Neuroplastic Response After Radiation Therapy for Pediatric Brain Tumors: A Pilot Study.
OBJECTIVE
Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect.


METHODS
Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (to estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory.


RESULTS
Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model.


CONCLUSIONS
Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.
Neuro-Oncology Section, Children's Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: armstrongc@email.chop.edu.
Carol L
CL
Armstrong
Neuro-Oncology Section, Children's Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Michael J
MJ
Fisher
Oncology Division, Children's Hospital of Philadelphia, and Department of Biostatistics and Epidemiology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Yimei
Y
Li
Department of Radiation Oncology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Robert A
RA
Lustig
Neuro-Oncology Section, Children's Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Jean B
JB
Belasco
Neuro-Oncology Section, Children's Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Jane E
JE
Minturn
Department of Radiation Oncology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Christine E
CE
Hill-Kayser
Department of Radiation Oncology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Sonny
S
Batra
Neuro-Oncology Section, Children's Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Peter C
PC
Phillips
D001921:Brain / Q000503:physiopathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000175:diagnosis / Q000503:physiopathology / Q000532:radiotherapy*; D002648:Child; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D016371:Cranial Irradiation / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009473:Neuronal Plasticity / Q000528:radiation effects*; D010865:Pilot Projects; D011832:Radiation Injuries / Q000209:etiology / Q000503:physiopathology*; D011879:Radiotherapy Dosage; D020127:Recovery of Function / Q000528:radiation effects; D016896:Treatment Outcome