304 - Glioblastoma Distant Recurrences Preferentially Occur Along White Matter Tracts Mapped Using Probabilistic Diffusion Tractography

02:15pm - 02:25pm ET

Room 253

Presenter(s)

Chengcheng Gui, MD - Johns Hopkins University School of Medicine, Baltimore, MD

C. Gui¹, M. Jenabi², L. A. Boe², C. W. Brennan², N. S. Moss², K. Yu², R. Bou-Nassif², V. S. Tabar², T. J. Kaley², L. R. G. Pike², J. N. Stember², R. J. Young², L. Pasquini³, K. Peck⁴, I. Mellinghoff², A. Holodny⁵, and B. S. Imber²; ¹Johns Hopkins University School of Medicine, Baltimore, MD, ²Memorial Sloan Kettering Cancer Center, New York, NY, ³Yale School of Medicine, New Haven, CT, ⁴Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, ⁵Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s):

Despite maximal safe resection and chemoradiotherapy, nearly all glioblastomas recur within two years of initial treatment. Although most recurrences are local, 10–20% occur distant to the primary tumor site, arising from disseminated microscopic disease. Aggressive local treatment strategies, including supratotal resection and dose-intensified radiotherapy, are associated with lower rates of local recurrence but higher rates of distant recurrence, up to 20–50%.

White matter tracts are a major pathway for microscopic glioblastoma dissemination. However, regional white matter anatomy is not routinely incorporated into radiotherapy target delineation. We hypothesized that distant glioblastoma recurrences preferentially occur near white matter tracts associated with the primary tumor site, and that these high-risk regions can be identified using probabilistic tractography, a diffusion tensor imaging–based technique, with direct implications for target delineation.

Materials/Methods:

We identified patients with glioblastoma who developed distant recurrence =2 cm from the primary tumor site and had diffusion tensor imaging prior to recurrence. Probabilistic tractography connection (PTC) maps were generated, initialized from the primary tumor volume with a uniform 1 cm expansion. The boundary of the PTC map was defined using a threshold of Z = 0, excluding low-probability voxels below the mean. The minimum distance from the PTC map to the recurrent tumor was measured. The probability of the recurrence occurring within 0.5 cm of the PTC map was evaluated using a one-sided binomial test.

Results:

Among 35 glioblastoma distant recurrences occurring at median 12.3 months after postoperative radiotherapy, 24 were ipsilateral to the primary site (66%), 10 contralateral (29%), and 2 transtentorial (6%). The median volume of the PTC map was 139 cc (range, 38–442 cc), corresponding to 9.7% of total brain volume (range, 3.4–35%). Overall, 29 of 35 recurrences were located within =0.5 cm of the PTC map (83%, p = 0.0002). The median distance from the PTC map to the recurrence was 0 cm, representing direct overlap (range, 0–1.7 cm). Proximity of recurrence to the PTC map was consistent across differences in primary tumor size, resection extent, and location of distant recurrence.

Conclusion:

Using a novel diffusion tensor imaging–based probabilistic tractography approach, we mapped major white matter tracts originating from the primary tumor site and demonstrated that over 80% of distant glioblastoma recurrences occurred within 0.5 cm of these tracts. These findings support the hypothesis that white matter pathways are critical conduits for microscopic glioblastoma dissemination. Current radiotherapy target delineation for glioblastoma relies on geometrically simplistic expansions that do not account for underlying white matter anatomy. Incorporation of probabilistic tractography may improve tumor control while preserving survival and neurologic function.