Background: IDH-wildtype Glioblastoma (GB) is the most prevalent primary malignant CNS tumour in adults. The standard treatment regimen involves radiotherapy, which can cause radionecrotic (postactinic) changes as a late-onset treatment complication. While radiation is thought to mainly affect resident brain tissue, progressive GB and radionecrotic changes can be challenging to differentiate, as they may present with similar symptoms and appear alike on MRI. Therefore, histopathological examination remains the gold standard of diagnostics.
Methods: The cohort comprised ten samples from nine patients diagnosed with GB, all of whom underwent first-line standard of care treatment including surgery, radio- and chemotherapy with temozolomide. Subsequent radiological examination identified tumour progression in all patients, thus necessitating a second surgery. Following histopathological examination of the material collected from the second surgery, four patients were histologically diagnosed with tumour recurrence, four exhibited no evidence of recurrence but manifested with radionecrotic changes, and one patient demonstrated both. The spatial single cell transcriptomic profiling of the samples was conducted using the Xenium platform.
Results: We generated a comprehensive spatial single cell transcriptomic atlas of progressive GB and brain tissue with radionecrotic changes. Tumour cells were detected in samples from both groups. The employment of the dataset revealed that progressive GB samples contained OPC/NPC-like and proliferating tumour cells with high EGFR expression. Conversely, in samples with radionecrotic changes, tumour cells downregulated their EGFR expression even in the presence of gene amplification and did not show proliferation markers. Additionally, border-associated macrophages infiltrated the tissue and might have promoted gliosis in samples with radionecrotic changes.
Conclusions: This study delineates a complex spatial architecture of brain tissue with post-treatment changes and its discrepancies from progressive GB, thus facilitating future research into novel treatment strategies.
Keywords: glioblastoma; necrosis; radiation; recurrence; spatial single cell transcriptomics.
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