Association of Isocitrate Dehydrogenase (IDH) Status With Edema to Tumor Ratio and Its Correlation With Immune Infiltration in Glioblastoma

Abstract

PurposeThe extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.MethodsA volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.ResultsThe edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups.ConclusionIn our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.

Factors Involved in Preoperative Edema in High-Grade Gliomas

“…suggested that IDH wild-type glioblastomas have a high peritumoral edema volume/tumor volume (E/T) ratio [13]. The results of this study based on quantitative evaluation of edema are consistent with this finding.…”

“…However, there are few quantitative studies of peritumoral edema in gliomas with an IDH mutation. Dubinski et al suggested that IDH wild-type glioblastomas have a high peritumoral edema volume/tumor volume (E/T) ratio [ 13 ]. The results of this study based on quantitative evaluation of edema are consistent with this finding.…”

DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions

“…For additional comparison of the main rCBV variables, an additional figure of dispersion graphics is also provided in Supplementary Material 3. cases, they may more closely align with pure edema. Indeed, this hypothesis aligns well with prior knowledge: Glioblastomas are known to generate more pronounced edema, whereas Astrocytomas manifest a more substantial proportion of non-enhancing tumor tissue in the T2-FLAIR abnormality [25].…”

“…Such regions may represent a greater degree of coexisting very-low vascularized infiltrated tissue in IDH-mutant cases, while in IDH-wildtype cases, they may more closely align with pure edema. Indeed, this hypothesis aligns well with prior knowledge: Glioblastomas are known to generate more pronounced edema, whereas Astrocytomas manifest a more substantial proportion of non-enhancing tumor tissue in the T2-FLAIR abnormality [ 25 ].…”

Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study

“…Finally, we suggested that Habitat 8, due to its reduced diffusivity, might identify areas of tumor infiltration beyond the CE vital core, while Habitat 7 areas of vasogenic edema (with no, or less prominent, tumor infiltration). Interestingly, in our series, the relative volume of pure edema (Habitat 7) was significantly higher in IDH-1 wild-type tumors, compared to IDH-1 mutated lesions, similarly to other recent studies (Dubinski et al, 2021).…”