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PubMed1994

Cognitive deficits in long-term survivors of childhood medulloblastoma and other noncortical tumors: age-dependent effects of whole brain radiation.

Twenty-four children, aged 1.5-20 yr at diagnosis, with noncortical brain tumors, primarily medulloblastoma, have been followed for 3-4 yr for intellectual status. All the children received craniospinal irradiation, and 19 of 24 received chemotherapy as well. For the group as a whole. Full Scale IQ fell from 104 at baseline to 91 at final follow-up. Children younger than 7 yr at diagnosis showed a significant decrease in IQ as early as year 1, and all changes from baseline to years 3 and 4 were significant. In contrast, children older than 7 yr at diagnosis did not show a significant IQ change from baseline to year 3 or 4. The Spearman correlation coefficient between IQ change and age at diagnosis from baseline to year 4 was 0.57 (P = 0.003). This study supports the hypothesis that children treated with whole brain radiation at a younger age have more severe cognitive impairment than those treated at a later age. Limitations in sample size and duration of observations do not permit us to identify whether a true plateau occurs 2-4 yr after irradiation versus a continued progressive decline in intellectual performance. Moreover, we cannot at this time distinguish between a true dementing process versus failure to acquire new cognitive skills at a rate comparable to age-matched peers.

Adolescent↗
PubMedDate not supplied

MR findings of posterior fossa hemangioblastomas.

MR findings of five posterior fossa hemangioblastomas were reported. In the cystic type, a cyst was low intensity on T1WI and high intensity on T2WI. Mural nodule was clearly enhanced by Gd-DTPA. In the solid type, the tumor was shown as an isointense lesion on T1WI and as high intensity on T2WI, but it was markedly and homogeneously enhanced by Gd-DTPA. Multiple extremely low-intensity serpentine "flow void" signs, indicating afferent and efferent vessels, were observed within or around the tumor. These were characteristic pictures in this tumor.

Adult↗
PubMedDate not supplied

Osseous metastasis in medulloblastoma: MRI findings in an unusual case.

An 11-year-old boy with a history of medulloblastoma developed blastic osseous metastases. The metastases were detected by noting diffuse areas of low signal intensity within the calvarium on T1-weighted and T2-weighted magnetic resonance (MR) scans of the brain. The MR appearance of osseous metastases in medulloblastoma has not been reported previously. Extraneural metastases in medulloblastoma are relatively rare. The literature is briefly reviewed.

Bone Neoplasms↗
PubMedDate not supplied

MRI of dorsal mesencephalic lipomas.

We detected 23 intracranial lipomas using MRI. Among them were nine pericallosal lipomas, six lipomas at the dorsal surface of the midbrain, and eight in other locations. In this paper, six lipomas at the dorsal surface of the midbrain were analyzed. Five of these lipomas were in the quadrigeminal cistern and one in the left-sided quadrigeminal cistern. Excluding the smallest lipoma, five of the six lipomas had irregular margins and were broadly based on the surface of the midbrain. In these five cases, deformities of the brain parenchyma were observed adjacent to the lipomas. A mildly dilated ventricular system was observed in one of the largest lipomas in a quadrigeminal cistern. Based on their characteristic shapes and locations, we termed them "dorsal mesencephalic lipomas." Thus, the two preferential sites of intracranial lipomas were pericallosal and dorsal mesencephalic.

Adolescent↗
PubMed1992

In vitro karyotypic and immunophenotypic characterisation of primitive neuroectodermal tumours: similarities to malignant gliomas.

Monoclonal antibody (Mab) mediated immunotherapy of brain tumours requires the identification of tumour-restricted cell surface antigens. We have characterised four primitive neuroectodermal tumours, which included pineoblastoma, medulloblastoma and ependymoblastoma cultures, that demonstrated in vitro evidence of malignant behaviour (anchorage-independent growth and nu/nu xenograft tumour formation). The cytogenetic findings ranged from normal G-banded and Q-banded karyotypes through mixed near-diploid/hyperdiploid. These cultures resembled the cell surface immunophenotypic spectrum of malignant gliomas. They were distinguished from normal glia in vitro by the expression of restricted fetal mesenchymal, neuronal, myoblastic, melanocytic, epidermal, chondrocytic, lymphoid and epithelial antigens. Certain antigens appeared sufficiently represented among central nervous system (CNS) neoplasms to afford potential targets for Mab-mediated immunotherapy.

Adolescent↗
PubMed2004

Further clues concerning the aetiology of childhood central nervous system tumours.

Previously, we reported space-time clustering and seasonal variation in childhood central nervous system (CNS) tumours for the period 1954-1998. These previous studies provided evidence that infections may be involved in aetiology. To determine whether there were also localised spatial factors involved in aetiology we analysed the geographical distribution of CNS tumours in children aged 0-14 years using Manchester Children's Tumour Registry (MCTR) data for the period 1976-2000. Specifically, the Potthoff-Whittinghill test for spatial clustering was applied and Poisson regression was used to analyse the relationship between incidence rates and small-area population density, ethnic composition and deprivation index. No relationships were seen for all CNS tumours together and only a few for the subgroups. The previous findings of space-time clustering and seasonal variation, involving astrocytoma and ependymoma, together with the lack of spatial clustering and ecological relationships for these tumours provide evidence that astrocytoma and ependymoma may be associated with a highly mobile transient aetiological agent. An example of such an agent is an infection that occurs in mini-epidemics.

Adolescent↗
PubMed2005

Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques?

PURPOSE: To calculate treatment plans and compare the dose distributions and dose-volume histograms (DVHs) for photon three-dimensional conformal radiation therapy (3D-CRT), electron therapy, intensity-modulated radiation therapy (IMRT), and standard (nonintensity modulated) proton therapy in three pediatric disease sites. METHODS AND MATERIALS: The tumor volumes from 8 patients (3 retinoblastomas, 2 medulloblastomas, and 3 pelvic sarcomas) were studied retrospectively to compare DVHs from proton therapy with 3D-CRT, electron therapy, and IMRT. In retinoblastoma, several planning techniques were analyzed: A single electron appositional beam was compared with a single 3D-CRT lateral beam, a 3D-CRT anterior beam paired with a lateral beam, IMRT, and protons. In medulloblastoma, three posterior fossa irradiation techniques were analyzed: 3D-CRT, IMRT, and protons. Craniospinal irradiation (which consisted of composite plans of both the posterior fossa and craniospinal components) was also evaluated, primarily comparing spinal irradiation using 3D-CRT electrons, 3D-CRT photons, and protons. Lastly, in pelvic sarcoma, 3D-CRT, IMRT, and proton plans were assessed. RESULTS: In retinoblastoma, protons resulted in the best target coverage combined with the most orbital bone sparing (10% was the mean orbital bone volume irradiated at > or =5 Gy for protons vs. 25% for 3D-CRT electrons, 69% for IMRT, 41% for a single 3D lateral beam, 51% for a 3D anterolateral beam with a lens block, and 65% for a 3D anterolateral beam without a lens block). A single appositional electron field was the next best technique followed by other planning approaches. In medulloblastoma, for posterior fossa and craniospinal irradiation, protons resulted in the least dose to the cochlea (for only posterior fossa irradiation at > or =20 Gy, 34% was the mean cochlear volume irradiated for protons, 87% for IMRT, 89% for 3D-CRT) and hypothalamus-pituitary axis (for only posterior fossa irradiation at > or =10 Gy, 21% was the mean hypothalamus-pituitary volume irradiated for protons, 81% for IMRT, 91% for 3D-CRT); additional dose reductions to the optic chiasm, eyes, vertebrae, mandible, thyroid, lung, kidneys, heart, and liver were seen. Intensity-modulated radiotherapy appeared to be the second best technique for posterior fossa irradiation. For spinal irradiation 3D-CRT electrons were better than 3D-CRT photons in sparing dose to the thyroid, heart, lung, kidney, and liver. With pelvic sarcoma, protons were superior in eliminating any dose to the ovaries (0% of mean ovarian volume was irradiated at > or =2 Gy with protons) and to some extent, the pelvic bones and vertebrae. Intensity-modulated radiotherapy did show more bladder dose reduction than the other techniques in pelvic sarcoma irradiation. CONCLUSIONS: In the diseases studied, using various techniques of 3D-CRT, electrons, IMRT, and protons, protons are most optimal in treating retinoblastomas, medulloblastomas (posterior fossa and craniospinal), and pelvic sarcomas. Protons delivered superior target dose coverage and sparing of normal structures. As dose-volume parameters are expected to correlate with acute and late toxicity, proton therapy should receive serious consideration as the preferred technique for the treatment of pediatric tumors.

Adolescent↗
PubMed2005

Meningiomas after medulloblastoma irradiation treatment in a patient with basal cell nevus syndrome.

A 23-year-old woman with basal cell nevus syndrome (BCNS), or Gorlin's syndrome, was given the diagnosis at age 2 years of a medulloblastoma that was resected and treated postoperatively with craniospinal irradiation. Multiple basal cell carcinomas developed at the craniospinal irradiation port site 8 years later. She subsequently developed multiple meningiomas within the area of irradiation at age 20 years. This case reviews early presentation of BCNS, newly described differences between medulloblastomas in patients with BCNS and nonsyndromic medulloblastomas, and global assessment of patients by the treating dermatologist of this patient population. This is the first report in the dermatologic literature, to our knowledge, of radiation-induced meningiomas in a patient with BCNS.

Adult↗
PubMed2004

In vivo quantification of the metabolites in normal brain and brain tumors by proton MR spectroscopy using water as an internal standard.

Metabolite concentrations in normal adult brains and in gliomas were quantitatively analyzed by in vivo proton magnetic resonance spectroscopy (MRS) using the fully relaxed water signal as an internal standard. Between January 1998 and October 2001, 28 healthy volunteers and 18 patients with gliomas were examined by in vivo proton MRS. Single-voxel spectra were acquired using the point-resolved spectroscopic (PRESS) pulse sequence with a 1.5 T scanner (TR/TE/Ave = 3000 ms/30 ms/64). The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre), choline (Cho), and water(H(2)O) in the normal hemispheric white matter were 23.59 +/- 2.62 mM (mean +/- SD), 13.06 +/- 1.8 mM, 4.28 +/- 0.8 mM, and 47280.96 +/- 5414.85 mM, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). The NAA/Cho and NAA/H(2)O ratios can distinguish the normal brain from gliomas and low-grade from high-grade astrocytoma (p < 0.001). The concentration of taurine (Tau) in medulloblastomas was 29.64 +/- 5.76 mM. This is the first quantitative analysis of Tau in medulloblastoma in vivo and confirms earlier in vitro findings.

Adolescent↗
PubMed2003

hTERT gene amplification and increased mRNA expression in central nervous system embryonal tumors.

High-level gains at 5p15, a chromosomal region including the human telomerase catalytic protein subunit (hTERT) gene, have been documented in several medulloblastomas. We therefore analyzed hTERT gene dosage in a group of medulloblastomas and other embryonal brain tumors using differential PCR. Amplification of the hTERT locus was detected in 15 of 36 (42%) tumors examined. To correlate gene amplification with message level, we used real-time quantitative PCR to measure hTERT mRNA in 50 embryonal brain tumors. hTERT mRNA was detected in all but one of these cases, and mRNA level correlated significantly with gene dosage (r = 0.82). Log-rank analysis of survival data revealed a trend toward poor clinical outcomes in patients with medulloblastomas containing high hTERT mRNA levels, but clinical follow-up was relatively short and the association was not statistically significant (P = 0.078). Comparative genomic hybridization was used to further analyze the tumor with the greatest hTERT gene dosage and mRNA level, a recurrent medulloepithelioma. hTERT was amplified in the recurrent tumor but not in the primary lesion, suggesting this locus can be involved in tumor progression. Our data indicate that hTERT gene amplification is relatively common in embryonal brain tumors, and that increased expression of hTERT mRNA may be associated with biologically aggressive tumor behavior.

Adolescent↗
PubMed2003

Development of brain metastasis 5 years before the appearance of the primary lung cancer: "messenger metachronous metastasis".

We report a patient with a brain metastasis that presented 5 years before the primary adenocarcinoma of the lung from which it originated. The metastasis and the primary tumor were removed. To confirm their common origin, we used comparative genomic hybridization. We have named this type of metastasis "messenger metachronous metastasis." The patient remains well 79 months after the brain metastasectomy and 18 months after the lung surgery.

Adenocarcinoma↗
PubMed1975

CCNU in brain tumours.

CCNU, a nitrosourea compound, has been found effective in the management of both primary and secondary tumours of the brain. It is proposed to carry out an investigation comparing radiotherapy alone with radiotherapy and CCNU combined, in cerebral gliomata.

Adolescent↗
PubMed1987

Second malignant neoplasms after childhood cancer: a report of three cases of osteogenic sarcoma.

The rising incidence of second malignant neoplasms after childhood cancer, whilst due in part to increasing numbers of survivors, is also thought to be related to increasingly more intensive combined modality treatment schedules. Three illustrative cases are reported in which radiation therapy in childhood for the first cancer is thought to have been a significant aetiological factor in the pathogenesis of the second malignancy (which in all three patients was an osteogenic sarcoma).

Bone Neoplasms↗
PubMed1987

Massive gastrointestinal hemorrhage in children with posterior fossa tumors.

Over a 12-month period (September 1984 to September 1985), 64 children with newly diagnosed brain tumors were admitted to the Neurosurgical Service at The Children's Hospital of Philadelphia. Of these children, 29 had posterior fossa tumors. Of this population of children with posterior fossa tumors, three patients aged 4 months, 22 months, and 4 years old developed massive exsanguinating upper gastrointestinal hemorrhage within seven days of their primary neurosurgical procedure. In each instance, large posterior duodenal ulcers were encountered and were treated with oversewing of the duodenal ulcer and vagotomy-pyloroplasty. Follow-up currently ranges from 18 to 26 months. All three children have survived and none have had any gastrointestinal bleeding since then. Massive exsanguinating hemorrhage was not seen in children with brain tumors in locations other than the posterior fossa. In this population of patients, we advocate the use of prophylactic cimetidine and titration of gastric acidity with antacids.

Antacids↗
PubMed1984

Nuclear magnetic resonance imaging of the brain in children.

Nuclear magnetic resonance imaging of the hydrogen nucleus provides a unique noninvasive display of proton dynamics in biologic tissues and fluids as well as internal anatomy in a sectional imaging format. No ionizing radiation is utilized. Our experience with NMR imaging of the brain in 14 pediatric patients is presented and compared with computed tomography. The major advantages of NMR over CT include its greater sensitivity to blood flow, edema, hemorrhage, and myelinization and its lack of beam-hardening artifacts. In addition, the potential for tissue characterization exists by determination of T1 and T2 relaxation times and of mobile proton density. Disadvantages of NMR over CT include its failure to demonstrate calcification and bone detail and longer data acquisition times.

Adolescent↗