METHODS: Thirty patients (16-76 aged) with two imaging (pre- and post-RT) and completed cognitive assessments were recruited. Cerebellum, right and left temporal lobes, corpus callosum, amygdala and spinal cord were delineated and their dosimetry parameters were collected. Cognitive assessments were given post-RT via telephone (Telephone Interview Cognitive Status (TICS), Telephone Montreal Cognitive Assessment (T-MoCA), Telephone Mini Addenbrooke's Cognitive Examination (Tele-MACE)). Regression models and deep neural network (DNN) were used to evaluate the relationship between brain volume, cognition and treatment dose in patients.
RESULTS: Cognitive assessments were highly inter-correlated (r > 0.9) and impairment was shown between pre- and post-RT findings. Brain volume atrophy was shown post-RT, and cognitive impairments were correlated with radiotherapy-associated volume atrophy and dose-dependent in the left temporal lobe, corpus callosum, cerebellum and amygdala. DNN showed a good area under the curve for cognitive prediction; TICS (0.952), T-MoCA (0.909) and Tele-MACE (0.822).
CONCLUSIONS: Cognition can be evaluated remotely in which radiotherapy-related brain injury is dose-dependent and volume-dependent. Prediction models can assist in the early identification of patients at risk for neurocognitive decline following RT for glioma, thus facilitating potential treatment interventions.
METHODS: We analysed expression of NFIA and NFIB in mRNA expression data of high-grade astrocytoma and with immunofluorescence co-staining. Furthermore, we induced NFI expression in patient-derived subcutaneous glioblastoma xenografts via in vivo electroporation.
RESULTS: The expression of NFIA and NFIB is reduced in glioblastoma as compared to lower grade astrocytomas. At a cellular level, their expression is associated with differentiated and mature astrocyte-like tumour cells. In vivo analyses consistently demonstrate that expression of either NFIA or NFIB is sufficient to promote tumour cell differentiation in glioblastoma xenografts.
CONCLUSION: Our findings indicate that both NFIA and NFIB may have an endogenous pro-differentiative function in astrocytomas, similar to their role in normal astrocyte differentiation. Overall, our study establishes a basis for further investigation of targeting NFI-mediated differentiation as a potential differentiation therapy.