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Tumor-associated alterations in white matter connectivity have prognostic significance in MGMT-unmethylated glioblastoma

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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.

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Acknowledgements

This work was supported by the Northwestern University Clinical and Translational Sciences Institute grant UL1TR001422; the authors thank the Northwestern Medicine Advanced Imaging Analytics Lab for their assistance.

Funding

Northwestern University Clinical and Translational Sciences Institute (UL1TR001422).

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Authors and Affiliations

  1. Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 1820, Chicago, IL, 60611, USA

    Nikhil Rammohan, Alexander Ho, Amishi Bajaj & Sean Sachdev

  2. Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Mohit Saxena & Alexander Korutz

  3. Turville Bay Radiation Oncology Center, SSM Health Dean Medical Group, Madison, WI, USA

    Tim J. Kruser

  4. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Craig Horbinski

  5. Department of Neurologic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Matthew Tate

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  1. Nikhil Rammohan
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  2. Alexander Ho
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  3. Mohit Saxena
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  4. Amishi Bajaj
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  8. Matthew Tate
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  9. Sean Sachdev
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Contributions

Project ideas and methods—N.R., M.T., and S.S.; Data curation—N.R., A.H., A.B., M.S., and C.H.; Data analysis—N.R., A.H., M.S., A.K., M.T. and S.S.; Writing (first draft and revisions)—N.R.; Writing (editing)—A.H., A.B., M.S., T.J.K, C.H., A.K., M.T., and S.S.

Corresponding author

Correspondence to Sean Sachdev.

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Conflict of interests

TJK serves on an advisory board and speakers bureau for AstraZeneca and is a consultant for Radialogica LLC. Other authors declare they have no competing interests to disclose.

Ethical approval

This study was performed with approval of Northwestern University Institutional Review Board (8/4/2020, STU00213078).

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Rammohan, N., Ho, A., Saxena, M. et al. Tumor-associated alterations in white matter connectivity have prognostic significance in MGMT-unmethylated glioblastoma. J Neurooncol 158, 331–339 (2022). https://doi.org/10.1007/s11060-022-04018-3

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