Abstract
Background
For diffuse glioma, tumor location is an important factor that influences symptomatology, treatment strategy and, ultimately, survival. Our previous research showed an association between overall survival (OS) and local involvement in eloquent gray and white matter areas in the left hemisphere. Also, involvement of central anatomical structures, such as midline corpus callosum, seem to relate to poorer survival rates, when predefined categories of survival groups (>6 months, 6-24, 24< months) are established. In this study, we investigated OS in relation to centrality of the tumor and its microstructural environment defined as the Clinical Target Volume (CTV) in diffuse glioma treated with radiotherapy in a data-driven fashion.
Material and Methods
We retrospectively included 273 adult patients with histologically proven diffuse glioma who received first radiotherapy between November 2014 and July 2020 at Unive rsity Medical Center Utrecht. CTV was spatially normalized to stereotaxic MNI152 space and its center of gravity (CoG) was subsequently calculated. Then, the distance between CoG of CTV to the center of the MNI brain was measured in millimeters (mm) for every tumor. A multivariable Cox-regression model included the distance between CoG of CTV and center of MNI brain, age, sex, total intracranial volume (TIV), Karnofsky Performance Status (KPS), WHO grade and extent of resection.
Results
During follow-up, 183 patients (67%) deceased and median OS of the population was 13.7 months (range 0.03 - 65.25) from start of radiotherapy. CoG of CTV to center of brain distance had a significantly inverse association with OS in a multivariable Cox-regression model (P < 0.001) with a hazard ratio 0.97 [95% Confidence Interval: 0.95-0.98] per mm.
Conclusion
In line with literature, centrality of diffuse glioma was associated with a poor survival in irradiated diffuse glioma. I n fact, this association was linear, showing a better OS the greater the distance between center of CTV and center of MNI brain after correcting for known prognostic factors such as WHO grade, KPS and extent of resection. Tumor centrality is not a biomarker of involvement in specific eloquent brain regions in and of itself, but a poorer OS in these areas might indicate a proximity to large bulk of commissural white matter tracts and tumor progression along these tracts. Structures of the memory circuit like the fornix and cingulum are also centrally located. Damage to these areas are highly associated with cognitive decline in the memory domain, which is independently related to decreased survival in diffuse glioma patients. Another factor could be tumor involvement of the subventricular zone along the walls of caudate and the lateral ventricles, in which we previously showed that is also associated with worsened survival.
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