The clinical impact of EGFR alterations in elderly glioblastoma patients: results from a real-life cohort.

Background: The incidence of glioblastoma in the elderly population is increasing as the worldwide population ages. The differential and poorer survival in the elderly population compared to younger patients is partially explained. The present study aimed to investigate the clinical impact of epidermal growth factor receptor EGFR-altered glioblastoma in a real-life elderly glioblastoma population.

Metabolic remodeling in glioblastoma: a longitudinal multi-omics study.

Monitoring tumor evolution and predicting survival using non-invasive liquid biopsy is an unmet need for glioblastoma patients. The era of proteomics and metabolomics blood analyzes, may help in this context. A case-control study was conducted.

Olaparib in recurrent isocitrate dehydrogenase mutant high-grade glioma: A phase 2 multicenter study of the POLA Network.

Background: Based on preclinical studies showing that IDH-mutant (IDHm) gliomas could be vulnerable to PARP inhibition we launched a multicenter phase 2 study to test the efficacy of olaparib monotherapy in this population.

Methods: Adults with recurrent IDHm high-grade gliomas (HGGs) after radiotherapy and at least one line of alkylating chemotherapy were enrolled. The primary endpoint was a 6-month progression-free survival rate (PFS-6) according to response assessment in neuro-oncology criteria.

Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients.

Background: Liquid biopsy application is still challenging in glioblastoma patients and the usefulness of short-length DNA (slDNA) fragments is not established. The aim was to investigate slDNA concentration as a prognostic marker in unresected glioblastoma patients.

Methods: Patients with unresected glioblastoma and treated by radiochemotherapy (RT/TMZ) were included.

A Multicenter Randomized Bioequivalence Study of a Novel Ready-to-Use Temozolomide Oral Suspension vs. Temozolomide Capsules.

Background: Temozolomide (TMZ) oral suspension (Ped-TMZ, KIZFIZO) is being developed for the treatment of relapsed or refractory neuroblastoma, a rare cancer affecting infants and young children. The study assessed the safety and the bioequivalence of this novel pediatric formulation with existing TMZ oral capsules.

Methods: In vitro dissolution profiles and the bioequivalence were evaluated following the European Medicines Agency "Guidelines on the investigation of Bioequivalence".

Compliance with good practice guidelines for the prevention of vascular access infections: the multi-centre PHYDEL survey in French haemodialysis units.

Background: French guidelines for the prevention of vascular access infections in a haemodialysis setting were released in 2005. Compliance with these guidelines is currently unknown. The aim of this study was to assess compliance with the guidelines for vascular access infection prevention in French haemodialysis units, and to describe the difficulties reported.

Target volume delineation for radiotherapy of meningiomas: an ANOCEF consensus guideline.

Purpose: Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations.

Impact of Covid-19 pandemic on neuro-oncology multidisciplinary tumor board in the pre-vaccine era: the Normandy experience.

Introduction: The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France).

Impact of EGFR mutation on relapse pattern in glioblastoma.

Background: Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFR) is associated with a more infiltrative phenotype. The primary objective of this study was to explore the impact of the EGFR mutation on the pattern of relapse after chemoradiotherapy-based treatment of patients suffering from newly diagnosed glioblastoma.

Heterogeneity in long-term outcomes for patients with Revised International Staging System stage II, newly diagnosed multiple myeloma.

In the era of personalized treatment in multiple myeloma, high-risk patients must be accurately identified. The International Myeloma Working Group recommends using the Revised International Staging System (R-ISS) to pick out high-risk patients. The main purpose of our work was to explore the heterogeneity of outcome among R-ISS stage II patients assessing the impact of International Staging System (ISS) stage, chromosomal abnormalities and lactate dehydrogenase level in this subgroup.

Usefulness of circulating tumor DNA from cerebrospinal fluid in recurrent high-grade glioma.

Molecular documentation at relapse of high-grade glioma is an urgent need for patient care. A prospective pilot study was conducted to assess the rate of mutation detection using targeted deep sequencing on circulating tumor DNA from cerebrospinal fluid (CSF) after chemo-radiotherapy based treatment. Fifteen patients were included: 13 patients with glioblastoma, 1 patient with gliosarcoma and 1 patient with anaplastic astrocytoma.

Integrative Metabolomics Reveals Deep Tissue and Systemic Metabolic Remodeling in Glioblastoma.

(1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension.

Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach.

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs.

Promoter Alterations in Glioblastoma: A Systematic Review.

Glioblastoma, the most frequent and aggressive primary malignant tumor, often presents with alterations in the telomerase reverse transcriptase promoter. Telomerase is responsible for the maintenance of telomere length to avoid cell death. Telomere lengthening is required for cancer cell survival and has led to the investigation of telomerase activity as a potential mechanism that enables cancer growth.

Simultaneous detection of EGFR amplification and EGFRvIII variant using digital PCR-based method in glioblastoma.

Epidermal growth factor receptor (EGFR) amplification and EGFR variant III (EGFRvIII, deletion of exons 2-7) are of clinical interest for glioblastoma. The aim was to develop a digital PCR (dPCR)-based method using locked nucleic acid (LNA)-based hydrolysis probes, allowing the simultaneous detection of the EGFR amplification and EGFRvIII variant. Sixty-two patients were included.

Early treatment with FCR versus watch and wait in patients with stage Binet A high-risk chronic lymphocytic leukemia (CLL): a randomized phase 3 trial.

We report a randomized prospective phase 3 study (CLL7), designed to evaluate the efficacy of fludarabine, cyclophosphamide, and rituximab (FCR) in patients with an early-stage high-risk chronic lymphocytic leukemia (CLL). Eight hundred patients with untreated-stage Binet A disease were enrolled as intent-to-treat population and assessed for four prognostic markers: lymphocyte doubling time <12 months, serum thymidine kinase >10 U/L, unmutated IGHV genes, and unfavorable cytogenetics (del(11q)/del(17p)/trisomy 12). Two hundred and one patients with ≥2 risk features were classified as high-risk CLL and 1:1 randomized to receive either immediate therapy with 6xFCR (Hi-FCR, 100 patients), or to be observed according to standard of care (Hi-W&W, 101 patients).

Deleterious impact of a generic temozolomide formulation compared with brand-name product on the kinetic of platelet concentration and survival in newly diagnosed glioblastoma.

Chemo-induced thrombocytopenia is a limiting toxicity among patients receiving temozolomide (TMZ) as first-line treatment for glioblastoma. We aimed to compare early platelet concentration kinetics, hematological safety profile, and impact on survival following the initiation of either the brand-name or a generic TMZ formulation. A retrospective trial was conducted in patients suffering from newly diagnosed glioblastoma.

TERTp Mutation Detection in Plasma by Droplet-Digital Polymerase Chain Reaction in Spinal Myxopapillary Ependymoma with Lung Metastases.

Background: Spinal myxopapillary ependymoma (SP-MPE) is a subgroup of ependymomas in which after initial gross tumor resection, recurrences occur in more than half of the patients. Anaplastic transformation may also occur and contributes to intraneural and extraneural metastatic dissemination. Extraneural metastases from SP-MPE are rare and worsen the prognosis.

Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial.

Background: In patients with chronic lymphocytic leukaemia, achievement of a complete response with minimal residual disease of less than 0·01% (ie, <1 chronic lymphocytic leukaemia cell per 10 000 leukocytes) in bone marrow has been associated with improved progression-free survival. We aimed to explore the activity of induction therapy for 9 months with obinutuzumab and ibrutinib, followed up with a minimal residual disease-driven therapeutic strategy for 6 additional months, in previously untreated patients.

Methods: We did a single-arm, phase 2 trial in 27 university hospitals, general hospitals, and specialist cancer centres in France.