Nikhil Rammohan1, Alexander Ho1, Mohit Saxena2, Amishi Bajaj1, Tim J Kruser3, Craig Horbinski4, Alexander Korutz2, Matthew Tate5, Sean Sachdev6. 1. Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 1820, Chicago, IL, 60611, USA. 2. Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 3. Turville Bay Radiation Oncology Center, SSM Health Dean Medical Group, Madison, WI, USA. 4. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 5. Department of Neurologic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 6. Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 1820, Chicago, IL, 60611, USA. sean.sachdev@northwestern.edu.
Abstract
PURPOSE: We investigated the prognostic significance of tumor-associated white matter (TA-WM) tracts in glioblastoma (GBM) using magnetic resonance-diffusion tensor imaging (MR-DTI). We hypothesized that (1) TA-WM tracts harbor microscopic disease not targeted through surgery or radiotherapy (RT), and (2) the greater the extent of TA-WM involvement, the worse the survival outcomes. METHODS: We studied a retrospective cohort of 76 GBM patients. TA-WM tracts were identified by MR-DTI fractional anisotropy (FA) maps. For each patient, 22 TA-WM tracts were analyzed and each tract was graded 1-3 based on FA. A TA-WM score (TA-WMS) was computed based on number of involved tracts and corresponding FA grade of involvement. Kaplan-Meier statistics were utilized to determine survival outcomes, log-rank test was used to compare survival between groups, and Cox regression was utilized to determine prognostic variables. RESULTS: For the MGMT-unmethylated cohort, there was a decrease in OS for increasing TA-WMS (median OS 16.5 months for TA-WMS 0-4; 13.6 months for TA-WMS 5-8; 7.3 months for TA-WMS > 9; p = 0.0002). This trend was not observed in the MGMT-methylated cohort. For MGMT-unmethylated patients with TA-WMS > 6 and involvement of tracts passing through brainstem or contralateral hemisphere, median OS was 8.3 months versus median OS 14.1 months with TA-WMS > 6 but not involving aforementioned critical tracts (p = 0.003 log-rank test). For MGMT-unmethylated patients, TA-WMS was predictive of overall survival in multivariate analysis (HR = 1.14, 95% CI 1.03-1.27, p = 0.012) while age, gender, and largest tumor dimension were non-significant. CONCLUSION: Increased TA-WMS and involvement of critical tracts are associated with decreased overall survival in MGMT-unmethylated GBM.
PURPOSE: We investigated the prognostic significance of tumor-associated white matter (TA-WM) tracts in glioblastoma (GBM) using magnetic resonance-diffusion tensor imaging (MR-DTI). We hypothesized that (1) TA-WM tracts harbor microscopic disease not targeted through surgery or radiotherapy (RT), and (2) the greater the extent of TA-WM involvement, the worse the survival outcomes. METHODS: We studied a retrospective cohort of 76 GBM patients. TA-WM tracts were identified by MR-DTI fractional anisotropy (FA) maps. For each patient, 22 TA-WM tracts were analyzed and each tract was graded 1-3 based on FA. A TA-WM score (TA-WMS) was computed based on number of involved tracts and corresponding FA grade of involvement. Kaplan-Meier statistics were utilized to determine survival outcomes, log-rank test was used to compare survival between groups, and Cox regression was utilized to determine prognostic variables. RESULTS: For the MGMT-unmethylated cohort, there was a decrease in OS for increasing TA-WMS (median OS 16.5 months for TA-WMS 0-4; 13.6 months for TA-WMS 5-8; 7.3 months for TA-WMS > 9; p = 0.0002). This trend was not observed in the MGMT-methylated cohort. For MGMT-unmethylated patients with TA-WMS > 6 and involvement of tracts passing through brainstem or contralateral hemisphere, median OS was 8.3 months versus median OS 14.1 months with TA-WMS > 6 but not involving aforementioned critical tracts (p = 0.003 log-rank test). For MGMT-unmethylated patients, TA-WMS was predictive of overall survival in multivariate analysis (HR = 1.14, 95% CI 1.03-1.27, p = 0.012) while age, gender, and largest tumor dimension were non-significant. CONCLUSION: Increased TA-WMS and involvement of critical tracts are associated with decreased overall survival in MGMT-unmethylated GBM.
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