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Background:  Post-treatment radiological deterioration of patients with an irradiated high-grade (WHO grade 3-4) glioma (HGG) may be the result of true progressive disease (PD) or treatment-induced effects (TIE). Differentiation between these entities is of great importance, but remains a diagnostic challenge. This study assesses the diagnostic value of conventional MRI characteristics to differentiate PD from TIE in HGGs.    Material and Methods:  In this single-centre, retrospective, consecutive cohort study, we included adults with a HGG, who were treated with (chemo-)radiotherapy and subsequently developed a new or increasing contrast-enhancing lesion on conventional follow-up MRI. TIE and PD were defined radiologically as stable/decreased for ≥6 weeks or RANO-progression, and histologically as TIE without viable tumour or PD. Two neuroradiologists assessed twenty-one preselected MRI characteristics of the progressive lesions. The statistical analysis included logistic regression to develop a) a full multivariable model b) a diagnostic model with model reduction, and a Cohen’s Kappa interrater reliability (IRR) coefficient.    Results:  210 patients (median age=61, IQR=54-68, 189 males) with 284 lesions were included, of which 141 (50%) had PD. Median time to PD was 2 (0.7-6.1) and to TIE 0.9 (0.7-3.5) months after radiotherapy. After multivariable modelling and model reduction, the following determinants prevailed: Radiation dose (Odds ratio (OR)=0.68, 95%-CI=0.49-0.93), longer time to progression (TTP, OR=3.56, 95%-CI=1.84-6.88), marginal enhancement (OR=2.04, 95%-CI=1.09-3.83), soap bubble enhancement (OR=2.63, 95%-CI=1.39-4.98) and isointense apparent diffusion coefficient (ADC)-signal (OR=2.11, 95%-CI=1.05-4.24). ORs&gt;1 indicate higher odds of PD. The Hosmer&amp;Lemeshow test showed good calibration (p=0.947) and the area under the ROC-curve was 0.722 (95%-CI=0.66-0.78). In the glioblastoma subgroup, TTP, marginal enhancement and ADC-signal were significant. IRR analysis between neuroradiologists revealed moderate to near-perfect agreement for the predictive items, but poor agreement for others.    Discussion:  Several characteristics from conventional MRI are significant predictors for the discrimination between PD and TIE. However, IRR was variable. Conventional MRI characteristics from this study should be incorporated into a multimodal diagnostic model with advanced imaging techniques.    Classification of Evidence:  This study provides Class II evidence that in patients with irradiated HGGs, radiation dose, longer time to progression, marginal enhancement, soap bubble enhancement and isointense apparent ADC-signal distinguish PD from TIE.

Conventional MRI Criteria to Differentiate Progressive Disease From Treatment-Induced Effects in High-Grade (WHO Grade 3–4) Gliomas