MRI-based contrast clearance analysis shows high differentiation accuracy between radiation-induced reactions and progressive disease after cranial radiotherapy

Abstract

Background: Pseudoprogression (PsP) or radiation necrosis (RN) may frequently occur after cranial radiotherapy and show a similar imaging pattern compared with progressive disease (PD). We aimed to evaluate the diagnostic accuracy of magnetic resonance imaging-based contrast clearance analysis (CCA) in this clinical setting.

Patients and methods: Patients with equivocal imaging findings after cranial radiotherapy were consecutively included into this monocentric prospective study. CCA was carried out by software-based automated subtraction of imaging features in late versus early T1-weighted sequences after contrast agent application. Two experienced neuroradiologists evaluated CCA with respect to PsP/RN and PD being blinded for histological findings. The radiological assessment was compared with the histopathological results, and its accuracy was calculated statistically.

Results: A total of 33 patients were included; 16 (48.5%) were treated because of a primary brain tumor (BT), and 17 (51.1%) because of a secondary BT. In one patient, CCA was technically infeasible. The accuracy of CCA in predicting the histological result was 0.84 [95% confidence interval (CI) 0.67-0.95; one-sided P = 0.051; n = 32]. Sensitivity and specificity of CCA were 0.93 (95% CI 0.66-1.00) and 0.78 (95% CI 0.52-0.94), respectively. The accuracy in patients with secondary BTs was 0.94 (95% CI 0.71-1.00) and nonsignificantly higher compared with patients with primary BT with an accuracy of 0.73 (95% CI 0.45-0.92), P = 0.16.

Conclusions: In this study, CCA was a highly accurate, easy, and helpful method for distinguishing PsP or RN from PD after cranial radiotherapy, especially in patients with secondary tumors after radiosurgical treatment.

Keywords: brain metastases; glioma; pseudoprogression; radiation necrosis; stereotactic radiosurgery.

Figure 1

Examples of contrast clearance analysis (CCA). The images show four different patients (A-D), each with a regular contrast-enhanced T1-MRI sequence, a late phase T1-sequence ∼1 h after contrast media application, and their CCA (from left to right). Tumor tissue is depicted as blue in the CCA, while reactive tissue is depicted as red. (A) Glioblastoma (WHO 2016 grade IV) IDH wt: a frontoparietal lesion showing tumor tissue in a circular formation with reactive components centrally and at the lesional border (Patient ID 17). (B) Lung adenocarcinoma with brain metastases: a right cerebellar lesion showing tumor tissue with reactive components in the surrounding area (Patient ID 03). (C) Glioblastoma (WHO 2016 grade IV) IDH wt: a periventricular lesion showing spotted areas with reactive tissue (Patient ID 20). (D) Maxillary squamous cell cancer with brain infiltration: a lesion in the right temporal lobe consisting nearly entirely of reactive tissue (Patient ID 25). IDH, isocitrate dehydrogenase; MRI, magnetic resonance imaging; WHO, World Health Organization; wt, wild type.