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Primary glioblastoma (GBM), IDH-wildtype, especially with multifocal appearance/growth (mGBM), is associated with very poor prognosis. Several clinical parameters have been identified to provide prognostic value in both unifocal GBM (uGBM) and mGBM, but information about the influence of radiological parameters on survival for mGBM cohorts is scarce. This study evaluated the prognostic value of several volumetric parameters derived from magnetic resonance imaging (MRI). Data from the Department of Neurosurgery, Leipzig University Hospital, were retrospectively analyzed. Patients treated between 2014 and 2019, aged older than 18 years and with adequate peri-operative MRI were included. Volumetric assessment was performed manually. One hundred and eighty-three patients were included. Survival of patients with mGBM was significantly shorter (p &lt, 0.0001). Univariate analysis revealed extent of resection, adjuvant therapy regimen, residual tumor volume, tumor necrosis volume and ratio of tumor necrosis to initial volume as statistically significant for overall survival. In multivariate Cox regression, however, only EOR (for uGBM and the entire cohort) and adjuvant therapy were independently significant for survival. Decreased ratio of tumor necrosis to initial tumor volume and extent of resection were associated with prolonged survival in mGBM but failed to achieve statistical significance in multivariate analysis.

Purpose: Familial glioblastoma multiforme (gbm) has been described in children with hereditary tumor syndromes. The occurrence of gbm in adult members of the same family and in the absence of tumor syndromes is extremely rare. We describe the cases of a brother and a sister with multifocal gbm diagnosed at the age of 63 years. We discuss three further paired gbm in adult patients from the literature. Patients and results: The sister was diagnosed with multifocal primary gbm in 2014 at the age of 63 years and 6 months. In 2018, her younger brother had to be operated on for a multifocal primary gbm at the age of 63 years and 9 months. Extended neuropathological examination revealed most markers to be similar, except for the percentage of O6-methylguanine-DNA methyltransferase promotor methylation, the presence of intratumoral immune cells and the immunohistochemical expression of C12ORF75. Comparison with further published cases of familial adult GBM reveals that most of these patients are male, about 65 years old and the tumor is localized predominantly in the left temporal lobe. Conclusion: Paired adult familial gbm occurs mainly in the elderly male patient with an integrative diagnosis of primary gbm. Whereas a statistical coincidence seems to be most likely in these rare cases, supplementary and improved genetic studies may identify pathogenetic causes of gbm.

Background. The evolution of primary glioblastoma (GBM) is poorly understood. Multifocal GBM (ie, multiple synchronous lesions in one patient) could elucidate GBM development. Methods. We present the first comprehensive study of 12 GBM foci from 6 patients using array-CGH, spectral karyotyping, gene expression arrays, and next-generation sequencing. Results. Multifocal GBMs genetically resemble primary GBMs. Comparing foci from the same patient proved their monoclonal origin. All tumors harbored alterations in the 3 GBM core pathways: RTK/PI3K, p53, and RB regulatory pathways with aberrations of EGFR and CDKN2A/B in all (100%) patients. This unexpected high frequency reflects a distinct genetic signature of multifocal GBMs and might account for their highly malignant and invasive phenotype. Surprisingly, the types of mutations in these genes/pathways were different in tumor foci from the same patients. For example, we found distinct mutations/aberrations in PTEN, TP53, EGFR, and CDKN2A/B, which therefore must have occurred independently and late during tumor development. We also identified chromothripsis as a late event and in tumors with wild-type TP53. Only 2 events were found to be early in all patients: single copy loss of PTEN and TERT promoter point mutations. Conclusions. Multifocal GBMs develop through parallel genetic evolution. The high frequency of alterations in 3 main pathways suggests that these are essential steps in GBM evolution; however, their late occurrence indicates that they are not founder events but rather subclonal drivers. This might account for the marked genetic heterogeneity seen in primary GBM and therefore has important implications for GBM therapy.

Background Multifocal glioblastoma is an uncommon and refractory subtype of high-grade glioma since the burden of masses could not be eliminated simply by operation, and it is getting even harder to control if some deep structures, like thalamus and pineal region, are involved. Case presentation Here we report a case of a 30-year-old male with multifocal glioblastoma affected his right thalamus, left lateral ventricle, and pineal region. Clinical manifestations include operation, concurrent radiochemotherapy, and a 12-cycle adjuvant temozolomide administration. The masses of this patient nearly disappeared after 15 months from the primary diagnosis, and no severe adverse event or neurological sequel occurred. Conclusions Long-term temozolomide might be an optimal choice for patients with multifocal glioblastoma, especially with deep-seated structure involvement.