Apparent diffusion coefficient (ADC) decrease to predict longer survival in glioblastoma patients treated by dendritic cell immunotherapy plus standard of care.

Abstract

2065 Background: The MRI follow –up of patients affected by glioblastoma (GBM) and treated with immunotherapy may be difficult, as immune responses may mimic tumor progression. To explore the potential contribution of quantitative MRI to the identification of patients with clinical benefit benefit, we used advanced MRI to study GBM patients treated with dendritic cell (DC) immunotherapy added to standard treatment (surgery, radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant TMZ; DENDR1 trial, EUDRACT N° 2008-005035-15). Methods: A retrospective analysis was performed on longitudinal MRIs obtained soon after radiotherapy, within two days before the first vaccination (basal MRI) and every two months, in 22 patients enrolled in DENDR1. The following parameters were collected: tumor volume of contrast–enhanced lesions, mean rCBV, maximal rCBV, mean ADC, minimal ADC, ADC skewness. Receiver Operating Characteristic (ROC) curves were used to determine optimal sensitivity and specificity in differentiating patients as responder or not responder. Association with PFS (as per RANO criteria) and OS was analyzed using log-rank test and Cox regression. Results: Ten patients with PFS > 12 months were defined as responders Their basal mean ADC was significantly higher than in non responders (1.34 ± 0.17 vs 1.14 ± 0.34, p = 0.03). After four DC vaccinations mean ADC significantly decreased in responders only from 1.34 ± 0.17 to 1.23 ±0.23 (p = 0.028); the decrease persisted during immunotherapy. A basal mean ADC value ≥ 1.07 and a decrease in mean ADC value ≥ 0.13 were significant predictors of longer PFS (15.4 vs 9 m p = 0.0006; 17.2 vs 10.2 p = 0.04) and OS (29 vs 12.5 mo p = 0.002; 33 vs 19.9 p = 0.04 No significant correlations between the other parameters and the outcome were observed. Conclusions: Association with prolonged survival may suggest that in DENDR1responders decreased ADC is partly contributed by immune cells infiltrating the tumor.