Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning.

PURPOSE: To characterize the association between neurocognitive outcomes (memory and processing speed) and radiation (RT) dose to the hippocampus, corpus callosum (CC), and frontal white matter (WM) in children with medulloblastoma treated on a prospective study, SJMB03. PATIENTS AND METHODS: Patients age 3-21 years with medulloblastoma were treated at a single institution on a phase III study. The craniospinal RT dose was 23.4 Gy for average-risk patients and 36-39.6 Gy for high-risk patients. The boost dose was 55.8 Gy to the tumor bed. Patients underwent cognitive testing at baseline and once yearly for 5 years. Performance on tests of memory (associative memory and working memory) and processing speed (composite processing speed and perceptual speed) was analyzed. Mixed-effects models were used to estimate longitudinal trends in neurocognitive outcomes. Reliable change index and logistic regression were used to define clinically meaningful neurocognitive decline and identify variables associated with decline. RESULTS: One hundred and twenty-four patients were eligible for inclusion, with a median neurocognitive follow-up of 5 years. Mean right and left hippocampal doses were significantly associated with decline in associative memory in patients without posterior fossa syndrome (all P < .05). Mean CC and frontal WM doses were significantly associated with decline in both measures of processing speed (all P < .05). Median brain substructure dose-volume histograms were shifted to the right for patients with a decline in associative memory or processing speed. The odds of decline in associative memory and composite processing speed increased by 23%-26% and by 10%-15% for every 1-Gy increase in mean hippocampal dose and mean CC or frontal WM dose, respectively. CONCLUSION: Increasing RT dose to the CC or frontal WM and hippocampus is associated with worse performance on tests of processing speed and associative memory, respectively. Brain substructure-informed RT planning may mitigate neurocognitive impairment.

Early Axial Growth Outcomes of Pediatric Patients Receiving Proton Craniospinal Irradiation.

Guidelines on proton craniospinal irradiation (p-CSI) target volume selection in children are lacking. We examined the impact of target volume selection on growth of children receiving p-CSI at a institution. Records of 58 patients who received p-CSI were reviewed. Median age at treatment initiation was 8 years (range, 2 to 18 y). Spinal target volumes included whole vertebral body (WVB) in 67% and partial vertebral body (PVB) in 33%. Height z-scores before and after p-CSI were assessed using Centers for Disease Control and Prevention stature-for-age charts. Maximal Cobb angle and height z-score change were compared for WVB versus PVB p-CSI using a t test. Among 93% of patients with detailed data, median follow-up was 19 months (range, 2 to 58 mo) after radiation therapy initiation. Quantitative growth evaluations were available for 64% of patients. Median change in height z-score was -0.5 (range, -2.1 to +0.7) after treatment, representing a decrease (P<0.001) in age-adjusted height. WVB patients had significantly greater reduction in height z-score versus PVB patients (P=0.004) but no difference in Cobb angle change (P>0.05). Despite reluctance surrounding its use in younger patients, PVB p-CSI was associated with similar spinal curvature and less growth suppression as compared with WVB p-CSI; a trial comparing WVB versus PVB in children may be warranted.

Electromagnetic Fields, Pulsed Radiofrequency Radiation, and Epigenetics: How Wireless Technologies May Affect Childhood Development.

Mobile phones and other wireless devices that produce electromagnetic fields (EMF) and pulsed radiofrequency radiation (RFR) are widely documented to cause potentially harmful health impacts that can be detrimental to young people. New epigenetic studies are profiled in this review to account for some neurodevelopmental and neurobehavioral changes due to exposure to wireless technologies. Symptoms of retarded memory, learning, cognition, attention, and behavioral problems have been reported in numerous studies and are similarly manifested in autism and attention deficit hyperactivity disorders, as a result of EMF and RFR exposures where both epigenetic drivers and genetic (DNA) damage are likely contributors. Technology benefits can be realized by adopting wired devices for education to avoid health risk and promote academic achievement.

Sunlight exposure and multiple sclerosis in a tropical country.

OBJECTIVE: We analysed past and current sun exposure in multiple sclerosis (MS) patients as compared with matched controls in Mexico, a country with tropical climate. METHODS: In a case-controlled study that include 83 MS patients and 166 matched controls, we inquired about sunlight exposure in two different periods: during adolescence and during the immediate past 5 years. Indicators were: exposure on quotidian and weekend outdoor activities with direct sunlight contact as expressed on frequency by mean number of days, daytime (morning, noon, afternoon), number of hours, visits to sunny places, and use of sunblocking agents. Additional elements were socioeconomic status, skin colour, and antecedent of varicella infection during childhood. RESULTS: MS patients showed a larger proportion of white skin. MS patients had more sunlight exposure during adolescence (80% versus 60%, P = 0·002); this tendency prevailed on current indicators (46% versus 30%, P = 0·02). However, current exposure on weekends (10% versus 22%, P = 0·02) and visits to the beach (64% versus 98%, P = 0·002) were lower in MS than in controls. DISCUSSION: Mexico gets more sunlight through the year than areas with high incidence of MS; nevertheless, its prevalence has greatly increased over the last decades, making it a relevant emerging disease. Our results indicate that in a tropical country, there is no association between sunlight exposure and the risk to develop MS, given the immunological effects of sunlight exposure either through UV radiation or vitamin D metabolism.

[Clinical immunological disorders in children from various observation cohorts exposed to radiation factor during various stages of oncogenesis].

The immune status disorders and features depending on the radiation impact type in various cohorts of radiation observations long after the Chernobyl (CNPP) disaster and the possible role of these disorders in development of chronic somatic pathology in children are shown. Lymphocyte depletion, T-cell immunity component disorders in the form of cell contraction with CD3, CD4, CD8 markers and the B-cell immunity component disorders in the form of reducing the quantity of CD10, CD23 marker cells were observed in children subject to combined chronic irradiation by 131I, 137Cs, 90Sr radionuclides. The descendants of irradiated parents (the 1st generation; children of the Chernobyl accident consequences liquidators, children of the citizens of radiation contaminated territories with various 137Cs levels) had immunity disorders of different type. A change in the total amount of NK-cells (CD16(+)-lymphocytes) is the general sign for all radiation risk groups; however, people subject to direct radiation impact demonstrated reduction of the antitumor protection potency, whereas descendants of irradiated ones demonstrated its activation with typically increasing number of CD16(+)-lymphocytes. In all radiation risk groups, a tendency to reduction of a number of cells involved in the leukocytal activation with the "pluripotential activation" marker (CD38 marker cells), proliferating cells (CD71 marker cells) and the increase of relative amount of cells with apoptosis marker (CD95(+)-lymphocytes). Immune disorder markers under the radiation impact in various cohorts of children's observation are suggested: antigens: CD4, CD8, CD10, CD23, CD16, CD38, CB71, CD95.

Late effects in long-term survivors after treatment for childhood acute leukemia.

BACKGROUND: This is a report of late effects in childhood cancer survivors seen in the follow-up clinic of a single institution. MATERIALS AND METHODS: There were 324 acute leukemia survivors in the database of the Long Term Follow Up Clinic of Children's National Medical Center from January 1, 1997, through June 30, 2005. RESULTS: Of the 324 acute leukemia survivors, 228 were white, 48 black, 20 Hispanic, and 12 other. Their follow-up time was 0 to 25 years (mean 5.3 years). One or more adverse events occurred in 74.1% of the 324 survivors. Defective physical growth was most commonly reported, followed by disturbed neurocognitive function, emotional difficulties, cardiac abnormalities, hypertension, osteoporosis/osteopenia, fractures, and second neoplasms. More black and Hispanic children had acute myeloid leukemia, relapses, cardiac problems, and hypertension than white and other subjects. CONCLUSION: Childhood cancer survivors require lifelong monitoring, with prompt identification and treatment of adverse late effects.

Growth and endocrine function in patients with Hurler syndrome after hematopoietic stem cell transplantation.

Short stature is characteristic of Hurler syndrome, or mucopolysaccharidosis type IH (MPS IH). Hematopoietic stem cell transplantation (HSCT) is used to treat children with MPS IH. While HSCT corrects some of the metabolic features of MPS IH, its effects on growth are not well delineated. We investigated growth in patients with MPS IH after HSCT and described accompanying endocrine abnormalities. A cohort of 48 patients with MPS IH who had received HSCT between 1983 and 2005 were included. The prevalence of short stature (height <-2 s.d. score, SDS) before HSCT was 9%, and increased to 71% at last follow-up (6.9+/-5.1 years after HSCT). Short stature was positively associated with increased age at HSCT (P=0.002) and TBI (P=0.009). In total, 23% had growth hormone deficiency and/or low insulin-like growth factor-1, one female patient had premature adrenarche, one precocious puberty and 27% had clinical or subclinical hypothyroidism. Growth failure is highly prevalent in children with MPS IH after HSCT. Children who had no TBI exposure and were younger at the time of HSCT had a better height outcome.

Growth and development after hematopoietic cell transplant in children.

Hematopoietic cell transplantation (HCT) following high-dose chemotherapy or chemoradiotherapy for children with malignant or nonmalignant hematologic disorders has resulted in an increasing number of long-term disease-free survivors. The preparative regimens include high doses of alkylating agents, such as CY with or without BU, and may include TBI. These agents impact the neuroendocrine system in growing children and their subsequent growth and development. Children receiving high-dose CY or BUCY have normal thyroid function, but those who receive TBI-containing regimens may develop thyroid function abnormalities. Growth is not impacted by chemotherapy-only preparative regimens, but TBI is likely to result in growth hormone deficiency and decreased growth rates that need to be treated with synthetic growth hormone therapy. Children who receive high-dose CY-only have normal development through puberty, whereas those who receive BUCY have a high incidence of delayed pubertal development. Following fractionated TBI preparative regimens, approximately half of the patients have normal pubertal development. These data demonstrate that the growth and development problems after HCT are dependent upon the preparative regimen received. All children should be followed for years after HCT for detection of growth and development abnormalities that are treatable with appropriate hormone therapy.

[Physical development of the teenagers who were exposed to radiation in utero after the accident on the Chernobyl Nuclear Power Plant].

Some features of physical development of teenagers exposed to radiation during utero development are revealed. These teenagers have been found to have more often, than in the control group disorders connected with harmonicity of physical development. Thus in the group of teenagers who have been exposed to acute radiation in utero period of their development prevails tall young men and girls while among the teenagers who have been born in 1986 and stayed living in the polluted territories low growth, subnanysm and nanysm is more often observed.