Advanced MRI Assessment during Dendritic Cell Immunotherapy Added to Standard Treatment Against Glioblastoma

• Main Authors: Valeria Cuccarini, Domenico Aquino, Andrea Gioppo, Elena Anghileri, Serena Pellegatta, Carla Schettino, Federica Mazzi, Gaetano Finocchiaro, Maria Grazia Bruzzone, Marica Eoli
• Format: Article
• Language: English
• Published: MDPI AG 2019-11-01
• Series: Journal of Clinical Medicine
• Subjects: glioblastoma; immunotherapy; pseudoprogression; dsc-mri; dwi-mri
• Online Access: https://www.mdpi.com/2077-0383/8/11/2007

Evaluating changes induced by immunotherapies (IT) on conventional magnetic resonance imaging (MRI) is difficult because those treatments may produce inflammatory responses. To explore the potential contribution of advanced MRI to distinguish pseudoprogression (PsP) and true tumor progression (TTP), and to identify patients obtaining therapeutic benefit from IT, we examined aMRI findings in newly diagnosed glioblastoma treated with dendritic cell IT added to standard treatment. We analyzed longitudinal MRIs obtained in 22 patients enrolled in the EUDRACT N&#176; 2008-005035-15 trial. According to RANO criteria, we observed 18 TTP and 8 PsP. Comparing MRI performed at the time of TTP/PsP with the previous exam performed two months before, a difference in cerebral blood volume &#916;rCBV_max &#8805; 0.47 distinguished TTP from PsP with a sensitivity of 67% and specificity of 75% (p = 0.004). A decrease in minimal apparent diffusion coefficient rADC_min (1.15 vs. 1.01, <i>p</i> = 0.003) was observed after four vaccinations only in patients with a persistent increase of natural killer cells (response effectors during IT) in peripheral blood. Basal rADC_min &gt; 1 was independent predictor of longer progression free (16.1 vs. 9 months, <i>p</i> = 0.0001) and overall survival (32.8 vs. 17.5 months, <i>p</i> = 0.0005). In conclusion, rADC predicted response to immunotherapy and survival; Apparent Diffusion Coefficient (ADC) and Cerebral Blood Volume (CBV) modifications over time help differentiating PsP from TTP at onset.