Assessing the added value of apparent diffusion coefficient, cerebral blood volume, and radiomic magnetic resonance features for differentiation of pseudoprogression versus true tumor progression in patients with glioblastoma

BACKGROUND: Pseudoprogression (PsPD) is a major diagnostic challenge in the follow-up of patients with glioblastoma (GB) after chemoradiotherapy (CRT). Conventional imaging signs and parameters derived from diffusion and perfusion-MRI have yet to prove their reliability in clinical practice for an accurate differential diagnosis. Here, we tested these parameters and combined them with radiomic features (RFs), clinical data, and MGMT promoter methylation status using machine- and deep-learning (DL) models to distinguish PsPD from Progressive disease. METHODS: In a single-center analysis, 105 patients with GB who developed a suspected imaging PsPD in the first 7 months after standard CRT were identified retrospectively. Imaging data included standard MRI anatomical sequences, apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) maps. Median values (ADC, nrCBV) and RFs (all sequences) were calculated from DL-based tumor segmentations. Generalized linear models with LASSO feature-selection and DL models were built integrating clinical data, MGMT methylation status, median ADC and nrCBV values and RFs. RESULTS: A model based on clinical data and MGMT methylation status yielded an areas under the receiver operating characteristic curve (AUC) = 0.69 (95% CI 0.55–0.83) for detecting PsPD, and the addition of median ADC and nrCBV values resulted in a nonsignificant increase in performance (AUC = 0.71, 95% CI 0.57–0.85, P = .416). Combining clinical/MGMT information with RFs derived from ADC, nrCBV, and from all available sequences both resulted in significantly (both P < .005) lower model performances, with AUC = 0.52 (0.38–0.66) and AUC = 0.54 (0.40–0.68), respectively. DL imaging models resulted in AUCs ≤ 0.56. CONCLUSION: Currently available imaging biomarkers could not reliably differentiate PsPD from true tumor progression in patients with glioblastoma; larger collaborative efforts are needed to build more reliable models.