Temporal Apparent Diffusion Coefficient (ADC) Changes During Chemoradiation: An Imaging Biomarker for Tumour Response Monitoring and Spatial Recurrence Prediction in Glioblastoma.

Abstract

Background: Apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) has been shown to detect early treatment response in glioblastoma. This prospective observational serial imaging study aimed to compare apparent diffusion coefficient (ADC) changes in gross tumour volume (GTV) regions that developed recurrence versus those that remained recurrence-free.

Methods: Patients with glioblastoma underwent DWI at radiation planning (baseline, Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after completing a 6-week course of chemoradiation (P1M). Recurrence was contoured at the earliest magnetic resonance imaging (MRI) showing progression. The intersection of the GTV and recurrence was labelled resistant-GTV, while non-intersecting GTV was labelled sensitive-GTV. ADC values and percentage changes from Fx0 were compared between these regions.

Results: Eighty patients were analyzed. Median absolute ADC values for resistant (0.94 μm²/ms, interquartile range [IQR]: 0.84, 1.08) and sensitive GTV (0.93 μm²/ms, IQR: 0.87, 1.13) were similar at baseline (P=0.193), but statistically significant differences were observed from the start of radiotherapy. Median ADC changes from baseline for resistant- and sensitive-GTV were +2.5% vs. +15.1% at Fx10 (P<0.001), +8.1% vs. +23.1% at Fx20 (P<0.001), and +21.2% vs. +36.4% at P1M (P<0.001), respectively. Smaller ADC changes at Fx10 (odds ratio [OR] 0.95, P=0.005) and Fx20 (OR 0.95, P=0.010) were independent predictors of increased risk of GTV failure, adjusting for MGMT 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 MRI-guided biologically adapted radiation clinical trials.