Laura Janzen

Impact of Craniospinal Dose, Boost Volume, and Neurologic Complications on Intellectual Outcome in Patients With Medulloblastoma

PURPOSE To examine the impact of radiation (ie, craniospinal irradiation [CSR] dose and boost volume) and complications (ie, hydrocephalus and other neurologic complications, including mutism) on patterns of change in intellectual functioning in medulloblastoma survivors. PATIENTS AND METHODS We conducted a retrospective review of 113 patients treated for medulloblastoma between 1983 and 2011 who were seen for neuropsychological assessment, including longitudinal follow-up of intellectual function. Patients were treated with either standard-dose CSR with a posterior fossa (PF) boost (n=51), standard-dose CSR plus tumor bed (TB) boost (n=9), reduced-dose CSR plus PF boost (n=28), or reduced-dose CSR plus TB boost (n=23), with or without chemotherapy. A subset of patients developed hydrocephalus that required cerebrospinal fluid (CSF) diversion (n=54) and/or other neurologic complications (n=40), more than half of which were postoperative mutism (n=25). Growth curve analysis was used to determine stability or change in intelligence scores over time. RESULTS Patients treated with reduced-dose CSR plus TB boost showed stable intellectual trajectories, whereas patients treated with higher doses and larger boost volumes experienced intellectual declines. Presence of complications was associated with worse intellectual outcome; however, hydrocephalus requiring CSF diversion and mutism differed in their pattern of decline. CONCLUSION These results improve our understanding of factors that impair intellectual outcome in patients treated for medulloblastoma. Lower doses of CSR and smaller boost volumes seem to mitigate intellectual decline. Our findings validate the use of TB boost and suggest PF boost should be reconsidered.

Longitudinal evaluation of neurocognitive function after treatment for central nervous system germ cell tumors in childhood.

Central nervous system germ cell tumors (CNS GCT) are typically localized to midline structures of the brain, including the pineal and suprasellar/pituitary regions. Management of these tumors depends on underlying histology (germinoma or nongerminomatous germ cell tumor). Knowledge about neurocognitive outcome in these patients is limited. Longitudinal neurocognitive outcome in CNS GCT patients seen for neuropsychological evaluation at a single institution was explored.

Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment.

This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research. It is concluded that neurocognitive outcomes for the majority of children with standard-risk ALL treated according to current chemotherapy protocols is relatively good, but subgroups of children are more significantly compromised. As medical treatments advance and survival rates continue to improve, neurocognitive outcomes and other quality of life indicators will become increasingly important. Preventing or ameliorating treatment-related neuropsychological sequelae represents the next major challenge in pediatric ALL.

White matter integrity and core cognitive function in children diagnosed with sickle cell disease.

Children diagnosed with sickle cell disease (SCD) have an increased risk of stroke, often associated with white matter damage and neurocognitive morbidity. Growing evidence suggests that subtle changes in white matter integrity, which do not pass the threshold to be visible on a clinical magnetic resonance image and classified as stroke, may contribute to decreased cognitive performance. We used archived diffusion-weighted imaging and neurocognitive assessment data to identify associations between microstructural changes in normal-appearing white matter and cognitive performance in children with SCD. Study participants included 10 healthy children and 15 pediatric SCD patients (5 with identified lesions and 10 without lesion). After excluding lesioned tissue from analyses, we detected significant increases in apparent diffusion coefficient across the brains of patients in comparison with control children, suggesting compromise to the structure of normal-appearing white matter. Deficits in working memory and processing speed were also apparent in patients. Increased apparent diffusion coefficient and deficiencies in processing speed were again detected in a subanalysis including only the patients without lesion. Correlation analyses evidenced associations between the microstructure of the right frontal lobe and cerebellum, and processing speed. This outcome suggests a relationship between tissue integrity and cognitive morbidity in SCD patients.

Parent-Reported Social Outcomes After Treatment for Pediatric Embryonal Tumors: A Prospective Longitudinal Study

PURPOSE To examine longitudinal parent-reported social outcomes for children treated for pediatric embryonal brain tumors. PATIENTS AND METHODS Patients (N=220) were enrolled onto a multisite clinical treatment protocol. Parents completed the Child Behavior Checklist/6-18 at the time of their childs diagnosis and yearly thereafter. A generalized linear mixed effects model regression approach was used to examine longitudinal changes in parent ratings of social competence, social problems, and withdrawn/depressed behaviors with demographic and treatment factors as covariates. RESULTS During the 5-year period following diagnosis and treatment, few patients were reported to have clinically elevated scores on measures of social functioning. Mean scores differed significantly from population norms, yet remained within the average range. Several factors associated with unfavorable patterns of change in social functioning were identified. Patients with high-risk treatment status had a greater increase in parent-reported social problems (P=.001) and withdrawn/depressed behaviors (P=.01) over time compared with average-risk patients. Patients with posterior fossa syndrome had greater parent-reported social problems over time (P=.03). Female patients showed higher withdrawn/depressed scores over time compared with male patients (P<.001). Patient intelligence, age at diagnosis, and parent education level also contributed to parent report of social functioning. CONCLUSION Results of this study largely suggest positive social adjustment several years after diagnosis and treatment of a pediatric embryonal tumor. However, several factors, including treatment risk status and posterior fossa syndrome, may be important precursors of long-term social outcomes. Future research is needed to elucidate the trajectory of social functioning as these patients transition into adulthood.

Intellectual Outcome in Molecular Subgroups of Medulloblastoma

Purpose To evaluate intellectual functioning and the implications of limiting radiation exposure in the four biologically distinct subgroups of medulloblastoma: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. Patients and Methods A total of 121 patients with medulloblastoma (n = 51, Group 4; n = 25, Group 3; n = 28, SHH; and n = 17, WNT), who were treated between 1991 and 2013 at the Hospital for Sick Children (Toronto, Ontario, Canada), Childrens National Health System (Washington, DC), or the Lucile Packard Childrens Hospital (Palo Alto, CA), had intellectual assessments. First, we compared intellectual trajectories between subgroups. Next, we evaluated the effect of treatment with reduced-dose craniospinal irradiation (CSI) plus a tumor bed boost versus treatments that deliver higher CSI doses and/or larger boost volumes to the brain (all other treatments) within subgroups. Linear mixed modeling was used to determine the stability or change in intelligence scores over time. Results Intellectual outcomes declined comparably in each subgroup except for processing speed; SHH declined less than Group 3 ( P = .04). SHH had the lowest incidence of cerebellar mutism and motor deficits. Treatment with reduced-dose CSI plus a tumor bed boost was associated with preserved intellectual functioning in WNT and Group 4 patients considered together (ie, subgroups containing patients who are candidates for therapy de-escalation), and not in Group 3 or SHH. Across all subgroups, patients in the all other treatments group declined over time (all P < .05). Conclusion SHH patients appear to have the most distinct functional (ie, motor deficits and mutism) outcomes and a unique processing speed trajectory. Only WNT and Group 4 patients seem to benefit from limiting radiation exposure. Our findings highlight the value of conducting subgroup-specific analyses, and can be used to inform novel biologically based treatment protocols for patients with medulloblastoma.

A Randomized Control Intervention Trial to Improve Social Skills and Quality of Life in Pediatric Brain Tumor Survivors.

To determine if a group social skills intervention program improves social competence and quality of life (QOL) in pediatric brain tumor survivors (PBTS).

Neurocognitive evaluation of long term survivors of atypical teratoid rhabdoid tumors (ATRT): The Canadian registry experience

Because atypical teratoid rhabdoid tumor(ATRT) is a rare disease of infancy carrying a grim prognosis, focus on long‐term outcome, especially neurocognitive remained very limited. With new era of multimodality therapy, an increasing proportion of patients are now long‐term survivors.

Determinants of quality of life outcomes for survivors of pediatric brain tumors: Barrera et al.

To describe the quality of life (QOL) of pediatric brain tumor survivors (PBTSs) prospectively and to identify potential medical, personal and family contextual factors associated with QOL.

Implementing guidelines: Proposed definitions of neuropsychology services in pediatric oncology

Several organizations have published guidelines for the neuropsychological care of survivors of childhood cancer. However, there is limited consensus in how these guidelines are applied. The model of neuropsychology service delivery is further complicated by the variable terminology used to describe recommended services. In an important first step to translate published guidelines into clinical practice, this paper proposes definitions for specific neuropsychological processes and services, with the goal of facilitating consistency across sites to foster future clinical program development and to clarify clinical practice guidelines.