Positron Emission Tomography/Computed Tomography (PET/CT) Imaging in Patients Diagnosed With a Glioma

A comparative evaluation of the predictive accuracy of pre-radiotherapy imaging modalities (V1) in forecasting the spatial location of future tumor progression (V2) defined by RANO (Response Assessment in Neuro-Oncology) 2.0 criteria. For each participant, two separate Dice Similarity Coefficients (DSC) will be calculated against the final progression volume (V2): one using the pre-radiotherapy PET High K influx map volume (V1_PETk) and one using the structural MRI target volume (V1_MRI). The primary endpoint (d-PETk-MRI) is the absolute difference calculated per patient as DSC_PETk minus DSC_MRI. The resulting continuous score ranges from -1 to +1. A positive score indicates that the novel kinetic PET parameter is a spatially superior predictor of subsequent localized tumor recurrence compared to standard clinical MRI planning fields.

The diagnostic sensitivity of PETk post-radiation (T2) (PETk-T2) with a predefined L/C ratio threshold of 1.60 to correctly identify true glioblastoma progression. The true disease status (ground truth) is defined by follow-up serial MRIs using RANO 2.0 criteria or histopathologic evidence from surgical re-resection. Sensitivity is calculated as the proportion of true-positive tumor progression cases correctly identified by PETk out of all true-positive cases.

The quantitative change in [18F]FETrp PET K values evaluated within the MRI-defined tumor mass from baseline to post treatment. The primary analysis will be performed on the per-protocol population, defined as participants who completed both pre- and post-treatment PET scans and demonstrated at least 80% drug compliance via pill counts and paper diaries. Changes will be calculated as post-treatment minus baseline values, with a negative value indicating a reduction in tumoral tryptophan metabolic rates resulting from kynurenine pathway inhibition.

A comparative evaluation of the predictive accuracy of pre-radiotherapy imaging modalities (V1) in forecasting the spatial location of future tumor progression (V2) defined by RANO 2.0 criteria. For each participant, two separate Dice Similarity Coefficients (DSC) will be calculated against the final progression volume (V2): one using the pre-radiotherapy PET High SUV volume (V1_PETsuv) and one using the structural MRI target volume (V1_MRI). The primary endpoint (d-PETk-MRI) is the absolute difference calculated per patient as DSC_PETsuv minus DSC_MRI. The resulting continuous score ranges from -1 to +1. A positive score indicates that the novel kinetic PET parameter is a spatially superior predictor of subsequent localized tumor recurrence compared to standard clinical MRI planning fields.

Assessment of pre-radiotherapy metabolic tumor volume (PETk-T1, in cm³) as an independent prognostic predictor of progression-free survival (PFS). A multivariable Cox proportional hazards regression model will calculate the adjusted hazard ratio (HR) and 95% confidence interval for PFS per unit increase in PETk-T1 volume. The model will adjust for baseline clinical covariates. PFS is defined as time from the date of diagnosis to the first documented and verified disease progression (defined by the RANO 2.0 criteria9). Patients who are lost to follow-up or without disease progression at time of data cut off are censored at the time of last known disease progression follow-up.

The diagnostic specificity of PETk post-radiation (T2) (PETk-T2) with a predefined L/C ratio threshold of 1.60 to correctly identify true glioblastoma progression. The true disease status (ground truth) is defined by follow-up serial MRIs using RANO 2.0 criteria or histopathologic evidence from surgical re-resection. Specificity is calculated as the proportion of true-negative cases (radiation injury) correctly identified by PETk out of all true-negative cases.

The proportion of participants with a positive [18F]FETrp PET K L/C ratio (≥ 1.60) who are confirmed to have true tumor progression via the composite ground truth reference standard (RANO 2.0 MRI follow-up or histopathology).

The proportion of participants with a negative [18F]FETrp PET K L/C ratio (< 1.60) who are confirmed to have radiation-induced injury via the composite ground truth reference standard (RANO 2.0 MRI follow-up or histopathology).

The total proportion of correctly classified cases (true positives plus true negatives) using the [18F]FETrp PET K L/C ratio threshold of 1.60 divided by the total number of evaluable suspicious contrast-enhancing lesions.

The partial area under the receiver operating characteristic (ROC) curve generated by varying the continuous [18F]FETrp PET K L/C ratio values to assess overall classification performance across a clinically relevant range of specificities, utilizing the composite ground truth reference standard.

The change in the [18F]FETrp PET K-map lesion-to-contralateral (L/C) ratio from baseline to 1 month post-treatment. It is analyzed in the per-protocol population (at least 80% pill compliance and evaluable paired imaging).