Towards establishing hippocampal dose constraints for pediatric brain tumor radiotherapy: protocol of the prospective multicentre IPANEMA study (Irradiation in pediatrics: Neurocognition, neuroimaging and evaluation of memory and attention)

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Background Cognitive sequelae affect 60% of pediatric brain tumor survivors treated with radiotherapy (RT), significantly impacting quality of life. While hippocampal irradiation correlates with memory deficits, dose constraints remain undefined in children. The IPANEMA study aims to establish the discriminative capacity of hippocampal dosimetry to identify declarative memory deficits. Methods IPANEMA (Irradiation in Pediatrics: Neurocognition, Neuroimaging, and Evaluation of Memory and Attention) is a prospective multicenter study recruiting 130 patients aged 4-12 years at RT for brain tumors (ependymomas, medulloblastomas, germ cell tumors, craniopharyngiomas, pinealoblastomas) across 13 French centers. Comprehensive neuropsychological assessments will be conducted at 2 and 4 years post-RT, evaluating declarative, procedural, and working memory. The primary endpoint is the area under the ROC curve for hippocampal dose discriminating declarative memory deficits at 2 years post-RT. Secondary objectives include dose-response relationships for hippocampus, striatum, and cerebellum; neuroimaging biomarkers using multimodal MRI; baseline neurodevelopmental factors; and longitudinal cognitive trajectory. An ancillary study at the coordinating center includes advanced functional MRI. Expected results and Discussion Building on the IMPALA pilot study demonstrating hippocampal dose-episodic memory correlations, IPANEMA will provide robust evidence to establish pediatric dose constraints for memory-related structures. This multicenter longitudinal study incorporates standardized neuropsychological assessment, multimodal neuroimaging, and baseline cognitive evaluation. Results will inform RT planning optimization to preserve cognitive function while maintaining tumor control. Trial registration ID-RCB 2024-A00007-40. NCT06599879. Funded by Institut National du Cancer (INCa).

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