A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of < 70 years (standard group) and 117 patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p < 0.001), including surgical resection (p < 0.001), Bevacizumab therapy (p < 0.001), and second line chemotherapy other than Temozolomide (p < 0.001). In multivariate analysis, Age ≥70 years was not an independent predictor of overall survival from recurrence (p = 0.602), RTOG-RPA classes 5–6 (p = 0.050) and KPS at recurrence <70 (p < 0.001), available in all cases, were independent significant predictors of shorter overall survival from recurrence. Initial removal of ≥ 90% of enhancing tumor (p = 0.004), initial completion of the standard combined chemoradiotherapy (p = 0.007), oncological treatment from recurrence (p < 0.001), and particularly surgical resection (p < 0.001), Temozolomide (p = 0.046), and Bevacizumab therapy (p = 0.041) were all significant independent predictors of longer overall survival from recurrence. Elderly patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.

Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?

Human gliomas are one of the most prevalent and challenging-to-treat adult brain tumors, and thus result in high morbidity and mortality rates worldwide. Current research and treatments of gliomas ...

Application of photodynamic therapy drugs for management of glioma

In this study, we evaluated the benefit on survival of the combination of methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.7) and the new calculated ones (9.1 and 9.8) to analyze the association with survival for different populations according to vascularity and MGMT methylation status. We found that patients included in the moderate-vascular group had longer survival when MGMT is methylated (significant median survival difference of 174 days, p = 0.0129*). However, we did not find significant differences depending on the MGMT methylation status for the high-vascular group (p = 0.9119). In addition, we investigated the combined correlation of MGMT methylation status and rCBV with the prognostic effect of the number of temozolomide cycles, and only significant results were found for the moderate-vascular group. In conclusion, there is a lack of benefit of extending temozolomide treatment for patients with high vascular glioblastomas, even presenting MGMT methylation. Preliminary results suggest that patients with moderate vascularity and methylated MGMT glioblastomas would benefit more from prolonged adjuvant chemotherapy.

Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT

/pdf/characterization-of-vascular-heterogeneity-of-astrocytomas-3mgqpt6e.pdf

Characterization of vascular heterogeneity of astrocytomas grade 4 for supporting patient prognosis estimation, and treatment response assessment

The identification of the cancer driver genes is essential for personalized therapy. The mutation frequency of most driver genes is in the middle (2-20%) or even lower range, which makes it difficult to find the driver genes with low-frequency mutations. Other forms of genomic aberrations, such as copy number variations (CNVs) and epigenetic changes, may also reflect cancer progression. In this work, a method for identifying the potential cancer driver genes (iPDG) based on molecular data integration is proposed. DNA copy number variation, somatic mutation, and gene expression data of matched cancer samples are integrated. In combination with the method of iKEEG, the "key genes" of cancer are identified, and the change in their expression levels is used for auxiliary evaluation of whether the mutated genes are potential drivers. For a mutated gene, the concept of mutational effect is defined, which takes into account the effects of copy number variation, mutation gene itself, and its neighbor genes. The method mainly includes two steps: the first step is data preprocessing. First, DNA copy number variation and somatic mutation data are integrated. Then, the integrated data are mapped to a given interaction network, and the diffusion kernel is used to form the mutation effect matrix. The second step is to obtain the key genes by using the iKGGE method, and construct the connection matrix by means of the gene expression data of the key genes and mutation impact matrix of the mutated genes. Experiments on TCGA breast cancer and Glioblastoma multiforme datasets demonstrate that iPDG is effective not only to identify the known cancer driver genes but also to discover the rare potential driver genes. When measured by functional enrichment analysis, we find that these genes are clearly associated with these two types of cancers.

A Novel Method for Identifying the Potential Cancer Driver Genes Based on Molecular Data Integration.

2029Background: Glioblastoma (GBM) gene expression subtypes have been described in last years, data in homogeneously treated patients is lacking. Methods: Clinical, molecular and immunohistochemist...

Glioblastoma gene expression subtypes and correlation with clinical, molecular and immunohistochemical characteristics in a homogenously treated cohort: GLIOCAT project.

2045Background: Elderly GB patients have a dismal prognosis. The optimal treatment in this population remains to be established. Methods: We performed a multicenter retrospective and prospective st...

Feasibility and efficacy of concomitant chemoradiation (Ch-RT) in the management of newly diagnosed elderly glioblastoma (GB) patients: Results from the GLIOCAT study.

MGMT methylated (Met) patients (p) with glioblastoma (GBM) have a better prognosis with an earlier response (ER) than those who have a late response or pseudoprogression (LR/PsP). Results of the Gliocat study

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Glioblastoma gene expression subtypes and correlation with clinical, molecular and immunohistochemical characteristics in a homogenously treated cohort: GLIOCAT project.

Feasibility and efficacy of concomitant chemoradiation (Ch-RT) in the management of newly diagnosed elderly glioblastoma (GB) patients: Results from the GLIOCAT study.

MGMT methylated (Met) patients (p) with glioblastoma (GBM) have a better prognosis with an earlier response (ER) than those who have a late response or pseudoprogression (LR/PsP). Results of the Gliocat study