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Abstract
Purpose: To determine the preirradiation baseline association of white matter integrity with neurocognitive function and to assess posttreatment changes in pediatric patients with craniopharyngioma treated with proton therapy.

Methods and materials: Ninety children and adolescents (2-20 years old) with craniopharyngioma were treated with proton therapy (54 Gy[RBE]) in a prospective therapeutic trial. Neurocognitive performance at the postoperative baseline before proton therapy and diffusion tensor imaging (DTI) data acquired at baseline and at annual follow-up were analyzed. Tract-based spatial statistics and structural connectomics were used to derive global and local white matter features from DTI. Baseline DTI features were compared for patients with average and below-average neurocognitive performance. Longitudinal DTI data were analyzed to determine the proton dose effect on white matter structures in relation to the irradiated brain volume and baseline age.

Results: Before proton therapy, patients with below-average working memory, processing speed, verbal fluency, verbal learning, or fine motor dexterity exhibited more globally degraded white matter structures compared with their counterparts with average performance, as indicated by lower mean fractional anisotropy, decreased global efficiency, or higher modularity. Surgery, obstructive hydrocephalus, and preoperative hypothalamic involvement appeared to be related to this degradation. In local analyses, tract-based spatial statistics revealed left-lateralized associations with verbal and motor functions, which supported surgical approaches to midline tumors via the right hemisphere. The mean fractional anisotropy of the brain and the global efficiency derived from DTI increased over the 5 years after proton therapy. The rate of increase was lower with larger irradiated brain volumes and in older children.

Conclusions: Below-average baseline neurocognitive performance in patients with craniopharyngioma before proton therapy appeared to be related to structural degradation of white matter tracts. Posttherapy longitudinal DTI showed improving trends in global integrity and efficiency measures, particularly in children in whom a smaller brain volume was irradiated.

Affiliations

Jinsoo Uh  1 , Thomas E Merchant  2 , Heather M Conklin  3 , Yousef Ismael  2 , Yimei Li  4 , Yuanyuan Han  4 , Noah D Sabin  5 , Abbas Babajani-Feremi  6 , Daniel J Indelicato  7 , Chia-Ho Hua  2
1 Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. Electronic address: jinsoo.uh@stjude.org.
2 Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
3 Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee.
4 Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
5 Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, Tennessee.
6 Department of Pediatrics and Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, and Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, Tennessee.
7 Department of Radiation Oncology, University of Florida, Jacksonville, Florida.