Biomedical subjects

Xiaoping Xiong

Publications and source records attributed to Xiaoping Xiong.

At least 19 recordsLinked to original sources

PubMed2005

Atypical white matter volume development in children following craniospinal irradiation.

Most children with medulloblastoma (MB), the second most common pediatric brain tumor, have a 70% probability of survival. However, survivors who receive aggressive therapy are at significant risk of cognitive deficits that have been associated with lower volumes of normal-appearing white matter (NAWM). We hypothesized that cranial irradiation inhibited normal brain volume development in these survivors. We retrospectively analyzed 324 MRI studies of 52 patients with histologically proven MB treated with surgery and 35 to 40 Gy craniospinal irradiation, with or without chemotherapy. The volume of NAWM and that of cerebrospinal fluid were quantified from a single index section and compared with those of healthy, age-similar control subjects. A quadratic random coefficient model was used to identify trends in brain volume with increasing age. Patients treated for MB at younger ages demonstrated substantially less development of NAWM volume than did their healthy peers. Younger age at the time of irradiation and the need for a ventricular shunt were significantly associated with reduced NAWM volume. NAWM and craniospinal fluid volume differences between patients who had shunts and those without resolved over a period of four to five years. NAWM volume is known to be associated with neurocognitive test performance, which shows deficiencies after cranial irradiation early in life. Therefore, volumetric monitoring of brain development can be used to guide the care of survivors, assess the toxicity of previous and current clinical trials, and aid in the design of therapies that minimize toxicity.

Abnormalities, Radiation-Induced↗

PubMed2005

Brain volume in pediatric patients with sickle cell disease: evidence of volumetric growth delay?

BACKGROUND AND PURPOSE: Despite the large body of data available about somatic growth delay in patients with sickle cell disease (SCD), virtually nothing is known about the effect of the disease on volumetric growth of the brain. This study was designed to test a hypothesis that children with SCD have a disease-related delay in brain volumetric growth compared with healthy children. METHODS: A cross-sectional study design was used to evaluate 83 children with SCD and 43 age-similar healthy children, including 27 patient siblings. Brain volume was measured by segmenting and classifying MR imaging data, by using at least three separate image sets (T1-, T2-, and proton density-weighted MR images). A linear model was used to compare the various brain volumes with the covariates of group (patient versus control) and age, with age treated as a continuous variable. RESULTS: With age controlled for, no significant difference was noted in total brain volume between patients and control subjects at age 9.5 years. However, patients showed a deficit specifically in gray matter volume (P=.005), without significant differences in white matter or ventricular volume. The deficit in patient gray matter was greater in central gray matter (P <.005) than in cortical gray matter (P <.02). In healthy control subjects, gray matter volume decreased significantly with age (P <.005), probably due to myelination of white matter tracts. In patients with SCD, gray matter volume did not change with age. CONCLUSION: Volumetric growth of brain gray matter may be delayed in children with SCD, suggesting that there may be neurodevelopmental consequences of this disease.

Adolescent↗

PubMed2005

Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate.

BACKGROUND AND PURPOSE: An effective treatment for acute lymphoblastic leukemia (ALL), intravenous (IV) methotrexate (MTX) has a notable toxic effect on the CNS, with leukoencephalopathy (LE) being the most common form. The purpose of this study was to use objective quantitative MR imaging to prospectively assess potential risk factors on the temporal evolution of LE in patients treated for ALL. METHODS: We evaluated the longitudinal prevalence of LE in 45 children treated for ALL in a single institutional protocol including seven courses of IV MTX and no cranial irradiation. Differences in signal intensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images between hyperintense regions and normal-appearing genu were used to quantitatively detect LE. Cox proportional regression was used to estimate the effect of covariates (e.g., sex, MTX dose, age at diagnosis) on the prevalence of LE. After influential factors were identified, a generalized linear model was determined to predict the probability of LE in new patients. The model was necessary to facilitate statistical testing between examinations. RESULTS: Increasing exposure, which corresponding to more courses and higher doses of IV MTX, influenced the prevalence of LE. The prevalence of LE was significant reduced approximately 1.5 years after the completion of IV MTX. CONCLUSION: Higher doses and more courses of IV MTX placed patients at a higher risk for LE; many of the changes resolved after the completion of therapy. The effect of these changes on neurocognitive functioning and quality of life in survivors remains to be determined.

Adolescent↗

PubMed2004

Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer.

PURPOSE: Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients. PATIENTS AND METHODS: We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners' Rating Scales and Social Skills Rating System. RESULTS: Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners' Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management. CONCLUSION: Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.

Adolescent↗

PubMed2004

Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma.

PURPOSE: We conducted a phase II trial of conformal radiation therapy (CRT) for localized childhood ependymoma to determine whether the irradiated volume could be reduced to decrease CNS-related side effects without diminishing the rate of disease control. PATIENTS AND METHODS: Between July 1997 and January 2003, 88 pediatric patients (median age, 2.85 +/- 4.5 years) received CRT in which doses (59.4 Gy to 73 patients or 54.0 Gy after gross-total resection to 15 patients younger than 18 months) were administered to the gross tumor volume and a margin of 10 mm. Patients were categorized according to extent of resection (underwent gross total resection, n = 74; near-total resection, n = 6; subtotal resection, n = 8), prior chemotherapy (n = 16), tumor grade (anaplastic, n = 35), and tumor location (infratentorial, n = 68). An age-appropriate neurocognitive battery was administered before and serially after CRT. RESULTS: The median length of follow-up was 38.2 months (+/- 16.4 months); the 3-year progression-free survival estimate was 74.7% +/- 5.7%. Local failure occurred in eight patients, distant failure in eight patients, and both in four patients. The cumulative incidence of local failure as a component of failure at 3 years was 14.8% +/- 4.0%. Mean scores on all neurocognitive outcomes were stable and within normal limits, with more than half the cohort tested at or beyond 24 months. CONCLUSION: Limited-volume irradiation achieves high rates of disease control in pediatric patients with ependymoma and results in stable neurocognitive outcomes.

Brain↗

PubMed2004

Early neuro-otologic effects of three-dimensional irradiation in children with primary brain tumors.

PURPOSE: Central nervous system (CNS) irradiation can cause sensorineural hearing loss. The relationship between the dose to the cochlea and the development of hearing loss is unknown. Conformal radiation therapy (CRT) techniques facilitate accurate cochlear dosimetry. We modeled hearing threshold levels (HTL) after CRT in children with localized primary brain tumors (ependymoma, low- or high-grade astrocytoma, craniopharyngioma, or CNS germinoma) by using cochlear dose and clinical variables. PATIENTS AND METHODS: We evaluated 72 children (median age, 9.5 years) with audiograms before and every 6 months after CRT (median follow-up, 16.6 months; range, 4.3-42.6 months). We used a mixed-effects model to predict change in hearing for each ear as a function of time, cochlear dose, and clinical variables. RESULTS: Hearing was affected the greatest in patients with CSF shunts and pre-CRT ototoxic chemotherapy, enhanced by cochlear dose, and was more prominent on the right side. Hearing impairment after CRT alone occurred at low and intermediate frequencies in patients with shunts and supratentorial tumors when the cochlear dose exceeded 32 Gy. Patients with shunts and central supratentorial tumors developed intermediate-frequency hearing loss after CRT alone regardless of dose. CONCLUSIONS: Hearing loss during the first 4 years after CRT alone is uncommon, although patients with shunts and supratentorial tumors appear to be at increased risk for low- and intermediate-frequency effects. CSF shunting and increased cochlear dose enhance the effect of ototoxic chemotherapy. If possible, the average cochlear dose should be <32 Gy over a 6-week course of treatment until more specific dose data become available.

Adolescent↗

PubMed2004

Efficacy of novel hemagglutinin-neuraminidase inhibitors BCX 2798 and BCX 2855 against human parainfluenza viruses in vitro and in vivo.

Human parainfluenza viruses are important respiratory tract pathogens, especially of children. However, no vaccines or specific therapies for infections caused by these viruses are currently available. In the present study we characterized the efficacy of the novel parainfluenza virus inhibitors BCX 2798 and BCX 2855, which were designed based on the three-dimensional structure of the hemagglutinin-neuraminidase (HN) protein. The compounds were highly effective in inhibiting hemagglutinin (HA) and neuraminidase (NA) activities and the growth of hPIV-1, hPIV-2, and hPIV-3 in LLC-MK(2) cells. The concentrations required to reduce the activity to 50% of that of a control ranged from 0.1 to 6.0 micro M in HA inhibition assays and from 0.02 to 20 micro M in NA inhibition assays. The concentrations required to inhibit virus replication to 50% of the level of the control ranged from 0.7 to 11.5 micro M. BCX 2798 and BCX 2855 were inactive against influenza virus HA and NA and bacterial NA. In mice infected with a recombinant Sendai virus whose HN gene was replaced with that of hPIV-1 [rSV(hHN)], intranasal administration of BCX 2798 (10 mg/kg per day) and of BCX 2855 (50 mg/kg per day) 4 h before the start of infection resulted in a significant reduction in titers of virus in the lungs and protection from death. Treatment beginning 24 h after the start of infection did not prevent death. Together, our results indicate that BCX 2798 and BCX 2855 are effective inhibitors of parainfluenza virus HN and may limit parainfluenza virus infections in humans.

Animals↗

PubMed2004

Generation of high-yielding influenza A viruses in African green monkey kidney (Vero) cells by reverse genetics.

Influenza A viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. The zoonotic nature of the disease and the vast viral reservoirs in the aquatic birds of the world mean that influenza will not easily be eradicated and that vaccines will continue to be needed. Recent technological advances in reverse genetics methods and limitations of the conventional production of vaccines by using eggs have led to a push to develop cell-based strategies to produce influenza vaccine. Although cell-based systems are being developed, barriers remain that need to be overcome if the potential of these systems is to be fully realized. These barriers include, but are not limited to, potentially poor reproducibility of viral rescue with reverse genetics systems and poor growth kinetics and yields. In this study we present a modified A/Puerto Rico/8/34 (PR8) influenza virus master strain that has improved viral rescue and growth properties in the African green monkey kidney cell line, Vero. The improved properties were mediated by the substitution of the PR8 NS gene for that of a Vero-adapted reassortant virus. The Vero growth kinetics of viruses with H1N1, H3N2, H6N1, and H9N2 hemagglutinin and neuraminidase combinations rescued on the new master strain were significantly enhanced in comparison to those of viruses with the same combinations rescued on the standard PR8 master strain. These improvements pave the way for the reproducible generation of high-yielding human and animal influenza vaccines by reverse genetics methods. Such a means of production has particular relevance to epidemic and pandemic use.

Animals↗

PubMed2004

Comparison of transcranial Doppler sonography with and without imaging in the evaluation of children with sickle cell anemia.

OBJECTIVE: High blood flow velocity in the middle cerebral artery or distal internal carotid artery, as measured by nonduplex transcranial Doppler sonography, predicts stroke in children with sickle cell anemia. However, velocities measured using the more widely available duplex transcranial Doppler imaging equipment may not be comparable. We sought to determine the magnitude and significance of the potential differences. SUBJECTS AND METHODS: We performed 55 paired examinations with duplex imaging and nonduplex nonimaging sonography machines on 53 children with sickle cell anemia. Examinations were performed consecutively by three sonographers blinded to the results of the opposing study. Velocities were measured in five clinically relevant vessels. RESULTS: Time-averaged mean maximum (TAMx) velocity measurements obtained with the duplex equipment were significantly lower than those made with the nonduplex equipment for all vessels except the posterior cerebral artery. The mean differences were 10.9% (p < 0.0001) in the middle cerebral artery, 12.7% (p = 0.002) in the anterior cerebral artery, 2.2% (p = 0.69) in the posterior cerebral artery, 21.0% (p < 0.0001) in the distal internal carotid artery, and 15.3% (p < 0.0001) at the bifurcation of the distal internal carotid artery. CONCLUSION: If TAMx velocities measured with duplex equipment are used to assign stroke risk in children with sickle cell anemia, we suggest that 180 cm/sec or more should be considered abnormal, and 153-179 cm/sec, as conditional. These values are 10% lower than those obtained from the nonduplex equipment used in the Stroke Prevention Trial in Sickle Cell Anemia study.

Adolescent↗

PubMed2004

The effects of hydrocephalus on intelligence quotient in children with localized infratentorial ependymoma before and after focal radiation therapy.

OBJECT: The goal of this study was to determine the influence of hydrocephalus on intelligence quotient (IQ) in children with infratentorial ependymoma before and after the administration of focal radiation. METHODS: Measurements of ventricular size, including Evans index (EI), cella media index (CMI), frontal horn diameter (FHD), and ventricular angle, were performed using magnetic resonance imaging at the time of diagnosis and again at 3, 6, 9, and 12 months after the initiation of radiation therapy. Of the 59 patients (median age at time of radiation treatment, 4.1 years), the clinical diagnosis established in 50 (85%) was hydrocephalus and 23 (39%) required placement of a cerebrospinal fluid (CSF) shunt. Extent of resection was gross or near total in 50 (85%). Before and after radiation treatment, IQ was measured using age-appropriate testing. The correlation between multiple ventricular measurements and IQ was investigated using standard regression techniques and a generalized linear model. Patients with a higher EI (p = 0.04), CMI (p = 0.001), and FHD (p = 0.0002) at the time of diagnosis were more likely to have lower IQ scores before radiation treatment. Patients with higher CMI (p = 0.04) and FHD (p = 0.01) at the time of diagnosis were more likely to exhibit an increase in IQ score after radiotherapy. The rate of change in IQ after radiation treatment was positively correlated with the CMI intercept (p = 0.015) and negatively correlated with the rate of FHD change (p = 0.006). CONCLUSIONS: Changes in IQ score before and after radiation treatment are significantly influenced by the extent and treatment of hydrocephalus at the time of diagnosis. Hydrocephalus is an important factor to include when analyzing the effects of treatment. Patients who undergo a second surgery for ependymoma are more likely to require the placement of a CSF shunt (p = 0.0001).

Adolescent↗

PubMed2004

Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation.

BACKGROUND AND PURPOSE: Children with medulloblastoma demonstrate post-treatment neurocognitive deficits in a number of areas, including memory performance. However, there is no definitive understanding of the neuropathology underlying these functional deficits. Previous literature has reported that hippocampal integrity is crucial to the acquisition of new episodic memories. Therefore, we hypothesized that longitudinal hippocampal volume measurements are abnormal in patients with medulloblastoma and thereby provide a possible substrate for explaining memory dysfunction. METHODS: Twenty-five pediatric patients underwent 159 serial MR imaging examinations (mean = six examinations per patient) for up to 5 years after irradiation and chemotherapy treatment for medulloblastoma. Right and left hippocampal volumes were obtained by manually tracing 1.5-mm contiguous coronal sections through the structure. Random coefficient models were used to examine longitudinal change in hippocampal volume as a function of time after diagnosis. RESULTS: Both right and left hippocampal volumes initially decreased after treatment. This abnormal volume pattern continued until approximately 2-3 years after diagnosis, when hippocampal volumes returned toward a normal positive growth pattern. Volume loss occurred predominately in the posterior regions. Female sex, low parental education, shunt placement, and positive seizure history all had a significant negative impact on hippocampal volume. CONCLUSION: Pediatric medulloblastoma survivors demonstrate an abnormal pattern of hippocampal volume development after treatment. Radiation dose mapping may expand our understanding of region-specific changes in hippocampal volume. Further exploration of the relationships between radiation therapy, memory dysfunction, and hippocampal pathology in this population is warranted.

Amnesia↗

PubMed2003

Brain imaging findings in pediatric patients with sickle cell disease.

PURPOSE: To determine prevalence of imaging abnormalities in the brain of children with sickle cell disease (SCD) and to identify clinical and methodological factors that influence prevalence estimate. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiographic findings for 185 patients with SCD examined at St Jude Children's Research Hospital since 1993 were reviewed. At least two readers independently reviewed images. Standard MR imaging criteria were used to identify lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy. Patients were assigned grades to indicate limited or extensive abnormalities. Standard MR angiographic criteria were used to identify arterial tortuosity (limited vasculopathy) and stenosis or occlusion (extensive vasculopathy). Findings were evaluated as a function of patient clinical status (including stroke) and diagnosis. Recent methods (T1- and T2-weighted MR imaging plus fluid-attenuated inversion recovery [FLAIR] at 3-mm section thickness) were compared with older methods (T1- and T2-weighted MR imaging without FLAIR at 5-mm section thickness). RESULTS: At mean age of 10 years, overall prevalence of infarction, ischemia, or atrophy in patients with SCD was 44% (82 of 185), and prevalence of vasculopathy was 55% (102 of 185), without evidence of a significant referral bias. Twenty-six of 27 patients with clinical stroke had abnormal findings at imaging, but even if patients with stroke were excluded, 35% (56 of 158) had a "silent infarction" (MR imaging-visible injury without clinical stroke), and 49% (78 of 158) had abnormal findings at MR angiography. Patients with clinically severe disease had more abnormalities at MR imaging (P <.001) and MR angiography (P <.004) than did patients with milder disease. Severe vasculopathy was more prevalent in patients with hemoglobin SS than in those with hemoglobin SC (P <.001). Recent imaging methods showed more abnormalities than did older methods (P <.01). With newer methods, 43% (29 of 67) of patients had extensive abnormalities, whereas with older methods, 28% (33 of 116) had extensive abnormalities. CONCLUSION: Prevalence of ischemic brain injury in pediatric patients with SCD is substantially higher than was previously reported, in part because of improvements in imaging methods.

Anemia, Sickle Cell↗

PubMed2003

Prospective brain imaging evaluation of children with sickle cell trait: initial observations.

PURPOSE: To determine whether sickle cell trait (hemoglobin AS) is associated with abnormalities in the brain of asymptomatic children. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiography were performed prospectively in 26 siblings (eight girls, 18 boys; mean age, 10.5 years) of patients with sickle cell disease. Two neuroradiologists, blinded as to whether a child had hemoglobin AS or AA, reviewed images obtained in siblings. With MR imaging, lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy was identified. With MR angiography, arterial stenosis, occlusion, or tortuosity was identified. Images with definite or possible abnormalities were mixed with randomly selected images and were referred to a third neuroradiologist for a completely blinded review. In cases in which all neuroradiologists concurred, a score was assigned that indicated the sibling had an abnormality. MR angiographic findings were assigned a score for tortuosity with a new quantitative scale. RESULTS: Among 26 siblings screened, 21 children had sickle cell trait. Among these 21 children, two had mild abnormalities at MR imaging (sample prevalence rate, 10% [95% CI: 1%, 29%]), and four had arterial tortuosity (sample prevalence rate, 19% [95% CI: 5%, 42%]). When children with sickle cell trait were compared with 31 control subjects without the trait, arterial tortuosity was significantly more common in children with sickle cell trait (P =.014). Among children with sickle cell trait, percentage of hemoglobin S was significantly greater in children who had tortuosity than percentage of hemoglobin S in children who had normal blood vessels at MR angiography (P <.03). CONCLUSION: Findings suggest that greater percentage of hemoglobin S is associated with mild vasculopathy. This vasculopathy may explain some of the excess risk of stroke among African Americans.

Adolescent↗

PubMed2003

Brain injury in children with sickle cell disease: prevalence and etiology.

Our objective was to evaluate the relationship between brain injury by magnetic resonance imaging (MRI) and vasculopathy by magnetic resonance angiography (MRA) in children with hemoglobin SS, the most serious form of sickle cell disease. We reviewed imaging for all 146 SS patients imaged at St. Jude Children's Research Hospital since 1993. Standard MRI criteria were used to identify cystic infarction, leukoencephalopathy, encephalomalacia, or atrophy. Standard MRA criteria were used to identify arterial tortuousity (limited vasculopathy), and stenosis or occlusion (extensive vasculopathy). At an average age of 10 years, the estimated prevalence of infarction, ischemic damage, or atrophy in SS patients was 46%, and of vasculopathy was 64%. Only 28% of patients were normal by both modalities, and patients abnormal by MRA often were abnormal by MRI (p < 0.00001). Patients with cystic infarction had limited vasculopathy, whereas patients with encephalomalacia had stenosis or occlusion (p < 0.0001). Large arteries were affected in 31% of brain injury patients, whereas small arteries are inferred to be abnormal in up to 69% of patients with brain injury. The degree of vasculopathy is closely related to the degree of brain injury, implying that vasculopathy is prodromal to most forms of brain injury in hemoglobin SS.

Adolescent↗

PubMed2003

Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma.

Fifty children diagnosed with medulloblastoma completed 188 psychological evaluations using the Wechsler Intelligence Scales for Children (D. Wechsler, 1974, 1991) over a 7-year study period following 35-40 Gy postoperative craniospinal irradiation. Random coefficient models were used to predict the trend in the children's intellectual performance as a function of time since diagnosis, with both patient and treatment variables as parameters of this function. A quadratic model demonstrated a delay prior to decline in performance for older patients, whereas the younger patients showed an immediate loss of performance with a plateau at approximately 6 years postdiagnosis. A steeper decline was found for those with higher baseline performance. Clinicians may use the proposed predictive model to identify those patients who are at risk of significant intellectual decline.

Adolescent↗

PubMed2003

Sequential conditional probability ratio tests for normalized test statistic on information time.

Sequential conditional probability ratio tests (SCPRTs) provide monitoring procedures with a unique property that a decision reached at early stopping is unlikely to be reversed should the trial continue to the planned end (Xiong, X., 1995, Journal of the American Statistical Association 90, 1463-1473; Tan, M., Xiong, X., and Kutner, M. H., 1998, Biometrics 54, 682-95). It actually provides a probability statement of a conclusion reversal, should the proposed interim analysis plan be used. To broaden its scope of applications, in this article we develop the SCPRT in terms of Brownian motion, which is applicable to most clinical trials with various endpoints. In addition, we utilize the unique structure of the SCPRT to derive a class of adaptive sequential tests that retain the significance level and power in the presence of a nuisance parameter. We illustrate the proposed methods with examples in clinical trials.

Biometry↗

PubMed2003

Risk factors for the development of obesity in children surviving brain tumors.

Hypothalamic obesity, a syndrome of intractable weight gain due to hypothalamic damage, is an uncommon but devastating complication for children surviving brain tumors. We undertook a retrospective evaluation of the body mass index (BMI) curves for the St. Jude Children's Research Hospital brain tumor population diagnosed between 1965 and 1995 after completion of therapy to determine risk factors for the development of obesity. Inclusion criteria were: diagnosis less than 14 yr of age, no spinal cord involvement, ambulatory, no supraphysiologic hydrocortisone therapy (>12 mg/m(2) x d), treatment and follow-up at St. Jude Children's Research Hospital, and disease-free survival greater than 5 yr (n = 148). Risk factors examined were age at diagnosis, tumor location, histology, extent of surgery, hydrocephalus requiring ventriculoperitoneal shunting, initial high-dose glucocorticoids, cranial radiation therapy, radiation dosimetry to the hypothalamus, intrathecal chemotherapy, and presence of endocrinopathy. Analyses were performed both between groups within a risk factor and against BMI changes for age in normal children older than 5.5 yr (the age of adiposity rebound). Risk factors were: age at diagnosis (P = 0.04), radiation dosimetry to the hypothalamus (51-72 Gy, P = 0.002 even after hypothalamic and thalamic tumor exclusion), and presence of any endocrinopathy (P = 0.03). In addition, risk factors when compared with BMI slope for the general American pediatric population included: tumor location (hypothalamic, P = 0.001), tumor histology (craniopharyngioma, P = 0.009; pilocytic astrocytoma, P = 0.043; medulloblastoma, P = 0.039); and extent of surgery (biopsy, P = 0.03; subtotal resection, P = 0.018). These results verify hypothalamic damage, either due to tumor, surgery, or radiation, as the primary cause of obesity in survivors of childhood brain tumors. In particular, hypothalamic radiation doses of more than 51 Gy are permissive. These results reiterate the importance of the hypothalamus in energy balance, provide risk assessment criteria for preventative measures before the development of obesity in at-risk patients, and suggest therapeutic strategies to reduce the future development of obesity.

Astrocytoma↗

PubMed2003

Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial.

Hypothalamic obesity is a devastating complication in children surviving brain tumors and/or cranial irradiation. These subjects are thought to exhibit autonomic dysregulation of the beta-cell, with insulin hypersecretion in response to oral glucose tolerance testing (OGTT). We report the results of a randomized, double-blind, placebo-controlled trial of octreotide therapy for pediatric hypothalamic obesity. Eighteen subjects [weight, 100.6 +/- 5.6 kg; body mass index (BMI), 37.1 +/- 1.3 kg/m(2)] received octreotide (5-15 microg/kg x d s.c.) or placebo for 6 months. With octreotide, Delta weight (mean +/- SEM) was +1.6 +/- 0.6 vs. +9.1 +/- 1.7 kg for placebo (P < 0.001). Delta BMI was -0.2 +/- 0.2 vs. +2.2 +/- 0.5 kg/m(2), respectively (P < 0.001). OGTT documented Delta insulin response (peak - basal) of -417 +/- 304 pM after octreotide vs. +216 +/- 215 pM after placebo (P = 0.034). Improvement in physical activity by parent report was noted with octreotide, but not placebo (P = 0.03). For the octreotide group, changes in quality of life positively correlated with changes in insulin response (P = 0.041). Complications and adverse events were mild and self-limited. These data demonstrate the beneficial effects of octreotide in pediatric hypothalamic obesity. Octreotide suppressed insulin, and stabilized weight and BMI. Improved quality of life correlated with the degree of insulin suppression. Octreotide was safe and well tolerated.

Adolescent↗