Abstract
BACKGROUND
Evaluating changes induced by immunotherapies on conventional brain MRI can be difficult because those treatments may produce an inflammatory response. To explore the contribution of quantitative MRI biomarkers, we examined advanced MRI findings in first diagnosis glioblastoma (GBM) patients treated with dendritic cell (DC) immunotherapy added to standard treatment.
METHODS
A retrospective analysis was performed on longitudinal MRIs obtained by 22 patients enrolled in the EUDRACT N° 2008-005035-15 trial. The following parameters were collected: tumor volume (TV), mean normalized tumoral CBV (rCBV), Mean normalized tumoral ADC (rADC), semi-automatic ADC mean (ADCmean), ADC mode (ADCmode), ADC kurtosis (ADCkurt), ADC skewness (ADCskew).
RESULTS
Ten patients were defined, based on PFS >12 months, to have received benefit from the treatment (responder patients). After the first four vaccinations rADC significantly decreased in responders only (1.34 ± 0.17 vs 1.23 ±0.23 p=0.028). A decrease in rADC mean value ≥ 0.13 and a change in ADCskew ≥ -0.14 were significant predictors of longer PFS (17.2 vs 10.2 p=0.04; 15.4 vs 9.3 m p=0.02) and OS (33 vs 19.9 p=0.003; 29 vs 12.4 p=0.002). During the follow-up 18 patients experienced progression and 7 pseudoprogression according to RANO criteria. A significant increase of rCBV (4.25 to 5.38, p=0.04), and a significant decrease in rADCmean (1.17 vs 1.01) (p=0.004) were only observed in patients with true tumor progression. A ΔrCBV value ≥ 2.07 was able to distinguish the two conditions with a sensitivity of 100% and specificity of 60% (p=0.004).
CONCLUSION
An early decrease in rADC and limited reduction of ADCskew are related to longer survival in GBM patients treated with DC immunotherapy, added to standard care, suggesting the relevance of hypercellularity in the first phase of the treatment. Modification of rCBV can be useful in distinguishing progression and pseudoprogression