Shape matters: morphological metrics of glioblastoma imaging abnormalities as biomarkers of prognosis.

Lacunarity, a quantitative morphological measure of how shapes fill space, and fractal dimension, a morphological measure of the complexity of pixel arrangement, have shown relationships with outcome across a variety of cancers. However, the application of these metrics to glioblastoma (GBM), a very aggressive primary brain tumor, has not been fully explored. In this project, we computed lacunarity and fractal dimension values for GBM-induced abnormalities on clinically standard magnetic resonance imaging (MRI). In our patient cohort (n = 402), we connect these morphological metrics calculated on pretreatment MRI with the survival of patients with GBM. We calculated lacunarity and fractal dimension on necrotic regions (n = 390), all abnormalities present on T1Gd MRI (n = 402), and abnormalities present on T2/FLAIR MRI (n = 257). We also explored the relationship between these metrics and age at diagnosis, as well as abnormality volume. We found statistically significant relationships to outcome for all three imaging regions that we tested, with the shape of T2/FLAIR abnormalities that are typically associated with edema showing the strongest relationship with overall survival. This link between morphological and survival metrics could be driven by underlying biological phenomena, tumor location or microenvironmental factors that should be further explored.

Image-based metric of invasiveness predicts response to adjuvant temozolomide for primary glioblastoma.

BACKGROUND: Temozolomide (TMZ) has been the standard-of-care chemotherapy for glioblastoma (GBM) patients for more than a decade. Despite this long time in use, significant questions remain regarding how best to optimize TMZ therapy for individual patients. Understanding the relationship between TMZ response and factors such as number of adjuvant TMZ cycles, patient age, patient sex, and image-based tumor features, might help predict which GBM patients would benefit most from TMZ, particularly for those whose tumors lack O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. METHODS AND FINDINGS: Using a cohort of 90 newly-diagnosed GBM patients treated according to the standard of care, we examined the relationships between several patient and tumor characteristics and volumetric and survival outcomes during adjuvant chemotherapy. Volumetric changes in MR imaging abnormalities during adjuvant therapy were used to assess TMZ response. T1Gd volumetric response is associated with younger patient age, increased number of TMZ cycles, longer time to nadir volume, and decreased tumor invasiveness. Moreover, increased adjuvant TMZ cycles corresponded with improved volumetric response only among more nodular tumors, and this volumetric response was associated with improved survival outcomes. Finally, in a subcohort of patients with known MGMT methylation status, methylated tumors were more diffusely invasive than unmethylated tumors, suggesting the improved response in nodular tumors is not driven by a preponderance of MGMT methylated tumors. CONCLUSIONS: Our finding that less diffusely invasive tumors are associated with greater volumetric response to TMZ suggests patients with these tumors may benefit from additional adjuvant TMZ cycles, even for those without MGMT methylation.