Clinical trial NCT04324450: Memory Neuroimaging in Children, Adolescents and Young Adults Following Pediatric Cancer
Official title: Memory Neuroimaging in Children, Adolescents and Young Adults Following Pediatric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer Brain
Pediatric Cancer
Keywords: brain tumour
child
memory
radiotherapy
MRI
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2020-03-27
Enrollment: 60
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.).

Primary outcomes:
measure: Structural characteristics of declarative memory neuronal substrate: volume of the hippocampus
timeFrame: Day 1
measure: Structural characteristics of declarative memory neuronal substrate: cortical thickness of the hippocampus
timeFrame: Day 1
measure: Structural characteristics of declarative memory neuronal substrate: Microstructural integrity of the hippocampus
timeFrame: Day 1
measure: Episodic memory performance
timeFrame: Day 2
Secondary outcomes:
measure: Declarative episodic memory assessment scores
timeFrame: Day 2
measure: Declarative semantic memory assessment scores
timeFrame: Day 2
measure: Procedural memory assessment scores
timeFrame: Day 2
measure: Short-term auditive memory assessment scores
timeFrame: Day 2
measure: Short-term visual memory assessment scores
timeFrame: Day 2
measure: Intellectual capacities assessment scores
timeFrame: Day 2
measure: Language assessment scores
timeFrame: Day 2
measure: Motor functions assessment scores
timeFrame: Day 2
measure: Executive functions assessment scores
timeFrame: Day 2
measure: Attentional capacities assessment scores
timeFrame: Day 2
measure: Cerebellar volume
timeFrame: Day 1
measure: Micro-structural integrity of the cerebellum
timeFrame: Day 1
measure: Cerebral blood volume obtained from brain perfusion imaging
timeFrame: Day 1
measure: Post-therapeutic hypoxia
timeFrame: Day 1
measure: Neuronal density
timeFrame: Day 1
measure: Functional connectivity index
timeFrame: Day 1
measure: Age at the time of treatment
timeFrame: Day 1
measure: Radiotherapy doses
timeFrame: Day 1
measure: Cerebellum and hippocampus Normal Tissue Complication Probability
timeFrame: Day 1
Other outcomes:
Locations:
city: Toulouse
country: France
facility: ToNIC / UMR1214
Study officials:
affiliation: ToNIC / UMR1214
name: Anne LAPRIE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baudou E, Pariente J, Peran P, Tensaouti F, Pollidoro L, Meligne D, Ducassou A, Gros-Dagnac H, Arribarat G, Desirat JP, Bertozzi AI, Gambart M, Larrieu-Ciron D, Barbolosi D, Muracciole X, Lemesle B, Sevely A, Roques M, Cazaux M, Tallet J, Danna J, Chaix Y, Laprie A. A prospective behavioral and imaging study exploring the impact on long-term memory of radiotherapy delivered for a brain tumor in childhood and adolescence. Clin Transl Radiat Oncol. 2021 Nov 7;33:7-14. doi: 10.1016/j.ctro.2021.10.006. eCollection 2022 Mar.