Neoplasms

Nervous System Diseases

All Conditions

Behaviors and Mental Disorders

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Quality of Life

Patients receive proton Radio(chemo)therapy according to clinical standard. Proton Treatment is indicated BEFORE inclusion into the trial ans is not part of the trial. Neurological status and neurocognitive testing on core executive functions (inhibition, working memory, cognitive flexibility) and Quality of life measurements are performed regularely during follow-up using standardized KINDL® questionnaires for general quality of life and specific for oncologic diseases. In addition to the treatment parameters of the radio(chemo)therapy protocol, further radiation doses to brain substructures and organs at risk are documented.

Patients are included AFTER surgery of their brain tumour and receive no radiotherapy due to their disease (i.e. according to clinical standard). This Treatment is not part of the trial, but stratifies the Patient in this second Group.

Neurological status and neurocognitive testing on core executive functions (inhibition, working memory, cognitive flexibility) and Quality of life measurements are performed regularely during follow-up using standardized KINDL® questionnaires for general quality of life and specific for oncologic diseases.

Healthy kids are recruited as Standard Group.

Neurological status and neurocognitive testing on core executive functions (inhibition, working memory, cognitive flexibility) and Quality of life measurements are performed regularely using standardized KINDL® questionnaires for general quality of life and specific for oncologic diseases.

Mechthild Krause, Prof. Dr.

Christian Beste, Prof. Dr.

Maja von der Hagen, Prof. Dr.

Brain tumors are the second most frequent malignant diseases in children and adolescents. In the study the short and medium term consequences of proton therapy on cognitive processes in particular on executive functions in pediatric patients shall be highlighted/analysed/evalutated. In a second step, these results are to be compared with

1. a group of children and adolescents who had only /exclusively had operative therapy and
2. with a healthy control group. Thus, the extent to which these treatment options differ in terms of their short and medium-term effect is assessed. Methods of neurocognitive/neurophysiology brain research approaches are applied that may potentially visualize even small / subtle changes in mental activities/neurocognitive function. Therefore the effects of treatment can be evaluated and the neuropsychological outcome of children and adolescents with brain tumors can be improved.

Radio(chemo)therapy with protons is conducted according to current treatment standards or, for patients participating in a clinical intervention study, according to the study protocols of the GPOH. Only patients with prescribed radiation doses \> 40 Gy (RBE) will be included. Treatment planning, the target volume and radiotherapy will be performed according to the current treatment standards. For patients participating in a clinical intervention study, radiotherapy is corresponding to study protocol of the GPOH. Risk organs (e.g. brain stem, chiasma, optic nerves, gll. Lacrimals, lenses, inner ears and spine) are contoured and the radiation doses for these organs are limited according to institutional guidelines. Radiotherapy is performed according to guidelines, i.e. 5 days a week for 4-6 weeks, usually on an outpatient basis.

Neurocognitive Function After Proton Therapy in Children and Adolescents

Neurocognitive Function /Executive Functions After Proton Therapy in Children and Adolescents.

Neurophysiological processes are examined while subjects perform the cognitive tests.

QoL Parameters are measured and reported using KINDL® questionnaires for general quality of life and specific for oncologic diseases (also KINDL®). Scales for QoL items are 0-100 (with 100 being the Optimum, i.e. lower values indicating worse outcome). Evaluation is performed according to the standard published with the validated questionnaires (https://www.kindl.org/deutsch/fragebögen/)

physical doses to substructures of the brain are collected and correlated with neurophysiological outcome measures

Gert und Susanna Mayer Stiftung

Technische Universität Dresden

Heart and Blood Diseases

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Parkinson Disease

Stroke

Parkinsonian Disorders

Ganglion Cysts

Synovial Cyst

Basal Ganglia Diseases

Movement Disorders

Synucleinopathies

Neurodegenerative Diseases

Neuropsychological assessment with:

* NADL-F
* Frontal Assessment Battery (FAB)
* functional scales assessing activities of daily living (ADL) and instrumental activities of daily living (I-ADL)
* Mini-Mental Parkinson (MMP) - For Parkinson's Disease patients
* Montreal Cognitive Assessment (MoCA) - for brain tumor and stroke patients

Neuropsychological tests

Nadia Bolognini, PhD

The present project aims to investigate the financial capacity in patients diagnosed with Parkinson's Disease or parkinsonism, brain tumor (glioma or meningioma) and cerebrovascular lesion (stroke), in order to evaluate the presence and degree of impairment, and the role of some factors as potential predictors of financial incapacity.

The term 'financial capacity' means both operations relating, for example, to asset management or investing money, and activities of daily life such as shopping or using small sums of money; these activities are mediated by different cognitive functions, from numerical and arithmetic skills to decision making. Financial capacity is, in fact, an instrumental activity of daily life (i.e. Instrumental Activity Of Daily Living, I-ADL) whose impairment negatively affects the functional autonomy of the individual, so as to be subject to legal protection.

To assess financial capacity, the Numerical Activities of Daily Living - Financial (NADL-F; Arcara et al., 2017) will be administered, a battery of tests aimed at investigating both financial performance and financial competence according to the most recent neuropsychological models proposed in the literature.

Neuropsychology of Financial Capacity

Assessment of financial capacity; score range=0-62; higher scores indicate higher financial capacities

Assessment of global cognitive functioning

Assessment of function independence in everyday life

Istituto Auxologico Italiano

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Substance Related Disorders

Rare Diseases

Syndrome

Lymphoma

Lymphoma, B-Cell

Cytokine Release Syndrome

Neurotoxicity Syndromes

Poisoning

Chemically-Induced Disorders

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

B-cell Lymphoma

Single arm All patient will undergo an MRI with contrast injection, a blood withdrawal and a neurological consultation with neuropsychological tests

Magnetic Resonance Imaging with contrast injection

Blood withdrawal : serum, plasma, cytokine assay

Blood withdrawal

The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and overall survival. Nevertheless, this therapy is frequently associated with cytokine release syndrome and in approximately 20% to 60% of patients with neurological complications that can sometimes be dramatic and are associated with a significant mortality rate.

The mechanisms behind this neurotoxicity are unclear.

Despite the frequent occurrence of neurological toxicity characterized in particular by headache, tremor, and encephalopathy that is most often transient, brain imaging by CT or, preferably, MRI are most often normal. The rare abnormalities that have been identified suggest the presence of cytotoxic edema associated with the existence of transient modifications of the blood-brain barrier.

To date, the management of neurotoxicity associated with CAR-T CELLS remains empirical. It combines early management of cytokine release syndrome (by administration of anti-IL6) and treatment with corticosteroids, the objective of which would be to control neurotoxicity more specifically. A better understanding of the pathophysiological mechanisms associated with this neurotoxicity appears essential today in order to be able to propose adapted prevention and treatment methods.

Main objectives are to compare tissue permeability by quantitative MRI measurement of Ktrans to the theoretical peak of neurotoxicity between patients with CAR-T Cell-induced neurotoxicity and those without neurotoxicity and to Study, by MRI, the evolution of tissue microcirculatory parameters (from D-3 to D7) between groups of patients with or without the occurrence of neurotoxicity associated with CAR-T CELL treatment.

For this purpose, 25 subjects will be included (the investigators hypothesize 40% with treatment-induced neurological impairment).

The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and overall survival. Nevertheless, this therapy is frequently associated with cytokine release syndrome and in approximately 20% to 60% of patients with neurological complications that can sometimes be dramatic and are associated with a significant mortality rate.

The mechanisms behind this neurotoxicity are unclear but may include :

* A "systemic" toxicity associated with the cytokine release syndrome. This toxicity would thus be favoured by the associated inflammatory response syndrome manifested in particular by hyperthermia, changes in blood pressure, and an increase in CRP, ferritin and the number of white blood cells.
* A breakdown of the blood-brain barrier, as evidenced by increased protein levels, cellularity and cytokine levels in the cerebrospinal fluid. Among other things, this rupture could be promoted by the synthesis of proinflammatory cytokines (IL6, TNF-alpha, IFN-gamma) that would promote endothelial activation.
* Direct toxicity to neurons and/or microglial cells.

Despite the frequent occurrence of neurological toxicity characterized in particular by headache, tremor, and encephalopathy that is most often transient, brain imaging by CT or, preferably, MRI are most often normal. The rare abnormalities that have been identified suggest the presence of cytotoxic edema associated with the existence of transient modifications of the blood-brain barrier.

To date, the management of neurotoxicity associated with CAR-T CELLS remains empirical. It combines early management of cytokine release syndrome (by administration of anti-IL6) and treatment with corticosteroids, the objective of which would be to control neurotoxicity more specifically. A better understanding of the pathophysiological mechanisms associated with this neurotoxicity appears essential today in order to be able to propose adapted prevention and treatment methods.

Objectives:

Main:

\* To Compare tissue permeability by quantitative MRI measurement of Ktrans to the theoretical peak of neurotoxicity between patients with CAR-T Cell-induced neurotoxicity and those without neurotoxicity.

Secondary:

* To Study, by MRI, the evolution of tissue microcirculatory parameters (from D-3 to D7) between groups of patients with or without the occurrence of neurotoxicity associated with CAR-T CELL treatment.
* To Correlate the values of the MRI parameters with the usual clinical and biological parameters known to be associated with the occurrence of neurotoxicity (at D0 and theoretical peak).
* To Correlate the values of the MRI parameters with the values (at D0 and at NADIR) of a panel of cytokines of interest (V-PLEX Neuroinflammation Panel Human 1 Kit, Meso Scale Discovery®).

Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome

Contribution of Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome

Quantitative measurement of KTRANS (rate of contrast agent transfer from plasma to the extravascular extracellular space, reflecting capillary permeability).

(Time in second)

FLAIR hypersignals analysis by MRI (signal of a tissue superior to the signal of the surrounding tissues) (visual assessment)

Analysis of contrast on injected 3DT1 MRI

AUC (area under the curve shows blood volume) (SI x Time)

Kep: rate of return transfer of the contrast agent from the extravascular extracellular space to the plasma (Volume/Time/Volume)

Ve: volume fraction of the extravascular space (Percentage %)

Vp: volume fraction of the plasma space. (Percentage %)

Cerebral blood flow analysis (3DPCASL) (L/min)

Cerebral volumetric analysis (3DT1) (cm3)

Perfusion factors (perfusion fraction f) (Percentage %)

Perfusion factors (pseudo-diffusion D\* at the microvascular compartment) (x10\^-3 mm²/s)

Presence, absence of neurotoxicity and inflammation

Comparison of MRI data with biological markers (such as CRP, ferritin, white blood cell count, LDH, procalcitonin, fibrinogen) and cytokine profile of neuroinflammation by multiplex immunoassay kit. An ultrasensitive multiplex using electrochemiluminescence.

University Hospital, Montpellier

Cognitive Dysfunction

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Neuroepithelioma

Neuropsychological tests for general cognition, social cognition and language.

Patients with gliomas often suffer from lower quality of life, and detrimental social interactions after diagnosis. Two cognitive processes are crucial for maintaining healthy social relationships and interacting with others: social cognition and language. Social cognition is the ability to recognize and process mental and emotional states and to react appropriately in social situations. Social cognition and language are separate cognitive functions that can be affected in different ways in patients with brain injury. Also, distinct cognitive measurement instruments are used to assess both processes. However, there appears to be a certain overlap between social cognition and language. Reacting adequately in social situations requires both verbal and non-verbal communication and to communicate feelings, thoughts and intentions, people often use language. That is, verbal communication is part of a symbolic system that makes social interaction possible. Therefore, language abilities seem to be important to social cognition. Research shows that language is frequently impaired in adult patients with gliomas. Importantly, recent evidence suggests that social cognition can also be impaired in this patient group. However, no studies have been conducted into the relationship between social cognition and language in patients with gliomas. Increasing knowledge on the overlap between both functions, more specifically the influence of language difficulties on social cognition, will improve diagnostic accuracy. Eventually, this will lead to better, tailor-made treatments for these problems that negatively affect daily functioning.

Objective: The main research objective is to examine the influence of language impairments on different social cognition processes, i.e., emotion recognition, Theory of Mind (ToM) and affective empathy, in patients with (suspected) gliomas. Secondary objectives are 1) to determine if patients with gliomas show impairments in different aspects of social cognition, i.e. emotion recognition, ToM, empathy and self-awareness; 2) to assess specific language impairments by looking at item-level characteristics of language tasks (e.g., analyses of word properties of fluency tasks, errors during object naming or spontaneous speech), and 3) to determine which tumor characteristics (low- or high-grade, genetic mutation, tumor location) are associated with different aspects of language and social cognition.

Social Cognition and Language in Patients With Gliomas

Social Cognition and Language in Patients With Gliomas: Putting Feelings Into Words

Questionnaire filled in by patient and proxy: IRI

Questionnaire filled in by patient and proxy: DEX

Questionnaire filled in by patient and proxy: CSI

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neurocognitive Function After Proton Therapy in Children and Adolescents	NCT04066465	Primary Brain T...		8 Years - 18 Years	Technische Universität Dresden
Neuropsychology of Financial Capacity	NCT05791006	Parkinson Disea... Brain Tumor Stroke	Neuropsychologi...	18 Years - 99 Years	Istituto Auxologico Italiano
Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome	NCT05510596	Lymphoma, B-Cel... Neurotoxicity	Magnetic Resona... Blood withdrawa... Neuropsychologi...	18 Years -	University Hospital, Montpellier
Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome	NCT05510596	Lymphoma, B-Cel... Neurotoxicity	Magnetic Resona... Blood withdrawa... Neuropsychologi...	18 Years -	University Hospital, Montpellier
Social Cognition and Language in Patients With Gliomas	NCT05764460	Glioma, Maligna... Cognitive Dysfu...	Neuropsychologi...	18 Years -	University Medical Center Groningen

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