Meetakshi Gupta

Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas (‘early glioblastoma’). Methodology: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers—MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Results: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2–90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. Conclusion: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.

Despite the increasing precision of radiotherapy delivery, it is still frequently associated with neurological complications. This is in part due to damage to eloquent white matter (WM) tracts, which is made more likely by the fact they cannot be visualised on standard structural imaging. WM is additionally more vulnerable than grey matter to radiation damage. Primary brain malignancies also are known to spread along the WM. Diffusion tensor imaging (DTI) is the only in vivo method of delineating WM tracts. DTI is an imaging technique that models the direction of diffusion and therefore can infer the orientation of WM fibres. This review article evaluates the current evidence for using DTI to guide intracranial radiotherapy and whether it constitutes a new state-of-the-art technique. We provide a basic overview of DTI and its known applications in radiotherapy, which include using tractography to reduce the radiation dose to eloquent WM tracts and using DTI to detect or predict tumoural spread. We evaluate the evidence for DTI-guided radiotherapy in gliomas, metastatic disease, and benign conditions, finding that the strongest evidence is for its use in arteriovenous malformations. However, the evidence is weak in other conditions due to a lack of case-controlled trials.