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Journal of Neurosurgery. Pediatrics Jun 2011Thalamopeduncular tumors arise at the junction of the inferior thalamus and cerebral peduncle and present with a common clinical syndrome of progressive spastic...
OBJECT
Thalamopeduncular tumors arise at the junction of the inferior thalamus and cerebral peduncle and present with a common clinical syndrome of progressive spastic hemiparesis. Pathologically, these lesions are usually juvenile pilocytic astrocytomas and are best treated with resection with the intent to cure. The goals of this study are to define a common clinical syndrome produced by thalamopeduncular tumors and to discuss imaging characteristics as well as surgical adjuncts, intraoperative nuances, and postoperative complications relating to the resection of these neoplasms.
METHODS
The authors present a retrospective review of their experience with 10 children presenting between 3 and 15 years of age with a thalamopeduncular syndrome. Formal preoperative MR imaging was obtained in all patients, and diffusion tensor (DT) imaging was performed in 9 patients. Postoperative MR imaging was obtained to evaluate the extent of tumor resection. A prospective analysis of clinical outcomes was then conducted by the senior author.
RESULTS
Pilocytic astrocytoma was the pathological diagnosis in 9 cases, and the other was fibrillary astrocytoma. Seven of 9 pilocytic astrocytomas were completely resected. Radical surgery was avoided in 1 child after DT imaging revealed that the corticospinal tract (CST) coursed through the center of the tumor, consistent with the infiltrative nature of fibrillary astrocytoma as identified by stereotactic biopsy. In 8 patients, tractography served as an important adjunct for designing a surgical approach that spared the CST. In 6 cases the CSTs were pushed anterolaterally, making a transsylvian approach a poor choice, as was evidenced by the first patient in the series, who underwent operation prior to the advent of tractography, and who awoke with a dense contralateral hemiparesis. Thus, subsequent patients with this deviation pattern underwent a transcortical approach via the middle temporal gyrus. One patient exhibited medial deviation of the tracts and another had lateral deviation, facilitating a transtemporal and a transfrontal approach, respectively.
CONCLUSIONS
The thalamopeduncular syndrome of progressive spastic hemiparesis presenting in children with or without symptoms of headache should alert the examiner to the possibility of a tumoral involvement of CSTs. Preoperative tractography is a useful adjunct to surgical planning in tumors that displace motor pathways. Gross-total resection of pilocytic astrocytomas usually results in cure, and therefore should be entertained when developing a treatment strategy for thalamopeduncular tumors of childhood.
Topics: Adolescent; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Diffusion Tensor Imaging; Female; Headache; Humans; Magnetic Resonance Imaging; Male; Mesencephalon; Neurosurgical Procedures; Paresis; Postoperative Complications; Retrospective Studies; Syndrome; Thalamic Diseases; Thalamus; Treatment Outcome
PubMed: 21631193
DOI: 10.3171/2011.4.PEDS119 -
Turkish Neurosurgery 2011Pilomyxoid astrocytoma (PMA) is a recently described neoplasm. PMA shares few features with pilocytic astrocytoma (PA), the most common central nervous system (CNS)...
Pilomyxoid astrocytoma (PMA) is a recently described neoplasm. PMA shares few features with pilocytic astrocytoma (PA), the most common central nervous system (CNS) tumor in the pediatric population, yet displays histological differences. Previous studies have shown that PMAs have more aggressive biological behavior as compared to PA. These findings suggest that PMA may be a unique and distinct neoplasm. We report a pilomyxoid astrocytoma of the hypothalamic-chiasmatic region with leptomeningeal dissemination in a 3-month old infant. This case report discusses the histological, clinical, and radiographic characteristics of PMA. In addition, the current treatment options and research potential involving this disease are also briefly described.
Topics: Astrocytoma; Fatal Outcome; Humans; Hypothalamic Neoplasms; Infant; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Optic Chiasm; Subarachnoid Space
PubMed: 21534206
DOI: 10.5137/1019-5149.JTN.2638-09.1 -
Journal of Korean Neurosurgical Society Nov 2010Pilomyxoid astrocytoma (PMA) is a newly recognized variant of a pilocytic astrocytoma. This report describes a case of a pilomyxoid astrocytoma that occurred in the...
Pilomyxoid astrocytoma (PMA) is a newly recognized variant of a pilocytic astrocytoma. This report describes a case of a pilomyxoid astrocytoma that occurred in the opticohypothalamus. The patient was a 18-year-old girl who complained decreased visual acuity and visual field over a period of two years. Magnetic resonance imaging (MRI) showed an irregular lobulated tumor with heterogeneous enhancement at the suprasellar region involving the hypothalamus. The mass was partially removed via the subfrontal approach. Its pathology was confirmed to be PMA. Adjuvant chemotherapy with cisplatin and vincristine was started following tumor resection. After four cycles, the mass showed a partial response to the chemotherapy. Although long-term outcome is yet to be determined, the administration of combined cisplatin and vincristine treatment seems to be an effective regimen for a pilomyxoid astrocytoma.
PubMed: 21286484
DOI: 10.3340/jkns.2010.48.5.445 -
Journal of Clinical Oncology : Official... Jan 2011A phase I trial of lenalidomide was performed in children with recurrent, refractory, or progressive primary CNS tumors to estimate the maximum-tolerated dose (MTD) and...
PURPOSE
A phase I trial of lenalidomide was performed in children with recurrent, refractory, or progressive primary CNS tumors to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile and pharmacokinetics.
PATIENTS AND METHODS
Lenalidomide was administered by mouth daily for 21 days, repeated every 28 days. The starting dose was 15 mg/m(2)/d orally, and the dose was escalated according to a modified continuous reassessment method. Correlative studies included pharmacokinetics obtained from consenting patients on course 1, day 1, and at steady-state (between days 7 and 21).
RESULTS
Fifty-one patients (median age, 10 years; range, 2 to 21 years) were enrolled. Forty-four patients were evaluable for dose finding, and 49 patients were evaluable for toxicity. The primary toxicity was myelosuppression, but the MTD was not defined because doses up to 116 mg/m(2)/d were well-tolerated during the dose-finding period. Two objective responses were observed (one in thalamic juvenile pilocytic astrocytoma and one in optic pathway glioma) at dose levels of 88 and 116 mg/m(2)/d. Twenty-three patients, representing all dose levels, received ≥ six cycles of therapy. Pharmacokinetic analysis demonstrated that the lenalidomide area under the concentration-time curve from 0 to 24 hours and maximum plasma concentration increased with dosage over the range studied.
CONCLUSION
Lenalidomide was tolerable in children with CNS tumors at doses of 116 mg/m(2)/d during the initial dose-finding period. The primary toxicity is myelosuppression. Antitumor activity, defined by both objective responses and long-term stable disease, was observed, primarily in patients with low-grade gliomas.
Topics: Administration, Oral; Adolescent; Antineoplastic Agents; Area Under Curve; Central Nervous System Neoplasms; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Lenalidomide; Male; Maximum Tolerated Dose; Recurrence; Thalidomide; Young Adult
PubMed: 21149652
DOI: 10.1200/JCO.2010.31.3601 -
AJNR. American Journal of Neuroradiology Feb 2011Focal anaplasia characterized by T2 hypointensity, signal-intensity enhancement on postcontrast T1-weighted MR imaging and restricted water diffusion has been reported... (Comparative Study)
Comparative Study
Quantitative diffusion-weighted and dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging analysis of T2 hypointense lesion components in pediatric diffuse intrinsic pontine glioma.
BACKGROUND AND PURPOSE
Focal anaplasia characterized by T2 hypointensity, signal-intensity enhancement on postcontrast T1-weighted MR imaging and restricted water diffusion has been reported in a patient with juvenile pilocytic astrocytoma. We identified T2(HOF) with these MR imaging characteristics in children with DIPG and hypothesized that these represent areas of focal anaplasia; and may, therefore, have increased perfusion properties and should be characterized by increased perfusion. Thus, we used DSC to investigate our hypothesis.
MATERIALS AND METHODS
We retrospectively reviewed the baseline MR imaging scans of 86 patients (49 girls, 37 boys; median age, 6.1 years; range, 1.1-17.6 years) treated for DIPG at our hospital (2004-2009). T2(HOF) with the described MR imaging characteristics was identified in 10 patients. We used a region of interest-based approach to compare the ADC, FA, rCBV, rCBF, and rMTT of T2(HOF) with those of the typical T2(HRT).
RESULTS
The ADC of T2(HOF) with the specified MR imaging characteristics was significantly lower than that of T2(HRT) (range, 0.71-1.95 μm(2)/ms versus 1.36-2.13 μm(2)/ms; P < .01); and the FA (range, 0.12-0.34 versus 0.07-0.24; P = .03) and rCBV (range, 0.4-2.62 versus 0.23-1.57; P = .01) values of T2(HOF)s were significantly higher.
CONCLUSIONS
Our data suggest that T2(HOF) in DIPG may represent areas of focal anaplasia and underline the importance of regional, rather than global, tumor-field analysis. T2(HOF) may be the ideal target when stereotactic biopsy of tumors that present with an inhomogeneous T2 signal intensity is considered.
Topics: Adolescent; Biopsy; Brain Stem Neoplasms; Child; Child, Preschool; Contrast Media; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Infant; Male; Necrosis; Retrospective Studies
PubMed: 21087935
DOI: 10.3174/ajnr.A2277 -
Child's Nervous System : ChNS :... Mar 2011This study seeks to characterize magnetic resonance imaging (MRI) changes following stereotactic radiosurgery (SRS) of pediatric brain malignancies.
PURPOSE
This study seeks to characterize magnetic resonance imaging (MRI) changes following stereotactic radiosurgery (SRS) of pediatric brain malignancies.
METHODS
Serial MRI evaluations were performed on 21 lesions treated with SRS for either medulloblastoma (n=12), juvenile pilocytic astrocytoma (n=4), ependymoma (n=2), atypical rhabdoid teratoid tumor (n=2), or pineocytoma (n=1). Prescription doses ranged from 14 to 30 Gy in one to five fractions. Tumor response was qualified as complete (CR), partial (PR), stable disease (SD), or progressive disease (PD) according to the RECIST v1.1. Median radiographic follow-up after SRS was 17 months.
RESULTS
A total of 80 follow-up MRI scans were reviewed with a median of eight per patient. During serial MRI evaluation, eight lesions met criteria for PD at a median of 6 months. However, of these, three (37%) represented transient tumor edema with two lesions later developing a CR at a median of 15 months and one persisting as SD at 12 months. The remaining five lesions were true local failures. Of the 13 lesions that did not show evidence of PD, a CR was obtained in 11 lesions at a median of 3 months (range, 2-6), and SD was seen in the remaining two tumors at last follow-up.
CONCLUSION
Lesion enlargement following SRS for pediatric intracranial tumors is common, and a proportion of patients meeting requirements for PD at early radiographic follow-up may later develop complete resolution of their lesions. Physicians should be aware of these radiographic changes to avoid unwarranted medical and surgical interventions.
Topics: Adolescent; Brain; Brain Neoplasms; Child; Child, Preschool; Glioma; Humans; Magnetic Resonance Imaging; Radiosurgery; Treatment Outcome; Young Adult
PubMed: 20927529
DOI: 10.1007/s00381-010-1288-6 -
Pediatric Blood & Cancer Oct 2010AZD6244 (ARRY-142886) is a potent small molecule inhibitor of MEK1/2 that is in phase 2 clinical development.
BACKGROUND
AZD6244 (ARRY-142886) is a potent small molecule inhibitor of MEK1/2 that is in phase 2 clinical development.
PROCEDURES
AZD6244 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel (1 nM-10 microM). In vivo AZD6244 was tested at a dose of 100 mg/kg administered orally twice daily 5 days per week for 6 weeks. Subsequently, AZD6244 was evaluated against two juvenile pilocytic astrocytoma (JPA) xenografts using once and twice daily dosing schedules. Phosphorylation of ERK1/2 was used as a surrogate for in vivo inhibition of MEK1/2 was determined by immunoblotting.
RESULTS
At the highest concentration used in vitro (10 microM) AZD6244 only inhibited growth by 50% in 5 of the 23 cell lines. Against the in vivo tumor panels, AZD6244 induced significant differences in EFS distribution in 10 of 37 (27%) solid tumor models and 0 of 6 acute lymphoblastic leukemia (ALL) models. There were no objective responses. Pharmacodynamic studies indicated at this dose and schedule AZD6244 completely inhibited ERK1/2 phosphorylation. AZD6244 was evaluated against two JPA xenografts, BT-35 (wild-type BRAF) and BT-40 (mutant [V600E] BRAF). BT-40 xenografts were highly sensitive to AZD6244, whereas BT-35 xenografts progressed on AZD6244 treatment.
CONCLUSIONS
At the dose and schedule of administration used, AZD6244 as a single agent had limited in vitro and in vivo activity against the PPTP tumor panels despite inhibition of MEK1/2 activity. However, AZD6244 was highly active against BT-40 JPA xenografts that harbor constitutively activated BRAF, causing complete regressions.
Topics: Animals; Benzimidazoles; Child; Drug Screening Assays, Antitumor; Female; Humans; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase Kinases; Mutation; Neoplasms; Proto-Oncogene Proteins B-raf; Xenograft Model Antitumor Assays
PubMed: 20806365
DOI: 10.1002/pbc.22576 -
Brain Pathology (Zurich, Switzerland) Jul 2010KIT receptor tyrosine kinase is expressed in tumor endothelial cells of adult glioblastomas, but its expression in pediatric brain tumor endothelial cells is unknown. We...
KIT receptor tyrosine kinase is expressed in tumor endothelial cells of adult glioblastomas, but its expression in pediatric brain tumor endothelial cells is unknown. We assessed expression of KIT, phosphorylated KIT, stem cell factor (SCF) and vascular endothelial growth factor receptor-2 (VEGFR-2) in 35 juvenile pilocytic astrocytomas and 49 other pediatric brain tumors using immunohistochemistry, and KIT messenger RNA (mRNA) using in situ hybridization. KIT and phospho-KIT were moderately or strongly expressed in tumor endothelia of 37% and 35% of pilocytic astrocytomas, respectively, whereas marked SCF and VEGFR-2 expression was uncommon. KIT mRNA was detected in tumor endothelial cells. Tumor endothelial cell KIT expression was strongly (P < 0.01) associated with endothelial cell phospho-KIT and SCF expression, and with tumor KIT (P = 0.0011) and VEGFR-2 expression (P = 0.022). KIT and phospho-KIT were present in endothelia of other pediatric brain tumors, notably ependymomas. Endothelial cell KIT expression was associated with a young age at diagnosis of pilocytic astrocytoma or ependymoma, and it was occasionally present in histologically normal tissue of the fetus and children. We conclude that KIT is commonly present in endothelial cells of juvenile brain tumors and thus may play a role in angiogenesis in these neoplasms.
Topics: Adolescent; Age Factors; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Endothelial Cells; Ependymoma; Humans; Immunohistochemistry; In Situ Hybridization; Infant; Infant, Newborn; Phosphorylation; Proto-Oncogene Proteins c-kit; RNA, Messenger; Statistics, Nonparametric; Vascular Endothelial Growth Factor Receptor-2; Young Adult
PubMed: 20030644
DOI: 10.1111/j.1750-3639.2009.00357.x -
British Journal of Cancer Aug 2009Juvenile pilocytic astrocytomas (JPA), a subgroup of low-grade astrocytomas (LGA), are common, heterogeneous and poorly understood subset of brain tumours in children....
BACKGROUND
Juvenile pilocytic astrocytomas (JPA), a subgroup of low-grade astrocytomas (LGA), are common, heterogeneous and poorly understood subset of brain tumours in children. Chromosomal 7q34 duplication leading to fusion genes formed between KIAA1549 and BRAF and subsequent constitutive activation of BRAF was recently identified in a proportion of LGA, and may be involved in their pathogenesis. Our aim was to investigate additional chromosomal unbalances in LGA and whether incidence of 7q34 duplication is associated with tumour type or location.
METHODS AND RESULTS
Using Illumina-Human-Hap300-Duo and 610-Quad high-resolution-SNP-based arrays and quantitative PCR on genes of interest, we investigated 84 paediatric LGA. We demonstrate that 7q34 duplication is specific to sporadic JPA (35 of 53 - 66%) and does not occur in other LGA subtypes (0 of 27) or NF1-associated-JPA (0 of 4). We also establish that it is site specific as it occurs in the majority of cerebellar JPA (24 of 30 - 80%) followed by brainstem, hypothalamic/optic pathway JPA (10 of 16 - 62.5%) and is rare in hemispheric JPA (1 of 7 - 14%). The MAP-kinase pathway, assessed through ERK phosphorylation, was active in all tumours regardless of 7q34 duplication. Gain of function studies performed on hTERT-immortalised astrocytes show that overexpression of wild-type BRAF does not increase cell proliferation or baseline MAPK signalling even if it sensitises cells to EGFR stimulation.
CONCLUSIONS AND INTERPRETATION
Our results suggest that variants of JPA might arise from a unique site-restricted progenitor cell where 7q34 duplication, a hallmark of this tumour-type in association to MAPK-kinase pathway activation, potentially plays a site-specific role in their pathogenesis. Importantly, gain of function abnormalities in components of MAP-Kinase signalling are potentially present in all JPA making this tumour amenable to therapeutic targeting of this pathway.
Topics: Adolescent; Astrocytoma; Biomarkers, Tumor; Blotting, Western; Brain Neoplasms; Carrier Proteins; Child; Child, Preschool; Chromosomes, Human, Pair 7; Female; Fluorescent Antibody Technique; Gene Dosage; Gene Duplication; Humans; Immunohistochemistry; Male; Mitogen-Activated Protein Kinases; Polymorphism, Single Nucleotide; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins B-raf; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction
PubMed: 19603027
DOI: 10.1038/sj.bjc.6605179 -
Child's Nervous System : ChNS :... Jul 2009The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear...
OBJECTIVE
The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator.
MATERIALS AND METHODS
Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1-18 months, with a median follow-up of 6 months.
RESULTS
Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3-18 months) with no in-field failures and were able to obtain encouraging toxicity profiles.
CONCLUSION
Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity.
Topics: Adolescent; Astrocytoma; Brain Neoplasms; Child; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Medulloblastoma; Neoplasm Metastasis; Pineal Gland; Pinealoma; Pituitary Neoplasms; Prolactinoma; Radiosurgery; Radiotherapy; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 19326128
DOI: 10.1007/s00381-009-0840-8