Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Advances in treatments of patients with classical and emergent neurological toxicities of anticancer agents.

The neurotoxicity associated to the anticancer treatments has received a growing body of interest in the recent years. The development of innovating therapies over the last 20years has led to the emergence of new toxicities. Their diagnosis and management can be challenging in the clinical practice and further research is warranted to improve the understanding of their pathogenic mechanisms. Conventional treatments as radiation therapy and chemotherapy are associated to well-known and under exploration emerging central nervous system (CNS) and peripheral nervous system (PNS) toxicities. The identification of the risk factors and a better understanding of their pathogeny through a "bench to bedside and back again" approach, are the first steps towards the development of toxicity mitigation strategies. New imaging techniques and biological explorations are invaluable for their diagnosis. Immunotherapies have changed the cancer treatment paradigm from tumor cell centered to immune modulation towards an efficient anticancer immune response. The use of the immune checkpoints inhibitors (ICI) and CAR-T cells (chimeric antigen receptor) lead to an increase in the incidence of immune-mediated toxicities and new challenges in the neurological patient's management. The neurological ICI related adverse events (n-irAE) are rare but potentially severe and may present with both CNS and PNS involvement. The most frequent and well characterized, from a clinical and biological standpoint, are the PNS phenotypes: myositis and polyradiculoneuropathy, but the knowledge on CNS phenotypes and their treatments is expanding. The n-irAE management requires a good balance between dampening the autoimmune toxicity without impairing the anticancer immunity. The adoptive cell therapies as CAR-T cells, a promising anticancer strategy, trigger cellular activation and massive production of proinflammatory cytokines inducing frequent and sometime severe toxicity known as cytokine release syndrome and immune effector cell-associated neurologic syndrome. Their management requires a close partnership between oncologist-hematologists, neurologists, and intensivists. The oncological patient's management requires a multidisciplinary clinical team (oncologist, neurologist and paramedical) as well as a research team leading towards a better understanding and a better management of the neurological toxicities.

Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.

Characterization of Skull Base Lesions Using Pseudo-Continuous Arterial Spin Labeling.

PURPOSE: Pseudo-continuous arterial spin labeling (pCASL) is a non-invasive magnetic resonance (MR) perfusion technique. Our study aimed at estimating the diagnostic performance of the pCASL sequence in assessing the perfusion of skull base lesions both qualitatively and quantitatively and at providing cut-off values for differentiation of specific skull base lesions. METHODS: In this study 99 patients with histopathologically confirmed skull base lesions were retrospectively enrolled. Based on a pathological analysis, the lesions were classified as hypervascular and non-hypervascular. Patients were divided into two subgroups according to the anatomical origin of each lesion. The MRI study included pCASL and 3D T1-weighted fat-saturated post-contrast sequences. Of the patients seven were excluded due to technical difficulties or patient movement. The lesions were classified by two raters, blinded to the diagnosis as either hyperperfused or non-hyperperfused, based on the pCASL sequence. The normalized tumor blood flow (nTBF) of each lesion was determined. Qualitative and quantitative characteristics of hypervascular and non-hypervascular lesions were compared. RESULTS: Visual assessment enabled correct classification of 98% of the lesions to be performed. Quantitatively, we found significant differences between the nTBF values for hypervascular and non-hypervascular lesions (p < 0.001) and provided cut-off values, allowing meningioma and schwannoma to be distinguished from meningioma and adenoma. Significant differences were also found within the hypervascular group, namely, paraganglioma was more hyperperfused than meningioma (p = 0.003) or metastases (p = 0.009). CONCLUSION: The present study demonstrates the high diagnostic performance of pCASL in characterizing skull base lesions by either visual assessment or nTBF quantification. Adding the pCASL sequence to the conventional protocol of skull base assessment can be recommended.

Capecitabine-induced acute toxic leukoencephalopathy.

A 45-year-old woman was treated by Capecitabine (Xeloda®) during 6days for breast cancer with metastatic bone lesions when she presented with nausea, headaches, muscle cramps, dysarthria and swallowing disorders. A stroke was first suspected. Brain CT was normal. MRI showed bilateral and symmetric high signal intensities of deep white matter, corpus callosum and corticospinal tracts on diffusion-weighted imaging and T2 fluid-attenuated inversion recovery (FLAIR) sequence, similar to 5-FU acute leukoencephalopathy. An acute toxic leukoencephalopathy was diagnosed prompting to discontinue capecitabine, which allowed a regression of the symptoms. Though acute toxic leukoencephalopathies with pseudo-stroke presentation have been reported with other chemotherapy agents such as methotrexate or 5-fluorouracil (5-FU), cases of leukoencephalopathy induced by capecitabine are less reported and less well known. This oral precursor of 5-FU is commonly used to treat colorectal, stomach or breast cancers. Neurotoxicity of other 5-FU derivates like cormafur and tergafur have rarely been depicted as well. Although 5-FU-induced leukoencephalopathy is known, the potential toxicity of its precursor should be acknowledged as well. Early detection of chemotherapy-induced toxicity by MRI is crucial as symptoms may be reversible to the condition that chemotherapy is immediately discontinued.

MR imaging of adult acute infectious encephalitis.

BACKGROUND: Imaging is a key tool for the diagnosis of acute encephalitis. Brain CT scan must be urgently performed to rule out a brain lesion with mass effect that would contraindicate lumbar puncture. Brain MRI is less accessible than CT scan, but can provide crucial information with patients presenting with acute encephalitis. METHOD: We performed a literature review on PubMed on April 1, 2015 with the search terms "MRI" and "encephalitis". RESULTS: We first described the various brain MRI abnormalities associated with each pathogen of acute encephalitis (HSV, VZV, other viral agents targeting immunocompromised patients or travelers; tuberculosis, listeriosis, other less frequent bacterial agents). Then, we identified specific patterns of brain MRI abnomalies that may suggest a particular pathogen. Limbic encephalitis is highly suggestive of HSV; it also occurs less frequently in encephalitis due to HHV6, syphillis, Whipple's disease and HIV primary infection. Rhombencephalitis is suggestive of tuberculosis and listeriosis. Acute ischemic lesions can occur in patients presenting with severe bacterial encephalitis, tuberculosis, VZV encephalitis, syphilis, and fungal infections. CONCLUSION: Brain MRI plays a crucial role in the diagnosis of acute encephalitis. It detects brain signal changes that reinforce the clinical suspicion of encephalitis, especially when the causative agent is not identified by lumbar puncture; it can suggest a particular pathogen based on the pattern of brain abnormalities and it rules out important differential diagnosis (vascular, tumoral or inflammatory causes).

Cerebral tumor or pseudotumor?

Pseudotumoral lesions are uncommon but important to identity lesions. They can occur during inflammatory diseases (systemic diseases, vasculitis, demyelinating diseases), infectious, and vascular diseases. Also, in a patient with a treated tumor, pseudo-progression and radionecrosis must be differentiated from the tumoral development. Diagnosis can be difficult on an MRI scan, but some MRI aspects in conventional sequences, diffusion, perfusion and spectroscopy can suggest the pseudotumoral origin of a lesion. Imaging must be interpreted according to the context, the clinic and the biology. The presence of associated intracranial lesions can orientate towards a systemic or infectious disease. A T2 hyposignal lesion suggests granulomatosis or histiocytosis, especially if a meningeal or hypothalamic-pituitary involvement is associated. Non-tumoral lesions are generally not hyperperfused. In the absence of a definitive diagnosis, the evolution of these lesions, whether under treatment or spontaneous, is fundamental.

[Clinical case of the month. Ulnar artery aneurysm in a roofer]. / Anévrisme de l'artère ulnaire chez un couvreur.

A case of ulnar artery aneurysm in an independent roofer is reported. It is a rare disease often associated with the Hammer Hypothenar Syndrome specifically found in manual workers and athletes exposed to repetitive palmar trauma.

Trigeminal neuralgia.

Two different clinical entities, essential or secondary neuralgia, are associated with different pathologies. The pathways of CN V comprise the cervical spine, the brainstem, the root of the nerve and the three peripheral branches: V1, V2 and V3. The lesions responsible for neuralgia are neoplastic, vascular, inflammatory, malformative or post-traumatic. The examination protocol should explore the set of CN V pathways. Neurovascular compression is the main cause of essential neuralgia. It is investigated by T2-weighted inframillimetric volume. Two conditions are necessary to diagnose a neurovascular compression: localised on the root entry zone [(REZ), 2-6mm from the emergence of the pons] and perpendicularly. In the absence of neurovascular compression, thin slices and a gadolinium injection are necessary.

Imaging findings of intraventricular and ependymal lesions.

Intraventricular and ependymal lesions comprise a wide spectrum of tumoral, cystic, vascular, infectious and inflammatory disorders. With respect to tumoral and cystic diseases, the location, age and CT and MRI patterns are the main factors for diagnosis. The MRI findings of infectious diseases are supported by the clinical history, immune status and laboratory findings. Intracranial associated lesions may be very helpful for the diagnosis of Sturge-Weber, subependymal giant cell astrocytoma and systemic diseases, such as sarcoidosis and histiocytosis. Intraventricular vascular lesions are rare but present typical features on neuroimaging. The aim of this review is to provide a detailed description of these disorders with an emphasis on the key imaging findings and to generate a narrow differential diagnosis. We present a diagnostic approach based on the solid or cystic aspect of the intraventricular focal mass, its origin from the ventricular wall or choroid plexus and its location within the ventricular system. We also propose a differential diagnosis for ependymal dissemination: the ependymal enhancement may be due to ventriculitis from adjacent parenchymal lesions, the ependymal spread of tumors or infectious or inflammatory/systemic diseases.

[Coccidioidomycosis presenting as a pulmonary nodule after pneumonia]. / Opacité tumorale apparue au decours d'une pneumonie fébrile révélant une coccidioïdomycose thoracique.

Coccidioidomycosis is a fungal infection endemic in the south west of the United States. Sixty percent of infected individuals remain asymptomatic. Symptomatic disease manifests itself with variable signs such as pneumonia, pleural effusion, empyema or acute respiratory distress syndrome. Residual disease includes pulmonary nodules and fibrosis. We report a case of a woman, returning from a trip to Arizona, presenting with an acute respiratory infection associated with erythema nodosum and arthralgia. She was successfully treated with routine antibiotics. The acute pneumonia resolved and the radiological infiltrate contract into a solitary pulmonary nodule. We suspected a malignant nodule in a previous smoker. The diagnosis of pulmonary Coccidioidomycosis was made after surgical resection. One year later, the patient is asymptomatic and well. This review focuses on the most common clinical manifestations, the diagnostic strategy and the treatment and management of pulmonary Coccidioidomycosis.

[Evaluation of a computer aided detection system for lung nodules with ground glass opacity component on multidetector-row CT]. / Evaluation d'un système de détection assisté par ordinateur des nodules parenchymateux pulmonaires avec verre dépoli au scanner multidétecteur.

PURPOSE: To determine the performance of a CAD system for lung nodules with ground glass opacity component on multidetector-row CT. Materials and methods. The CT examinations of 17 patients with at least one persistent subsolid nodule were reviewed. A first non-blinded consensus review by two expert radiologists resulted in the detection of 104 subsolid nodules larger than 3 mm (74 nodules of ground glass attenuation and 30 mixed nodules with solid and ground glass components). The results from this review were used as a gold standard to determine the performances of the CAD system and 3 independent clinical radiologists involved with the primary interpretations. RESULTS: The sensitivity of the CAD system for the detection of ground glass opacities and mixed nodules was 53% and 73% respectively. These values were not statistically different from the values for the 3 independent observers (42-66% for ground glass opacities and 63-80% for mixed nodules). The sensitivity of each observer significantly increased when the nodules detected by the CAD system were added to those detected by each observer (p<0.0001). CONCLUSION: A CAD system has a potential impact on the detection rate of subsolid nodules by radiologists.

[Skin sensitisation profiles of outpatients with symptoms of respiratory allergies]. / Profils de sensibilisation cutanée aux pneumallergènes des patients consultant pour allergie respiratoire.

AIM: The main objective of the survey was to determine the frequency of the mono and polysensitizations in patients consulting for respiratory allergy, rhinitis or/and asthma. The secondary objectives were to evaluate the severity, the number and the type of the sensitizations, the frequency of the asthma or rhinitis as a function of the sensitizations, the evolution of the sensitizations with age, and identify the principal responsible pneumallergens. PATIENTS AND METHODS: The multicentric survey included a patient questionnaire allowing the collection and anonymous treatment of data on socio-demographic characteristics, clinical symptoms, cutaneous tests and sensitizations. RESULTS: A sample of 505 patients, mean age 24 years, consulting for rhinitis or asthma, monosensitized (36%) or polysensitized (64%), was evaluated. The percentage of polysensitized patients was similar in asthmatics, patients with rhinitis, and patients with both asthma and rhinitis (60%, 65%, and 63%, respectively). The mean number of the sensitizations was 2.4 for patients with asthma, 2.6 for those with rhinitis, and 2.6 for patients with both asthma and rhinitis. The greater the severity of the rhinitis or asthma, the higher the number of the sensitizations. Sensitizations to acarids, gramineae and cat were the most frequent. When practioners were asked about their intention to undertake desensitization in polysensitized patients, 52% of them replied positively. CONCLUSION: Data collected during this survey showed that a large proportion of the patients who consulted for rhinitis or asthma were monosensitized (36%). Sensitization to acarids was the most frequent. Even in polysensitized patients, more than half the practioners said they would use desensitization.