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1.
J Neurol ; 269(8): 4349-4362, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35441889

ABSTRACT

BACKGROUND: Brainstem gliomas are rare in adults. The diagnosis is often difficult, as some teams still consider brainstem biopsies dangerous and often avoid this procedure. The aim of this study was to describe differential diagnoses that can mimic brainstem glioma, to help clinicians avoid diagnostic and therapeutic mistakes, and to propose a diagnostic algorithm according to radiological presentations. METHODS: The French network of adult brainstem gliomas (GLITRAD) retrospectively collected all reported cases of differential diagnoses between 2006 and 2017. The inclusion criteria were as follows: age over 18 years, lesion epicenter in the brainstem, radiological pattern suggestive of a glioma and diagnostic confirmation (histopathological or not, depending on the disease). RESULTS: We identified a total of 68 cases. Most cases (58/68, 85%) presented as contrast-enhancing lesions. The most frequent final diagnosis in this group was metastases in 24/58 (41%), followed by central nervous system lymphoma in 8/58 (14%). Conversely, MRI findings revealed 10/68 nonenhancing lesions. The most frequent diagnosis in this group was demyelinating disease (3/10, 30%). CONCLUSION: The risk of diagnostic mistakes illustrates the need to consider the more systematic use of a brainstem biopsy when reasonably possible. However, we propose an MRI-based approach to the differential diagnosis of gliomas to limit the risk of misdiagnosis in cases where a biopsy is not a reasonable option.


Subject(s)
Brain Neoplasms , Brain Stem Neoplasms , Glioma , Adolescent , Adult , Brain Neoplasms/diagnosis , Brain Stem Neoplasms/diagnostic imaging , Diagnosis, Differential , Glioma/diagnostic imaging , Glioma/pathology , Humans , Magnetic Resonance Imaging , Retrospective Studies
2.
Cancers (Basel) ; 13(14)2021 Jul 12.
Article in English | MEDLINE | ID: mdl-34298693

ABSTRACT

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

3.
J Neurol ; 268(9): 3072-3080, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33387015

ABSTRACT

BACKGROUND: Cancer patients may be at higher risk for severe coronavirus infectious disease-19 (COVID-19); however, the outcome of Primary Central Nervous System Lymphoma (PCNSL) patients with SARS-CoV-2 infection has not been described yet. METHODS: We conducted a retrospective study within the Lymphomes Oculo-Cérébraux national network (LOC) to assess the clinical characteristics and outcome of SARS-CoV-2 infection in PCNSL patients (positive real-time polymerase chain reaction of nasopharyngeal swab or evocative lung computed tomography scan). We compared clinical characteristics between patients with severe (death and/or intensive care unit admission) and mild disease. RESULTS: Between March and May 2020, 13 PCNSL patients were diagnosed with SARS-CoV-2 infection, 11 (85%) of whom were undergoing chemotherapy at the time of infection. The mortality rate was 23% (3/13), and two additional patients (15%) required mechanical ventilation. Two patients (15%) had no COVID-19 symptoms. History of diabetes mellitus was more common in severe patients (3/5 vs 0/8, p = 0.03). Two patients recovered from COVID-19 after mechanical ventilation during more than two weeks and resumed chemotherapy. In all, chemotherapy was resumed after COVID-19 recovery in nine patients (69%) after a median delay of 16 days (range 3-32), none of whom developed unusual chemotherapy complication nor SARS-Cov2 reactivation. CONCLUSION: This preliminary analysis suggests that, while being at higher risk be for severe illness, PCNSL patients with COVID-19 might be treated maximally especially if they achieved oncological response at the time of SARS-CoV-2 infection. Chemotherapy might be resumed without prolonged delay in PCNSL patients with COVID-19.


Subject(s)
COVID-19 , Lymphoma , Central Nervous System , Humans , Lymphoma/complications , Lymphoma/epidemiology , Lymphoma/therapy , RNA, Viral , Retrospective Studies , SARS-CoV-2
4.
Curr Treat Options Neurol ; 21(8): 39, 2019 Jul 19.
Article in English | MEDLINE | ID: mdl-31324993

ABSTRACT

PURPOSE OF REVIEW: This review focuses on the findings of recent randomized prospective trials evaluating new therapeutic options for primary central nervous system lymphoma (PCNSL) in first-line treatment and on the most promising novel agents. RECENT FINDINGS: The current standard treatment of newly diagnosed PCNSL has long been depending on high-dose methotrexate (HD-MTX)-based polychemotherapy followed by whole-brain radiotherapy (WBRT). Recent randomized trials have provided evidence that high-dose chemotherapy with autologous stem cell transplantation (ASCT) is a valuable alternative option to WBRT as consolidation after induction HD-MTX-based chemotherapy. For the elderly, cumulative studies confirm that chemotherapy alone as initial treatment is the best approach in this frail population in order to reduce chemoradiation neurotoxicity. If the role of rituximab needs to be further investigated, novel agents such as imids and ibrutinib have shown to be promising drugs to be incorporated in innovative combination treatment. The role of WBRT, at least at conventional dose, is declining in first-line treatment in favor of intensive consolidation chemotherapy with or without ASCT and possibly maintenance chemotherapy in the elderly. Despite their rarity, it has been shown that ambitious randomized trials in PCNSL are feasible thanks to collaborative networks.

5.
Curr Neurol Neurosci Rep ; 18(3): 13, 2018 03 09.
Article in English | MEDLINE | ID: mdl-29520561

ABSTRACT

PURPOSE OF REVIEW: Personalized medicine is a challenge to improve survival and quality of life of patients suffering from primary malignant brain tumor. Molecular biology is integrated in initial diagnosis and relapse, and, in the nearest future, over treatment schedule and monitoring. Liquid biopsy is a minimally invasive way to obtain tumor material. RECENT FINDINGS: Over the past years, three fluids have been explored to provide tumor information in primary malignant brain tumor: blood, cerebrospinal fluid, and vitreous liquid. Different tumor components were identified: (1) circulating tumor cells, (2) circulating tumor DNA, (3) RNA and non-coding miRNA, and (4) extracellular vesicles. The performance of the liquid biopsy depends on the tumor type and on the method of detection. Liquid biopsy could be a valuable tool to improve patient care in primary malignant brain tumor. Improvement of its sensitivity is the major challenge to generalize its use in daily practice.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/diagnosis , Brain Neoplasms/metabolism , DNA, Neoplasm/metabolism , Neoplastic Cells, Circulating/metabolism , Biomarkers, Tumor/genetics , Biopsy/methods , Brain Neoplasms/genetics , DNA, Neoplasm/genetics , Humans , Liquid Biopsy/methods , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplastic Cells, Circulating/pathology , Precision Medicine/methods , Quality of Life , RNA, Untranslated/genetics
6.
J Neurooncol ; 133(3): 603-607, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28492978

ABSTRACT

Drug-resistant epilepsy (DRE) occurs commonly in gliomas, possibly due to a shared mechanism of AMPA-activation involving both seizure activity and tumor growth. We tested the AMPA-receptor blocker perampanel (PER) in patients with DRE in low- and high-grade gliomas. Seizure response was defined as 50% drop in seizure frequency or as seizure-freedom. Cognitive function was examined by computerized test on cognitive speed (CTCS), which is sensitive to the type of cognitive dysfunction associated with epilepsy and use of anticonvulsants. Treatment policy included reduction of dose or discontinuation of one or more concurrent AEDs, once a seizure-free response was observed. Twelve patients were included patients, median age 41 years, 9 men versus 3 women and 6 months median duration of follow-up. An objective seizure response (75%) was observed in 9 (75%) out of 12 patients: 50%-seizure response in 3, seizure-freedom in 6, which is plainly more than seen with other types of DRE. Side-effects occurred in six patients. Cognitive function as examined by CTCS improved in six out of eight associated withlowering of concurrent AEDs. The final median dose of PER was 8 mg (varying between 2 and 12 mg). These results of an objective seizure response in 9 (75%) out of 12 patients treated by PER in DRE may be interpreted as a surrogate-marker of tumor response secondary to AMPA blockade, advancing confirmation by MR imaging. These results warrant further study of PER on tumor activity in gliomas.


Subject(s)
Anticonvulsants/therapeutic use , Drug Resistant Epilepsy/drug therapy , Glioma/complications , Pyridones/therapeutic use , Seizures/drug therapy , Adult , Aged , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Dose-Response Relationship, Drug , Drug Resistant Epilepsy/complications , Drug Resistant Epilepsy/physiopathology , Drug Resistant Epilepsy/psychology , Female , Follow-Up Studies , Glioma/drug therapy , Glioma/physiopathology , Glioma/psychology , Humans , Male , Middle Aged , Nitriles , Seizures/complications , Seizures/physiopathology , Seizures/psychology , Treatment Outcome
7.
J Neurooncol ; 129(2): 347-53, 2016 09.
Article in English | MEDLINE | ID: mdl-27311728

ABSTRACT

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60-90). After a median follow-up of 5.8 months (IQR 3.7-13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5-19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9-71.2 %) and 6.6 % (95 % CI 1.0- 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9-7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4-52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among "very elderly" patients affected by GBM. Patients 80 and older should be considered for management based on RT.


Subject(s)
Brain Neoplasms/radiotherapy , Cranial Irradiation/methods , Glioblastoma/radiotherapy , Aged, 80 and over , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/diagnostic imaging , Cohort Studies , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Female , Glioblastoma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Radiation Dose Hypofractionation , Survival Analysis , Temozolomide , Tomography Scanners, X-Ray Computed , Treatment Outcome
8.
Neuroradiology ; 58(3): 221-35, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26700824

ABSTRACT

INTRODUCTION: Cerebral punctate and curvilinear gadolinium enhancements (PCGE) correspond to opacification of small vessel lumen or its perivascular areas in case of blood-brain barrier (BBB) disruption. We will discuss the possible causes of intra-parenchymal central nervous system PCGE. METHODS: Our review is based on French database including patients presenting with central nervous system PCGE and literature search using PubMed database with the following keywords: punctate enhancement, linear enhancement, and curvilinear enhancement. Disorders which displayed linear leptomeningeal or periventricular enhancements without intra-parenchymal PCGE are excluded of this review. RESULTS: Among our 39 patients with PCGE, 16 different diagnoses were established. After combining our PCGE causes with those described in the literature, we propose a practical approach. Besides physiologic post-contrast enhancement of small vessels, three pathologic conditions may exhibit PCGE: (1) small collateral artery network seen in Moyamoya syndrome, (2) small veins congestions related to developmental or acquired venous outflow disturbance, and (3) disorders causing small vessels BBB disruption indicated by T2 and FLAIR hyperintensities in the corresponding areas of PCGE. Disruption of the BBB could be caused by a direct injury of the endothelial cell, as in posterior reversible encephalopathy syndrome, Susac syndrome, and radiochemotherapy-induced injuries, or by an angiocentric cellular infiltrate, as in inflammatory disorders, demyelinating diseases, host immune responses fighting against infections, prelymphoma states, lymphoma, and in CLIPPERS. CONCLUSION: PCGE may conceal several causes, including physiological and pathological conditions. Nevertheless, a practical approach could improve its management and limit the indications of brain biopsy to very specific situations.


Subject(s)
Brain/diagnostic imaging , Brain/pathology , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/pathology , Magnetic Resonance Angiography/methods , Adult , Aged , Brain/blood supply , Contrast Media , Diagnosis, Differential , Female , Humans , Image Enhancement/methods , Male , Middle Aged
9.
CNS Oncol ; 4(5): 347-56, 2015.
Article in English | MEDLINE | ID: mdl-26478444

ABSTRACT

Epilepsy develops in more than 70-90% of oligodendroglial tumors and represents a favorable indicator for long-term survival if present as the first clinical sign. Presence of IDH1 mutation is frequently associated with seizures in oligodendrogliomas, next to alterations of glutamate and GABA metabolism in the origin of glioma-associated epilepsy. Treatment by surgery or radiotherapy results in seizure freedom in about two-thirds of patients, and chemotherapy to a seizure reduction in about 50%. Symptomatic anticonvulsive therapy with levetiracetam and valproic acid as monotherapy are both evidence-based drugs for the partial epilepsies, and their effective use in brain tumors is supported by a large amount of additional data. Pharmacoresistance against anticonvulsants is more prevalent among oligodendrogliomas, occurring in about 40% despite polytherapy with two anticonvulsants or more. Toxic signs of anticonvulsants in brain tumors involve cognition, bone marrow and skin. Previous neurosurgery, radiation therapy or chemotherapy add to the risks of cognitive dysfunction.


Subject(s)
Brain Neoplasms/complications , Glioma/complications , Seizures/etiology , Humans
10.
Expert Rev Mol Diagn ; 15(10): 1311-23, 2015.
Article in English | MEDLINE | ID: mdl-26394701

ABSTRACT

Glioblastoma (GBM) is the most common and devastating primary malignant brain tumor in adults. The past few years have seen major progress in our understanding of the molecular basis of GBM. These advances, which have contributed to the development of novel targeted therapies, will change the paradigms in GBM therapy from disease-based to individually tailored molecular target-based treatment. No validated circulating biomarkers have yet been integrated into clinical practice for GBM. There is thus a critical need to implement minimally invasive clinical tests enabling molecular stratification and prognosis assessment, as well as the prediction and monitoring of treatment response. After examination of data from recent studies exploring several categories of tumor-associated biomarkers (circulating tumor cells, extracellular vesicles, nucleic acids and oncometabolites) identified in the blood, cerebrospinal fluid and urine, this article discusses the challenges and prospects for the development of circulating biomarkers in GBM.


Subject(s)
Biomarkers, Tumor/blood , Brain Neoplasms/blood , Glioblastoma/blood , DNA, Neoplasm/blood , Extracellular Vesicles/metabolism , Glioblastoma/pathology , Humans , MicroRNAs/blood , Neoplastic Cells, Circulating
11.
J Neurooncol ; 124(3): 385-92, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26224161

ABSTRACT

DNA and histone methylation are post-transcriptional modifications that have been recently described in gliomas. Indeed, glioma CpG island hypermethylated phenotype has been identified as prognostic biomarker and as a surrogate marker of IDH1/2 mutations. However, the role of DNA methylation in glioblastoma progression is unknown. We sought to analyze DNA methylation levels in paired (initial and recurrent) primary glioblastoma samples to identify candidate pathways that may prone to glioblastoma progression. We have analyzed 12 samples (5 paired samples, two of them with three surgeries) using methylation arrays. We have analyzed differential methylation at probe and at gene region level. Finally, pathway analysis has been performed using differentially methylated regions. All analysis has been performed with R and Bioconductor packages. Mean methylation level at initial sample compared to recurrence was strongly positively correlated (R(2) = 0.98). There was no differentially methylation at probe level. However, at gene level 3080 regions were differentially methylated. Interestingly, pathways analysis showed that the most differentially methylated genes are involved in cellular response to macrophage colony-stimulating factor stimulus (GO:0036006). Methylation levels were strongly conserved when comparing initial to recurrence in primary glioblastomas. Interestingly, differentially methylated pathway analysis suggests that a modulation of methylation in immune response genes may play a role in glioblastoma progression. Further studies are needed to validate the role of methylation of glioblastoma immune response genes in tumor progression.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/immunology , Glioblastoma/genetics , Glioblastoma/immunology , Isocitrate Dehydrogenase/genetics , Mutation/genetics , CpG Islands/genetics , DNA Methylation/genetics , DNA Modification Methylases/genetics , DNA Modification Methylases/metabolism , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , Disease Progression , Female , Humans , Male , Oligonucleotide Array Sequence Analysis , Statistics, Nonparametric , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism
12.
Expert Rev Anticancer Ther ; 15(8): 955-62, 2015.
Article in English | MEDLINE | ID: mdl-26118895

ABSTRACT

Gliomas are the most common primary malignant brain tumor. Over the last decade, significant advances have been made in the molecular characterization of this tumor group, identifying predictive biomarkers or molecular actionable targets, and paving the way to molecular-based targeted therapies. This personalized therapeutic approach is effective and illustrated in the present review. Among many molecular abnormalities, BRAF mutation and mTOR activation in pilocytic astrocytomas and subependymal giant cell astrocytomas are actionable targets sensitive to vemurafenib and everolimus, respectively. Chromosome arms 1p/19q co-deletion and IDH mutational status are pivotal in driving delivery of early procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendroglial tumors. Although consensus to assess MGMT promoter methylation is not reached yet, it may be useful in predicting resistance to temozolomide in elderly patients.


Subject(s)
Brain Neoplasms/therapy , Glioma/therapy , Molecular Targeted Therapy , Aged , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Drug Resistance, Neoplasm , Glioma/genetics , Glioma/pathology , Humans , Precision Medicine/methods
13.
Bull Acad Natl Med ; 199(8-9): 1323-1329, 2015 11.
Article in French | MEDLINE | ID: mdl-29874421

ABSTRACT

Glioblastoma is the most common primary malignant brain tumor in adults. Despite very intensive treatments (i.e. maximal safe surgery, radiotherapy and cytotoxic chemotherapy), the prognosis of glioblastoma patients remains dismal with a median overall survival below 2 years. More effective and better tolerated treatments are needed. Over the last years, major advances have been accomplished in the molecular characterization of glioblastoma mainly thanks to high throughput molecular biology techniques. In parallel to these biological advances, pharmacological progresses have been made with the development of molecular targeted therapies or precision medicine or smart drugs targeting these molecular alterations detected in cancer cells but absent in normal cells of the body. These targeted molecular therapies, more effective and less toxic, have already revolutionized the prognosis of several systemic cancers (e.g., melanoma, lung cancer). On the basis of our knowledge of glioblastoma molecular biology, these molecular targeted therapies also appear promising in glioblastomas. Anti-angiogenic drugs are the most advanced molecular targeted therapies in their evaluation. Promising results were observed in recurrent glioblastoma patients. Other molecular targeted therapies are currently under preclinical or clinical evaluations. Similarly, to several systemic cancers, molecular targeted therapies will most likely find quickly their place in the therapeutic arsenal directed against glioblastomas to improve survival and quality of ife of patients suffering from this cancer type.


Subject(s)
Brain Neoplasms/therapy , Glioblastoma/therapy , Molecular Targeted Therapy , Precision Medicine , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/diagnosis , Brain Neoplasms/pathology , Glioblastoma/diagnosis , Glioblastoma/pathology , Humans , Immunotherapy/methods , Immunotherapy/trends , Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trends , Precision Medicine/methods , Precision Medicine/trends , Prognosis , Protein Kinase Inhibitors/therapeutic use
14.
Oncologist ; 19(7): 751-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24899645

ABSTRACT

Brain tumor-related epilepsy (BTE) is common in low- and high-grade gliomas. The risk of seizures varies between 60% and 100% among low-grade gliomas and between 40% and 60% in glioblastomas. The presence of seizures in patients with brain tumors implies favorable and unfavorable factors. New-onset seizures represent an early warning sign for the presence of a brain tumor and count as a good prognostic factor for survival. Recurrence or worsening of seizures during the course of disease may signal tumor progression. Each of the modalities for tumor control (i.e., surgery, radiotherapy, chemotherapy) contributes to seizure control. Nevertheless, one third of BTE shows pharmacoresistance to antiepileptic drugs (AEDs) and may severely impair the burden of living with a brain tumor. For symptomatic therapy of BTE, seizure type and individual patient factors determine the appropriate AED. Randomized controlled trials in partial epilepsy in adults to which type BTE belongs and additional studies in gliomas indicate that levetiracetam is the agent of choice, followed by valproic acid (VPA). In the case of recurring seizures, combining these two drugs (polytherapy) seems effective and possibly synergistic. If either one is not effective or not well tolerated, lacosamide, lamotrigine, or zonisamide are additional options. A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. A practice guideline on symptomatic medical management including dose schedules of AEDs is supplied.


Subject(s)
Anticonvulsants/therapeutic use , Brain Neoplasms/physiopathology , Epilepsy/drug therapy , Epilepsy/etiology , Glioma/physiopathology , Brain Neoplasms/drug therapy , Glioma/drug therapy , Humans , Prognosis
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