The Use of Apparent Diffusion Coefficient Values for Differentiating Bevacizumab-Related Cytotoxicity from Tumor Recurrence and Radiation Necrosis in Glioblastoma

Abstract

Objectives: Glioblastomas (GBM) are the most common primary invasive neoplasms of the brain. Distinguishing between lesion recurrence and different types of treatment related changes in patients with GBM remains challenging using conventional MRI imaging techniques. Therefore, accurate and precise differentiation between true progression or pseudoresponse is crucial in deciding on the appropriate course of treatment. This retrospective study investigated the potential of apparent diffusion coefficient (ADC) map values derived from diffusion-weighted imaging (DWI) as a noninvasive method to increase diagnostic accuracy in treatment response. Methods: A cohort of 21 glioblastoma patients (mean age: 59.2 ± 11.8, 12 Male, 9 Female) that underwent treatment with bevacizumab were selected. The ADC values were calculated from the DWI images obtained from a standardized brain protocol across 1.5-T and 3-T MRI scanners. Ratios were calculated for rADC values. Lesions were classified as bevacizumab-induced cytotoxicity based on characteristic imaging features (well-defined regions of restricted diffusion with persistent diffusion restriction over the course of weeks without tissue volume loss and absence of contrast enhancement). The rADC value was compared to these values in radiation necrosis and recurrent lesions, which were concluded in our prior study. The nonparametric Wilcoxon signed rank test with p < 0.05 was used for significance. Results: The mean ± SD age of the selected patients was 59.2 ± 11.8. ADC values and corresponding mean rADC values for bevacizumab-induced cytotoxicity were 248.1 ± 67.2 and 0.39 ± 0.10, respectively. These results were compared to the ADC values and corresponding mean rADC values of tumor progression and radiation necrosis. Significant differences between rADC values were observed in all three groups (p < 0.001). Bevacizumab-induced cytotoxicity had statistically significant lower ADC values compared to both tumor recurrence and radiation necrosis. Conclusion: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity.