A new landscape for systemic pharmacotherapy of recurrent glioblastoma?

Glioblastoma is the most common and aggressive primary malignant brain tumor in adult patients [...

Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO)

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, we addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care

Oligosarcomas, IDH‑mutant are distinct and aggressive

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile

EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood

In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy — Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers

High-field intraoperative MRI in glioma surgery: A prospective study with volumetric analysis of extent of resection and functional outcome

International audienceBackground: High-field intraoperative MRI (IoMRI) is a useful tool to improve the extent of glioma resection (EOR).Objective: To compare the interest of 1.5T IoMRI in glioma surgery between enhancing and non-enhancing tumors, based on volumetric analysis.Methods: A prospective single-center study included consecutive adult patients undergoing glioma surgery with IoMRI. Volumetric evaluation was based on FLAIR hypersignal after gadolinium injection in non-enhancing tumors and T1 hypersignal after gadolinium injection in enhancing tumors. Endpoints comprised: residual tumor volume (RTV), EOR, workflow and clinical outcome on Karnofsky performance score (KPS).Results: Fifty-three surgeries were performed from July 2014 to January 2016. Thirty-four patients underwent one IoMRI, and 19 two IoMRIs. In non-enhancing tumors, intraoperative RTV on 1st IoMRI T2/FLAIR was higher than in enhancing tumors on T1 sequences (7.25cm3 vs. 0.74cm3, respectively; P=0.008), whereas the RTV on 2nd IoMRIs and final RTV were no longer significantly different. After IoMRI, 72% of patients underwent additional resection. In non-enhancing tumors, EOR increased from 77.3% on 1st IoMRI to 97.4% on last MRI (P<0.001). Taking all tumors together, final RTV values were: median=0cm3, mean=3.9cm3. Mean final EOR was 94%. In 25% of patients, KPS was reduced during early postoperative course; at 3 and 6 months postoperatively, median KPS was 90.Conclusion: Intraoperative MRI guidance significantly enhanced the extent of glioma resection, especially for non- or minimally enhancing tumors, while preserving patient autonomy

Gender issues from the perspective of health-care professionals in Neuro-oncology: An EANO and EORTC Brain Tumor Group survey

Background: Women represent an increasing proportion of the overall workforce in medicine but are underrepresented in leadership roles. Methods: To explore gender inequalities and challenges in career opportunities, a web-based survey was conducted among the membership of the European Association of Neuro-Oncology and the Brain Tumor Group of the European Organisation for Research and Treatment of Cancer. Results: A total of 228 colleagues responded to the survey: 129 women (median age 45 years; range, 25-66 years) and 99 men (median age 48 years; range, 24-81 years); 153 participants (67%) were married and 157 participants (69%) had at least 1 child. Women less often declared being married (60% vs 77%, P =. 007) or having a child (63% vs 77%, P =. 024). Men more frequently had a full-time position (88% vs 75%, P =. 036). Women and men both perceived an underrepresentation of women in leadership positions. Half of participants agreed that the most important challenges for women are leading a team and obtaining a faculty position. Fewer women than men would accept such a position (42% vs 56%). The main reasons were limited time for career and an inappropriate work and life balance. Women specifically cited negative discrimination, limited opportunities, and lack of self-confidence. Discrimination of women at work was perceived by 64% of women vs 47% of men (P =. 003). Conclusion: Women are perceived as experiencing more difficulties in acquiring a leadership position. Personal preferences may account for an underrepresentation of women in leadership positions, but perceived gender inequalities extend beyond disparities of access to leadership

EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood

In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy - Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers

PET Imaging in Patients with Brain Metastasis - Report of the RANO/PET Group

Brain metastases (BM) from extracranial cancer are associated with significant morbidity and mortality. Effective local treatment options are stereotactic radiotherapy, including radiosurgery or fractionated external beam radiotherapy, and surgical resection. The use of systemic treatment for intracranial disease control also is improving. BM diagnosis, treatment planning, and follow-up is most often based on contrast-enhanced magnetic resonance imaging (MRI). However, anatomic imaging modalities including standard MRI have limitations in accurately characterizing posttherapeutic reactive changes and treatment response. Molecular imaging techniques such as positron emission tomography (PET) characterize specific metabolic and cellular features of metastases, potentially providing clinically relevant information supplementing anatomic MRI. Here, the Response Assessment in Neuro-Oncology working group provides recommendations for the use of PET imaging in the clinical management of patients with BM based on evidence from studies validated by histology and/or clinical outcome