There is a need for more accurate and comparable incidence and prevalence estimates of primary brain tumors across the world. A standardized approach to the study of the epidemiology of these tumors is needed to better understand the burden of brain tumors and the possible geographical variations in their incidence.

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Patients with glioblastoma (GBM), the most common primary brain tumor in adults, have a median survival of about one year. In 2005, Stupp et al 1 published the results of a randomized controlled clinical trial in GBM demonstrating a significant survival benefit by adding temozolomide (TMZ) to radiation. In this study, patients with newly diagnosed GBM were treated with low dose temozolomide daily during radiation therapy (termed "concurrent treatment") followed by six monthly cycles of TMZ administered five days out of every 28 ABSTRACT: Introduction: Chemoradiotherapy followed by monthly temozolomide (TMZ) is the standard of care for patients with glioblastoma multiforme (GBM). Case reports have identified GBM patients who experienced transient radiological deterioration after concurrent chemoradiotherapy which stabilized or resolved after additional cycles of adjuvant TMZ, a phenomenon known as radiographic pseudoprogression. Little is known about the natural history of radiographic pseudoprogression. Methods: We retrospectively evaluated the incidence of radiographic pseudoprogression in a population-based cohort of GBM patients and determined its relationship with outcome and MGMT promoter methylation status. Results: Out of 43 evaluable patients, 25 (58%) exhibited radiographic progression on the first MRI after concurrent treatment. Twenty of these went on to receive adjuvant TMZ, and subsequent investigation demonstrated radiographic pseudoprogression in 10 cases (50%). Median survival (MS) was better in patients with pseudoprogression (MS 14.5 months) compared to those with true radiologic progression (MS 9.1 months, p=0.025). The MS of patients with pseudoprogression was similar to those who stabilized/responded during concurrent treatment (p=0.31). Neither the extent of the initial resection nor dexamethasone dosing was associated with pseudoprogression. Conclusions: These data suggest that physicians should continue adjuvant TMZ in GBM patients when early MRI scans show evidence of progression following concurrent chemoradiotherapy, as up to 50% of these patients will experience radiologic stability or improvement in subsequent treatment cycles. RÉSUMÉ: Étude de population sur la pseudoprogression après la chimioradiothérapie dans le glioblastome multiforme. Introduction : Le traitement standard du glioblastome multiforme (GBM) est la chimioradiothérapie suivie de l'administration mensuelle de témozolomide (TMZ). Certains cas de patients atteints de GBM, qui ont présenté une détérioration radiologique transitoire après la chimioradiothérapie qui s'est stabilisée ou s'est résorbée après des cycles additionnels de TMZ, un phénomène connu sous le nom de pseudoprogression radiologique, ont été rapportés. Méthodes : Nous avons évalué rétrospectivement l'incidence de la pseudoprogression radiologique chez une cohorte de patients atteints de GBM tirée de la population et nous avons déterminé sa relation avec le résultat du traitement et avec l'état de méthylation du promoteur MGMT. Résultats : Vingt-cinq des...

Abstract. In glioblastoma (GBM), promoter methylation of the DNA repair gene MGMT is associated with benefit from chemotherapy. Because MGMT promoter methylation status can not be determined in all cases, a surrogate for the methylation status would be a useful clinical tool. Correlation between methylation status and magnetic resonance imaging features has been reported suggesting that non-invasive MGMT promoter methylation status detection is possible. In this work, a retrospective analysis of T2, FLAIR and T1-post contrast MR images in patients with newly diagnosed GBM is performed using L1-regularized neural networks. Tumor texture, assessed quantitatively was utilized for predicting the MGMT promoter methylation status of a GBM in 59 patients. The texture features were extracted using a space-frequency texture analysis based on the S-transform and utilized by a neural network to predict the methylation status of a GBM. Blinded classification of MGMT promoter methylation status reached an average accuracy of 87.7%, indicating that the proposed technique is accurate enough for clinical use.

Background Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. Methods This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS). Results Enrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91–1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3–5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction. Conclusions In this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results. Clinical trials registration NCT02511405

Based on these results, a clinical pharmacist should become a permanent member of the outpatient NeuroOncology clinic.

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