Spatial distribution of malignant transformation in patients with low-grade glioma

Abstract

Background: Malignant transformation represents the natural evolution of diffuse low-grade gliomas (LGG). This is a catastrophic event, causing neurocognitive symptoms, intensified treatment and premature death. However, little is known concerning the spatial distribution of malignant transformation in patients with LGG.

Materials and methods: Patients histopathological diagnosed with LGG and subsequent radiological malignant transformation were identified from two different institutions. We evaluated the spatial distribution of malignant transformation with (1) visual inspection and (2) segmentations of longitudinal tumor volumes. In (1) a radiological transformation site < 2 cm from the tumor on preceding MRI was defined local transformation. In (2) overlap with pretreatment volume after importation into a common space was defined as local transformation. With a centroid model we explored if there were particular patterns of transformations within relevant subgroups.

Results: We included 43 patients in the clinical evaluation, and 36 patients had MRIs scans available for longitudinal segmentations. Prior to malignant transformation, residual radiological tumor volumes were > 10 ml in 93% of patients. The transformation site was considered local in 91% of patients by clinical assessment. Patients treated with radiotherapy prior to transformation had somewhat lower rate of local transformations (83%). Based upon the segmentations, the transformation was local in 92%. We did not observe any particular pattern of transformations in examined molecular subgroups.

Conclusion: Malignant transformation occurs locally and within the T2w hyperintensities in most patients. Although LGG is an infiltrating disease, this data conceptually strengthens the role of loco-regional treatments in patients with LGG.

Keywords: Brain neoplasm; Glioma; Neurosurgery; Transformation; Treatment.

Fig. 1

Overview of the processing pipeline to visualize all MRI volumes for a same patient in the same space. The first row (P) represents the pre-operative MRI volume, the second row (PT) the pre-transformation MRI volume, and the third row (T) the transformation MRI volume. The columns are describing for one patient: (1) the initial MRI volumes with manual tumor segmentation (red for pre-operative, green for pre-transformation and blue for transformation), (2) the automatic brain segmentation (in yellow) for skull stripping, (3) the results of the volume registration in the pre-operative space, (4) the post-registration tumor volumes overlap

Fig. 2

Different examples showcasing the pre-operative volume (in red), the pre-transformation volume (in green) and the transformation volume (in blue) on top of the pre-operative MRI volume (n = 35). Each row is representing a different patient, and each column is representing a different view. First row; local transformation within preoperative volume. Second row; local transformation without overlap. Third row; local transformation with border overlap. Fourth row; distant transformation

Fig. 3

Overall distribution of the relative position of the centroid of the transformation volume over the centroid of the pre-operative volume for the different molecular marker groups. The few distant transformations are excluded in this model (n = 3). White represents the borders of the unitary pre-operative volume, red represents oligodendroglioma, green the IDH mut astrocytomas, and blue the IDH wt astrocytomas