Executive and social functioning in pediatric posterior fossa tumor survivors and healthy controls.

Background: Executive and social functioning difficulty is well established in pediatric brain tumor survivors. Few studies have compared posterior fossa (PF) tumor survivors in comparison to their peers. The relationship between attention, processing speed, working memory, fatigue, and executive and social functioning was investigated to better understand the factors that impact executive and social functioning in PF tumor populations. Methods: Sixteen medulloblastomas, 9 low-grade astrocytomas (LGAs), and 17 healthy controls recruited from 4 sites completed measures of working memory and processing speed, and self-reported fatigue. One parent completed questionnaires on executive and social functioning. Results: There were no significant differences among all 3 groups on parent-reported executive and social functioning; of note, parents of LGA survivors expressed greater concerns regarding behavioral and cognitive regulation than did parents of medulloblastoma survivors and healthy controls. Parent-reported attention was related to parent-reported emotion, behavior, and cognitive regulation. Worse self-reported fatigue was associated with greater emotional dysregulation for the 2 PF tumor groups. Conclusions: Parents of PF tumor survivors described their children as performing similarly to their peers in most facets of executive and social functioning. While LGA survivors are traditionally thought to have more favorable outcomes, our finding of parent-reported executive functioning concerns to be worse for this group highlights the importance of long-term follow-up for all PF tumor survivors. Additionally, significant effects of attention on aspects of executive functioning in PF tumor survivors may inform current clinical practice and the future development of more effective interventions.

Comparison of neuropsychological functioning in pediatric posterior fossa tumor survivors: Medulloblastoma, low-grade astrocytoma, and healthy controls.

BACKGROUND: Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. PROCEDURE: Forty-two children (16 MB, nine LGA, and 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine-motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. RESULTS: MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors' mean scores were below normative expectations in working memory, processing speed, and fine-motor functioning. In this overall sample, processing speed difficulties were independent of fine-motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. CONCLUSION: The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.

Differential trajectories of neurocognitive functioning in females versus males following treatment for pediatric brain tumors.

BACKGROUND: Female and male trajectories of cerebellar and lobar brain structures are sexually dimorphic, making sex a potential candidate moderator of neurocognitive late effects from radiation treatment. We sought to evaluate longitudinal neurocognitive functioning in male versus female children treated for posterior fossa brain tumors. METHODS: Fifty-one female and 63 male survivors of posterior fossa tumors completed neuropsychological testing at 2 timepoints. We included patients treated with surgical resection, chemotherapy, and radiation therapy. Multilevel mixed modeling was used to predict IQ score as a function of patient sex following treatment (~2 or ~4 years post treatment). Effect sizes were used as a measure of clinical significance. RESULTS: Multilevel models resulted in a significant sex by time interaction (F = 6.69, P = 0.011). Females' cognitive scores were considerably higher compared with males at 4 years posttreatment. Females demonstrated an average improvement of 7.61 standard score IQ points compared with a decline of 2.97 points for males at 4 years follow-up. Effect sizes for female IQ compared with male IQ at 4 years posttreatment were between 0.8 and 0.9. CONCLUSION: Trajectories of neurocognitive functioning following posterior fossa tumor treatment differed between female and male children. Sexual dimorphism in radiation late effects may alter treatment decisions in children. Research into sex-specific neuroprotective mechanisms underlying neurocognitive development following pediatric brain tumor treatments is warranted.

Recursive partitioning for risk stratification in men undergoing repeat prostate biopsies.

BACKGROUND: The current study was performed to identify risk factors and risk groups for carcinoma detection in men undergoing repeat prostate biopsies. METHODS: The medical records of all men who had a negative initial prostate biopsy and underwent at least one repeat biopsy between 1992 and 2003 were reviewed to extract age, race, family history of prostate carcinoma, body mass index, referral indication, all prostate-specific antigen (PSA) values, digital rectal examination, PSA density (PSAD), the presence of a hypoechoic lesion, and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy. Risk factors for a subsequent diagnosis of prostate carcinoma were identified using the log-rank test and a stepwise, stratified Cox regression model. Based on the risk factors identified by Cox regression analysis, recursive partitioning was further used for risk stratification. RESULTS: A total of 373 patients underwent 975 biopsy procedures. During a median follow-up of 37.0 months, prostate carcinoma was detected in 107 of 373 patients (28.9%). Independent predictors of a positive biopsy (P < 0.05) were PSA doubling time (PSADT), PSAD, referral indication, the presence of HGPIN, patient age, and family history of prostate carcinoma. Recursive partitioning identified 4 distinct risk groups that were characterized by their PSADT and PSAD and the presence of HGPIN and had estimated 2-year and 5-year carcinoma detection rates of 3 +/- 1% and 21 +/- 4%, 28 +/- 5% and 40 +/- 7%, 22 +/- 6% and 58 +/- 8%, and 66 +/- 9% and 100%, respectively. CONCLUSIONS: The authors identified a series of independent risk factors for prostate carcinoma detection after an initial negative prostate biopsy and characterized clinically meaningful and distinct patient risk groups. Despite a negative initial biopsy, patients with high-risk features remain at risk for the detection of prostate carcinoma.