Temporal Apparent Diffusion Coefficient Changes During Chemoradiation: An Imaging Biomarker for Tumor Response Monitoring and Spatial Recurrence Prediction in Glioblastoma

PURPOSE: Apparent diffusion coefficient (ADC) from diffusion-weighted imaging has been shown to detect early treatment response in glioblastoma. This prospective observational serial imaging study aimed to compare ADC changes in gross tumor volume (GTV) regions that developed recurrence versus those that remained recurrence-free. METHODS AND MATERIALS: Patients with glioblastoma underwent diffusion-weighted imaging at radiation planning (baseline, fraction 0), fraction 10, fraction 20, and 1 month after completing a 6-week course of chemoradiation. Recurrence was contoured at the earliest magnetic resonance imaging showing progression. The intersection of the GTV and recurrence was labeled resistant-GTV, whereas nonintersecting GTV was labeled sensitive-GTV. ADC values and percentage changes from fraction 0 were compared between these regions. RESULTS: Eighty patients were analyzed. Median absolute ADC values for resistant (0.94 μm²/ms; IQR, 0.84-1.08) and sensitive-GTV (0.93 μm²/ms; IQR, 0.87-1.13) were similar at baseline (P = .193), but statistically significant differences were observed from the start of radiation therapy. Median ADC changes from baseline for resistant- and sensitive-GTV were +2.5% versus +15.1% at fraction 10 (P < .001), +8.1% versus +23.1% at fraction 20 (P < .001), and +21.2% versus +36.4% at 1 month after completing a 6-week course of chemoradiation (P <.001), respectively. Smaller ADC changes at fraction 10 (odds ratio, 0.95; P = .005) and fraction 20 (odds ratio, 0.95; P = .010) were independent predictors of increased risk of GTV failure, adjusting for O6-methylguanine DNA methyltransferase promoter methylation and extent of surgical resection. CONCLUSIONS: Temporal ADC changes are promising imaging biomarkers for treatment response and spatial recurrence prediction and may provide a target for magnetic resonance imaging-guided biologically adapted radiation clinical trials.