collect data on imaging-based disease monitoring in patients with IDH-mutant gliomas. Specifically, this study aims to investigate longitudinal changes of amino acid PET tracer uptake during treatment in IDH-mutant gliomas and to evaluate the correlation between amino acid PET uptake at baseline and response to postoperative standard of care treatment.

Patient cohort/methods: Adult (age ≥ 18 years) patients diagnosed and/or treated at the Medical University of Vienna (Vienna, Austria) or the LMU Hospital Munich (Munich, Germany) with histologically verified diffuse IDH-mutant glioma (oligodendroglioma, astrocytoma of all grades) and PET imaging for routine follow-up before, during and after treatment will be included. Clinical and imaging data will be collected in a standardized manner and correlated with treatment response. Primary endpoint is progression-free survival (PFS) according to RANO 2.0 criteria, secondary endpoints include PFS according to PET-RANO 1.0 criteria, time to next intervention (TTNI) and overall survival (OS).

Originality/relevance: This study will generate data that will inform future response assessment frameworks and the design of future clinical trials in IDH-mutant glioma.

Inclusion Criteria:

• ≥ 18 years
• Histologically verified diffuse IDH-mutant glioma (astrocytoma, oligodendroglioma) of any grade as defined in the WHO classification of tumors of the central nervous system
• Postoperative treatment according to current standard of care at the time of study inclusion
• Performance of amino acid PET as part of clinical routine

Exclusion Criteria:

• Inclusion in another clinical trial/investigational study involving an experimental therapy or study medication
• Inclusion criteria not met

Adult (age ≥ 18 years) patients diagnosed and/or treated at the Medical University of Vienna (Vienna, Austria) or the LMU Hospital Munich (Munich, Germany) with histologically verified diffuse IDH-mutant glioma (oligodendroglioma, CNS WHO grades 2 and 3; astrocytoma, CNS WHO grades 2, 3 and 4) and PET imaging for routinely performed response assessment before, during and after first-line treatment will be included after obtaining informed consent. In total, we expect the inclusion of 100 patients over an accrual period of 3 years.

IPD may be considered upon reasonable request, depending on ethics approval