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

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 Overview

• Status: Completed
• Conditions: Pediatric Cancer; Cancer Brain
• Intervention / Treatment: Device: MRI; Behavioral: Cognitive assessment

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31024
    • ToNIC / UMR1214

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients radiotherapy +; Patients cured of a brain tumour and who have received radiotherapy in childhood	Device: MRI; The MRI protocol is composed of: T1-weighted anatomical sequences; DTI sequences; resting functional MRI; 3D MR spectroscopic imaging; Behavioral: Cognitive assessment; Battery of neuropsychological tests
Experimental: Patients radiotherapy -; Patients cured of a brain tumour and who have received surgery and/or chemotherapy but were not irradiated	Device: MRI; The MRI protocol is composed of: T1-weighted anatomical sequences; DTI sequences; resting functional MRI; 3D MR spectroscopic imaging; Behavioral: Cognitive assessment; Battery of neuropsychological tests
Experimental: Healthy volunteers; Healthy volunteers (control group) matched in age, manual laterality, gender and parental education to "Patients radiotherapy +"	Device: MRI; The MRI protocol is composed of: T1-weighted anatomical sequences; DTI sequences; resting functional MRI; 3D MR spectroscopic imaging; Behavioral: Cognitive assessment; Battery of neuropsychological tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural characteristics of declarative memory neuronal substrate: volume of the hippocampus	Volume of the hippocampus obtained from T1-weighted anatomical	Day 1
Structural characteristics of declarative memory neuronal substrate: cortical thickness of the hippocampus	Cortical thickness of the hippocampus obtained from T1-weighted anatomical	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	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)	Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Declarative episodic memory assessment scores	Scores obtained at memory clinical scale for children	Day 2
Declarative semantic memory assessment scores	Scores obtained at Wechsler Intelligence Scale for Children	Day 2
Procedural memory assessment scores	Scores obtained at Serial Reaction Time Task	Day 2
Short-term auditive memory assessment scores	Scores obtained at Wechsler Intelligence Scale for Children	Day 2
Short-term visual memory assessment scores	Scores obtained at Wechsler Memory Scale	Day 2
Intellectual capacities assessment scores	Scores obtained at Wechsler Intelligence Scale for Children	Day 2
Language assessment scores	Scores obtained at Peabody Picture Vocabulary Test	Day 2
Motor functions assessment scores	Scores obtained at Purdue Pegboard Test	Day 2
Executive functions assessment scores	Scores obtained at TMT A and B, Stroop Test and Wisconsin Card Sorting Test	Day 2
Attentional capacities assessment scores	Scores obtained at Test of Attentional Performance 2.3.1	Day 2
Cerebellar volume	Cerebellar volume obtained from T1-weighted anatomical sequences	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	Day 1
Cerebral blood volume obtained from brain perfusion imaging	Cerebral blood volume obtained from brain perfusion imaging	Day 1
Post-therapeutic hypoxia	Post-therapeutic hypoxia as measured by magnetic resonance spectrometry of the hippocampus and cerebellum	Day 1
Neuronal density	Neuronal density as measured by magnetic resonance spectrometry of the hippocampus and cerebellum	Day 1
Functional connectivity index	Functional connectivity index, obtained via resting functional MRI.	Day 1
Age at the time of treatment	Age at the time of treatment from the patients' medical records	Day 1
Radiotherapy doses	Radiotherapy doses received in the cerebellum, in the hippocampus, and in the whole brain from the patients' medical records	Day 1
Cerebellum and hippocampus Normal Tissue Complication Probability	Cerebellum and hippocampus Normal Tissue Complication Probability (NTCP)	Day 1

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Anne LAPRIE, ToNIC / UMR1214

Publications and helpful links

General Publications

• 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.
• Baudou E, Danna J, Tallet J, Pollidoro L, Tensaouti F, Bertozzi AI, Pariente J, Courbieres N, Dufour C, Grill J, Chaix Y, Laprie A. Impact of a pediatric posterior fossa tumor and its treatments on motor procedural learning. Eur J Paediatr Neurol. 2023 May;44:37-45. doi: 10.1016/j.ejpn.2023.03.005. Epub 2023 Apr 10.
• Baudou E, Peran P, Tensaouti F, Arribarat G, Pariente J, Courbieres N, Pollidoro L, Bertozzi AI, Gambart M, Sevely A, Roques M, Ducassou A, Danna J, Tallet J, Dufour C, Chaix Y, Laprie A. The long-term impact of irradiation on functional connectivity in brain circuits involved in memory processes after pediatric posterior fossa tumor. Radiother Oncol. 2024 Feb;191:110073. doi: 10.1016/j.radonc.2023.110073. Epub 2023 Dec 23.
• Habibi AT, Alaya IB, Tensaouti F, Baudou E, Arribarat G, Pollidoro L, Peran P, Chaix Y, Labidi S, Laprie A. Impact of Pediatric Posterior Fossa Tumor Treatments on Working Memory Tracts Using Resting-State fMRI and Tractography. J Neuroimaging. 2025 Jan-Feb;35(1):e70007. doi: 10.1111/jon.70007.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Actual): August 19, 2021
• Study Completion (Actual): August 19, 2021

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: MRI; memory; radiotherapy; child; brain tumour
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms; Brain Neoplasms; Behavioral Disciplines and Activities; Psychological Tests; Neuropsychological Tests; Mental Status and Dementia Tests
• Other Study ID Numbers: C19-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No