Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: lessons from the French POLA cohort.

Background: In POLA cohort, three pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis).

Methods: 494 patients from the POLA cohort, with a median follow up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement in group 1 on overall survival (OS) or progression free survival (PFS), survival curves were obtained (Kaplan-Meier method) and compared (log-rank test).

Survival Outcomes Associated With First-Line Procarbazine, CCNU, and Vincristine or Temozolomide in Combination With Radiotherapy in IDH-Mutant 1p/19q-Codeleted Grade 3 Oligodendroglioma.

Purpose: Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens.

Methods: The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3.

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.

REVOLUMAB: A phase II trial of nivolumab in recurrent IDH mutant high-grade gliomas.

Background: Novel effective treatments are needed for recurrent IDH mutant high-grade gliomas (IDHm HGGs). The aim of the multicentric, single-arm, phase II REVOLUMAB trial (NCT03925246) was to assess the efficacy and safety of the anti-PD1 Nivolumab in patients with recurrent IDHm HGGs.

Patients And Methods: Adult patients with IDHm WHO grade 3-4 gliomas recurring after radiotherapy and ≥ 1 line of alkylating chemotherapy were treated with intravenous Nivolumab until end of treatment (12 months), progression, unacceptable toxicity, or death.

A threshold for mitotic activity and post-surgical residual volume defines distinct prognostic groups for astrocytoma IDH-mutant.

Aims: The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow-up and adjuvant treatment for resected astrocytomas IDH-mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre-IDH era.

Methods: Maximal mitotic activity in consecutive high-power fields corresponding to 3 mm was examined for 118 lower-grade astrocytomas IDH-mutant.

A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas.

Background: IDH mutant and 1p/19q codeleted oligodendrogliomas are the gliomas associated with the best prognosis. However, despite their sensitivity to treatment, patient survival remains heterogeneous. We aimed to identify gene expressions associated with response to treatment from a national cohort of patients with oligodendrogliomas, all treated with radiotherapy +/- chemotherapy.

T2-Fluid-attenuated inversion recovery (FLAIR) pseudoprogression in patients with anaplastic oligodendrogliomas treated with procarbazine, lomustine and vincristine (PCV) chemotherapy alone.

Background: Pseudoprogression in gliomas has been extensively described after radiotherapy with or without chemotherapy, but not after chemotherapy alone. Here we describe the occurrence of pseudoprogression in patients with anaplastic oligodendrogliomas treated with postoperative procarbazine, lomustine and vincristine (PCV) chemotherapy alone.

Methods: We retrospectively reviewed the medical and radiological files of patients with 1p/19q codeleted, IDH-mutant anaplastic oligodendrogliomas treated with PCV chemotherapy alone who presented magnetic resonance imaging (MRI) modifications suggestive of tumour progression and in whom the final diagnosis was a pseudoprogression.

In Vivo 2-Hydroxyglutarate Monitoring With Edited MR Spectroscopy for the Follow-up of -Mutant Diffuse Gliomas: The Prospective Study.

Background And Objectives: D-2-hydroxyglutarate (2HG) characterizes -mutant gliomas and can be detected and quantified with edited MRS (MEGA-PRESS). In this study, we investigated the clinical, radiologic, and molecular parameters affecting 2HG levels.

Methods: MEGA-PRESS data were acquired in 71 patients with glioma (24 untreated, 47 treated) on a 3 T system.

Chemotherapy is an efficient treatment in primary CNS MALT lymphoma.

Background: Mucosae-associated lymphoid tissue (MALT) lymphomas are a rare and poorly understood form of primary central nervous system lymphoma (PCNSL). The aim of this study was to better describe these tumors, their management and their long-term prognosis.

Methods: Patients with primary CNS MALT lymphoma (PCNSML) were retrospectively selected from the database on PCNSL of the Pitié-Salpêtrière Hospital.

Characteristics of Anaplastic Oligodendrogliomas Short-Term Survivors: A POLA Network Study.

Background: Anaplastic oligodendrogliomas IDH-mutant and 1p/19q codeleted (AO) occasionally have a poor outcome. Herein we aimed at analyzing their characteristics.

Methods: We retrospectively analyzed the characteristics of 44 AO patients with a cancer-specific survival <5 years (short-term survivors, STS) and compared them with those of 146 AO patients with a survival ≥5 years (classical survivors, CS) included in the POLA network.

Sustained Tumor Control With MAPK Inhibition in V600-Mutant Adult Glial and Glioneuronal Tumors.

Objective: To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with V600-mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort.

Methods: We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminated V600-mutant GGNTs treated with RAFi/MEKi.

Results: Twenty-eight adults with recurrent or disseminated V600-mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study.

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors.

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms.

An AI-Powered Blood Test to Detect Cancer Using NanoDSF.

Glioblastoma is the most frequent and aggressive primary brain tumor. Its diagnosis is based on resection or biopsy that could be especially difficult and dangerous in the case of deep location or patient comorbidities. Monitoring disease evolution and progression also requires repeated biopsies that are often not feasible.

Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort.

Background: IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.

Methods: In a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.

Rare Primary Central Nervous System Tumors in Adults: An Overview.

Overall, tumors of primary central nervous system (CNS) are quite common in adults with an incidence rate close to 30 new cases/100,000 inhabitants per year. Significant clinical and biological advances have been accomplished in the most common adult primary CNS tumors (i.e.

Mechanisms and therapeutic implications of hypermutation in gliomas.

A high tumour mutational burden (hypermutation) is observed in some gliomas; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood. Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and mismatch repair (MMR) genes, and a more common post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas that recur after treatment with the chemotherapy drug temozolomide.

Germline mutations in the new E1' cryptic exon of the gene in patients with tumours of von Hippel-Lindau disease spectrum or with paraganglioma.

Backgrounds: The incidence of germline mutations in the newly discovered cryptic exon (E1') of gene in patients with von Hippel-Lindau (VHL) disease and in patients with paraganglioma or pheochromocytoma (PPGL) is not currently known.

Methods: We studied a large international multicentre cohort of 1167 patients with a previous negative genetic testing. Germline DNA from 75 patients with a single tumour of the VHL spectrum ('Single VHL tumour' cohort), 70 patients with multiple tumours of the VHL spectrum ('Multiple VHL tumours' cohort), 76 patients with a VHL disease as described in the literature ('VHL-like' cohort) and 946 patients with a PPGL were screened for E1' genetic variants.

CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas.

Background: The 2016 World Health Organization (WHO) classification of central nervous system tumors stratifies isocitrate dehydrogenase (IDH)-mutant gliomas into 2 major groups depending on the presence or absence of 1p/19q codeletion. However, the grading system remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification.

Methods: In a large cohort of 911 high-grade IDH-mutant gliomas from the French national POLA network (including 428 IDH-mutant gliomas without 1p/19q codeletion and 483 anaplastic oligodendrogliomas, IDH-mutant and 1p/19q codeleted), we investigated the prognostic value of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene homozygous deletion as well as WHO grading criteria (mitoses, microvascular proliferation, and necrosis).