Evaluation of Pre–Radiation Therapy Apparent Diffusion Coefficient (ADC): Patterns of Recurrence and Progression-Free Survival Analysis in Patients With GBM

Abstract

To investigate the association of pre-radiation therapy ADC abnormalities with patterns of recurrence and outcomes in patients with GBM and to determine if ADC analysis can identify high risk regions of hypercellularity which may influence treatment planning. Fifty-two patients with GBM were retrospectively evaluated. Diffusion MRI ADC images were acquired for all patients postoperatively prior to radiation therapy. All patients had documented recurrence based on multidisciplinary evaluation including radiographic or histopathologic confirmation. Pre-radiation therapy ADC images were evaluated for geographic regions of diffusion restriction (hypointensity) within the FLAIR volume, and ADC histogram analysis was performed within the FLAIR volume. For cases with an ADC hypointensity, the pre-treatment ADC map and the T1+C MRI at the time of recurrence were registered to the original planning CT and dose file to determine the spatial localization of the ADC abnormality with respect to the recurrence and the 60 Gy isodose line (IDL). Recurrences were defined as central, marginal, or distant if > 80%, 20-80%, or < 20% of the recurrence volume was included within 95% of the 60 Gy IDL. Progression-free survival (PFS) was evaluated with respect to the presence or absence of an identifiable diffusion restriction as well as to ADC histogram parameters. Normalized ADC values (nADC) were generated relative to contralateral white matter. A discrete region of ADC hypointensity was identified in 32 of 52 (62%) cases. The recurrence pattern in these cases was central in 27/32 (84%), marginal in 4/32 (13%) and distant in 1/32 (3%). The recurrent tumor overlapped with the ADC hypointensity in 28 (88%) patients (25 central recurrences and 3 marginal recurrences). At least 95% of the ADC hypointensity volume was covered by 95% of the 60 Gy IDL in all cases. Patients with an ADC hypointensity had a lower mean (1.61 vs 1.88 p = 0.01) and minimum (0.253 vs 0.458 p = 0.02) nADC within the FLAIR volume than those without an ADC hypointensity. The two groups were similar with respect to age, performance status, radiation therapy dose, and extent of resection. Kaplan-Meier analysis revealed superior PFS after radiation therapy in patients without an ADC hypointensity compared to those with (Median PFS 8.0 mo. vs 3.2 mo.), HR = 1.96 (p = 0.01 by log-rank test). ADC Histogram analysis revealed superior PFS for patients with a minimum nADC of > 0.3 vs those with a minimum nADC < 0.3 (Median PFS 8.1 mo. vs 3.3 mo.), HR = 1.8 (p = 0.02 by log-rank test). The presence of an ADC hypointensity on pre-radiation therapy diffusion MRI is associated with the location of tumor recurrence as evidenced by the frequency of overlap in this series, and is associated with reduced PFS. This abnormality may reflect a high risk region of hypercellularity and may warrant consideration with respect to radiation therapy planning.