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Journal of AAPOS : the Official... Oct 2017To describe the clinical characteristics and visual and ocular motor outcomes of a large cohort of pediatric patients treated for tumors of the posterior cranial fossa.
PURPOSE
To describe the clinical characteristics and visual and ocular motor outcomes of a large cohort of pediatric patients treated for tumors of the posterior cranial fossa.
METHODS
The medical records of all patients with posterior fossa tumors evaluated by the ophthalmology services at two large tertiary care academic hospitals between 2005 and 2011 were reviewed retrospectively. Data abstracted for each study patient included demographic information, presenting signs and symptoms, pathologic diagnosis, and results of the most recent ophthalmology examination.
RESULTS
A total of 139 patients were included. Visual outcomes were categorized as "good" (bilateral acuity of 20/20-20/40) in 101 patients (72.7%), "fair" (<20/40-20/200 in one or both eyes) in 12 patients (8.6%), or "poor" (<20/200 in one or both eyes) in 9 patients (6.5%). Patients with medulloblastoma and ependymoma had a significantly greater risk of a poor or fair visual outcome than those with juvenile pilocytic astrocytoma (both P < 0.05), independent of age and sex. Thirty-two patients (23.0%) developed nystagmus, and 59 patients (42.4%) developed strabismus. Twenty-four patients (17.3%) underwent eye muscle surgery for persistent strabismus.
CONCLUSIONS
The majority of patients had good visual outcomes, although ocular motor abnormalities were common. Tumor type was a significant risk factor for permanent vision loss.
Topics: Adolescent; Astrocytoma; Child; Child, Preschool; Ependymoma; Female; Humans; Infant; Infratentorial Neoplasms; Magnetic Resonance Imaging; Male; Medulloblastoma; Nystagmus, Pathologic; Oculomotor Muscles; Retrospective Studies; Strabismus; Visual Acuity
PubMed: 28867398
DOI: 10.1016/j.jaapos.2017.05.032 -
Clinical Cancer Research : An Official... Jun 2017Although the neurofibromatoses consist of at least three autosomal dominantly inherited disorders, neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and... (Review)
Review
Although the neurofibromatoses consist of at least three autosomal dominantly inherited disorders, neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis, NF1 represents a multisystem pleiotropic condition very different from the other two. NF1 is a genetic syndrome first manifesting in childhood; affecting multiple organs, childhood development, and neurocognitive status; and presenting the clinician with often complex management decisions that require a multidisciplinary approach. Molecular genetic testing (see article for detailed discussion) is recommended to confirm NF1, particularly in children fulfilling only pigmentary features of the diagnostic criteria. Although cancer risk is not the major issue facing an individual with NF1 during childhood, the condition causes significantly increased malignancy risks compared with the general population. Specifically, NF1 is associated with highly elevated risks of juvenile myelomonocytic leukemia, rhabdomyosarcoma, and malignant peripheral nerve sheath tumor as well as substantial risks of noninvasive pilocytic astrocytoma, particularly optic pathway glioma (OPG), which represent a major management issue. Until 8 years of age, clinical assessment for OPG is advised every 6 to 12 months, but routine MRI assessment is not currently advised in asymptomatic individuals with NF1 and no signs of clinical visual pathway disturbance. Routine surveillance for other malignancies is not recommended, but clinicians and parents should be aware of the small risks (<1%) of certain specific individual malignancies (e.g., rhabdomyosarcoma). Tumors do contribute to both morbidity and mortality, especially later in life. A single whole-body MRI should be considered at transition to adulthood to assist in determining approaches to long-term follow-up. .
Topics: Adolescent; Central Nervous System Neoplasms; Child; Humans; Infant; Magnetic Resonance Imaging; Neurilemmoma; Neurofibromatoses; Neurofibromatosis 1; Optic Nerve Glioma; Skin Neoplasms
PubMed: 28620004
DOI: 10.1158/1078-0432.CCR-17-0589 -
Japanese Journal of Radiology Aug 2017To investigate the contribution of preoperative apparent diffusion coefficient (ADC) values in the differential diagnosis of pediatric posterior fossa tumors.
PURPOSE
To investigate the contribution of preoperative apparent diffusion coefficient (ADC) values in the differential diagnosis of pediatric posterior fossa tumors.
METHODS
Forty-two pediatric patients (mean age 7.76 ± 4.58 years) with intra-axial tumors in the infra-tentorial region underwent magnetic resonance imaging. ADC measurement was performed using regions of interest, obtained from the solid component of the mass lesions. ADC ratios were calculated by dividing the ADC values from the mass lesions by the ADC values from normal cerebellar parenchyma. Lesions were categorized as juvenile pilocytic astrocytoma (JPA), ependymoma and medulloblastoma based on histopathological diagnosis. ADC values of the lesions and histopathological diagnoses were statistically correlated.
RESULTS
Histopathological diagnosis showed that 14 lesions were JPA, 10 were ependymoma; 18 were medulloblastoma. Both ADC values and ADC ratios were significantly correlated with tumor types (p <0.05). Astrocytoma was distinguished from ependymoma with sensitivity 85.7% and specificity 90% using an ADC ratio ≥1.7 and medulloblastoma was distinguished from ependymoma with sensitivity 100% and specificity 88.89% using an ADC ratio ≤1.18.
CONCLUSION
Preoperative ADC values could differentiate the main histological subtypes of pediatric posterior fossa tumors with high sensitivity and specificity.
Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Female; Humans; Infant; Infratentorial Neoplasms; Male; Sensitivity and Specificity
PubMed: 28550357
DOI: 10.1007/s11604-017-0652-9 -
Journal of Neuro-oncology Jun 2017Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae....
Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA -0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p < 0.0001). The cortical thickness change of the right temporal lobe substructures exhibited similar, though attenuated trends (p = 0.002). MB patients exhibit overall increased cortical thickness rather than cortical thinning as seen in JPA patients and as expected in normal cortical development. These observations are possibly due to chemoradiation induced-disruption of normal neuronal mechanisms. Longitudinal image analysis may identify early biomarkers for neurocognitive function with routine imaging.
Topics: Adolescent; Brain Neoplasms; Cerebral Cortex; Chemoradiotherapy; Child; Child, Preschool; Female; Functional Laterality; Humans; Infant; Longitudinal Studies; Magnetic Resonance Imaging; Male; Medulloblastoma; Radiation Injuries; Retrospective Studies; Young Adult
PubMed: 28534154
DOI: 10.1007/s11060-017-2453-5 -
PloS One 2017Growth monitoring of apparently healthy children aims at early detection of serious conditions through the use of both clinical expertise and algorithms that define...
BACKGROUND
Growth monitoring of apparently healthy children aims at early detection of serious conditions through the use of both clinical expertise and algorithms that define abnormal growth. Optimization of growth monitoring requires standardization of the definition of abnormal growth, and the selection of the priority target conditions is a prerequisite of such standardization.
OBJECTIVE
To obtain a consensus about the priority target conditions for algorithms monitoring children's growth.
METHODS
We applied a formal consensus method with a modified version of the RAND/UCLA method, based on three phases (preparatory, literature review, and rating), with the participation of expert advisory groups from the relevant professional medical societies (ranging from primary care providers to hospital subspecialists) as well as parent associations. We asked experts in the pilot (n = 11), reading (n = 8) and rating (n = 60) groups to complete the list of diagnostic classification of the European Society for Paediatric Endocrinology and then to select the conditions meeting the four predefined criteria of an ideal type of priority target condition.
RESULTS
Strong agreement was obtained for the 8 conditions selected by the experts among the 133 possible: celiac disease, Crohn disease, craniopharyngioma, juvenile nephronophthisis, Turner syndrome, growth hormone deficiency with pituitary stalk interruption syndrome, infantile cystinosis, and hypothalamic-optochiasmatic astrocytoma (in decreasing order of agreement).
CONCLUSION
This national consensus can be used to evaluate the algorithms currently suggested for growth monitoring. The method used for this national consensus could be re-used to obtain an international consensus.
Topics: Algorithms; Child; Consensus; Growth and Development; Humans; Interdisciplinary Studies; Pilot Projects
PubMed: 28448550
DOI: 10.1371/journal.pone.0176464 -
International Journal of Particle... 2017Proton therapy is increasingly used to treat pediatric brain tumors. However, the response of both tumors and healthy tissues to proton therapy is currently under...
PURPOSE
Proton therapy is increasingly used to treat pediatric brain tumors. However, the response of both tumors and healthy tissues to proton therapy is currently under investigation. One way of assessing this response is magnetic resonance (MR) diffusion tensor imaging (DTI), which can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). In addition, DTI may reveal axonal fiber directional information in white matter, quantified by fractional anisotropy (FA). Here we report use of DTI to assess tumor and unexposed healthy brain tissue responses in a child who received proton therapy for juvenile pilocytic astrocytoma.
MATERIALS AND METHODS
A 10-year-old boy with recurrent juvenile pilocytic astrocytoma of the left thalamus received proton therapy to a dose of 50.4Gy (RBE) in 28 fractions. Functional magnetic resonance imaging was used to select beam angles for treatment planning. Over the course of the 7-year follow-up period, magnetic resonance imaging including DTI was done to assess response. The MR images were registered to the treatment-planning computed tomography scan, and the gross tumor volume (GTV) was mapped onto the MR images at each follow-up. The GTV contour was then mirrored to the right side of brain through the midline to represent unexposed healthy brain tissue.
RESULTS
Proton therapy delivered the full prescribed dose to the target while completely sparing the contralateral brain. The MR ADC images obtained before and after proton therapy showed that enhancement corresponding to the GTV had nearly disappeared by 25 months. The ADC and FA measurements confirmed that contralateral healthy brain tissue was not affected, and the GTV reverted to clinically normal ADC and FA values.
CONCLUSION
Use of DTI allowed quantitative evaluation of tumor and healthy brain tissue responses to proton therapy.
PubMed: 31772991
DOI: 10.14338/IJPT-16-00024.1 -
BMJ Case Reports Dec 2016
Topics: Astrocytoma; Cerebellar Neoplasms; Cerebellum; Child; Computed Tomography Angiography; Cranial Fossa, Posterior; Fatal Outcome; Humans; Intracranial Aneurysm; Magnetic Resonance Imaging; Male; Subarachnoid Hemorrhage
PubMed: 27927709
DOI: 10.1136/bcr-2016-217583 -
Neurosurgery Dec 2016Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation,...
BACKGROUND
Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense.
OBJECTIVE
To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease.
METHODS
Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue.
RESULTS
NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71).
CONCLUSION
With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity.
ABBREVIATIONS
5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.
Topics: Adult; Aminolevulinic Acid; Brain Neoplasms; Coloring Agents; Contrast Media; Female; Fluorescence; Gadolinium; Ganglioglioma; Glioma; Humans; Indocyanine Green; Magnetic Resonance Imaging; Male; Middle Aged; Optical Imaging; Spectroscopy, Near-Infrared
PubMed: 27741220
DOI: 10.1227/NEU.0000000000001450 -
International Journal of Particle... 2016To describe volume changes following proton beam therapy (PBT) for juvenile pilocytic astrocytoma (JPA), we analyzed post-PBT magnetic resonance imaging (MRI) to clarify...
PURPOSE
To describe volume changes following proton beam therapy (PBT) for juvenile pilocytic astrocytoma (JPA), we analyzed post-PBT magnetic resonance imaging (MRI) to clarify survivorship, response rate, and the concept of pseudoprogression.
MATERIALS AND METHODS
Pediatric patients with a histologic diagnosis of JPA after a biopsy or subtotal resection and at least 4 post-PBT MRIs were retrospectively reviewed. After PBT, tumors were contoured on follow-up T1-contrasted MRIs, and 3-dimensional volumes were plotted against time, with thresholds for progressive disease and partial response. Patterns of response, pseudoprogression, and progression were uncovered. Post-PBT clinical course was described by the need for further intervention and survivorship.
RESULTS
Fifteen patients with a median of 10 follow-up MRIs made up this report: 60% were heavily pretreated with multiple lines of chemotherapy, and 67% had undergone subtotal resection. With a median follow-up of 55.3 months after a median of 5400 centigray equivalents PBT, estimates of 5-year overall survival and intervention-free survival were 93% and 72%, respectively. The crude response rate of 73% included pseudoprogressing patients, who comprised 20% of the entire cohort; the phenomenon peaked between 3 and 8 months and resolved by 18 months. One nonresponder expired from progression. Post-PBT intervention was required in 53% of patients, with 1 patient resuming chemotherapy. There were no further resections or radiotherapy. One patient developed acute lymphoblastic leukemia, and another developed biopsy-proven radionecrosis.
CONCLUSION
The PBT for inoperable/progressive JPA provided 72% 5-year intervention-free survival in heavily pretreated patients. Although most patients responded, 20% demonstrated pseudoprogression. The need for post-PBT surveillance for progression and treatment-induced sequelae should not be underestimated in this extended survivorship cohort.
PubMed: 31772980
DOI: 10.14338/IJPT-16-00020.1 -
Journal of Neurosurgery. Pediatrics Oct 2016OBJECTIVE The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing...
OBJECTIVE The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers. METHODS Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age- and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses. RESULTS Using optimal urinary cutoff values of bFGF > 1.0 pg/μg and TIMP3 > 3.5 pg/μg, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size. CONCLUSIONS This study identifies 2 urinary biomarkers-bFGF and TIMP3-that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.
Topics: Arteriovenous Malformations; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Cell Line, Tumor; Child; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast Growth Factor 2; Fluorescent Antibody Technique; Follow-Up Studies; Humans; Longitudinal Studies; Male; Matrix Metalloproteinase 13; Medulloblastoma; Moyamoya Disease; Multivariate Analysis; Tissue Inhibitor of Metalloproteinase-3
PubMed: 27314542
DOI: 10.3171/2015.12.PEDS15448