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.

Low-dose oral etoposide-based induction regimen for children with acute lymphoblastic leukemia in first bone marrow relapse.

We evaluated the clinical response to low-dose etoposide in relapsed acute lymphoblastic leukemia (ALL). Of the 45 patients with ALL in first bone marrow relapse enrolled on the ALL R15 protocol, 44 had received epipodophyllotoxins during frontline therapy. In the first week of remission induction therapy, patients received etoposide (50 mg/m(2) per day) administered orally as a single agent once or twice daily.

Search for B0s-->micro+micro- and B0d-->micro+micro- decays in pp collisions at square root s = 1.96 TeV.

We report on a search for B(0)(s)-->micro(+)micro(-) and B(0)(d)-->micro(+)micro(-) decays in pp collisions at square root of s=1.96 TeV using 171 pb(-1) of data collected by the CDF II experiment at the Fermilab Tevatron Collider. The decay rates of these rare processes are sensitive to contributions from physics beyond the standard model.

Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor.

Purpose: To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients.

Patients And Methods: After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks.

Late neurocognitive sequelae in survivors of brain tumours in childhood.

As survival among children treated for cancer continues to improve, more attention is being focussed on the late effects of cancer treatment. In children treated for brain tumours, chronic neurocognitive effects are especially challenging. Deficits in cognitive development have been described most thoroughly among children treated for posterior-fossa tumours, specifically medulloblastomas and ependymomas, which account for about 30% of all newly diagnosed cases of brain tumours in children.

Second neoplasms in pediatric patients with primary central nervous system tumors: the St. Jude Children's Research Hospital experience.

Background: Details on second neoplasms (SNs) following pediatric central nervous system (CNS) tumors are scant, because of the rarity of such SNs. The goal of the current study was to investigate and characterize these rare SNs.

Methods: The authors reviewed clinical and treatment data on all institutional patients age < 22 years at diagnosis of a primary CNS tumor who developed any type of SN.

Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist.

Pediatric high-grade gliomas represent a heterogeneous group of tumors that accounts for 15%-20% of all pediatric central nervous system tumors. These neoplasms predominantly involve the supratentorial hemispheres or the pons, in which case the tumors are usually called diffuse brainstem gliomas. The diagnosis of supratentorial neoplasms is dependent on their histologic appearance.

Phase I and pharmacokinetic study of topotecan administered orally once daily for 5 days for 2 consecutive weeks to pediatric patients with refractory solid tumors.

Purpose: We conducted a phase I trial of the injectable formulation of topotecan given orally once daily for 5 days for 2 consecutive weeks (qd x 5 x 2) in pediatric patients with refractory solid tumors.

Patients And Methods: Cohorts of two to six patients received oral topotecan at 0.8, 1.

Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse.

Using flow cytometric techniques capable of detecting 0.01% leukemic cells, we prospectively studied minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) after first relapse. At the end of remission reinduction, 41 patients had a bone marrow sample adequate for MRD studies; 35 of these were in morphologic remission.

Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma.

Purpose: To assess the feasibility of performing central molecular analyses of fresh medulloblastomas obtained from multiple institutions and using these data to identify prognostic markers for contemporaneously treated patients.

Materials And Methods: Ninety-seven samples of medulloblastoma were collected. Tumor content in samples was judged by frozen section review.

Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10 patients.

Background: Clear cell ependymoma (CCE) is an uncommon central nervous system tumor with a predilection for the supratentorial region in children. Histologically, it may mimic oligodendroglioma, central neurocytoma, hemangioblastoma, and renal cell carcinoma.

Methods: The authors reviewed the clinical, radiographic, and pathologic features, therapy, and outcome in 10 children with CCE who were treated at St.

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 mechanistic mathematical model of temozolomide myelosuppression in children with high-grade gliomas.

Temozolomide (TMZ) is currently being evaluated for the treatment of high-grade gliomas in children. Myelosuppression (the suppression of bone marrow activity) is the dose-limiting toxicity for TMZ in adults and children. Empirical methods (i.

ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma.

Purpose: This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades II-IV) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade.

Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry, respectively. Mutation and expression of TP53 were also determined in these same samples by direct sequence analysis of microdissected tumor material and immunohistochemistry, respectively.

Population pharmacokinetics of temozolomide and metabolites in infants and children with primary central nervous system tumors.

Purpose: To construct a population pharmacokinetic model for temozolomide (TMZ), a novel imidazo-tetrazine methylating agent and its metabolites MTIC and AIC in infants and children with primary central nervous system tumors.

Methods: We evaluated the pharmacokinetics of TMZ and MTIC in 39 children (20 boys and 19 girls) with 132 pharmacokinetic studies (109 in the training set and 23 in the validation set). The median age was 7.

Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors.

Background: The primary objective of this study was to test the hypothesis that, among survivors of pediatric brain tumors, the association between reduced volumes of normal-appearing white matter (NAWM) and intellectual/academic achievement deficits can be explained by patient problems with memory and attention.

Methods: Quantitative tissue volumes from magnetic resonance imaging scans and neurocognitive assessments were obtained for 40 long-term survivors of pediatric brain tumors. They were treated with radiotherapy (RT) with or without chemotherapy 2.

Effect of intrapatient dosage escalation of irinotecan on its pharmacokinetics in pediatric patients who have high-grade gliomas and receive enzyme-inducing anticonvulsant therapy.

The authors set out to determine the effect of intrapatient dose escalation of irinotecan on its disposition in pediatric patients with high-grade glioma who received concomitant enzyme-inducing anticonvulsants (EIAs). During Course 1, a 60-minute intravenous infusion of irinotecan (20 mg/m(2) per day) was administered once daily for 5 days on each of 2 consecutive weeks. The authors measured the concentrations of the lactone forms of irinotecan and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38), SN-38 glucuronide, and 7-ethyl-10-[4-N-(5-aminopeptanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC) in serial plasma samples collected on Days 1 and 12 of Course 1.

Pharmacokinetics and pharmacodynamics of oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia.

Purpose: To study the pharmacokinetics and pharmacodynamics of once- versus twice-daily oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia (ALL).

Patients And Methods: Fifty-eight patients were randomly assigned to etoposide at 50 mg/m(2)/d with once- versus twice-daily doses for 22 days. On day 8, vincristine, asparaginase, and dexamethasone were started.

Urolithiasis in pediatric patients with acute lymphoblastic leukemia.

We evaluated the incidence, timing, and consequences of urolithiasis in children with acute lymphoblastic leukemia (ALL). A total of 20 patients with urolithiasis were identified from 2095 patients with ALL treated at St Jude Children's Research Hospital on consecutive protocols between 1968 and 1998. For remission induction therapy, all patients received daily prednisone; continuation chemotherapy regimens differed by protocol with some including pulses of prednisone or dexamethasone and others no glucocorticoid.

A pilot study of protracted topotecan dosing using a pharmacokinetically guided dosing approach in children with solid tumors.

Purpose: To assess the use of a pharmacokinetically guided topotecan strategy and evaluate the toxicity of protracted i.v. topotecan in children with recurrent solid tumors.

Survival and functional outcome of children with hypothalamic/chiasmatic tumors.

Background: The management of children with hypothalamic (H) and/or chiasmatic (C) tumors remains controversial. We evaluated the impact of clinical and neuroimaging parameters and primary therapy on overall (OS) and progression-free (PFS) survival and on neuroendocrine and neurocognitive outcome in children with H and/or C tumors.

Methods: Records were reviewed for 73 children with H and/or C tumors treated at St.

Risk factors for traumatic and bloody lumbar puncture in children with acute lymphoblastic leukemia.

Context: Traumatic or bloody lumbar puncture (LP) reduces the diagnostic value of the procedure and may worsen the outcome of patients with acute lymphoblastic leukemia (ALL). Little is known about the risk factors for traumatic and bloody LP.

Objectives: To determine the risk factors for traumatic and bloody LP.

Medulloblastoma metastatic to the suprasellar region at diagnosis: a report of six cases with clinicopathologic correlation.

The presence of metastatic disease in patients newly diagnosed with medulloblastoma remains one of the most important prognostic factors that determines event-free survival. In the present study, anatomic distribution and the signal characteristics and enhancement patterns of subtle anterior third ventricular recess metastases were compared with those of the original tumor; medical records were reviewed for clinical presentation, surgical stage, treatment and long-term outcomes. All foci were clinically occult; 5 out of 6 had negative cerebrospinal fluid cytology, and in 4 out of 6, the only evidence of metastatic disease was documented suprasellar disease that resolved or significantly improved following irradiation and chemotherapy.

Decline in corpus callosum volume among pediatric patients with medulloblastoma: longitudinal MR imaging study.

Background And Purpose: A decline in intrahemispheric cerebral white matter volume in children treated for brain tumors with cranial irradiation has been well documented. It was hypothesized that the development of the corpus callosum, the largest white matter commissure of the brain, would also be adversely affected after treatment with cranial irradiation in pediatric patients treated for medulloblastoma.

Methods: After diagnosis, 35 patients (22 male and 13 female patients) with histologically proved medulloblastoma were treated by maximal surgical resection, risk-adapted craniospinal irradiation, and chemotherapy.