Memory Neuroimaging in Children, Adolescents and Young Adults Following Pediatric Cancer

Institut National de la Santé Et de la Recherche Médicale, France60 enrolled

Overview

Brain tumours are the leading cause of cancer-related death and morbidity in children, adolescents and young adults. The brain is also one of the most sensitive organs to treatments used in pediatric oncology, even for cancers not related to the central nervous system. Therapeutic index is therefore a major issue in pediatric neuro-oncology. The efficacy of the therapy as well as its toxicity are difficult to measure using standard tests. In order to optimize therapies that could have an impact on the brain, and consequently on the quality of life of patients, it becomes crucial to optimize the means of evaluation. Few studies to date have focused on the various components of memory impacted following treatment of a posterior fossa tumour. However, supra-tentorial structures such as the hippocampus, which have long been described for their role in memory, are either partially irradiated (irradiated in their lower part due to their proximity to the target volume during irradiation of the posterior fossa) or completely irradiated (e.g. included in the prophylactic irradiation of medulloblastoma prior to dose supplementation in the posterior fossa). On the other hand, the cerebellum plays a central role in learning and procedural memory involved in motor and cognitive learning, as it enables automation and procedural retention such as reading (automation of the grapho-phonemic conversion procedure) or arithmetic (mental arithmetic). IMPALA study is aimed at investigating the impact of different irradiation doses received by children treated with radiotherapy on cognitive functions related to the hippocampus and to the cerebellum. This exploratory study will thus provide elements enabling a better limitation of radiotherapy doses on regions linked to the development of cognition and memory. The project brings together researchers and clinicians with complementary expertise in oncology, neurology and imaging in both children and adults. This study will also provide a better understanding of the role of the cerebellum in memory and executive functions, and develop a method that can then be used in a prospective longitudinal multicentre form.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Eligibility

Sex: ALLHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: FOR ALL PARTICIPANTS * Affiliation to or beneficiary of a social security scheme * French mother tongue * Sufficient visual, auditory (hearing aids permitted), speaking and writing skills for proper performance of neuropsychological tests * Written informed consent of the adult participant, or of the representatives of parental authority, if applicable FOR IRRADIATED PATIENTS * Patient treated before 18 years old * Patient considered cured after irradiation of a brain tumour (complete clinical and iconographic response at 5 years after the end of radiotherapy). * Patient who has received localized brain irradiation or craniospinal irradiation for a brain tumour whose treatment includes first-line radiotherapy (ependymomas, medulloblastomas, malignant germinal tumours) * Patient who received 54 or 59.4 Gy in a localized part of the posterior fossa or supra-tentorial brain; or patients who received 54 Gy over all or part of the posterior fossa and prophylactic irradiation of the entire brain FOR PATIENTS TREATED BY SURGERY AND/OR CHEMOTHERAPY * Patients resected from a posterior fossa tumour without radiotherapy (i.e., brain tumours whose treatment does not include first-line radiotherapy: low-grade gliomas including pilocytic astrocytomas) * Patient treated before 18 years old * Patient considered cured at 5 years after the end of treatment Exclusion Criteria: FOR ALL PARTICIPANTS * Individual under legal protection of adults (judicial safeguard, guardianship, curatorship, institutionalized, or under a mandate for future protection) * Severe ataxia * Individual who participated in another research study that included treatment within the previous 3 years * Individual with a contraindication to MRI (i.e. in particular, cardiac pacemaker or defibrillator carriers, implanted equipment activated by an electrical, magnetic or mechanical system, carriers of haemostatic clips on intracerebral aneurysms, carriers of orthopaedic implants, claustrophobic) FOR HEALTHY VOLUNTEERS * Known neurological or psychiatric history * History of learning disability or neurodevelopmental disorder follow-up * Patients undergoing psychotropic treatment (methylphenidate, antidepressants, etc.).

Outcomes

Primary Outcomes

Structural characteristics of declarative memory neuronal substrate: volume of the hippocampus

Volume of the hippocampus obtained from T1-weighted anatomical

Time frame: Day 1

Structural characteristics of declarative memory neuronal substrate: cortical thickness of the hippocampus

Cortical thickness of the hippocampus obtained from T1-weighted anatomical

Time frame: Day 1

Structural characteristics of declarative memory neuronal substrate: Microstructural integrity of the hippocampus

Microstructural integrity of the hippocampus obtained from Diffusion Tensor Imaging (DTI) sequences used to calculate the fraction of anisotropy and the mean diffusion sequences

Time frame: Day 1

Episodic memory performance

Episodic memory performance of the participants in the different groups when evaluating episodic declarative memory, assessed with Children's Memory Scale in participants under 16 years old and with Wechsler Memory Scale MEM-III in participants over 16 years old (Day 2)

Time frame: Day 2

Secondary Outcomes

Declarative episodic memory assessment scores

Scores obtained at memory clinical scale for children

Time frame: Day 2

Declarative semantic memory assessment scores

Scores obtained at Wechsler Intelligence Scale for Children

Time frame: Day 2

Procedural memory assessment scores

Scores obtained at Serial Reaction Time Task

Time frame: Day 2

Short-term auditive memory assessment scores

Scores obtained at Wechsler Intelligence Scale for Children

Time frame: Day 2

Short-term visual memory assessment scores

Scores obtained at Wechsler Memory Scale

Time frame: Day 2

Intellectual capacities assessment scores

Scores obtained at Wechsler Intelligence Scale for Children

Time frame: Day 2

Language assessment scores

Scores obtained at Peabody Picture Vocabulary Test

Time frame: Day 2

Motor functions assessment scores

Scores obtained at Purdue Pegboard Test

Time frame: Day 2

Executive functions assessment scores

Scores obtained at TMT A and B, Stroop Test and Wisconsin Card Sorting Test

Time frame: Day 2

Attentional capacities assessment scores

Scores obtained at Test of Attentional Performance 2.3.1

Time frame: Day 2

Cerebellar volume

Cerebellar volume obtained from T1-weighted anatomical sequences

Time frame: Day 1

Micro-structural integrity of the cerebellum

Micro-structural integrity of the cerebellum achieved by using DTI sequences to calculate the fraction of anisotropy and average diffusivity

Time frame: Day 1

Cerebral blood volume obtained from brain perfusion imaging

Time frame: Day 1

Post-therapeutic hypoxia

Post-therapeutic hypoxia as measured by magnetic resonance spectrometry of the hippocampus and cerebellum

Time frame: Day 1

Neuronal density

Neuronal density as measured by magnetic resonance spectrometry of the hippocampus and cerebellum

Time frame: Day 1

Functional connectivity index

Functional connectivity index, obtained via resting functional MRI.

Time frame: Day 1

Age at the time of treatment

Age at the time of treatment from the patients' medical records

Time frame: Day 1

Radiotherapy doses

Radiotherapy doses received in the cerebellum, in the hippocampus, and in the whole brain from the patients' medical records

Time frame: Day 1

Cerebellum and hippocampus Normal Tissue Complication Probability

Cerebellum and hippocampus Normal Tissue Complication Probability (NTCP)

Time frame: Day 1

Memory Neuroimaging in Children, Adolescents and Young Adults Following Pediatric Cancer

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes